Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

According to CLP Regulation and based on the available data, the substance is not classified for toxicity to reproduction.

Effects on developmental toxicity

Description of key information
Toxicity to reproduction: key study: results from a study report leading to the conclusion that the NOAEL maternal toxicity is 1000 mg / kg bw/day in rats.
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 22th to May 28th 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliance
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoe: WISKf (SPF71)
- Age at study initiation:65-70 days
- Weight at study initiation: 191 + / - 6 g
- Housing: individually in plastic cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days prior the test
- Sex: female

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 ° C
- Humidity (%): 49-53%
- Air changes (per hr): 16-20/h
- Photoperiod (hrs dark / hrs light): 12 light hours a day

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: the substance was dissolved fresh daily in a concentration of 200 g/l in sesame oil. The applied fluid volume was in all animals 5 ml/kg body weight.

VEHICLE
- Amount of vehicle (if gavage): 5 ml/kg bw dose
Details on mating procedure:
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy
Duration of treatment / exposure:
days 7 to 16 of gravity
Frequency of treatment:
once daily, administered within three hours
Duration of test:
Sacrifice at day 21 of gravity
No. of animals per sex per dose:
20 mated females: test group
21 mated females: control group
Control animals:
yes
Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: once a week and a day after the last application

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: uterus, ovaries

OTHER:
Macroscopic examination and weighing of the organs: heart, liver, kidneys and spleen
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
Fetal examinations:
- External examinations: Yes
- Skeletal examinations: Yes: half per litter
- Body cross-sections for Wilson, photography: half per litter
Statistics:
Comparisons between body weights and organ weights in the test and control group were performed with a classical analysis of variance (MANOVA); to evaluate the relative feed intake, a analysis of variance according to Puri & Sen (1985).
Corpora lutea and implantations were performed with the Mantel-Haenszel x2 test (Mantel & Haenszel, 1959), as well as live and dead fetuses and resorptions. Other parameters according to an analysis of variance.
The body cross-sectional study of fetuses and skeletal findings were studied with the Fisher Exact test.


Historical control data:
To compare the data with historical controls, normal ranges were calculated for groups.
Details on maternal toxic effects:
Maternal toxic effects:no effects
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: embryotoxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity
Abnormalities:
not specified
Developmental effects observed:
not specified
All findings did not differ from those of control group out of the spontaneous rate.
Conclusions:
No maternal toxic effects, no embryonic/fetal toxic effects and no teratogenic effect at oral doses of 1000 mg/kg bw/day in rats.

Executive summary:

Isobornylacetate-extra was tested in a limit test of a group of 20 female Wistar rats from 7 to 16 day of gravity, administered once daily in a dose of 1000 mg / kg bw. As a control, was an equally large group of control animals that received the vehicle without substance addition.On 21 days of gestation were killed the mother animals and examined. Fetuses were morphologically observed for developmental disorders. The morphological examination of fetuses revealed no evidence for embryotoxic and teratogenic effects of the substance. The findings are assigned to the spontaneous rate. Neither maternal nor embryonic/fetal toxicity was found at oral doses of 1000 mg/kg bw/day IBA in rats.An indication of teratogenic effect could not be noticed.


Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Key study: experimental result from a study report. In rats, oral gavage, from day 7 to 16 of gravity. It is concluded that no maternal toxic effects, no embryonic/fetal toxic effects and no teratogenic effect were observed at oral doses of 1000 mg / kg bw/day.

Justification for classification or non-classification

According to CLP Regulation and the available data,the substance under study does not meet the criteria to be classified.

Additional information