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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 July 2019 to 23 January 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
N/A

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
Deviations:
no
Principles of method if other than guideline:
N/A
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
o-xylene
EC Number:
202-422-2
EC Name:
o-xylene
Cas Number:
95-47-6
Molecular formula:
C8H10
IUPAC Name:
o-xylene
Test material form:
liquid
Details on test material:
Batch Number: STBH7551
Appearance: Clear colourless liquid
Retest date: 22 July 2024 and 17 September 2024
Quantity supplied: 7 x 1 L
Purity: 99%
The test iten was stored at room temperatue and a certificated of analysis for it is present as Appendix 16 in the study report
Specific details on test material used for the study:
N/A

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
The rat is a suitable rodent species for toxicity testing, acceptable to regulatory authorities and for which extensive background data are available.
Sex:
male/female
Details on test animals or test system and environmental conditions:
40 male and 40 female rats of the Crl:WI(Han) strain were supplied by Charles River (UK) Limited, Margate, Kent, CT9 4LT, England. The animals were 5 to 6 weeks of age on arrival and on examination were found to be healthy. After 12 days acclimatisation, they were re-examined and confirmed to be suitable for use. On the first day of dosing the males weighed 169 to 231 g and the females weighed 141 to 184 g.

Allocation to groups was performed using the Provantis stratified randomisation procedure based on individual body weights recorded on arrival. The cages were positioned in the battery using a specific cage-plan. Each animal was uniquely identified by a subcutaneously implanted micro-identification device. To aid identification, animals were tail marked with their own unique identification numbers using an indelible pen.

Animals were housed in groups up to five, by sex, in solid-floor cages with bedding provided. Bedding was changed as often as necessary to maintain hygiene.
The study room was illuminated to give a cycle of 12 hours light and 12 hours dark and was air-conditioned. The target ranges for temperature and humidity were 19 °C to 23 °C and 40 % to 70 %, respectively. Recorded values were within, or only marginally outside, these limits.

A pelleted diet, Teklad 2014C Rodent Maintenance Diet, supplied by Envigo RMS (UK) Limited, and mains tap water (in bottles) were freely available.
Certificates of analysis for diet and water are held centrally and retained within the Sequani archives. It was considered that none of the contaminants that were monitored was present at a level that might have prevented the study objective from being achieved.

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
Animals were dosed once daily for at least 90 days, by gavage using a rubber catheter and disposable syringe, at a constant dose volume of 4 mL/kg body weight, until necropsy. Individual doses were adjusted according to the most recent body weight.
Vehicle:
corn oil
Details on oral exposure:
not specified
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples were sent to the Principal Investigator, Dale Burton, at Covance, Eye, Suffolk, IP23 7PX, England for analysis (Covance reference number: WP50YW). The method of analysis used to analyse the dose formulation was validated in Covance Study Number TK45GM
Duration of treatment / exposure:
at least 90 days
Frequency of treatment:
once daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Group 1
Dose / conc.:
100 mg/kg bw/day (nominal)
Remarks:
Group 2
Dose / conc.:
300 mg/kg bw/day (nominal)
Remarks:
Group 3
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
Group 4
No. of animals per sex per dose:
10 animals per sex per dose
Control animals:
yes, concurrent vehicle
Details on study design:
A total of 80 animals were used in this study, where animals were dosed once daily for at least 90 days, by gavage using a rubber cather and disposable syringe, at a constant dose volume of 4 mL/kg body weight, until necropsy. Individual doses were adjusted according to the most recent body weight.
Positive control:
N/A

Examinations

Observations and examinations performed and frequency:
Clinical observations
- Animals were examined twice daily for mortality and mobility
- Detailed clinical examination once each week
- Animals were observed approx. 1 and 2 hours after dosing
- Following the onset of clinical signs, animals were observed at approximately 15 minutes and at one and around four hours after dosing and at the weekend they were observed either at one hour after dosing or at the end of the working day, whichever was sooner
Ophthalmoscopy
- Both eyes of all animals were examined before the start of treatment
Body weight
- All animals were weighed at the start of dosing and then weekly until necropsy
Food intake
- During the treatment period, the amount of food consumed by each cage of animals was recorded weekly until necropsy.
Behavioural observations
- All animals were observed once weekly, starting predose, for their behaviour both within their cage and then after placement in an open arena
Functional observation battery
- During Week 12/13, sensorimotor responses to visual, acoustic, tactile or proprioceptive stimuli, grip strength and motor activity were recorded for all animals on two occasions for each animal, one before dosing and the second after dosing on the same day
Sacrifice and pathology:
Sacrifice
At the end of the treatment period, all animals were killed by exposure to carbon dioxide gas in a rising concentration, weighed and examined externally. The abdominal cavity was opened and the animals were exsanguinated from the caudal vena cava. The cranial and thoracic cavities were opened, a full internal examination was performed and all macroscopic abnormalities were recorded and retained.

Pathology
- macroscopic and microscopic pathology on:
Macroscopic and microscopic pathology on adrenal glands, pancreas, aorta, pituitary, bone marrow smear, prostate & seminal vesicles (incl. coagulating gland), brain (10 levels examined), rectum, caecum, salivary gland (submandibular), colon, sciatic nerve (LS and TS), duodenum, site of mammary gland, epididymides, skeletal muscle, eyes (incl. optic nerves), skin, femur & join (incl. Marrow), spinal cord (3 levels examined LS and TS), Harderian glands, spleen, heart, stomach, ileum, (incl. Peyer’s patch), submandibular lymph nodes, jejunum, testes, kidneys, thymus, lacrimal glands, thyroids (incl. parathyroids), larynx, trachea, liver, urinary bladder, lungs (incl. mainstem bronchi), uterus (incl. uterine cervix and oviducts), mesenteric lymph nodes, vagina, oesophagus, all gross lesions, and ovaries.
Other examinations:
Clinical laboratory studies
- Blood sample collection: blood samples (1.5 mL) were taken under isoflurane anaesthesia from the sublingual vein of all animals on the day of necropsy (0.5 mL into EDTA for haematology; 0.5 mLinto 3.2% w/v aqueous trisodium citrate for coagulation; 0.5 mL into lithium heparin for blood chemistry).
1. Haematology:
Haemoglobin concentration (Hb), platelet count (plate), red blood cell count (RBC), total leucocyte count (WBC), packed cell volume (PCV), neutrophils (Neut), mean cell volume (MCV), lymphocytes (Lymph), mean cell haemoglobin (MCH), monocytes (Mono), mean cell haemoglobin concentration (MCHC), eosinophils (Eosin), mean platelet volume (MPV), basophils (Baso), mean corpuscular volume retics (MCHr), large unstained cells (LUC), platelet distribution width (PDW), reticulocytes (Retics), cellular haemoglobin retics (CHr), plateletcrit (PCT), red blood cell distribution width (RDW), absolute reticulocyte count (A Retic), haemoglobin distribution width (HDW), and cell morphology*)
(*blood smears were prepared and were examined when warranted by machine morphology flags. All parameters were measured on the ADVIA 120 haematology analyser)
2. Coagulation (measured on the ACL Elite Pro):
Prothrombin time (PT) and activated partial thromboplastin time (APTT)
3. Blood chemistry:
Urea, globulin (Glob), creatinine (Cluc), albumin/globulin ratio (A/G), glucose (Gluc), total bilirubin (BiliT), alkaline phosphatase (ALP), cholesterol (Chol), alanine aminotransferase (ALT), sodium (Na), aspartate aminotransferase (AST), chloride (Cl), bile acids (B.Acids), calcium (Ca), total protein (T.Prot), potassium (K), albumin (Alb), HDL cholesterol (HDL), and cholesterol (LDL).

Thyroid hormone assessment - blood sampling and analysis

Vaginal smears - taken by lavage, examined under light microscopy and the stage of oestrous cycle was determined by the type of cell present.but

Organ weights: the following organs were weighed after trimming of fat and other contiguous tissue (contralateral organs were weighed together):
Adrenal glands, prostate & seminal vesicls (incl. coagulating gland), brain, epididymides, spleen, heart, testes, kidneys, thymus, liver, thyroids (incl. parathyroids), ovaries, uterus (incl. uterine cervix), and pituitary
Statistics:
Data were processed to give group mean values and standard deviations, where appropriate. Where the data allowed, the following methods were used for statistical analysis, comparing Groups 2, 3 and 4 against Group 1.

Depending on the nature of the data set that was to be analysed, appropriate tests were applied. Where parametric tests were appropriate they were preceded by a check for homogeneity of variance using the Levene test and, where available, the Shapiro-Wilks test for normality. If either of these two assumptions failed, a log transformation was applied before retesting. If the transformation failed, appropriate non-parametric tests were applied.

Probability values of less than 5 % were regarded as providing sufficient evidence to reject the null hypothesis and therefore statistical significance was identified at the p<0.05 level. For illustrative purposes, significance levels of p<0.01 and p<0.001 were also noted.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Males and females given 1000 mg/kg/day showed decreased activity and unsteady gait from Days 19/18 of dosing onwards (from approximately 15 minutes after dosing persisting for up to four hours), respectively. The incidence of these clinical signs decreased with time and by Day 72 of dosing, only one male was showing decreased activity and abnormal gait and over Days 84 to 92 of dosing; at the most, eight out of ten females showed these signs after dosing.
Mortality:
no mortality observed
Description (incidence):
There were no deaths during the study
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
For the first 3 weeks of dosing the body weights of males given 300 or 1000 mg/kg/day were very close to those of the Controls but by Week 4 it appeared that they were starting to diverge from the Controls and by Week 5 this was more pronounced. The Week 5 body weights of males given 300 or 1000 mg/kg/day were 5 % lower than those of the Controls and their body weight gains over Weeks 1 to 5 were 13 % and 15 % lower (p≤ 0.05). This separation of the growth curves continued such that by Week 14 males given 300 or 1000 mg/kg/day weighed 6 % and 11 % (p≤ 0.05), less than the Controls, with corresponding reductions in overall body weight gain compared with Controls of 12 % (p≤ 0.05) and 21 % (p≤ 0.01) over the duration of the study.

There was no effect on body weight for males given 100 mg/kg/day or for females.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
There was no adverse effect on food intake in either sex at any dose level. Although there were occasional weeks where the food intake of males given o-xylene was statistically significantly higher than that of the Controls, this clearly reflected an unusual pattern of variation in the Controls. Whereas Controls had some weeks of much lower food intake, male groups given o-xylene maintained a more consistent pattern of food intake overall.
Food efficiency:
not examined
Description (incidence and severity):
N/A
Water consumption and compound intake (if drinking water study):
not examined
Description (incidence and severity):
N/A
Ophthalmological findings:
no effects observed
Description (incidence and severity):
There were no ocular changes or abnormalities that were considered to be related to administration of o-xylene.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
There were no effects on haematology or coagulation parameters that were considered to be test item related. Although a number of parameters showed statistically significant differences between Control and treated groups the differences were minor, not consistent between sexes, lacked a strict dose-response relationship or biological plausibility and so were considered to reflect normal biological variation or to be fortuitous. Mean cell haemoglobin concentration (MCHC) was negligibly (1 %), but statistically significantly lower (p≤ 0.05) in males given 1000 mg/kg/day than in Controls. However, as most values were within the historical range and there were no changes in the primary red cell variates (red blood cell count, haemoglobin concentration, packed cell volume), this trivial difference in this derived parameter was considered not to be meaningful. Group mean platelet count for males given 1000 mg/kg/day was marginally (11 %), but statistically significantly higher than in Controls (p≤ 0.05) and group mean mean platelet volume (MPV) for males given 300 or 1000 mg/kg/day (p≤ 0.05) and plateletcrit (PCT) for males given 1000 mg/kg/day (p≤ 0.01) were also statistically significantly higher than in Controls. Individual platelet counts were within the historical Control range. Although, MPV and PCT values for all animals, including the Controls were outside the historical range, based on the magnitude of differences, which was marginal to negligible, these findings were considered not to be test item related. Group mean neutrophil counts were statistically significantly (p≤ 0.05) higher for males given 300 or 1000 mg/kg/day, however, this was not dose-related, individual values were within historical Control values and as there were no effects on other white blood cell parameters, these differences were considered not to be test item related. Activated partial thromboplastin time (APTT) was marginally (around one second), but significantly (p≤ 0.05) lower, relative to Controls in all male groups given o-xylene. Prothrombin time was marginally (up to 1.5 seconds), but significantly (p≤ 0.05), lower in males given 300 or 1000 mg/kg/day. Since apparent differences in these clotting times were no greater at 1000 mg/kg/day than at 300 mg/kg/day, all individual values were within the historical Control range and, as an increase in these parameters would normally be sought for evidence of impairment of the intrinsic or extrinsic clotting pathways, these variations were considered not to be meaningful. Females given 1000 mg/kg/day had slightly higher red blood cell count (p≤ 0.05) and packed cell volume (p≤ 0.01) than Controls and a lower MCHC (p≤ 0.05). As decreases in primary red cell variates would be more of a concern, and as values remained within normal range, these variations are considered likely to be fortuitous. Group mean total white blood cell count in females given 1000 mg/kg/day was statistically significantly higher (p≤ 0.05) than in Controls as a result of an increase in lymphocyte count (p≤ 0.01). Therefore, as all individual values were well within historical Control ranges these differences are considered of no consequence. Group mean platelet distribution width (PDW) was statistically significantly higher (p≤ 0.01) for females given 1000 mg/kg/day and there was a non-dose related lowering in PCT (p≤ 0.05) for females given o-xylene when compared with Controls. However, as there was no difference in platelet count, these minor differences in these derived indices are considered not to be test item related.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Plasma albumin concentration in males and females given 1000 mg/kg/day was slightly higher than the Control means (p≤ 0.001), leading to increases in the albumin/globulin ratio for these animals (p≤ 0.01 for males and p≤ 0.001 for females). All of the individual albumin values were within the historical background ranges and this effect was considered to be non-adverse given that a reduction would more normally be sought as evidence of impaired hepatic protein synthesis or of reduced dietary protein intake. Statistically significant inter-group differences in globulin concentrations between females given test item and those given vehicle alone were due to unusually high (above the upper limit of the historical background range) individual values in the Control group. Other statistically significant inter-group differences were minor, not consistent between sexes or lacked a strict dose relationship and so were considered to either reflect normal biological variation or to be fortuitous. These are detailed below:
Plasma sodium was negligibly (<2 %), but significantly, (p≤ 0.01 to p≤ 0.001), higher in males given 300 or 1000 mg/kg/day than in Controls and plasma chloride was negligibly (<1 %), but significantly (p≤ 0.05) lower in males given 1000 mg/kg/day than in Controls. These trivial differences within the normal range were considered to be fortuitous. Males given 1000 mg/kg/day had a higher group mean alanine aminotransferase (ALT) activity (p≤ 0.05) than Controls, with five out of ten individual values above the historical background range. However, in the absence of degenerative pathology changes in the liver, this increased activity was considered to be non-adverse. The slight increase in plasma ALT in males given 1000 mg/kg/day may reflect the observed hepatic hypertrophy in this group. Glucose was lower in a non-dose related manner in males given o-xylene when compared with Controls (p≤ 0.01). Plasma urea was lower in a non-dose related manner for females given o-xylene (p≤ 0.05 to p≤ 0.01), relative to Controls. Cholesterol (p≤ 0.05) and high density lipoproteins (HDL) (p≤ 0.01) were higher in females given 1000 mg/kg/day than in Controls. These differences are considered likely to be entirely fortuitous as they either lacked a dose
relationship, were very minor in degree or, for urea, moved in the wrong direction for diagnostic evidence of renal dysfunction.
Endocrine findings:
not examined
Description (incidence and severity):
N/A
Urinalysis findings:
not examined
Description (incidence and severity):
N/A
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
There were no effects on sensory reaction or grip strength elicited by o-xylene. During the weekly functional observations, in the open arena, males given 1000 mg/kg/day exhibited effects on arousal (hypoactivity or hyperactivity), unusual posture and abnormal gait. Twitches were observed in one male given 300 mg/kg/day and one male given 1000 mg/kg/day. Increased episodes of arousal in the arena and abnormal gait were observed between Days 21 to 63 and Days 21 to 56 of dosing, respectively. Excessive salivation in the arena was also noted between Days 14 and 70 of dosing for males given 300 or 1000 mg/kg/day, with incidence generally increasing with time. Excessive rearing was noted in a small number of males given 1000 mg/kg/day but this was also seen in one male given 100 mg/kg/day and one Control male and therefore considered not to be test item related. A few females given 300 or 1000 mg/kg/day salivated on removal from the cage between Days 14 to 42. Females given 1000 mg/kg/day also exhibited effects on arousal in the arena (both hyperactivity and hypoactivity), unusual flattened posture, abnormal gait and salivation. In addition, a small number of females exhibited twitching or excessive rearing. Although incidences generally increased with time similarly to the males, these effects were not seen after Day 77 of dosing. During the last week of treatment when the functional observations were performed before and after dosing three females given 1000 mg/kg/day had abnormal gait after dosing, that had not been seen before dosing. In males given 100, 300 or 1000 mg/kg/day o-xylene, movement counts and distance travelled were statistically significantly lower than in Controls (p≤ 0.05 to p≤ 0.01) during a number of post dose counting periods and this was, on occasions, accompanied by a statistically significant increase in time at rest (p≤ 0.05 to p≤ 0.01). There were fewer instances where there were similar statistically significant effects on movement in females and these effects were not dose-related.
Immunological findings:
not examined
Description (incidence and severity):
N/A
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Body weight related liver weights for both sexes given 300 or 1000 mg/kg/day (p≤ 0.05 to p≤ 0.001) and females given 100 mg/kg/day (p≤ 0.05) were statistically significantly higher than Controls. Most of the individual relative liver weights for males and females given 1000 mg/kg/day were also above the upper limit of the historical background range. When adjusted for brain weight liver weight was 19 % heavier than Controls in males and 40 % heavier in females (p≤ 0.001) given 1000 mg/kg/day.
Body weight related kidney weights for both sexes given 300 or 1000 mg/kg/day (p≤ 0.01 to p≤ 0.001) and females given 100 mg/kg/day (p≤ 0.05) were statistically significantly higher than Controls. Most of the individual weights were within the historical background range. When adjusted for brain weight kidney weights for both sexes given 300 mg/kg/day were 15 % and 7 % respectively, heavier than those of Controls (p≤ 0.01) and 26 % and 17 % respectively, heavier at 1000 mg/kg/day (p≤ 0.001). Thyroid weights (relative to body weight or brain weight) of females given 1000 mg/kg/day were all heavier than those of Controls (p≤ 0.01 to p≤ 0.001), however, most of the individual weights were within the historical background range.
The adrenals (relative but not absolute weights), of males given 1000 mg/kg/day were 19 % heavier than those of Controls (p≤ 0.05). However, there were no macroscopic or microscopic findings in the adrenals and as all individual values were within the historical control range this increase in adrenal weight was considered not to be adverse. The remaining organ weight differences for relative brain, heart, testes and epididymis weights between Controls and males given up to 1000 mg/kg/day were considered to be due to the slight growth retardation which was evident by the reduced body weight gains over the duration of the study.
Gross pathological findings:
no effects observed
Description (incidence and severity):
A variety of spontaneous changes was noted in Control and animals given o-xylene with no indication of an effect of treatment. The spectrum of these findings is generally consistent with changes encountered in rats of this age kept under laboratory conditions.
Neuropathological findings:
not specified
Description (incidence and severity):
N/A
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Findings considered to be related to treatment were seen in the liver (hepatocellular hypertrophy) and thyroid (follicular cell hypertrophy) and in the kidneys (eosinophilic inclusions (hyaline droplets) in the tubular epithelium (males only)). Although there were indications of positive α2μ-globulin staining in 3/10 males given 1000 mg/kg/day, there was also minimal staining in 2/10 Controls, thus failing to conclusively indicate that the increased number of hyaline droplets was related to α2μ-globulin. Thus, the mechanism of the increased incidence/severity of hyaline droplets seen within the cortical tubules of male kidneys in this study remained unestablished. A variety of other spontaneous changes was noted in Control and treated animals with no indication of an effect of treatment. The spectrum of these findings is generally consistent with changes encountered in rats of this age kept under laboratory conditions.
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
N/A
Other effects:
effects observed, non-treatment-related
Description (incidence and severity):
Thyroid Hormone Analysis

As samples were obtained at only a single timepoint, these findings represent only a snapshot of thyroid hormone levels. In addition, due to the relatively small group size (n=10), the analysis lacks sufficient statistical power. There was some variation in thyroid hormones within groups with no evidence of a consistent pattern of change elicited by o-xylene. There were no statistically significant inter-group differences for TSH that showed a clear dose response relationship and there were no statistically differences for triiodothyronine (T3) for either sex at any dose. T4 concentrations in females given 1000 mg/kg/day was actually slightly (25 %), but significantly, (p< 0.05) higher than that in Controls but within normal biological variability and, T4 in males given 1000 mg/kg/day was marginally (10 %) lower than in Controls, this difference did not attain statistical significance compared to Controls, nor did it show a dose response relationship. Any of the changes in circulating T4 concentrations
were considered to be within normal biological variability and likely due to the natural diurnal variation in thyroid hormone concentrations.

Oestrous cycles

There was no effect of o-xylene on the oestrous cycles; the data were variable with the majority of females in all groups being in dioestrus.
Details on results:
N/A

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
Key result
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
behaviour (functional findings)
body weight and weight gain
clinical signs
histopathology: non-neoplastic
organ weights and organ / body weight ratios

Target system / organ toxicity

Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
300 mg/kg bw/day (nominal)
System:
urinary
Organ:
kidney
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
no

Any other information on results incl. tables

Table 1. body weights (g) – group mean values

Sex: Male

body weight (week number)

Group

1 (#)

2

3

4

5

6

7

Group 1

Control

0 mg/kg/day

Mean

192.5

232.3

265.9

292.1

315.6

335.4

349.1

SD

11.1

14.9

17.6

19.8

22.2

24.8

25.5

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 2

o-xylene

100 mg/kg/day

Mean

194.2

234.3

265.7

290.1

309.3

327.2

341.7

SD

14.4

19.1

22.8

25.6

29.6

31.8

32.3

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

193.2

231.9

259.8

282.1

299.9

314.9

328.7

SD

13.6

16.4

16.4

19.2

21.6

23.4

24.4

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

195.5

231.5

261.7

282.6

299.9

313.5

324.8

SD

15.5

16.5

19.4

25.4

33.2

35.9

34.7

N

10

10

10

10

10

10

10

Trend

> 0.05

-

-

-

-

-

-

(#) – Williams, Anova & Dunnett

 

Table 1. body weights (g) – group mean values (Continued)

Sex: Male

body weight (week number)

Group

8

9

10

11

12

13

14 (#)

Group 1

Control

0 mg/kg/day

Mean

362.8

375.6

388.1

397.1

404.6

413.2

420.2

SD

27.6

29.8

31.5

32.7

32.4

32.5

35.2

N

10

10

10

10

10

10

10

Trend

-

0

-

-

-

-

Group 2

o-xylene

100 mg/kg/day

Mean

354.8

366.2

378.4

388.5

396.4

405.3

414.3

SD

33.6

36.1

37.4

36.5

37.3

38.4

39.8

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

342.0

352.3

360.9

371.0

377.8

386.5

393.8

SD

25.0

27.4

29.7

32.5

32.1

34.5

33.0

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

336.8

344.4

351.3

360.2

366.4

372.4

375.7

SD

38.3

38.8

39.3

41.1

41.6

42.1

41.6

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

≤ 0.05 *

(#) – Williams, Anova & Dunnett: * = p0.05

Table 1. body weights (g) – group mean values (Continued)

Sex: Female

body weight (week number)

Group

1 (#)

2

3

4

5

6

7

Group 1

Control

0 mg/kg/day

Mean

160.4

178.4

189.5

199.4

210.1

220.3

224.5

SD

14.8

14.6

13.9

15.3

15.4

15.5

15.1

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 2

o-xylene

100 mg/kg/day

Mean

159.4

177.1

186.8

198.9

208.8

216.4

221.2

SD

10.8

12.5

13.6

13.8

12.3

12.4

14.7

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

161.7

178.8

189.6

199.5

208.8

217.1

223.7

SD

13.0

16.1

15.4

17.3

15.0

17.2

18.5

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

160.4

181.9

192.3

205.2

214.5

224.3

226.6

SD

13.0

15.0

16.5

18.9

20.1

21.6

23.3

N

10

10

10

10

10

10

10

Trend

> 0 .05

-

-

-

-

-

-

(#) – Williams, Anova & Dunnett

 

Table 1. body weights (g) – group mean values (Continued)

Sex: Female

body weight (week number)

Group

8

9

10

11

12

13

14 (#)

Group 1

Control

0 mg/kg/day

Mean

228.0

231.6

237.0

239.6

239.9

241.3

247.7

SD

18.9

17.6

19.3

18.0

18.8

19.0

19.2

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 2

o-xylene

100 mg/kg/day

Mean

227.4

232.5

236.7

239.2

240.2

244.0

246.7

SD

13.7

10.1

12.1

13.7

14.5

12.2

13.4

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

225.3

232.5

234.6

238.1

239.0

241.5

245.2

SD

18.9

10.1

21.2

21.0

22.3

21.1

23.8

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

231.3

238.5

241.2

242.2

244.4

249.4

249.0

SD

21.5

21.8

22.1

23.1

23.4

23.7

25.9

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

> 0.05

(#) – Williams, Anova & Dunnett

Table 2. body weight gains (g) – group mean values

Sex: Male

body weight (week number)

 

Group

1 to 5 (#)

5 to 14 (#)

1 to 14 (#)

Group 1

Control

0 mg/kg/day

Mean

123.1

104.6

227.7

SD

15.8

17.0

30.1

N

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

115.1

105.0

220.1

SD

21.5

16.8

35.9

N

10

10

10

Trend

> 0.05

-

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

106.7

93.9

200.6

SD

15.1

18.0

30.3

N

10

10

10

Trend

≤ 0.05*

> 0.05

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

104.4

75.8

180.2

SD

24.1

12.4

33.3

N

10

10

10

Trend

≤ 0.05*

≤ 0.001***

≤0.01**

(#) – Williams, Anova & Dunnett: *= p0.05, **= p≤ 0.01, ***=p≤ 0.001

 

Table 2. body weight gains (g) – group mean values (Continued)

Sex: Female

body weight (week number)

 

Group

1 to 5 (#)

5 to 14 (#)

1 to 14 (#)

Group 1

Control

0 mg/kg/day

Mean

49.7

37.6

87.3

SD

3.6

5.9

5.7

N

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

49.3

38.0

87.3

SD

6.1

5.8

9.9

N

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

47.1

36.4

83.5

SD

7.2

10.4

14.4

N

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

54.1

34.5

88.6

SD

8.4

8.8

14.0

N

10

10

10

Trend

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett

Table 3. Food intake (g/animal/day) – group mean cage values

Sex: Male

Food Intake Per Animal / Day (g) (Week Number)

Group

1 to 2 (#)

2 to 3 (#)

3 to 4 (#)

4 to 5 (#)

5 to 6 (#)

6 to 7 (#)

7 to 8 (#)

Group 1

Control

0 mg/kg/day

Mean

22.2

22.8

22.1

21.4

20.5

19.7

19.5

SD

1.4

0.8

0.8

1.5

1.1

1.3

1.2

N

4

4

4

4

4

4

4

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

22.9

22.8

21.6

21.1

20.7

20.7

20.7

SD

1.1

1.6

1.0

1.4

0.6

0.3

0.3

N

4

4

4

4

4

1

4

Trend

-

-

-

-

-

> 0.05

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

22.6

22.7

21.8

21.2

21.0

21.4

21.1

SD

0.6

0.8

1.4

1.1

0.9

0.7

0.5

N

4

4

4

4

4

4

1

Trend

-

-

-

-

-

≤ 0.05*

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

22.1

24.3

22.6

22.4

22.3

22.0

21.5

SD

1.3

2.4

2.3

3.1

2.9

1.4

1.6

N

4

4

4

4

4

4

4

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

≤ 0.05*

(#) – Williams, Anova & Dunnett: * = p0.05

 

Table 3. Food intake (g/animal/day) – group mean cage values (Continued)

Sex: Male

Food Intake Per Animal / Day (g) (Week Number)

Group

8 to 9 (#)

9 to 10 (#)

10 to 11 (#)

11 to 12 (#)

12 to 13 (#1)

13 to 14 (#)

1 to 14 (#)

Group 1

Control

0 mg/kg/day

Mean

19.1

18.9

18.3

17.8

18.1

17.2

19.8

SD

1.6

1.6

1.3

1.2

1.7

1.3

1.2

N

4

4

4

4

4

4

4

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

20.3

20.2

20.3

20.3

21.1

19.1

20.9

SD

0.6

0.7

0.4

0.3

0.2

1.2

0.6

N

4

4

4

4

4

4

4

Trend

-

-

≤ 0.05*

≤ 0.05*

≤ 0.05*

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

20.6

20.3

20.7

20.5

20.0

19.0

21.0

SD

1.0

0.9

0.6

0.6

0.3

0.4

0.6

N

4

4

4

4

4

4

1

Trend

> 0.05

-

≤ 0.05*

≤ 0.05*

≤ 0.05*

> 0.05

-

Group 4

o-xylene

1000 mg/kg/day

Mean

21.3

20.6

20.9

21.5

21.3

19.7

21.7

SD

1.6

1.8

2.1

2.9

2.4

2.4

2.0

N

4

4

4

4

4

4

4

Trend

≤ 0.05*

> 0.05

≤ 0.05*

≤ 0.05*

≤ 0.05*

≤ 0.05*

> 0.05

(#) – Williams, Anova & Dunnett: * = p0.05

(#1) – Shirley, Kruskal-Wallis & Steel: * = p0.05

Table 3. Food intake (g/animal/day) – group mean cage values (Continued)

Sex: Female

Food Intake Per Animal / Day (g) (Week Number)

Group

1 to 2 (#)

2 to 3 (#)

3 to 4 (#)

4 to 5 (#)

5 to 6 (#)

6 to 7 (#)

7 to 8 (#)

Group 1

Control

0 mg/kg/day

Mean

14.8 n

14.3 n

15.1 n

15.1 n

15.2 n

14.1 n

14.3 n

SD

1.4

0.2

0.5

0.7

0.6

0.6

0.6

N

2

2

2

2

2

2

2

Group 2

o-xylene

100 mg/kg/day

Mean

14.3 n

14.1 n

14.6 n

14.5 n

14.6 n

14.0 n

14.2 n

SD

1.2

0.9

1.2

1.3

1.4

1.7

1.6

N

2

2

2

2

2

2

2

Group 3

o-xylene

300 mg/kg/day

Mean

14.4 n

14.5 n

15.0 n

15.1 n

14.9 n

14.2 n

14.1

SD

0.7

0.6

0.8

0.9

1.2

0.9

1.2

N

2

2

2

2

2

2

2

Group 4

o-xylene

1000 mg/kg/day

Mean

13.7 n

15.4 n

15.7 n

15.3 n

15.4 n

14.6 n

14.8 n

SD

0.0

0.6

0.5

0.5

0.6

0.2

0.2

N

2

2

2

2

2

2

2

(#) – Shirley, Kruskal-Wallis & Steel: n – inappropriate for statistics

 

Table 3. Food intake (g/animal/day) – group mean cage values (Continued)

Sex: Female

Food Intake Per Animal / Day (g) (Week Number)

Group

8 to 9 (#)

9 to 10 (#)

10 to 11 (#)

11 to 12 (#)

12 to 13 (#)

13 to 14 (#)

1 to 14 (#)

Group 1

Control

0 mg/kg/day

Mean

13.9 n

13.9 n

13.3 n

13.2 n

13.6 n

12.2 n

14.1 n

SD

0.4

0.6

0.8

0.9

1.3

0.5

0.6

N

2

2

2

2

22

2

2

Group 2

o-xylene

100 mg/kg/day

Mean

13.8 n

14.1 n

13.2 n

13.2 n

12.9 n

12.2 n

13.8 n

SD

1.2

1.1

1.9

1.9

1.1

2.0

1.4

N

2

2

2

2

2

2

2

Group 3

o-xylene

300 mg/kg/day

Mean

14.0 n

14.0 n

13.9 n

13.7 n

13.4 n

12.6 n

14.1 n

SD

1.0

1.1

1.1

1.5

1.4

1.2

1.0

N

2

2

2

2

2

2

2

Group 4

o-xylene

1000 mg/kg/day

Mean

14.6 n

14.5 n

14.0 n

14.2 n

13.2 n

12.8 n

14.5 n

SD

0.0

0.6

0.3

0.3

0.5

0.0

0.1

N

2

2

2

2

2

2

2

(#) – Shirley, Kruskal-Wallis & Steel: n – inappropriate for statistics

Table 4. Thyroid analysis – group mean values

Sex: Male

Mean Total

T3 (ng/mL)

Mean Total

T4 (ng/mL)

Mean Total

TSH (ng/mL)

Group

(#)

(#)

(#1)

Group 1

Control

0 mg/kg/day

Mean

16.639

427.735

0.498

SD

2.676

82.494

0.210

N

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

16.682

440.194

0.510

SD

5.221

46.662

0.152

N

9

9

9

Group 3

o-xylene

300 mg/kg/day

Mean

19.031

437.204

0.555

SD

5.116

89.539

0.192

N

9

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

18.468

383.893

0.605

SD

4.758

44.318

0.314

N

9

10

10

Trend

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett

(#1) – Shirley, Kruskal-Wallis & Steel

 

Table 4. Thyroid analysis – group mean values (Continued)

Sex: Male

Mean Total

T3 (ng/mL)

Mean Total

T4 (ng/mL)

Mean Total

TSH (ng/mL)

Group

(#)

(#)

(#1)

Group 1

Control

0 mg/kg/day

Mean

17.233*

277.065

0.673*

SD

5.928

37.594

0.303

N

8

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

12.174

291.000

0.497

SD

3.053

71.508

0.182

N

8

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

14.009

296.776

0.421*

SD

3.301

59.956

0.066

N

9

10

10

Trend

-

> 0.05

-

Group 4

o-xylene

1000 mg/kg/day

Mean

19.130

346.589

0.595

SD

6.317

56.001

0.209

N

10

10

10

Trend

> 0.05

≤ 0.05*

> 0.05

(#) – Williams, Anova & Dunnett: * = p≤ 0.05

(#1) – Williams, Anova & Dunnett(Log): * = p0.05

Table 5. Functional observation battery – rodents – key values

HOME CAGE

ON REMOVAL FROM CAGE

PERFORMANCE IN OPEN FIELD

RESPONSE TO SENSORIMOTOR STIMULI

Arousal upon openingcage

0 = normal

1 = increased

2 = decreased

 

Dispersion in cage

0 = normal

1 = closely bunched

2 = loosely bunched

 

Excessive vocalisation

0 = absent

1 = present

 

Fighting

0 = absent

1 = present

 

Stereotypical behaviour

0 = absent

1 = present

 

Aggressive behaviour

0 = absent

1 = present

 

Convulsions

0 = absent

1 = short

2 = sustained

Reaction to handling

0 = normal

1 = no resistance

2 = vocalising

3 = tense

4 = squirming

 

Lacrimation

0 = normal

1 = excess at eyelid margin

2 = extends beyond margin

 

Salivation

0 = normal

1 = slight

2 = marked

 

Chromodacryorrhea

0 = absent

1 = present

 

Exophthalmos

0 = absent

1= present

 

Arousal in arena

0 = normal

1 = hyperactive

2 = hypoactive

 

Unusual posture

0 = absent

1 = hunched

2 = flattened

 

Abnormal gait

0 = absent

1 = slight

2 = marked

 

Convulsions arena

0 = absent

1 = slight

2 = marked

 

Tremors

0 = none

1 = intermittent

2 = constant

 

Twitches

0 = normal

1 = slight

2 = marked

 

Urination

0 = none

1 = present

2 = excess

Defecation

0 = none

1 = present

2 = soft/liquid faeces

 

Excessive vocalisation

0 = absent

1 = present

 

Piloerection

0 = normal

1 = roughened fur

2 = piloerection

 

Palpebral closure

0 = normal

1 = partially closed

2 = shut

 

Respiration

0 = normal

1 = rapid

2 = slow

3 = laboured

 

Straub tail

0 = absent

1 = present

 

Salivation

0 = absent

1 = present

2 = excessive

 

Excessive rearing

0 = absent

1 = present

Approach response

0 = present

1 = absent

2 = excessive

 

Touch response

0 = present

1 = absent

2 = excessive

 

Aud Startle response

0 = present

1 = absent

2 = excessive

 

Tail pinch response

0 = present

1 = absent

2 = excessive

 

Forelimb reflex

0 = early extension

1 = extension after contact

2 = no extension

 

Righting reflex

0 = present

1 = slow

2 = absent

 

Table 5. Functional observation battery – home and arena – group mean values

Sex: Male

Arousal open cage (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

Table 5. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Arousal open cage (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

Table 5.2. Functional observation battery – home and arena – group mean values (Continued)

Sex: Male

Dispersion in cage (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

12

0

0

0

0

0

0

SD

3

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Dispersion in cage (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Fighting (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Fighting (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Excessive vocalisation cage (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Excessive vocalisation cage (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Stereotyped behaviour (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Stereotyped behaviour (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

Tabl e 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Aggressive behaviour (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Aggressive behaviour (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Convulsions cage (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Convulsions cage (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Reacting to handling (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Reacting to handling (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Lacrimation (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Lacrimation (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Salivation (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Salivation (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Chromodacryorrhea (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Chromodacryorrhea (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Exophthalmos (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Exophthalmos (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Arousal in arena (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

4

0

SD

0

0

0

0

0

2

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

2

0

0

0

0

SD

0

0

2

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

4

0

1

2

SD

0

0

0

2

0

1

2

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Arousal in arena (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

1

0

0

1

0

0

SD

1

0

0

1

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

2

0

0

0

0

0

SD

2

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

5

0

3

0

0

0

SD

2

0

2

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Unusual posture (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

4

0

SD

0

0

0

0

0

2

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Unusual posture (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

4

0

0

0

SD

0

0

2

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Abnormal gait (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

1

0

1

0

SD

0

0

0

1

0

1

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Abnormal gait (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

1

0

0

0

0

0

SD

1

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

1

1

0

0

0

0

SD

1

1

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Convulsions arena (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Convulsions arena (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Tremors (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Tremors (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Twitches (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

1

0

SD

0

0

0

0

0

1

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Twitches (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

1

0

0

0

0

0

SD

1

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Excessive vocalisation arena (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Excessive vocalisation arena (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Piloerection (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Piloerection (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Palpebral closure (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Palpebral closure (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Respiration (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Respiration (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Straub tail (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Straub tail (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Salivation arena (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

6

4

0

3

0

SD

0

0

1

1

0

2

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Salivation arena (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

1

0

0

2

0

0

SD

1

0

0

1

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

1

3

1

0

0

0

SD

1

2

1

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Excessive rearing (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

1

0

1

0

SD

0

0

0

1

0

1

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Excessive rearing (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

1

0

0

SD

0

0

0

1

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

1

0

0

SD

0

0

0

1

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

1

0

0

0

0

0

SD

1

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Urination (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

5

1

0

7

2

3

5

SD

1

1

0

1

1

1

1

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

5

0

1

6

5

3

5

SD

1

0

1

1

2

1

1

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

3

2

0

6

6

6

4

SD

1

1

0

1

2

1

1

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

2

0

0

7

9

3

3

SD

1

0

0

1

2

1

1

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Urination (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

4

3

1

4

5

7

SD

1

1

1

1

1

1

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

2

4

4

2

5

4

SD

1

1

1

1

1

1

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

1

4

7

3

6

5

SD

1

2

2

1

1

1

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

6

6

4

2

2

8

SD

2

2

1

1

1

1

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Defecation (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

2

0

1

0

0

0

0

SD

1

0

1

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

2

1

0

0

0

0

1

SD

1

1

0

0

0

0

1

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Male

Defecation (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Arousal open cage (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Arousal open cage (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Dispersion in cage (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Dispersion in cage (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Fighting (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Fighting (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Stereotyped behaviour (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Stereotyped behaviour (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Aggressive behaviour (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Aggressive behaviour (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Convulsions (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Convulsions (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Reaction to handling (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Reaction to handling (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Lacrimation (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Lacrimation (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Salivation (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

1

1

0

1

0

SD

0

0

1

1

0

1

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

2

4

0

3

4

SD

0

0

1

1

0

2

2

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Salivation (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Chromodacryorrhea (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Chromodacryorrhea (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Exophthalmos (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Exophthalmos (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Arousal in arena (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

1

2

6

0

SD

0

0

0

1

2

2

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Arousal in arena (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

1

0

SD

0

0

0

0

1

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

2

1

0

SD

0

0

0

2

1

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

6

0

2

4

3

0

SD

2

0

2

2

2

0

N

10

10

10

9

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Unusual posture (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

3

0

0

0

SD

0

0

0

2

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Unusual posture (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Abnormal gait (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

6

5

1

2

0

SD

0

0

2

2

1

2

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Abnormal gait (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

2

1

0

3

4

0

SD

2

1

0

1

2

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Convulsions (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Convulsions (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Tremors (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Tremors (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Twitches (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

1

0

0

SD

0

0

0

0

1

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Twitches (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

1

0

SD

0

0

0

0

1

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Excessive vocalisation arena (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Excessive vocalisation arena (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Piloerection (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Piloerection (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Palpebral closure (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Palpebral closure (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Respiration (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Respiration (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Straub tail (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Straub tail (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Salivation arena (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

2

1

0

1

0

SD

0

0

1

1

0

1

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

4

5

0

1

5

SD

0

0

2

1

0

1

2

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Salivation arena (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Excessive rearing (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

1

0

0

SD

0

0

0

0

1

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

1

0

0

0

0

SD

0

0

1

0

0

0

0

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Excessive rearing (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

1

0

SD

0

0

0

0

1

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

1

0

0

0

0

SD

0

1

0

0

0

0

N

10

10

10

9

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Urination (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

4

4

4

2

2

0

2

SD

1

1

1

1

1

0

1

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

4

4

5

1

1

1

2

SD

1

1

1

1

1

1

1

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

5

5

5

0

3

2

0

SD

1

1

1

0

1

1

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

4

6

5

0

5

3

1

SD

1

1

1

0

1

1

1

N

10

10

10

10

10

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Urination (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

2

0

2

0

0

0

SD

1

0

1

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

2

0

2

0

1

1

SD

1

0

1

0

1

1

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

1

0

1

0

1

1

SD

1

0

1

0

1

1

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

2

0

1

1

0

1

SD

1

0

1

1

0

1

N

10

10

10

9

10

10

 

 

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Defecation (Day number)

Group

-1

7

14

21

28

35

42

Group 1

Control

0 mg/kg/day

Mean

2

0

0

0

0

0

0

SD

1

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

1

1

0

0

0

0

0

SD

1

1

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

0

SD

0

0

0

0

0

0

0

N

10

10

10

10

10

10

10

Table 5.2. Functional observation battery – home and arena – group mean values (continued)

Sex: Female

Defecation (Day number)

Group

49

56

63

70

77

84

Group 1

Control

0 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

0

0

0

0

0

0

SD

0

0

0

0

0

0

N

10

10

10

9

10

10

Table 5.3. Functional observation battery – sensory reaction – group mean values

Sex: Male

Approach response

(Day Number)

Touch response

(Day Number)

Aud startle response

(Day Number)

Tail pinch response

(Day Number)

Righting reflex

(Day Number)

Forelimb reflex

(Day Number)

Group

84

84

84

84

84

84

Group 1

Control

0 mg/kg/day

Sum

0

0

0

0

0

0

Max

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 2

o-xylene

100 mg/kg/day

Sum

0

0

0

0

0

0

Max

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Sum

0

0

0

0

0

0

Max

0

0

0

0

0

0

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Sum

0

0

0

0

0

0

Max

0

0

0

0

0

0

N

10

10

10

10

10

10

Table 6. Motor activity – group mean values

Sex: Male

Movements Counts Period 1 (Day Number [Time])

Movements Counts Period 2 (Day Number [Time])

Movements Counts Period 3 (Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#2)

87 (Pre) (#1)

87 (Post) (#)

Group 1

Control

0 mg/kg/day

Mean

1626.9

1327.9

751.6

536.2

713.6

322.0

SD

531.7

338.9

178.5

189.9

235.8

236.5

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

1573.9

1392.9

788.5

528.4

628.1

187.4

SD

526.8

433.1

325.1

284.7

232.2

249.6

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

1715.3

1639.8

824.7

241.0

739.5

66.2

SD

480.3

490.7

253.4

268.8

297.2

105.8

N

10

10

10

10

10

10

Trend

-

-

-

≤ 0.05*

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

1759.8

1388.4

846.9

361.9

653.1

63.1

SD

420.4

283.3

185.6

230.2

191.7

85.0

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

≤ 0.05*

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
(#1) – Williams, Anova & Dunnett
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes

Table 6. Motor activity – group mean values (Continued)

Sex: Male

Movements Counts Period 4 (Day Number [Time])

Movements Counts Period 5 (Day Number [Time])

Movements Counts Period 6 (Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

609.8

184.5

534.2

207.7

348.6

307.4

SD

248.8

182.0

308.3

265.3

320.3

257.7

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

511.3

94.1

388.6

165.7

483.9

48.4

SD

250.6

131.8

182.4

181.6

263.4

45.3

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

618.1

174.0

482.3

173.5

619.4

150.1

SD

236.9

447.4

326.7

259.0

239.1

287.1

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

631.7

144.4

656.7

63.0

530.8

67.0

SD

279.7

205.3

252.4

85.4

317.6

80.9

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.01**

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05, ** = p ≤ 0.01
Note: a period equates to an interval of 10 minutes

 

Table 6. Motor activity – group mean values (Continued)

Sex: Male

Distance Travelled

 Period 1 (cm)

(Day Number [Time])

Distance Travelled

Period 2 (cm)

(Day Number [Time])

Distance Travelled 

Period 3 (cm)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#2)

87 (Pre) (#1)

87 (Post) (#)

Group 1

Control

0 mg/kg/day

Mean

5816.4

4677.8

2713.8

1843.6

2560.2

1150.7

SD

1844.6

1078.4

617.9

627.7

805.3

840.3

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

5490.4

4891.8

2780.4

1809.1

2250.5

691.4

SD

1745.2

1486.0

1045.6

1000.9

785.7

895.2

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

5985.6

5742.6

2883.6

888.6

2614.6

226.3

SD

1391.4

1698.6

756.4

985.9

921.2

378.4

N

10

10

10

10

10

10

Trend

-

-

-

≤ 0.05*

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

6203.2

4901.9

3020.6

1325.6

2299.5

231.3

SD

1458.0

887.0

672.9

806.6

725.1

311.6

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

≤ 0.05*

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
(#1) – Williams, Anova & Dunnett
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes

Table 6. Motor activity – group mean values (Continued)

Sex: Male

Distance Travelled

 Period 4 (cm)

(Day Number [Time])

Distance Travelled

Period 5 (cm)

(Day Number [Time])

Distance Travelled 

Period 6 (cm)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

2203.2

690.5

1872.3

758.4

1217.7

1105.2

SD

844.1

678.4

1075.8

946.8

1128.6

928.5

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

1778.3

335.3

1389.1

628.4

1736.8

188.7

SD

805.9

473.1

631.9

633.4

902.8

178.6

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

2208.3

663.9

1683.1

616.3

2183.2

583.4

SD

826.5

1737.8

1129.1

884.6

867.6

1144.4

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

2279.0

530.0

2389.6

261.1

1913.9

286.5

SD

982.1

741.5

918.9

339.9

1128.2

379.5

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
Note: a period equates to an interval of 10 minutes

 

Table 6. Motor activity – group mean values (Continued)

Sex: Male

Time at Rest

 Period 1 (sec)

(Day Number [Time])

Time at Rest

Period 2 (sec)

(Day Number [Time])

Time at Rest

Period 3 (sec)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

192.24

222.86

352.51

402.95

378.37

485.26

SD

51.03

31.87

41.15

52.02

45.85

75.47

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

213.17

229.32

356.78

424.38

401.15

535.23

SD

63.64

54.46

69.94

68.61

44.74

77.33

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

-

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

191.09

210.50

342.61

509.99

381.13

573.65

SD

40.81

55.31

36.64

85.99

47.78

38.76

N

10

10

10

10

10

10

Trend

-

-

-

≤ 0.01**

-

≤ 0.01**

Group 4

o-xylene

1000 mg/kg/day

Mean

185.55

251.46

315.97

478.05

374.80

576.28

SD

51.53

56.02

48.14

57.20

46.83

30.29

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

≤ 0.01**

> 0.05

≤ 0.01**

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01
(#1) – Shirley, Kruskal-Wallis & Steel: ** = P ≤ 0.01
Note: a period equates to an interval of 10 minutes

Table 6. Motor activity – group mean values (Continued)

Sex: Male

Time at Rest

 Period 4 (sec)

(Day Number [Time])

Time at Rest

Period 5 (sec)

(Day Number [Time])

Time at Rest

Period 6 (sec)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

381.50

530.45

418.34

526.97

482.49

485.85

SD

71.63

64.27

76.12

88.22

93.95

93.98

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

434.02

562.75

460.00

537.47

448.13

577.65

SD

68.85

44.44

54.98

62.10

71.05

19.71

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

409.75

560.82

451.52

551.08

394.73

558.46

SD

58.66

83.77

82.21

58.74

71.75

62.24

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

393.14

549.64

377.74

570.89

427.71

560.74

SD

70.03

65.92

83.92

39.77

86.48

59.90

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett
(#1) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes

 

Table 6. Motor activity – group mean values (Continued)

Sex: Female

Movements Counts Period 1 (Day Number [Time])

Movements Counts Period 2 (Day Number [Time])

Movements Counts Period 3 (Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

2114.7

1665.9

1102.5

466.3

725.6*

302.5

SD

371.3

396.2

333.5

269.5

207.1

298.1

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

1857.3

1531.4

1001.0

451.0

724.2

148.3

SD

409.8

400.4

237.0

369.9

299.5

212.2

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

2003.6

2051.1

1187.8

480.3

1016.7*

216.9

SD

470.9

584.9

352.6

443.9

284.6

446.7

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

1915.0

1793.1

890.0

386.0

787.0

232.0

SD

383.9

443.1

158.2

255.3

202.5

409.7

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#1) – Williams, Anova & Dunnett(Log)
Note: a period equates to an interval of 10 minutes

Table 6. Motor activity – group mean values (Continued)

Sex: Female

Movements Counts Period 4

(Day Number [Time])

Movements Counts Period 5

(Day Number [Time])

Movements Counts Period 6

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#2)

87 (Post) (#1)

87 (Pre) (#2)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

589.6

281.7*

720.6*

223.1*

527.7

176.1

SD

359.5

254.6

532.1

169.2

258.7

230.3

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

562.1

599.0

548.9

396.2

485.2

123.4

SD

348.2

239.6

262.8

385.5

379.8

152.8

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

804.6

266.0

847.2

75.5

780.6

95.6

SD

388.1

403.5

198.6

94.7

379.3

197.4

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

662.1

175.4

476.3

517.8

568.6

532.0

SD

173.7

220.6

216.5

1170.3

214.9

979.6

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes

 

 

Table 6. Motor activity – group mean values (Continued)

Sex: Female

Distance Travelled

Period 1 (cm)

(Day Number [Time])

Distance Travelled

Period 2 (cm)

(Day Number [Time])

Distance Travelled

Period 3 (cm)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#2)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

7391.1

5577.7

3817.2

1643.2

2587.0*

1055.8

SD

1312.6

1322.0

1250.4

909.6

725.1

1031.4

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

6428.7

5204.1

3466.0

1587.1

2576.7

509.9

SD

1420.9

1331.6

856.8

1308.7

1047.6

737.6

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

6904.0

7088.8

4136.6

1698.9

3550.3*

757.0

SD

1576.0

2110.0

1201.7

1541.3

913.3

1511.2

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

6876.3

6205.6

3111.1

1416.3

2776.5

811.3

SD

1467.8

1568.0

576.9

920.5

694.4

1310.0

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#1) – Williams, Anova & Dunnett(Log)
Note: a period equates to an interval of 10 minutes

 

Table 6. Motor activity – group mean values (Continued)

Sex: Female

Distance Travelled

Period 4 (cm)

(Day Number [Time])

Distance Travelled

Period 5 (cm)

(Day Number [Time])

Distance Travelled

Period 6 (cm)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#2)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

2097.3

1024.7*

2535.8*

815.6*

1833.5

640.0

SD

1355.4

931.7

1774.8

606.9

939.0

835.5

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

2002.8

2157.5

1956.6

1403.0

1690.7

448.6

SD

1211.8

858.5

919.7

1307.8

1274.2

542.5

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

2761.4

944.9

2991.4

272.3

2697.8

340.8

SD

1208.8

1366.2

642.6

347.4

1121.6

687.1

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

2332.6

644.1

1676.2

1762.3

2017.6

1809.4

SD

668.9

752.0

762.8

3809.9

750.0

3317.7

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes

 

 

Table 6. Motor activity – group mean values (Continued)

Sex: Female

Time at Rest

Period 1 (sec)

(Day Number [Time])

Time at Rest

Period 2 (sec)

(Day Number [Time])

Time at Rest

Period 3 (sec)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

160.07

219.67

308.45

435.42

385.41

495.37

SD

24.59

32.86

60.91

83.04

52.63

89.78

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

196.85

242.53

352.58

458.20

377.76

543.62

SD

41.86

45.75

43.06

104.53

66.03

73.66

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

181.10

206.38

293.82

461.68

333.71

546.50

SD

31.18

41.86

57.89

89.51

46.60

84.64

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

174.38

242.06

323.42

482.62

352.10

529.45

SD

36.07

70.90

32.09

77.68

43.82

95.51

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett
(#1) – Shirley, Kruskal-Wallis & Steel
Note: a period equates to an interval of 10 minutes

 

 

 

Table 6. Motor activity – group mean values (Continued)

Sex: Female

Time at Rest

Period 4 (sec)

(Day Number [Time])

Time at Rest

Period 5 (sec)

(Day Number [Time])

Time at Rest

Period 6 (sec)

(Day Number [Time])

Group

87 (Pre) (#)

87 (Post) (#)

87 (Pre) (#)

87 (Post) (#1)

87 (Pre) (#)

87 (Post) (#1)

Group 1

Control

0 mg/kg/day

Mean

418.03

507.99**

390.11*

519.29*

424.27

545.19

SD

72.03

87.76

97.35

56.43

67.91

65.46

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

425.42

433.41

429.39

477.85

448.53

537.92

SD

89.59

64.02

71.58

99.69

99.18

86.64

N

10

10

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

373.63

535.23

358.65

574.15

382.03

576.31

SD

70.10

75.36

40.71

32.05

57.40

37.08

N

10

10

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

381.21

539.32

443.96

487.60

416.35

486.54

SD

55.76

65.39

48.84

185.18

68.71

188.67

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett* = p ≤ 0.05, ** = p ≤ 0.01
(#1) – Shirley, Kruskal-Wallis & Steel* = p ≤ 0.05
Note: a period equates to an interval of 10 minutes

 

 

 

Table 7. Grip strength – group mean values

Sex: Male

Forelimb

Mean (g)

(Day Number [Time])

Hindlimb

Mean (g)

(Day Number [Time])

Group

80 (Pre) (#)

80 (Post) (#)

80 (Pre) (#)

80 (Post) (#)

Group 1

Control

0 mg/kg/day

Mean

363.40

244.40

334.37

238.70

SD

51.49

64.49

63.75

79.05

N

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

317.13

221.07

270.83

271.37

SD

91.79

77.99

91.58

80.18

N

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

317.27

258.00

305.03

303.53

SD

86.71

61.10

73.54

78.44

N

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

335.27

262.63

270.00

254.80

SD

86.06

100.24

56.60

64.46

N

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett

Table 7. Grip strength – group mean values (Continued)

Sex: Female

Forelimb

Mean (g)

(Day Number [Time])

Hindlimb

Mean (g)

(Day Number [Time])

Group

81 (Pre) (#)

81 (Post) (#)

81 (Pre) (#)

81 (Post) (#)

Group 1

Control

0 mg/kg/day

Mean

304.77

222.70

205.07

189.90*

SD

60.96

89.31

36.81

55.79

N

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

317.73

209.80

178.63

195.37

SD

97.52

70.94

47.39

38.48

N

10

10

10

10

Group 3

o-xylene

300 mg/kg/day

Mean

305.83

209.20

225.70

221.17

SD

105.24

48.88

95.66

41.77

N

10

10

10

10

Group 4

o-xylene

1000 mg/kg/day

Mean

326.47

254.30

234.47

162.43

SD

66.72

49.54

42.46

36.70

N

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett* = p ≤ 0.05
(#1) – Williams, Anova & Dunnett(Log)

 

 

 

 

 

 

Table 8. Haematology – group mean values

Sex: Male

RBC

10^6/ul

(Week Number)

Hb

g/dl

(Week Number)

PCV

%

(Week Number)

MCV

fl

(Week Number)

MCH

Pg

(Week Number)

MCHC

g/dl

(Week Number)

Group

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

8.877

15.51

45.44

51.22

17.50

34.14

SD

0.407

0.38

1.49

1.34

0.58

0.57

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

8.761

15.29

44.74

51.07

17.44

34.17

SD

0.182

0.19

0.69

1.16

0.45

0.42

N

9

9

9

9

9

9

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

8.716

15.31

44.91

51.54

17.59

34.09

SD

0.291

0.42

1.07

1.43

0.76

0.58

N

10

10

10

10

10

10

Trend

-

-

-

-

-

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

8.908

15.40

45.79

51.43

17.29

33.65

SD

0.384

0.52

1.58

1.12

0.53

0.48

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett* = p ≤ 0.05

Table 8. Haematology – group mean values (Continue)

Sex: Male

RDW

%

(Week Number)

HDW

g/dl

(Week Number)

Plate

10^3/ul

(Week Number)

MPV

fl

(Week Number)

PDW

%

(Week Number)

PCT

%

(Week Number)

Group

14 (#)

14 (#1)

14 (#1)

14 (#1)

14 (#1)

14 (#1)

Group 1

Control

0 mg/kg/day

Mean

13.28

2.850

831.2

9.70

43.54

0.80

SD

1.92

0.213

76.6

0.33

1.86

0.09

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

12.77

2.937

790.7

9.54

43.19

0.77

SD

0.71

0.148

77.6

0.25

1.54

0.07

N

9

9

9

9

9

9

Trend

-

-

-

> 0.05

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

13.78

2.924

809.5

10.06

43.62

0.80

SD

3.34

0.196

72.6

0.43

2.26

0.07

N

10

10

10

10

10

10

Trend

-

-

> 0.05

≤ 0.05*

-

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

12.98

2.809

924.7

10.01

42.95

0.92

SD

1.24

0.231

106.2

0.34

1.50

0.10

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

≤ 0.05*

≤ 0.05*

> 0.05

≤ 0.01**

(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett* = p ≤ 0.05, ** = p ≤ 0.01

 

 

Table 8. Haematology – group mean values (Continue)

Sex: Male

Retics

%RBC

(Week Number)

A retics

10^6/ul

(Week Number)

MC/Vr

fl

(Week Number)

CHr

pg

(Week Number)

WBC

10^3/ul

(Week Number)

Neut

10^3/ul

(Week Number)

Group

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

1.80

0.1598

62.02

18.21

6.253

0.656

SD

0.24

0.0243

0.97

0.50

1.820

0.160

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

1.78

0.1559

61.84

18.23

6.841

0.778

SD

0.19

0.0167

1.34

0.42

1.431

0.205

N

9

9

9

9

9

9

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

1.89

0.1642

62.13

18.28

7.084

0.924

SD

0.31

0.0252

0.86

0.37

1.049

0.262

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

1.85

0.1639

62.45

18.10

6.874

0.863

SD

0.30

0.0213

1.04

0.32

1.139

0.287

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett* = p ≤ 0.05

Table 8. Haematology – group mean values (Continue)

Sex: Male

Lymph

10^3/ul

(Week Number)

Mono

10^3/ul

(Week Number)

Eosin

10^3/ul

(Week Number)

Baso

10^3/ul

(Week Number)

LUC

10^3/ul

(Week Number)

Neut

%

(Week Number)

Group

14 (#)

14 (#1)

14 (#2)

14 (#1)

14 (#2)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

5.379

0.091

0.070

0.028

0.029

12.24

SD

1.767

0.047

0.029

0.017

0.021

8.39

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

5.823

0.086

0.101

0.026

0.031

11.49

SD

1.228

0.034

0.058

0.014

0.020

2.59

N

9

9

9

9

9

9

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

5.898

0.094

0.101

0.036

0.034

12.98

SD

0.863

0.024

0.044

0.022

0.011

2.66

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

5.772

0.097

0.083

0.025

0.036

12.57

SD

0.991

0.031

0.034

0.015

0.013

3.72

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett(Log)
(#2) – Williams, Anova & Dunnett

 

 

Table 8. Haematology – group mean values (Continue)

Sex: Male

Lymph

%

(Week Number)

Mono

%

(Week Number)

Eosin

%

(Week Number)

Baso

%

(Week Number)

LUC

%

(Week Number)

APIT

sec

(Week Number)

Group

14 (#)

14 (#1)

14 (#2)

14 (#1)

14 (#1)

14 (#1)

Group 1

Control

0 mg/kg/day

Mean

84.08

1.56

1.29

0.40

0.43

15.76

SD

9.51

0.72

0.97

0.18

0.25

0.94

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

85.02

1.26

1.47

0.38

0.42

14.96

SD

2.65

0.37

0.69

0.13

0.23

1.04

N

9

9

9

9

9

9

Trend

-

-

-

-

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

83.29

1.34

1.42

0.47

0.50

14.68

SD

2.90

0.34

0.50

0.26

0.16

0.97

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

83.95

1.45

1.18

0.35

0.51

14.68

SD

4.00

0.40

0.40

0.15

0.16

0.94

N

10

10

10

10

10

9

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#2) – Williams, Anova & Dunnett(Log)

 

Table 8. Haematology – group mean values (Continue)

Sex: Male

PT

sec

(Week Number)

Group

14 (#)

Group 1

Control

0 mg/kg/day

Mean

23.89

SD

1.67

N

9

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

23.03

SD

0.72

N

9

Trend

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

22.26

SD

0.87

N

9

Trend

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

22.76

SD

1.13

N

9

Trend

≤ 0.05*

 (#) – Williams, Anova & Dunnett: * = p ≤ 0.05

 

Table 8. Haematology – group mean values (Continued)

Sex: Female

RBC

10^6/ul

(Week Number)

Hb

g/dl

(Week Number)

PCV

%

(Week Number)

MCV

fl

(Week Number)

MCH

Pg

(Week Number)

MCHC

g/dl

(Week Number)

Group

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

7.758

14.20

41.42

53.41

18.33

34.32

SD

0.228

0.35

1.16

1.41

0.52

0.32

N

9

9

9

9

9

9

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

7.723

14.28

41.74

54.09

18.50

34.19

SD

0.193

0.30

0.81

1.62

0.61

0.37

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

7.922

14.45

42.11

53.20

18.25

34.29

SD

0.274

0.46

1.28

1.66

0.75

0.46

N

10

10

10

10

10

10

Trend

-

-

-

-

-

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

8.054

14.56

43.10

53.54

18.11

33.80

SD

0.258

0.31

0.93

1.14

0.55

0.47

N

9

9

9

9

9

9

Trend

≤ 0.05*

> 0.05

≤ 0.01**

> 0.05

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett* = p ≤ 0.05; ** = p ≤ 0.01

 

 

 

 

Table 8. Haematology – group mean values (Continue)

Sex: Female

RDW

%

(Week Number)

HDW

g/dl

(Week Number)

Plate

10^3/ul

(Week Number)

MPV

fl

(Week Number)

PDW

%

(Week Number)

PCT

%

(Week Number)

Group

14 (#)

14 (#1)

14 (#1)

14 (#1)

14 (#1)

14 (#1)

Group 1

Control

0 mg/kg/day

Mean

11.91

2.332

871.8

10.23

42.01

0.90

SD

2.09

0.157

173.1

0.50

2.29

0.17

N

9

9

9

9

9

9

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

12.14

2.261

778.5

10.01

42.61

0.78

SD

3.15

0.166

127.3

0.33

1.56

0.15

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

12.25

2.402

787.4

10.05

43.05

0.79

SD

2.24

0.172

64.1

0.37

1.50

0.09

N

10

10

10

10

10

10

Trend

-

-

-

-

> 0.05

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

11.71

2.419

752.0

10.18

44.37

0.76

SD

0.36

0.124

94.8

0.28

1.65

0.10

N

9

9

9

9

9

9

Trend

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.01**

≤ 0.05*

(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett* = p ≤ 0.05, ** = p ≤ 0.01

 

 

Table 8. Haematology – group mean values (Continue)

Sex: Female

Retics

%RBC

(Week Number)

A retics

10^6/ul

(Week Number)

MC/Vr

fl

(Week Number)

CHr

pg

(Week Number)

WBC

10^3/ul

(Week Number)

Neut

10^3/ul

(Week Number)

Group

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

2.26

0.1747

64.30

19.17

4.157

0.551

SD

0.40

0.0337

1.40

0.60

0.851

0.168

N

9

9

9

9

9

9

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

2.45

0.1897

64.45

19.16

3.788

0.438

SD

0.67

0.0485

2.04

0.48

0.973

0.171

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

2.21

0.1757

63.63

18.91

3.915

0.486

SD

0.46

0.0346

2.12

0.54

0.810

0.123

N

10

10

10

10

10

10

Trend

-

-

-

-

> 0.05

-

Group 4

o-xylene

1000 mg/kg/day

Mean

2.42

0.1947

64.10

18.87

5.296

0.579

SD

0.40

0.0279

1.73

0.44

0.903

0.162

N

9

9

9

9

9

9

Trend

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.05*

> 0.05

(#) – Williams, Anova & Dunnett* = p ≤ 0.05

 

 

 

Table 8. Haematology – group mean values (Continue)

Sex: Female

Lymph

10^3/ul

(Week Number)

Mono

10^3/ul

(Week Number)

Eosin

10^3/ul

(Week Number)

Baso

10^3/ul

(Week Number)

LUC

10^3/ul

(Week Number)

Neut

%

(Week Number)

Group

14 (#)

14 (#1)

14 (#1)

14 (#)

14 (#1)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

3.441

0.069

0.068

0.011

0.016*

13.49

SD

0.787

0.013

0.026

0.011

0.005

4.05

N

9

9

9

9

9

9

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

3.209

0.066

0.049

0.011

0.014

11.70

SD

0.832

0.037

0.011

0.012

0.007

3.71

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

3.283

0.065

0.056

0.009

0.012

12.41

SD

0.685

0.021

0.030

0.007

0.006

2.01

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

4.529

0.088

0.061

0.018

0.021

10.93

SD

0.802

0.024

0.040

0.013

0.008

2.59

N

9

9

9

9

9

9

Trend

≤ 0.01**

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett** = p ≤ 0.01
(#1) – Williams, Anova & Dunnett(Log) * = p ≤ 0.05

 

Table 8. Haematology – group mean values (Continue)

Sex: Female

Lymph

%

(Week Number)

Mono

%

(Week Number)

Eosin

%

(Week Number)

Baso

%

(Week Number)

LUC

%

(Week Number)

APIT

sec

(Week Number)

Group

14 (#)

14 (#)

14 (#1)

14 (#)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

82.50

1.71

1.64

0.27

0.40

16.23

SD

3.83

0.43

0.42

0.19

0.16

1.52

N

9

9

9

9

9

7

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

84.52

1.72

1.37

0.27

0.40

16.37

SD

4.47

0.59

0.55

0.20

0.19

1.35

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

83.91

1.70

1.42

0.26

0.32

15.78

SD

2.36

0.45

0.57

0.16

0.08

1.28

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

85.46

1.68

1.17

0.29

0.43

15.32

SD

3.06

0.51

0.55

0.20

0.19

1.60

N

9

9

9

9

9

9

Trend

> 0.05

> 0.05

≤ 0.05*

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05

 

 

Table 8. Haematology – group mean values (Continue)

Sex: Female

PT

sec

(Week Number)

Group

14 (#)

Group 1

Control

0 mg/kg/day

Mean

23.61

SD

2.18

N

7

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

23.83

SD

1.29

N

10

Trend

-

Group 3

o-xylene

300 mg/kg/day

Mean

23.60

SD

0.85

N

10

Trend

-

Group 4

o-xylene

1000 mg/kg/day

Mean

23.16

SD

0.65

N

9

Trend

> 0.05

 (#) – Shirley, Kruskal-Wallis & Steel

 

Table 9. Blood chemistry – group mean values

Sex: Male

Urea

mg/dl

(Week Number)

Cren

mg/dl

(Week Number)

Na

mmol/l

(Week Number)

K

mmol/l

(Week Number)

Cl

mmol/l

(Week Number)

ALT

U/l

(Week Number)

Group

14 (#)

14 (#1)

14 (#1)

14 (#1)

14 (#1)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

31.29

0.273

140.1

4.94

99.9

42.0

SD

5.65

0.028

1.5

0.42

1.3

10.5

N

9

9

9

9

9

9

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

32.39

0.292

140.7

4.92

100.3

43.8

SD

4.38

0.023

1.0

0.42

1.2

4.6

N

9

9

9

9

9

9

Trend

-

-

> 0.05

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

32.34

0.274

141.8

4.99

99.9

46.1

SD

3.23

0.037

0.9

0.43

1.2

6.4

N

10

10

10

10

10

10

Trend

-

-

≤ 0.01**

-

> 0.05

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

30.67

0.264

142.4

4.74

98.7

50.9

SD

3.06

0.031

1.0

0.28

0.8

9.4

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

≤ 0.001***

> 0.05

≤ 0.05*

≤ 0.05*

(#) – Williams, Anova & Dunnett(Log)
(#1) – Williams, Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤ 0.001
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

 

 

Table 9. Blood chemistry – group mean values (Continued)

Sex: Male

AST

U/l

(Week Number)

ALP

U/l

(Week Number)

BiliT

mg/dl

(Week Number)

B. Acids

umol/l

(Week Number)

T. Prot

g/dl

(Week Number)

Ab

g/dl

(Week Number)

Group

14 (#)

14 (#)

14

14 (#1)

14 (#1)

14 (#1)

Group 1

Control

0 mg/kg/day

Mean

57.2

118.7

-

30.80

6.42

3.84

SD

11.7

37.1

-

19.10

0.21

0.11

N

9

9

0

9

9

9

Trend

-

Group 2

o-xylene

100 mg/kg/day

Mean

56.9

111.4

-

33.70

6.44

3.93

SD

4.5

20.4

-

17.37

0.20

0.13

N

9

9

0

9

9

9

Trend

-

-

-

-

-

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

57.7

118.2

-

34.31

6.55

4.03

SD

2.0

34.0

-

13.56

0.22

0.16

N

10

10

0

10

10

10

Trend

-

-

-

-

-

≤ 0.01**

Group 4

o-xylene

1000 mg/kg/day

Mean

58.0

135.0

0.150

45.26

6.48

4.11

SD

6.1

23.4

-

15.53

0.24

0.20

N

10

10

1

10

10

10

Trend

> 0.05

> 0.05

-

> 0.05

> 0.05

≤ 0.001***

(#) – Williams, Anova & Dunnett(Log)
(#1) – Williams, Anova & Dunnett: ** = p ≤ 0.01; *** = p ≤ 0.001
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

Table 9. Blood chemistry – group mean values (Continued)

Sex: Male

Glob

g/dl

(Week Number)

A/G

ratio

(Week Number)

Ca

mg/dl

(Week Number)

Chol

mg/dl

(Week Number)

HDL

mg/dl

(Week Number)

LDL

mg/dl

(Week Number)

Group

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

2.58

1.50

10.30

64.0

46.98

8.1

SD

0.22

0.14

0.11

8.6

6.34

2.4

N

9

9

9

9

9

9

Trend

-

Group 2

o-xylene

100 mg/kg/day

Mean

2.51

1.58

10.32

73.8

55.11

10.9

SD

0.23

0.17

0.22

16.7

11.96

4.1

N

9

9

9

9

9

9

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

2.52

1.61

10.40

67.6

51.16

8.2

SD

0.23

0.19

0.12

11.1

8.25

2.6

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

2.37

1.74

10.31

69.9

53.83

8.6

SD

0.17

0.16

0.16

9.4

6.93

2.0

N

10

10

10

10

10

10

Trend

≤ 0.05*

≤ 0.01**

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

Table 9. Blood chemistry – group mean values (Continued)

Sex: Male

Gluc

g/dl

(Week Number)

Group

14 (#)

Group 1

Control

0 mg/kg/day

Mean

198.9

SD

17.3

N

9

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

174.1

SD

13.1

N

9

Trend

≤ 0.01**

Group 3

o-xylene

300 mg/kg/day

Mean

174.7

SD

19.0

N

10

Trend

≤ 0.01**

Group 4

o-xylene

1000 mg/kg/day

Mean

167.4

SD

25.6

N

10

Trend

≤ 0.01**

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

 

 

Table 9. Blood chemistry – group mean values (Continued)

Sex: Female

Urea

mg/dl

(Week Number)

Cren

mg/dl

(Week Number)

Na

mmol/l

(Week Number)

K

mmol/l

(Week Number)

Cl

mmol/l

(Week Number)

ALT

U/l

(Week Number)

Group

14 (#)

14 (#)

14 (#)

14 (#1)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

36.94

0.304

141.7

4.00

101.3*

37.6

SD

5.50

0.022

0.5

0.69

1.2

5.4

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

32.21

0.294

142.3

3.89

101.9

39.3

SD

3.87

0.033

1.1

0.19

1.7

12.2

N

10

10

10

10

10

10

Trend

≤ 0.05*

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

32.54

0.292

142.3

3.68

102.0

34.7

SD

4.50

0.033

1.1

0.09

1.4

5.3

N

10

10

10

10

10

10

Trend

≤ 0.05*

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

31.15

0.280

142.4

3.84

100.3

42.1

SD

4.39

0.016

1.3

0.30

0.9

11.1

N

10

10

10

10

10

10

Trend

≤ 0.01**

> 0.05

> 0.05

> 0.05

≤ 0.05*

> 0.05

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01
(#1) – Shirley, Kruskal-Wallis & Steel
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

Table 9. Blood chemistry – group mean values (Continued)

Sex: Female

AST

U/l

(Week Number)

ALP

U/l

(Week Number)

BiliT

mg/dl

(Week Number)

B. Acids

umol/l

(Week Number)

T. Prot

g/dl

(Week Number)

Ab

g/dl

(Week Number)

Group

14 (#)

14 (#)

14

14 (#1)

14 (#1)

14 (#1)

Group 1

Control

0 mg/kg/day

Mean

58.1

52.6

-

33.11

6.82

4.50

SD

5.2

17.6

-

17.93

0.22

0.14

N

10

10

0

10

10

10

Trend

-

Group 2

o-xylene

100 mg/kg/day

Mean

63.4

49.9

-

43.88

6.81

4.69

SD

18.4

16.3

-

25.72

0.30

0.28

N

10

10

0

9

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

56.4

52.6

-

36.63

6.74

4.66

SD

9.6

16.0

-

19.90

0.39

0.28

N

10

10

0

10

10

10

Trend

-

-

-

-

-

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

58.7

64.6

0.150

43.93

6.90

4.98

SD

6.0

21.0

0.000

23.86

0.32

0.28

N

10

10

2

10

10

10

Trend

> 0.05

> 0.05

-

> 0.05

> 0.05

≤ 0.001***

(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett: *** = p ≤ 0.001
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

 

 

Table 9. Blood chemistry – group mean values (Continued)

Sex: Female

Glob

g/dl

(Week Number)

A/G

ratio

(Week Number)

Ca

mg/dl

(Week Number)

Chol

mg/dl

(Week Number)

HDL

mg/dl

(Week Number)

LDL

mg/dl

(Week Number)

Group

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

14 (#)

Group 1

Control

0 mg/kg/day

Mean

2.32

1.96

10.36

50.3

42.32

- n

SD

0.21

0.20

0.21

5.8

4.96

-

N

10

10

10

10

10

0

Trend

-

Group 2

o-xylene

100 mg/kg/day

Mean

2.12

2.22

10.42

54.0

47.30

5.5 n

SD

0.11

0.18

0.28

12.1

10.88

1.3

N

10

10

10

10

10

4

Trend

≤ 0.01**

≤ 0.01**

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

2.08

2.25

10.34

50.1

44.02

5.0 n

SD

0.17

0.17

0.24

10.3

9.54

-

N

10

10

10

10

10

1

Trend

≤ 0.001***

≤ 0.001***

-

> 0.05

> 0.05

-

Group 4

o-xylene

1000 mg/kg/day

Mean

1.91

2.60

10.44

62.1

53.94

5.5 n

SD

0.12

0.22

0.23

10.8

9.86

0.7

N

10

10

10

10

10

2

Trend

≤ 0.001***

≤ 0.001***

> 0.05

≤ 0.05*

≤ 0.01**

-

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤ 0.001
(#1) – Shirley, Kruskal-Wallis & Steel: n – inappropriate for statistics
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

Table 9. Blood chemistry – group mean values (Continued)

Sex: Female

Gluc

g/dl

(Week Number)

Group

14 (#)

Group 1

Control

0 mg/kg/day

Mean

168.1

SD

11.1

N

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

168.8

SD

9.9

N

10

Trend

-

Group 3

o-xylene

300 mg/kg/day

Mean

170.2

SD

8.8

N

10

Trend

-

Group 4

o-xylene

1000 mg/kg/day

Mean

169.5

SD

20.0

N

10

Trend

> 0.05

(#) – Williams, Anova & Dunnett
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl) are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not included

Table 10.1. Organ weights – absolute and relative to body weight - group mean values

Sex: Male

Brain

(g)

Adjusted Brain Wt

Brain %

Body Weight

Pituitary

(g)

Adjusted Pituitary Wt

Pituitary % Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

2.112

2.076

0.508

0.0077

0.0073

0.0018

SD

0..95

-

0.031

0.0020

-

0.0004

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

2.115

2.089

0.516

0.0089

0.0086

0.0022

SD

0.086

-

0.032

0.0019

-

0.0004

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

2.077

2.092

0.535

0.0067

0.0069

0.0017

SD

0.093

-

0.033

0.0012

-

0.0003

N

10

10

10

10

10

10

Trend

-

-

> 0.05

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

2.083

2.130

0.564

0.0080

0.0085

0.0021

SD

0.097

-

0.046

0.0026

-

0.0007

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

≤ 0.01**

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)

 

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Male

Thymus

(g)

Adjusted Thymus Wt

Thymus %

Body Weight

Heart

(g)

Adjusted

Heart Wt

Heart %

Body Weight

Group

(#)

(#1)

(#)

(#2)

(#3)

(#2)

Group 1

Control

0 mg/kg/day

Mean

0.3846

0.357

0.0928

1.153

1.110

0.279

SD

0.0590

-

0.0164

0.158

-

0.057

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.4145

0.394

0.0997

1.207

1.155

0.293

SD

0.1070

-

0.0199

0.156

-

0.025

N

10

10

10

10

10

10

Trend

-

-

-

-

-

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

0.3755

0.387

0.0957

1.262

1.160

0.325

SD

0.0743

-

0.0135

0.252

-

0.067

N

10

10

10

10

10

10

Trend

-

-

> 0.05

-

-

≤ 0.01**

Group 4

o-xylene

1000 mg/kg/day

Mean

0.3443

0.381

0.0918

1.208

1.160

0.325

SD

0.1127

-

0.0257

0.166

-

0.034

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.001***

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
(#2) – Shirley, Kruskal-Wallis & Steel: * = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤ 0.001
(#3) – Shirley, Kruskal-Wallis & Steel
(Covariate(s): Dead body weight)

 


Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Male

Spleen

(g)

Adjusted

Spleen Wt

Spleen %

Body Weight

Liver

(g)

Adjusted

Liver Wt

Liver %

Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

0.581

0.551

0.139

13.773

12.907

3.292

SD

0.092

-

0.013

1.833

-

0.262

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.605

0.583

0.147

13.888

13.246

3.364

SD

0.076

-

0.010

1.642

-

0.154

N

10

10

10

10

10

10

Trend

-

-

-

-

> 0.05

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

0.562

0.574

0.145

14.144

14.502

3.629

SD

0.076

-

0.019

1.199

-

0.100

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

≤ 0.001***

≤ 0.001***

Group 4

o-xylene

1000 mg/kg/day

Mean

0.554

0.593

0.149

16.174

17.325

4.329

SD

0.072

-

0.014

2.375

-

0.243

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

≤ 0.01**

≤ 0.001***

≤ 0.001***

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: *** = p ≤ 0.001
(Covariate(s): Dead body weight)

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Male

Adrenals

(g)

Adjusted

Adrenal Wt

Adrenals %

Body Weight

Kidneys

(g)

Adjusted

Kidneys Wt

Kidneys %

Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

0.0599

0.0569

0.0143

2.361

2.361

0.565

SD

0.0128

-

0.0028

0.313

-

0.048

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.0608

0.0586

0.0148

2.423

2.423 n

0.589

SD

0.0098

-

0.0023

0.235

-

0.036

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

> 0.05

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

0.0584

0.0596

0.0149

2.648

2.648 n

0.683

SD

0.0098

-

0.0018

0.095

-

0.053

N

10

10

10

10

10

10

Trend

-

-

> 0.05

≤ 0.05*

≤ 0.05*

≤ 0.001***

Group 4

o-xylene

1000 mg/kg/day

Mean

0.0635

0.0675

0.0170

2.934

2.934 n

0.785

SD

0.0156

-

0.0036

0.433

-

0.043

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

≤ 0.05*

≤ 0.01**

≤ 0.001***

≤ 0.001***

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: * = p ≤ 0.05; *** = p ≤ 0.001; n = Mean = Raw Mean as Adjusted mean is not available
(Covariate(s): Dead body weight)

 

 

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Male

Testes

(g)

Adjusted

Testes Wt

Testes %

Body Weight

Epididymides

(g)

Adjusted Epididymides Wt

Epdidymides

% Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

3.612

3.580

0.872

1.406

1.359

0.338

SD

0.323

-

0.116

0.131

-

0.035

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

3.840

3.816

0.938

1.444

1.409

0.352

SD

0.189

-

0.091

0.128

-

0.034

N

10

10

10

10

10

10

Trend

-

-

-

-

-

> 0.05

Group 3

o-xylene

300 mg/kg/day

Mean

3.707

3.720

0.953

1.443

1.462

0.370

SD

0.368

-

0.094

0.191

-

0.035

N

10

10

10

10

10

10

Trend

-

-

> 0.05

-

-

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

3.803

3.846

1.029

1.401

1.463

0.377

SD

0.324

-

0.110

0.179

-

0.036

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

≤ 0.01**

> 0.05

> 0.05

≤ 0.05*

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)

 

 

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Male

Prostate /

Seminal Vesicles

(g)

Adjusted

Prostate / Seminal Vesicles

Prostate / Seminal Vesicles

%

Body Weight

Thyroids

(g)

Adjusted Thyroids Wt

Thyroids

% Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

2.284

2.205

0.545

0.0226

0.0215

0.0054

SD

0.406

-

0.075

0.0049

-

0.0009

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

2.376

2.137

0.577

0.0243

0.0235

0.0059

SD

0.301

-

0.063

0.0050

-

0.0011

N

10

10

10

10

10

10

Trend

-

-

> 0.05

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

2.515

2.548

0.650

0.0204

0.0209

0.0052

SD

0.267

-

0.094

0.0046

-

0.0011

N

10

10

10

10

10

10

Trend

-

-

≤ 0.05*

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

2.211

2.316

0.596

0.0197

0.0212

0.0053

SD

0.264

-

0.057

0.0035

-

0.0009

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

≤ 0.05*

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)

 

 

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Male

Dead

Body Weight

(g)

Group

(#)

Group 1

Control

0 mg/kg/day

Mean

417.24

SD

33.93

N

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

412.25

SD

38.39

N

10

Trend

-

Group 3

o-xylene

300 mg/kg/day

Mean

389.96

SD

33.70

N

10

Trend

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

372.30

SD

40.15

N

10

Trend

≤ 0.05*

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05

Table 10.1. Organ weights – absolute and relative to body weight - group mean values

Sex: Female

Brain

(g)

Adjusted Brain Wt

Brain %

Body Weight

Pituitary

(g)

Adjusted Pituitary Wt

Pituitary % Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

1.969

1.969

0.810

0.0112

0.112

0.0046

SD

0.113

-

0.044

0.0018

-

0.0006

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

2.004

2.005

0.825

0.0105

0.0105

0.0043

SD

0.097

-

0.034

0.0028

-

0.0011

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

1.945

1.951

0.812

0.0104

0.0105

0.0043

SD

0.071

-

0.071

0.0028

-

0.0011

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

1.913

1.906

0.782

0.0094

0.0093

0.0038

SD

0.099

-

0.060

0.0020

-

0.0007

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)

 

 

 

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Female

Thymus

(g)

Adjusted Thymus Wt

Thymus %

Body Weight

Heart

(g)

Adjusted

Heart Wt

Heart %

Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

0.3438

0.344

0.1411

0.833

0.833

0.343

SD

0.0449

-

0.0163

0.062

-

0.035

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.3091

0.310

0.1268

0.895

0.896

0.368

SD

0.0590

-

0.0208

0.079

-

0.038

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

0.2821

0.284

0.1170

0.878

0.882

0.365

SD

0.0616

-

0.0234

0.129

-

0.053

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

0.3151

0.313

0.1290

0.815

0.811

0.332

SD

0.0712

-

0.0299

0.080

-

0.021

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)

 


Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Female

Spleen

(g)

Adjusted

Spleen Wt

Spleen %

Body Weight

Liver

(g)

Adjusted

Liver Wt

Liver %

Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

0.431

0.431

0.176*

7.969

7.964

3.276

SD

0.062

-

0.015

0.698

-

0.251

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.489

0.490

0.201*

8.493

8.510

3.492

SD

0.072

-

0.027

0.956

-

0.339

N

10

10

10

10

10

10

Trend

-

-

-

-

≤ 0.05*

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

0.423

0.428

0.176

8.311

8.418

3.453

SD

0.056

-

0.018

0.955

-

0.235

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

≤ 0.05*

≤ 0.05*

Group 4

o-xylene

1000 mg/kg/day

Mean

0.456

0.450

0.185

10.841

10.742

4.403

SD

0.083

-

0.025

1.161

-

0.107

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

≤ 0.001***

≤ 0.001***

≤ 0.001***

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: * = p ≤ 0.05; *** = p ≤ 0.001
(Covariate(s): Dead body weight)

 

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Female

Adrenals

(g)

Adjusted

Adrenal Wt

Adrenals %

Body Weight

Kidneys

(g)

Adjusted

Kidneys Wt

Kidneys %

Body Weight

Group

(#)

(#1)

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

0.0712

0.0712

0.0291

1.509

1.508

0.620

SD

0.0127

-

0.0039

0.100

-

0.029

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.0677

0.0678

0.0279

1.577

1.579

0.649

SD

0.0143

-

0.0062

0.106

-

0.039

N

10

10

10

10

10

10

Trend

-

-

-

> 0.05

≤ 0.05*

≤ 0.05*

Group 3

o-xylene

300 mg/kg/day

Mean

0.0707

0.0713

0.0294

1.598

1.609

0.665

SD

0.0108

-

0.0044

0.083

-

0.035

N

10

10

10

10

10

10

Trend

-

-

-

≤ 0.05*

≤ 0.01**

≤ 0.01**

Group 4

o-xylene

1000 mg/kg/day

Mean

0.0703

0.0696

0.0286

1.719

1.707

0.699

SD

0.0159

-

0.0057

0.147

-

0.019

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

0.05

≤ 0.001***

≤ 0.001***

≤ 0.001***

(#) – Williams, Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤ 0.001
(Covariate(s): Dead body weight)

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Female

Ovaries

(g)

Adjusted

Ovaries Wt

Ovaries %

Body Weight

Uterus

(g)

Adjusted

Uterus Wt

Uterus %

Body Weight

Group

(#)

(#1)

(#)

(#2)

(#3)

(#2)

Group 1

Control

0 mg/kg/day

Mean

0.0872

0.0872

0.0359

0.822

0.7320

0.3450

SD

0.0168

-

0.0070

0.450

-

0.2059

N

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.0900

0.0902

0.0371

0.631

0.6080

0.2604

SD

0.0156

-

0.0066

0.197

-

0.0838

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

0.1002

0.1010

0.0414

0.632

0.6030

0.2629

SD

0.0163

-

0.0040

0.219

-

0.0919

N

10

10

10

10

10

10

Trend

-

-

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

0.0934

0.0925

0.0381

0.677

0.6310

0.2758

SD

0.0214

-

0.0083

0.294

-

0.1198

N

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
(#2) – Williams, Anova & Dunnett(Log)
(#3) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)

 

Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)

Sex: Female

Thyroids

(g)

Adjusted Thyroids Wt

Thyroids

% Body Weight

Dead

Body Weight

(g)

Group

(#)

(#)

(#)

(#)

Group 1

Control

0 mg/kg/day

Mean

0.0174

0.0174

0.0072

243.65

SD

0.0035

-

0.0017

18.19

N

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

0.0186

0.0186

0.0077

243.07

SD

0.0028

-

0.0011

12.07

N

10

10

10

10

Trend

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

0.0190

0.0190

0.0079

241.20

SD

0.0034

-

0.0017

21.45

N

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

-

Group 4

o-xylene

1000 mg/kg/day

Mean

0.0235

0.0235

0.0096

246.14

SD

0.0033

-

0.0013

24.57

N

10

10

10

10

Trend

≤ 0.001***

≤ 0.001***

≤ 0.01**

> 0.05

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: *** = p ≤ 0.001
(Covariate(s): Dead body weight)

 

Table 10.2. Organ weights – relative to brain weight - group mean values

Sex: Male

Brain

(g)

Pituitary %

Brain

Thymus %

Brain

Heart %

Brain

Spleen %

Brain

Liver %

Brain

Adrenals %

Brain

Group

(#)

(#)

(#)

(#)

(#1)

(#)

(#)

Group 1

Control

0 mg/kg/day

Mean

2.112

0.3629

18.2834

54.776

27.433

651.021

2.8287

SD

0.095

0.0873

3.1413

8.986

3.650

73.244

0.5587

N

10

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

2.115

0.4208

19.4780

56.971

28.553

655.321

2.8799

SD

0.086

0.0899

4.4219

5.624

2.892

57.041

0.4688

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

2.077

0.3236

17.9913

60.779

27.120

680.905

2.8119

SD

0.093

0.0614

2.9087

11.833

3.969

46.905

0.4588

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

> 0.05

-

Group 4

o-xylene

1000 mg/kg/day

Mean

2.083

0.3807

16.5254

57.997

26.536

774.952

3.0393

SD

0.097

0.1114

5.2816

7.264

2.716

96.415

0.6922

N

10

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.001***

> 0.05

(#) – Williams, Anova & Dunnett: *** = p ≤ 0.001
(#1) – Shirley, Kruskal-Wallis & Steel

 

 

 

Table 10.2. Organ weights – relative to brain weight - group mean values (Continued)

Sex: Male

Kidneys %

Brain

Testes %

Brain

Epididymides

% Brain

Prostate/Seminal

Vesicles

% Brain

Thyroids %

Brain

Group

(#)

(#)

(#)

(#)

(#)

Group 1

Control

0 mg/kg/day

Mean

111.525

171.470

66.612

107.790

1.0677

SD

11.534

18.410

6.063

16.758

0.2082

N

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

114.541

181.831

68.302

112.328

1.1467

SD

9.719

11.508

5.730

13.472

0.2194

N

10

10

10

10

10

Trend

> 0.05

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

127.698

178.552

69.348

121.650

0.9800

SD

6.766

16.851

7.508

17.369

0.2127

N

10

10

10

10

10

Trend

≤ 0.01**

-

-

-

-

Group 4

o-xylene

1000 mg/kg/day

Mean

140.568

182.798

67.210

105.847

0.9454

SD

17.332

16.490

7.618

8.184

0.1583

N

10

10

10

10

10

Trend

≤ 0.001**

> 0.05

> 0.05

> 0.05

> 0.05

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01; *** = p ≤ 0.001

Table 10.2. Organ weights – relative to brain weight - group mean values (Continued)

Sex: Female

Brain

(g)

Pituitary %

Brain

Thymus %

Brain

Heart %

Brain

Spleen %

Brain

Liver %

Brain

Adrenals %

Brain

Group

(#)

(#)

(#)

(#)

(#1)

(#)

(#)

Group 1

Control

0 mg/kg/day

Mean

1.969

0.5677

17.4350

42.494

21.880

405.271

3.6106

SD

0.113

0.0785

1.8612

4.851

2.771

34.390

0.5934

N

10

10

10

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

2.004

0.5222

15.3804

44.647

24.355

423.402

3.3807

SD

0.097

0.1272

2.5131

3.132

3.098

39.853

0.7085

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

1.945

0.5319

14.4757

45.122

21.712

427.949

3.6392

SD

0.071

0.1304

2.9491

6.138

2.351

42.274

0.5491

N

10

10

10

10

10

10

10

Trend

-

-

-

-

-

> 0.05

-

Group 4

o-xylene

1000 mg/kg/day

Mean

1.913

0.4927

16.5734

42.571

23.778

566.272

3.6741

SD

0.099

0.1016

4.1431

3.125

3.688

47.251

0.7690

N

10

10

10

10

10

10

10

Trend

> 0.05

> 0.05

> 0.05

> 0.05

> 0.05

≤ 0.001***

> 0.05

(#) – Williams, Anova & Dunnett: *** = p ≤ 0.001

 

 

Table 10.2. Organ weights – relative to brain weight - group mean values (Continued)

Sex: Female

Kidneys %

Brain

Ovaries %

Brain

Uterus %

Brain

Thyroids %

Brain

Group

(#)

(#)

(#1)

(#)

Group 1

Control

0 mg/kg/day

Mean

76.672

4.4277

41.760

0.8902

SD

3.349

0.8274

22.997

0.1964

N

10

10

10

10

Trend

Group 2

o-xylene

100 mg/kg/day

Mean

78.773

4.4844

31.509

0.9313

SD

5.252

0.6896

9.662

0.1573

N

10

10

10

10

Trend

> 0.05

-

-

-

Group 3

o-xylene

300 mg/kg/day

Mean

82.191

5.1599

32.259

0.9785

SD

3.847

0.8705

10.091

0.1792

N

10

10

10

10

Trend

≤ 0.01**

-

-

> 0.05

Group 4

o-xylene

1000 mg/kg/day

Mean

89.819

4.8763

35.237

1.2302

SD

5.293

1.0270

14.803

0.1774

N

10

10

10

10

Trend

≤ 0.001***

> 0.05

> 0.05

≤ 0.001***

(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01; *** = p ≤ 0.001
(#1) – Williams, Anova & Dunnett(Log)

 

Microscopic Pathology

 

Males

Females

Group

1

2

3

4

1

2

3

4

Dose Level (mg/kg/day)

0

100

300

1000

0

100

300

1000

Number of rats examined

10

10

10

10

10

10

10

10

Liver

Hypertrophy, centrilobular hepatocytes

Minimal

0

0

2

7

0

0

2

6

Slight

0

0

0

1

0

0

0

1

Total

0

0

2

8

0

0

2

7

Thyroid Gland

Hypertrophy, follicular epithelium

Minimal

1

2

3

3

1

1

1

5

Slight

0

2

1

3

0

0

0

0

Moderate

0

0

0

0

0

0

0

0

Total

1

4

4

6

1

1

1

5

Kidney

Eosinophilic inclusions, proximal tubule

Minimal

0

0

0

0

0

-

-

0

Slight

0

6

9

7

0

-

-

0

Moderate

0

0

0

2

0

-

-

0

Total

0

6

9

9

0

-

-

0

Basophilia, cortex, tubules

Minimal

1

3

8

4

0

-

-

0

Slight

0

0

0

1

0

-

-

0

Moderate

0

0

0

0

0

-

-

0

Total

1

3

8

5

0

-

-

0

α2μ-globulin positive staining

Minimal

2

0

0

2

-

-

-

-

Moderate

0

0

0

1

-

-

-

-

Total

2

0

0

3

-

-

-

-

Applicant's summary and conclusion

Conclusions:
In conclusion, when administered by gavage to the Han Wistar rat, once daily for at least 90 days, o-xylene was generally well tolerated in-life at 100 and 300 mg/kg/day with, at the latter dose, only a mild retardation of body weight gain in males and clinical signs being limited to some transient excessive salivation after dosing. However, more profound (decreased activity, unsteady gait, effects on arousal, unusual posture), but transient, clinical signs were apparent at 1000 mg/kg/day and a more marked retardation of body weight gains in males. Target organ pathology was restricted to rat specific adaptive responses consisting of hepatic centrilobular hypertrophy and secondary thyroid follicular hypertrophy consistent with enzyme induction and adverse renal tubular changes in males only likely reflecting proteinuria and inclusion of non α2μ-globulin proteins. Therefore, the No Observed Adverse Effect Level (NOAEL) was defined as 300 mg/kg/day o-xylene in the female rat because of the severity of clinical signs at 1000 mg/kg/day and as 100 mg/kg/day in the male rat, because of the incidence and severity of the renal changes. However, given the physiological differences between the male rat kidney and human, the observed tubular changes are unlikely to represent a hazard to man. Therefore, if the findings in the kidney are disregarded as being human relevant, the NOAEL for the male would be 300 mg/kg/day.
Executive summary:

An OECD 408 rat study was conducted to assess the potential toxicity of o-xylene when administered by gavage to the rat once daily for at least 90 days. The test material, o-xylene (CAS 95-47 -6), was administered to male and female rats by oral gavage. Dose levels were 0, 100, 300, and 1000 mg/kg/day (Groups 1 through 4, respectively), with 10 animals/sex/group dosed daily for at least 90 days.The following were investigated: clinical observations, ophthalmoscopy, body weight, food intake, functional observation battery, haematology, blood chemistry, thyroid hormone analysis, organ weights, macroscopic and microscopic pathology.

There were no deaths during the study. Males and females given 1000 mg/kg/day showed decreased activity and unsteady gait from Days 19/18 of dosing onwards (persisting for up to 4 hours after dosing), respectively. The incidence of these clinical signs decreased with time and by Day 72 of dosing, only one male was showing decreased activity and abnormal gait. Over Days 84 to 92 of dosing at most eight out of ten females showed one or both of these signs after dosing. No effects on sensory reaction or grip strength were elicited by o-xylene. In open arena testing, males given 1000 mg/kg/day exhibited effects on arousal, unusual posture and abnormal gait. Twitches or extended rearing were also observed in a small number of individual males given 1000 mg/kg/day. Increased episodes of arousal in the arena and abnormal gait were observed between Days 21 to 70 and Days 21 to 56 of dosing, respectively. Excessive salivation in the arena was also noted between Days 14 and 70 of dosing for males given 300 or 1000 mg/kg/day, with incidence increasing with time. Females given 1000 mg/kg/day also exhibited effects on arousal in the arena, abnormal gait and salivation. Although incidences increased with time similarly to the males, these observations were not seen in either sex after Day 77 of dosing. Movement counts and distance travelled were reduced in males given 100, 300 or 1000 mg/kg/day and this was occasionally accompanied by an increased time at rest. Males given 300 or 1000 mg/kg/day gained less weight over the study than Controls with terminal body weights that were 6 % and 11 % respectively, lower than those of the Controls. There was no effect on body weight for females and no effect on food intake in either sex. There were slight increases in Thyroxine (T4) and no effect on thyroid stimulating hormone (TSH) or triiodothyronine (T3) levels at the end of the treatment period and no adverse effects on haematology, coagulation or blood chemistry parameters. Both sexes given 300 or 1000 mg/kg/day and females given 100 mg/kg/day had statistically significantly higher liver and kidney weights when compared with Controls. In addition, thyroid weights for females given 1000 mg/kg/day were also higher than Controls.

Histopathology findings considered to be related to o-xylene were seen in the liver (hepatocellular hypertrophy) and thyroid (follicular cell hypertrophy) in both sexes and, in the kidneys, eosinophilic inclusions (hyaline droplets) in the tubular epithelium (males only). Following α2μ-globulin staining of the kidneys, although positive staining was observed in 3/10 high dose males, minimal staining was also observed in 2/10 Controls. The precise content of the hyaline droplets observed at an increased incidence/severity of within the cortical tubules of male kidneys therefore remained unestablished. Given the physiological differences between the male rat kidney and human, these findings are considered unlikely to represent a hazard to man.

In conclusion, when administered by gavage to the Han Wistar rat, once daily for at least 90 days, o-xylene was generally well tolerated in-life at 100 and 300 mg/kg/day with, at the latter dose, only a mild retardation of body weight gain in males and clinical signs being limited to some transient excessive salivation after dosing. However, more profound (decreased activity, unsteady gait, effects on arousal, unusual posture), but transient, clinical signs were apparent at 1000 mg/kg/day and a more marked retardation of body weight gains in males. Target organ pathology was restricted to rat specific adaptive responses consisting of hepatic centrilobular hypertrophy and secondary thyroid follicular hypertrophy consistent with enzyme induction and adverse renal tubular changes in males only likely reflecting proteinuria and inclusion of non α2μ-globulin proteins. Therefore, the No Observed Adverse Effect Level (NOAEL) was defined as 300 mg/kg/day o-xylene in the female rat because of the severity of clinical signs at 1000 mg/kg/day and as 100 mg/kg/day in the male rat, because of the incidence and severity of the renal changes. However, given the physiological differences between the male rat kidney and human, the observed tubular changes are unlikely to represent a hazard to man. Therefore, if the findings in the kidney are disregarded as being human relevant, the NOAEL for the male would be 300 mg/kg/day.