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EC number: 268-452-3 | CAS number: 68092-28-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- October 1986 to December 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- Study conducted to GLP in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. Reliability of 2 given since the data is based on read across, not the target substance.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 992
- Reference Type:
- publication
- Title:
- Toxicity of Diethanolamine. 1. Drinking Water and Topical Application Exposures in F344 Rats
- Author:
- Melnick, R.L., Mahler, J., Bucher, J.R., Thompson, M., Hejtmancik, M., Ryan, M.J. & Mezza, L.E.
- Year:
- 1 994
- Bibliographic source:
- J. Appl. Toxicol. 14, 1-9 (1994)
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Diethanolamine (DEA)
- IUPAC Name:
- Diethanolamine (DEA)
- Reference substance name:
- 2,2'-iminodiethanol
- EC Number:
- 203-868-0
- EC Name:
- 2,2'-iminodiethanol
- Cas Number:
- 111-42-2
- Molecular formula:
- C4H11NO2
- IUPAC Name:
- 2,2'-iminodiethanol
- Test material form:
- liquid
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: ca. 7 weeks of age
- Weight at study initiation: Males had a mean initial bodyweight of 120 to 124 g; females had a mean initial bodyweight of 106 to 114 g.
- Housing: animals were housed individually.
- Diet (e.g. ad libitum): diet in pellet form was available ad libitum.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 20 to 24 °C (72 ± 3 °F)
- Humidity (%): 50 ± 15 % relative humidity
- Air changes (per hr): 10 to 12 fresh-air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h per day of subdued fluorescent light
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- ethanol
- Details on exposure:
- TEST SITE
- Area of exposure: The dosing solution was applied to the shaved back of each animal from the mid-back to the interscapular region using a calibrated micropipette.
- Time intervals for shavings or clippings: Rats were shaved at 1 week intervals.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The volume of the dosing solution was adjusted weekly based on the most recent mean body weight of each dose group at concentrations of 0, 37.5, 75, 150, 300 and 600 mg/mL (0, 32, 63, 125, 250 and 500 mg/kg)
- Concentration (if solution): The test material was administered as a 95 % solution in ethanol.
USE OF RESTRAINERS FOR PREVENTING INGESTION: no - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Dose formulations were analysed by gas chromatography before and after administration to animals and found to be within 10 % of the theoretical values.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Once per day, except for weekends and holidays
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 32, 63, 125, 250 and 500 mg/kg
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 10 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: the dose levels were selected on the basis of a two-week study conducted prior to the 13 week study.
In the two week study, rats of both sexes received the test material in ethanol (95 %) at doses of 0, 63, 125, 250, 500 and 1000 mg/mL with target doses of 0, 125, 250, 500, 1000, and 2000 mg/kg bodyweight. Early deaths of male rats occurred in the highest dose group and in female rats in the 2 highest dose groups (1000 and 2000 mg/kg). Bodyweight gains were reduced in the higher dose groups.
Animals exhibited ulcerative skin lesions at the site of application, accompanied by inflammatory cell infiltration, hyperkeratosis, and acanthosis (hyperplasia) of the epidermis. Hyperkeratosis, without ulceration, was observed in some animals.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule for examinations: Animals were examined twice daily for mortality and moribundity.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Clinical observations were recorded weekly and at necropsy.
BODY WEIGHT: Yes
- Time schedule for examinations: Observations were recorded weekly and at necropsy.
FOOD CONSUMPTION AND COMPOUND INTAKE: No
FOOD EFFICIENCY: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Water consumption was measured twice weekly.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the study, blood samples were collected in Microtainers containing dipotassium EDTA and analysed with an Ortho ELT-8 laser haematology counter (Ortho Instruments, Westwood, MA).
- Anaesthetic used for blood collection: Yes. Animals were anesthetized with carbon dioxide and blood samples were collected from the retroorbital sinus.
- Animals fasted: No data
- How many animals: Clinical pathology studies were performed on all rats that survived until the end of the study.
- Parameters evaluated included: erythrocyte count (RBC), leukocyte count (WBC), mean corpuscular volume (MCV), Mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), haemoglobin (HGB), haematocrit (HCT), differential leukocyte count, erythrocyte morphological assessment, reticulocyte count, platelet count and platelet morphological assessment.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of the study, biochemical analyses were performed on blood samples collected in Microtainers (Becton Dickinson, Rutherford, NJ) with no preservative or anticoagulant And analysed using a Hitachi 704 automatic chemistry analyser (Boehringer-Mannheim Diagnostics, Indianapolis, IN).
- Anaesthetic used for blood collection: Yes. Animals were anesthetized with carbon dioxide and blood samples were collected from the retroorbital sinus.
- Animals fasted: No data
- How many animals: Clinical pathology studies were performed on all rats that survived until the end of the study.
- Parameters evaluated included: serum sorbitol dehydrogenase (SDH), alanine arninotransferase (ALT), total protein (TP), albumin, urea nitrogen (UN), creatinine, glucose and total bile acids.
URINALYSIS: Yes
- Time schedule for collection of urine: During the 12th week of the study.
- Metabolism cages used for collection of urine: Yes. Urine samples were collected over a 16 hour period from rats housed individually in polycarbonate metabolism cages.
- Animals fasted: Yes, food was removed from the cages.
- Methods: Collection tubes were immersed in ice-water baths.
- Parameters evaluated: Volume, appearance, specific gravity and pH were measured for each urine sample. Concentrations of glucose, protein, urea nitrogen and creatinine, and activities of alkaline phosphatase and lactate dehydrogenase, were measured using a Hitachi 704 chemistry analyser (Boehringer-Mannheim Diagnostics, Indianapolis, IN).
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes. Complete necropsies were performed on all animals. The brain, heart, right kidney, liver, lung, right testis and thymus were weighed. Organs and tissues were examined for gross lesions and fixed in 10 % neutral buffered formalin. Tissues were trimmed, embedded in paraffin, sectioned, stained with haematoxylin and eosin and examined microscopically.
HISTOPATHOLOGY: Yes. Complete histopathological examinations were performed on all control animals, all early death animals and all animals in the highest dose groups with at least 60 % survivors. Target tissues were examined in animals from lower dose groups until a no-effect level was determined. All lesions observed at necropsy were examined microscopically.
These tissues included: adrenal glands, brain (3 sections), clitoral glands, eyes (if grossly abnormal), bone (femur, sternebrae, or vertebrae) with marrow, gross lesions, heart/aorta, intestine-large (cecum, colon, rectum), intestine-small (duodenum, jejunum, ileum), kidneys, liver, lung/mainstem bronchi, lymph nodes (mandibular, mesenteric), mammary gland, nasal cavity and turbinates (3 sections), oesophagus, ovaries, pancreas, parathyroid glands, pituitary gland, preputial glands, prostate gland, salivary glands, seminal vesicles, skin (skin sections of gross lesions at the site of application, skin at the site of application without gross lesions, and undosed inguinal control skin), spinal cord and sciatic nerve, spleen, stomach (forestomach and glandular stomach), testes with epididymis, thymus, thyroid gland, trachea, urinary bladder, and uterus. - Other examinations:
- Vaginal cytology and sperm morphology evaluations were performed, using the methods described by Morrissey et al. (1988) on animals receiving 0, 63, 125 and 250 mg/kg.
- For the 7 days prior to sacrifice, females were subjected to vaginal lavage with saline. The aspirated cells were scored for the relative preponderance of leukocytes, nucleated epithelial cells, and large squamous epithelial cells to identify the stages of the estrual cycle.
- Sperm motility was evaluated at necropsy: sperm that were extruded from a small cut made in the epididymis were dispersed in a warm, buffered solution, and the number of moving and non-moving sperm in 5 fields of 30 sperm or less per field were counted. After sperm sampling for motility evaluation, the cauda was placed in phosphate buffered saline and incised with a razor blade, the solution mixed gently, then heat-fixed at 65 °C. Sperm density was subsequently determined using a hemocytometer. To quantify spermatogenesis, testicular spermatid head count was determined by removing the tunica albuginea and homogenising the left testis in PBS containing 10 % DMSO. Homogenisation-resistant spermatid nuclei were enumerated using a haemocytometer. - Statistics:
- Analysis of Continuous Variables
Two approaches were employed to assess the significance of pairwise comparisons between dosed and control groups in the analysis of continuous variables. Organ and body weight data, which are approximately normally distributed, were analysed using the parametric multiple comparisons procedures of Williams (1971; 1972) and Dunnett (1955). Clinical chemistry and haematology data were analysed using the nonparametric multiple comparisons methods of Shirley (1977) and Dunn (1964). Jonckheere's test (1954) was used to assess the significance of dose-response trends and to determine whether a trend-sensitive test (Williams, Shirley) was more appropriate for pairwise comparisons than a test capable of detecting departures from monotonic dose-response (Dunnett, Dunn). If the P-value from Jonckheere's test was greater than or equal to 0.10, Dunn's or Dunnett's test was used rather than Shirley's or Williams' test.
The outlier test of Dixon and Massey (1951) was employed to detect extreme values. No value selected by the outlier test was eliminated unless it was at least twice the next largest value or at most half of the next smallest value.
Analysis of Vaginal Cytology data
Since the data are proportions (the proportion of the observation period that an animal was in a given estrous state), an arcsine transformation was used to bring the data into closer conformance with normality assumptions. Treatment effects were investigated by applying a multivariate analysis of variance (Morrison, 1976) to the transformed data to test for the simultaneous equality of measurements across dose levels.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- see below
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- see below
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- One 500 mg/kg male died during week 9 and 2 females administered 500 mg/kg were killed in a moribund condition during week 10 (Table 1). Final mean bodyweights of males receiving doses of 250 or 500 mg/kg, and of females receiving doses of 125 mg/kg or higher, were lower than those of controls. The primary clinical signs of toxicity in the 3 highest dose groups were irritation and crusting of the skin at the site of test material application.
A moderate, poorly regenerative, microcytic, normochromic anaemia developed in male and female rats (Table 2). Decreases in red blood cell variables were observed even at the lowest dose, 32 mg/kg; thus, a no-observable-adverse-effect level (NOAEL) for test material-induced anaemia was not achieved. No histologic changes in femoral bone marrow were observed. Serum biochemical changes in male rats included mild increases in concentrations of UN and albumin at the 4th and 2nd highest dose groups, respectively, and mild increases in activities of ALT in animals in the 3 highest dose groups. In female rats, UN, albumin, and total protein increased in all dose groups (except at the lowest dose for total protein), and total bile acids increased in the 2 highest dose groups. A mild increase in activity of ALT occurred in female rats in the highest dose group.
The kidney was identified as a target organ: absolute and relative kidney weights were increased in male and female rats (Table 3). These weight changes were associated with increased severity or increased incidences of nephropathy, renal tubular cell necrosis or tubular mineralisation (Table 4). A dose-dependent increase in incidence and severity of nephropathy was evident at the lower dose levels in females, but there was no clear treatment effect on this lesion in males.
Tubular necrosis was observed in females in the 2 highest dose groups, but no active necrosis was found in the corresponding male groups. Tubular mineralisation, consistent with previous necrosis, was present in high-dose males, as well as being increased in incidence and severity in most treated female groups.
There was a dose-dependent increase in absolute and relative liver weights in both male and female rats (Table 3). Although mild serum biochemical changes occurred, no corresponding microscopic lesion was observed. Dermal exposure was not associated with testicular or epididymal changes; sperm morphology and vaginal cytology evaluations did not show adverse effects.
Lesions of the treated skin were dose-related in incidence and severity (Table 4). The lesion was diagnosed as ulceration and ranged from small, superficial foci of epidermal loss to extensive areas of coagulation necrosis of the epidermis and dermis. The ulcers were accompanied by inflammatory cell infiltration that was prominent at the borders between necrotic and viable tissue. Inflammation was primarily neutrophilic, but was designated "chronic-active" due to the frequent appearance of fibrovascular tissue proliferation in the vicinity of ulcers. Minimal to moderate acanthosis (epidermal hyperplasia) invariably was present at ulcer margins in the higher dose groups; at lower dose levels, only minimal acanthosis and hyperkeratosis were present.
Demyelination in the medulla oblongata was observed in all males and females in the 500 mg/kg dose group, and in 7 females in the 250 mg/kg dose group (Table 4). The lesion was characterised by intramyelinic vacuoles arranged symmetrically around the medial medulla oblongata in the region of the tectospinal tract. However, all lesions were minimal in severity and there was no spinal cord involvement.
All early-death rats in this study had lesions of the kidney, skin, and brain as described above. The severity of these lesions, however, was no greater than was seen in animals that survived to the end of the study.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: A NOAEL was not achieved for the haematological changes.
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
- Dose descriptor:
- LOAEL
- Effect level:
- 32 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based upon haematological changes, nephropathy and hyperkeratosis of the skin.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1 Summary of Survival and Weight Gain
Sex |
Dose (mg/kg) |
Survival |
Mean Bodyweight (g) |
Final Weight Relative to Controls (%) |
||
Initial |
Final |
Change |
||||
Male |
0 32 63 125 250 500 |
10/10 10/10 10/10 10/10 10/10 9/10 |
124 122 123 120 124 120 |
342 337 323 336 294 237 |
218 215 200 216 170 117 |
- 99 94 98 86 69 |
Female |
0 32 63 125 250 500 |
10/10 9/10 10/10 10/10 10/10 8/10 |
107 113 114 106 109 109 |
192 193 191 178 172 151 |
85 80 77 72 63 42 |
- 100 99 93 90 79 |
Survival is represented as the number of animals surviving at 13 weeks / number of animals per dose group
Table 2 Haematological Changes in Peripheral Blood
Sex |
Parameter |
Dose (mg/kg) |
|||||
0 |
32 |
63 |
125 |
250 |
500 |
||
Male |
RBC (10⁶/µL) HGB (g/dL) HCT (%) MCV (fL) MCH (pg) Reticulocytes (10⁶/µL) |
8.87 15.5 47.6 54 17.5 0.20 |
8.81 15.3 46.4 53** 17.3** 0.21 |
8.79 15.1* 45.6* 52** 17.1** 0.20 |
8.57* 14.3** 43.1** 50** 16.7** 0.21 |
7.90** 12.9** 3838** 49** 16.3** 0.18 |
6.80** 11.0** 32.6** 48** 16.1** 0.18 |
Female |
RBC (10⁶/µL) HGB (g/dL) HCT (%) MCV (fL) MCH (pg) Reticulocytes (10⁶/µL) |
8.45 15.5 48.9 58 18.4 0.16 |
8.14** 14.8** 46.7** 57 18.2 0.13* |
7.83** 14.1** 44.2** 56** 18.1* 0.12** |
7.38** 13.2** 40.6** 55** 17.8** 0.10** |
6.91** 12.0** 36.9** 53** 17.4** 0.14* |
6.23** 10.5** 31.9** 51** 16.8** 0.12** |
* = Significantly different from control group (p 0.05) by Dunn’s or Shirley’s test
** = Significantly different from control group (p 0.01) by Dunn’s or Shirley’s test
Table 3 Kidney and Liver Weights
Organ weights and bodyweights are given in grams; organ weight to bodyweight ratios are given as mg organ weight/g bodyweight
Sex |
Parameter |
Dose (mg/kg) |
|||||
0 |
32 |
63 |
125 |
250 |
500 |
||
Male |
Necropsy weight Kidney Weight Relative kidney weight Liver Weight Relative liver weight |
347 1.17 3.39 13.25 38.2 |
342 1.41** 4.12** 14.10 41.2* |
328 1.21 3.68** 13.29 40.5** |
342 1.32* 3.87** 16.00* 46.6** |
300 1.20 4.04** 15.12* 50.3** |
241** 1.31 5.38** 14.05* 58.3** |
Female |
Necropsy weight Kidney Weight Relative kidney weight Liver Weight Relative liver weight |
193 0.69 3.59 6.48 33.5 |
194 0.97** 5.00** 7.56** 38.9** |
191 0.90** 4.69** 7.59** 39.7** |
180** 0.92** 5.12** 7.79** 43.4** |
174** 0.91** 5.25** 8.17** 47.1** |
154** 1.05** 6.83** 9.00** 58.4** |
* = Significantly different from control group (p 0.05) by Williams’ or Dunnett’s test
** = Significantly different from control group (p 0.01) by Williams’ or Dunnett’s test
Table 4 Incidence and Severity of Kidney, Brain and Skin Lesions
Sex |
Parameter |
Dose (mg/kg) |
|||||
0 |
32 |
63 |
125 |
250 |
500 |
||
Male |
Kidney Nephropathy Tubular epithelial necrosis Tubular mineralisation Brain, medulla Demyelination Skin Ulcer Chronic active inflammation Acanthosis Hyperkeratosis |
9/10 (1.0) 0/10 0/10
0/10
0/10 0/10 0/10 0/10 |
6/10 (1.0) 0/10 0/10
0/10
0/10 0/10 0/10 0/10 |
5/10 (1.0) 0/10 0/10
0/10
0/10 0/10 3/10 (1.0) 5/10 (1.0) |
6/10 (1.0) 0/10 0/10
0/10
0/10 0/10 6/10 (1.0) 10/10 (1.1) |
4/10 (1.0) 0/10 0/10
0/10
3/10 (1.3) 3/10 (1.3) 6/10 (1.5) 10/10 (1.4) |
5/10 (1.0) 0/10 9/10 (1.9)
10/10 (1.0)
10/10 (2.6) 10/10 (1.7) 10/10 (2.2) 10/10 (1.9) |
Female |
Kidney Nephropathy Tubular epithelial necrosis Tubular mineralisation Brain, medulla Demyelination Skin Ulcer Chronic active inflammation Acanthosis Hyperkeratosis |
3/10 (1.0) 0/10 4/10 (1.0)
0/10
0/10 0/10 0/10 0/10 |
9/10 (1.3) 0/10 9/10 (1.0)
0/10
0/10 0/10 0/10 5/10 (1.0) |
10/10 (1.4) 0/10 10/10 (1.6)
0/10
0/10 0/10 1/10 (1.0) 6/10 (1.0) |
10/10 (1.7) 0/10 10/10 (1.9)
0/10
1/10 (1.0) 3/10 (1.0) 6/10 (1.2) 9/10 (1.2) |
7/10 (1.1) 2/10 (1.0) 10/10 (1.1)
7/10 (1.0)
7/10 (1.9) 7/10 (1.6) 7/10 (2.0) 10/10 (1.7) |
4/10 (1.0) 10/10 (1.0) 10/10 (1.0)
9/10 (1.0)
10/10 (3.4) 10/10 (2.5) 10/10 (2.6) 10/10 (2.1) |
The severity score, represented by ( ), is based on a scale of 1 to 4: 1 = minimal, 2 = mild, 3 = moderate, 4 = marked. Severity scores are averages based on the number of animals with lesions.
Applicant's summary and conclusion
- Conclusions:
- A No-Observed-Adverse-Effect Level (NOAEL) was not achieved for the haematological changes. On this basis, it is considered that the LOAEL level for rats is 32 mg/kg bw/day and as a result the test material requires classification as STOT RE Category 2 in accordance with EU criteria.
- Executive summary:
The repeated dose toxicity of the test material was investigated in a procedure equivalent to the standardised guideline OECD 411 under GLP conditions.
The test material was administered to male and female F344 rats for 13 weeks' duration, 5 days per week, to the shaved interscapular region. Doses ranged from 32 to 500 mg/kg bw/day prepared in 95 % ethanol.
Early deaths were observed in the highest dose groups and bodyweight gains were reduced in animals given the higher doses. Animals exhibited dose-dependent haematologic and renal function changes, in addition to skin lesions at the site of application which included ulceration and inflammation, hyperkeratosis, and acanthosis. Liver weights were increased in males and females, but there were no associated histopathological changes.
Other treatment-related effects observed included demyelination in the brain and spinal cord and nephropathy, renal tubular necrosis, and/or tubular mineralisation.
A No-Observed-Adverse-Effect Level (NOAEL) was not achieved for the haematological changes. On this basis, it is considered that the LOAEL level for rats is 32 mg/kg bw/day and as a result the test material requires classification as STOT RE Category 2 in accordance with EU criteria and as defined in Annex VI, Regulation 1272/2008.
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Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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