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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1993-09-29 to 1993-10-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restriction because although the study closely adhered to OECD 407 guidelines, haematology, clinical biochemistry, and neurobehavioral assessments were not conducted.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
Haematology, clinical chemistry, and neurobehavioural tests were not performed
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nexbase 2006 FG
- Substance type: 1-Decene, homopolymer, hydrogenated
- Physical state: Liquid
- Analytical purity: Not reported
- Composition of test material, percentage of components: Not reported
- Lot/batch No.: 2309
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported
- Storage condition of test material: Cool temperature (not to exceed 15 decrees Celsius) in the dark
- Other: Identity, strength, composition, and stability were stated to be the responsibility of the sponsor.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Limited, England
- Age at study initiation: 35 to 42 days old
- Weight at study initiation: Not reported, but stated to weight between 59 and 76 grams the day after arrival
- Housing: Five per stainless steel cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55%
- Air changes (per hr): At least 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light


IN-LIFE DATES: From:1993-09-29 To: 1993-10-28

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with ground diet
- Storage temperature of food: 21 degrees Celsius


Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Homogeneity was tested on the lowest and highest concentration by taking 6 samples from different positions in the mixer. The dose formulation was determined to be homogeneous. Stability was determined on the highest and lowest concentrations after 1 and 2 weeks. The dose formulation was determined to be stable for at least 2 weeks. Dietary concentrations were analysed during week 1 and 4. Dose formulations were within 10% of nominal dose.
Duration of treatment / exposure:
29 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0; 8000; 20,000; or 50,000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
Five per sex per dose
Control animals:
yes, plain diet
Details on study design:
- Dose selection rationale: Based on studies performed using similar materials
- Rationale for animal assignment (if not random): Random
Positive control:
None

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations included overt signs of toxicity and faecal examination.


DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: Yes
- Time schedule for examinations: Study initiation, twice weekly during treatment, and at study termination


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes


WATER CONSUMPTION: Yes
- Time schedule for examinations:No quantitative measurement was made, but water bottles were observed daily to check for any changes that might indicate a treatment-related change in fluid balance


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: No


CLINICAL CHEMISTRY: No


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, detailed necropsy was performed.
HISTOPATHOLOGY: Yes, although numerous tissues and organs were preserved, only the liver and mesenteric lymph nodes were examined histologically.
Other examinations:
Organs provided in table 1 were weighed.
Statistics:
A Bartlett's test was used to test for homogeneity of the data. Depending on the results a Behrens-Fisher or Dunnett's test were performed. Fischer's exact test was used on microscopic and macroscopic findings.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY: There were no treatment-related effects.


BODY WEIGHT AND WEIGHT GAIN: High-dose females had a marginal increase in body weight gain. However, this was related to increased food consumption so was considered due to individual variability and not treatment-related.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): High-dose females had a slight increase in food consumption. Compound intake in males was 1030, 2538, and 6248 mg/kg/day for the 8000 ppm; 20,000 ppm; and 50,000 ppm dose groups, respectively. Compound intake in females was 995, 2481, and 6771 mg/kg/day, respectively.


FOOD EFFICIENCY: There were no treatment-related effects.


ORGAN WEIGHTS: There was a slight, but dose-related, decrease in absolute and relative mandibular weight in males and females that reached statistical significance in high-dose females only.


GROSS PATHOLOGY: There were no treatment-related effects.


HISTOPATHOLOGY: There were no treatment-related effects.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
6 245 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
other: Overall effects
Dose descriptor:
NOAEL
Effect level:
6 771 mg/kg bw/day (actual dose received)
Sex:
female
Basis for effect level:
other: Overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Although there was an apparent dose-related decrease in mandibular lymph node weight, the results only reached significance in high-dose females; therefore, this is not considered biologically significant and not likely adverse since there were no other findings.

Applicant's summary and conclusion

Conclusions:
The systemic NOAEL for Nexbase 2006 FG in the diet is 50,000 ppm, which is equivalent to a daily intake of 6245 mg/kg/day in males and 6771 mg/kg/day in females.
Executive summary:

In a repeated dose oral toxicity study, Nexbase 2006 FG was administered to F-344 rats (5 sex/dose) in the diet for four weeks at nominal concentrations of 0, 8000; 20,000; or 50,000 ppm (equivalent overall mean daily intakes were 1039, 2538, or 6245 mg/kg/day for males and 995, 2481, or 6771 mg/kg/day for females).

 

There was no overt toxicity or mortality observed in male or female rats during the study. Overall body weight gain and food consumption of females in the 50,000 ppm dose group was higher than the corresponding controls. A dose-dependent decrease in mandibular lymph node weights (absolute and relative to body weight) was observed in males and females; however, these results were statistically significant only for 50,000 pm females. Gross necroscopy, histopathology, and microscopic findings did not reveal any significant treatment-related findings in either male or female rats. Dietary administration of Nexbase 2006 FG to male and female F-344 rats at levels up to 50,000 ppm for 4 weeks did not produce toxicologically significant effects. Therefore, the subacute oral NOAEL for Nexbase 2006 FG is 6245 mg/kg/day in males and 6771 mg/kg/day in females.

 

 This study received a Klimisch score of 2 and is classified as reliable with restrictions because although the study closely adhered to OECD 407 guidelines, haematology, clinical biochemistry, and neurobehavioral assessments were not conducted. This study will influence the DNEL.