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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from authoritative database

Data source

Reference
Reference Type:
review article or handbook
Title:
The Teratogenic Effects of the test chemical on the ICR Mice.
Author:
RD Lyng
Year:
1981
Bibliographic source:
Indiana Univ-Purdue Univ At Fort Wayne, 31 Mar 1981

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as below
Principles of method if other than guideline:
The Teratogenic Effects of the test chemical on the ICR Mice
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Fuel JP-10 ((3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene)
Cas Number:
2825-82-3
Molecular formula:
C10H16
IUPAC Name:
Fuel JP-10 ((3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene)
Details on test material:
- Name of test material (as cited in study report): Fuel JP-10 ((3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene)
- Molecular formula (if other than submission substance): C10H16
- Molecular weight (if other than submission substance): 136.2364 g/mole
- Substance type: Organic
Specific details on test material used for the study:
- Name of test material (as cited in study report): Fuel JP-10 ((3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene)
- Molecular formula (if other than submission substance): C10H16
- Molecular weight (if other than submission substance): 136.2364 g/mole
- Substance type: Organic

Test animals

Species:
mouse
Strain:
ICR
Details on test animals or test system and environmental conditions:
- Source: Harlan Industries.
- Age at study initiation: (P) x wks; (F1) x wks: not specified
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g: not specified
- Fasting period before study: not specified
- Housing: Animals were housed in plastic cages on wood chip
Bedding. Pregnant females were moved to wire bottomed cages.
- Diet (e.g. ad libitum): Purina Mouse Chow, ad libitum
- Water (e.g. ad libitum): Water , ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%):not specified
- Air changes (per hr):not specified
- Photoperiod (hrs dark / hrs light): 12 hour light cycle.

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
soya oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:The test chemical diluted with soybean oil at doses of 0, 188, 376, 564 and 752 mg/kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency):not specified
- Mixing appropriate amounts with (Type of food): not specified
- Storage temperature of food:not specified

VEHICLE
- Justification for use and choice of vehicle (if other than water): soybean oil
- Concentration in vehicle: 0, 188, 376, 564 and 752 mg/kg/day
- Amount of vehicle (if gavage): not specified
- Lot/batch no. (if required): not specified
- Purity:not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Details on mating procedure:
- M/F ratio per cage: Four to five females were kept with each male.
- Length of cohabitation: not specified
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy The day that a vaginal plug was found was designated as day zero of pregnancy.
Duration of treatment / exposure:
4 days (6, 7, 8 and 9 of gestation)
Frequency of treatment:
Daily
Duration of test:
17 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
188 mg/kg bw/day
Dose / conc.:
376 mg/kg bw/day
Dose / conc.:
564 mg/kg bw/day
Dose / conc.:
752 mg/kg bw/day
No. of animals per sex per dose:
Total: 46
0 mg/kg/day: 8 female
188 mg/kg/day: 9 female
376 mg/kg/day: 9 female
564 mg/kg/day: 9 female
752 mg/kg/day: 11 female
Control animals:
yes, concurrent vehicle
Details on study design:
not specified

Examinations

Maternal examinations:
Body weight were examined.
Ovaries and uterine content:
Resorptions and Implants were examined.
Fetal examinations:
Viable fetuses, Number and position of each fetus, Number of litters and Body weight and Gross pathology, visceral and skeletal abnormalities were examined.
Statistics:
Using the methods from Olson and Back (1978) and Wilson and Warkany (1965), the number and position of each fetus was recorded, weighed and examined for abnormalities.
The Students T test was used to test for statistical significance
between mean values and the Fisher exact test was used to test for significant differences in frequency of resorption and skeletal and soft tissue abnormalities using the litter as the experimental unit.
Indices:
Number and position of each fetus, Number of litters with resorptions and weigh were observed.
Historical control data:
not specified

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
When treated with 188, 376 and 752 mg/kg bw, increase in body weight gain were observed in the females mice as compared to control and 569 mg/kg bw teated mice.

The increased maternal weight in the 188 and 376 mg/kg is apparently due to increased fetal weight and the increased maternal weight gain in the 752 mg/kg group is due to slightly larger average litter size.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
No significant effect on mean implants/female were observed as compared to control.
Early or late resorptions:
no effects observed
Description (incidence and severity):
No effect on frequency of resorptions of treated female mice were observed as compared to control.
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
not specified

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
752 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
early or late resorptions
maternal abnormalities
total litter losses by resorption
other: No effect observed
Remarks on result:
other: No toxic effects were observed

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
When treated with 188 and 376 mg/kg bw, increase in mean fetal weights were observed as compared to control and 569 and 752 mg/kg bw treated mice.

The increased fetal weight in the mouse is not easily explained particularly when no such increase occurred in the groups receiving 569 and 752 mg/kg.

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effect on viability of pups were observed as compared to control.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
No external abnormalities were observed in any as compared to control.
Skeletal malformations:
no effects observed
Description (incidence and severity):
No Skeletal findings were observed in any as compared to control.
Visceral malformations:
no effects observed
Description (incidence and severity):
No Soft Tissue were observed in any as compared to control.
Other effects:
not specified

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
752 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reduction in number of live offspring
fetal/pup body weight changes
external malformations
skeletal malformations
visceral malformations
other: No effect observed
Remarks on result:
other: No effects on developmental parameters were observed

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 752 mg/kg/day for P and F1 generation when ICR female mice treated with test chemical orally by gavage for 4 days (6, 7, 8 and 9 of gestation).
Executive summary:

In a Teratogenicity study, ICR female mice were treated with test chemical in the concentration of 0, 188, 376, 569 and 752 mg/kg/day orally by gavage in Soybean oil for 4 days (6, 7, 8 and 9 of gestation). Increase in body weight gain were observed in the females mice at 188, 376 and 752 mg/kg bw as compared to control and 569 mg/kg bw treated mice.The increased maternal weight in the188 and 376 mg/kg is apparently due to increased fetal weight and the increased maternal weight gain in the 752 mg/kg group is due to slightly larger average litter size. Similarly, No significant effect on mean implants/female, mean resorptions/litter and frequency of resorptions of treated female mice were observed as compared to control. In addition, No developmental effect such as viability of pups were observed as compared to control. Increase in mean fetal weights were observed in male and female pups at 188 and 376 mg/kg bw as compared to control and 569 and 752 mg/kg bw treated mice.The increased fetal weight in the mouse is not easily explained particularly when no such increase occurred in the groups receiving 569 and 752 mg/kg. No external abnormalities, Soft Tissue and or Skeletal findings were observed in any pup as compared to control. Therefore, NOAEL was considered to be 752 mg/kg/day for P and F1 generation when ICR female mice treated with test chemical orally by gavage for 4 days (6, 7, 8 and 9 of gestation).