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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:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Limited information on study designs and methodology. Deviations from OECD Guideline 407: no data regarding observation period, test substance or animal husbandry; only 2 test groups were dosed compared to 3 test groups as recommended in the guideline; hematology, clinical biochemistry were not performed; no detailed data provided on gross autopsy results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1968
Report date:
1968

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
No data provided regarding observation period, test substance or animal husbandry, only 2 test groups were dosed compared to 3 test groups as recommended in the guideline, hematology, clinical biochemistry were not performed.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Test material form:
liquid
Details on test material:
- Physical state: liquid
- Storage condition of test material: Room temperature
Specific details on test material used for the study:
No test item information

Test animals

Species:
rat
Strain:
other: Albino (MR Wistar)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Mean weight at study initiation:
0% concentration in diet
113.3 g

0.083% concentration in diet
113.3 g

0.208% concentration in diet
113.4 g

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
No data on feeding conditions.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
31 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: % nominal in diet
Dose / conc.:
0.083 other: % nominal in diet
Dose / conc.:
0.208 other: % nominal in diet
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
yes
Details on study design:
No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: No data

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: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

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: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: The animals were sacrificed at the end of the feeding period and were subjected to a thorough gross autopsy. Autopsy results were not provided.
HISTOPATHOLOGY: No data
Other examinations:
Food intake; weight gain measured.
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
The overall appearance of the treated and control animals was good.
Mortality:
no mortality observed
Description (incidence):
The overall appearance of the treated and control animals was good.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Since weight gain depends, in part, upon the amount of food consumed, the variances and covariance of body weight and food intake were analyzed. Male ate and gained significantly more than the females. There were no significant interactions between sex and treatment, indicating that the responses of males and females to the treatments were similar. Therefore, observations on males and females were combined for comparison of the treatment groups with the control group. There were no significant differences between the 0.208% group or the 0.083% group and the control group in mean food intake or mean weight gain, even after allowances were made for variations in food consumption.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Since weight gain depends, in part, upon the amount of food consumed, the variances and covariance of body weight and food intake were analyzed. Male ate and gained significantly more than the females. There were no significant interactions between sex and treatment, indicating that the responses of males and females to the treatments were similar. Therefore, observations on males and females were combined for comparison of the treatment groups with the control group. There were no significant differences between the 0.208% group or the 0.083% group and the control group in mean food intake or mean weight gain, even after allowances were made for variations in food consumption.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
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:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No relevant gross pathology was noted at autopsy in animals of either sex.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Dose descriptor:
NOEL
Effect level:
>= 0.208 other: %
Based on:
other: dietary concentrations
Sex:
male/female
Basis for effect level:
other: overall effects mortality; body weight; food consumption; gross pathology

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Summary of results of thirty-one daily doses in the diets of male and female albino rats

Concentration in diet (%)

0

0.083

0.208

Number of rats (M +F)

5+5

5+5

5+5

Mean dosage (g/kg/day)

-

0.093

0.239

Mean initial weight (g)

113.3

113.3

113.4

Mean food intake (g)

618.4

606.9

615.1

Mean weight gain (g)

119.9

124.6

118.0

Mean weight gain, adjusted for food intake (g)

119.0

124.2

118.7

 

Applicant's summary and conclusion

Conclusions:
Male and remale rats were exposed to 0.083 and 0.208% of the test substance incorporated into the diet in a 30 day repeated dose study. This 30 day exposure did not produce any mortality or evidence of systemic toxicity. No changes were observed for food intake, or body weight gain for the study animals. There were no histopathological findings noted on any of the study animals at necropsy. The no observable effect level (NOEL) for systemic toxicity was the highest dose level tested, 0.208%.

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