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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Remarks:
Prenatal developmental toxicity study
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes (incl. QA statement)
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
α,α-dimethylphenethyl acetate
EC Number:
205-781-3
EC Name:
α,α-dimethylphenethyl acetate
Cas Number:
151-05-3
Molecular formula:
C12H16O2
IUPAC Name:
2-methyl-1-phenylpropan-2-yl acetate
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
A total number of 80 (30 male and 50 female) Sprague Dawley rats of about 12 to 13 weeks were received along with their health certificate for the Study.
Rats were housed in an experimental room maintained at 20.1 to 23.6 °C and 51 to 66% relative humidity with adequate fresh air supply (minimum 12 air changes/hour). Light and dark cycles of 12 hours, each were maintained throughout the experimental phase.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.1% Tween 80 (polysorbate 80, polyoxyethylene sorbitan monooleate) in water
Details on mating procedure:
After completion of acclimatization period, females were housed with males for pairing or cohabitation based on 1:1 ratio (one male: one female) for 14 days or until the evidence of mating, whichever is earlier. Each day, the evidence of mating was confirmed by presence of sperms in the vaginal lavage. The day of presence of sperms in the vaginal lavage was considered as day ‘0’ of the pregnancy or ‘GD 0 – (Gestation Day – 0)’ for the particular female. Subsequently, post detection of sperms in the vaginal lavage, females were separated from the male partner and housed individually through gestation period until their euthanasia on day 20 of gestation (GD20).
The cohabitation or pairing was done till availability of sufficient number (50 female) of confirmed mating (sperm positive in vaginal lavage) females. Sufficient number of confirmed mated females are achieved within 11 days.
After completion of successful cohabitation period, all the males were sent back to VBS animal holding/stock and extra females (both mated but negative for sperms and non-mated) was sent for euthanasia.
Frequency of treatment:
The vehicle (G1 - 0.1% Tween 80) and the test item, Dimethyl Benzyl Carbinyl Acetate (G2: 1000 mg/kg body weight) was administered orally gavage once daily to the pregnant females starting from Gestation Day 5 (GD 5) to till 19 (GD 19) of the respective females.
Doses / concentrations
Dose / conc.:
10 mg/kg bw/day (nominal)

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Description (incidence and severity):
There were no treatment related clinical signs noticed in females of vehicle control (G1- 0
mg/kg body weight) and limit test Dose- G2 1000 mg/kg body weight throughout the
experiment period.
Mortality:
no mortality observed
Description (incidence):
There were no mortality and morbidity in the present study in vehicle control G1 and limit
test Dose- G2 1000 mg/kg body weight.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no treatment related statistical significant changes noticed in the body weights,
body weight gain and feed consumption on female from limit dose G2 group animals when
compared with G1 group animals.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No statistical significant changes were observed in female of G2 group when compared
with G1 group females.
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
On completion of the gross pathology examination, no abnormalities were observed in any
of the organs in gross pathology examination and no organs were collected and preserved.
Gross pathological findings:
no effects observed
Description (incidence and severity):
External examination of none of the terminally euthanized female animals belonging to the
control (G1) and limit dose groups G2) did not revealed any external and internal
abnormalities, during gross pathology observation.
Neuropathological findings:
no effects observed
Description (incidence and severity):
External examination of none of the terminally euthanized female animals belonging to the
control (G1) and limit dose groups G2) did not revealed any external and internal
abnormalities, during gross pathology observation.

Maternal developmental toxicity

Details on maternal toxic effects:
Evaluation of maternal parameters viz: gravid uteri, total implantation, live fetus, number of corpora lutea, implantation sites, early and late resorptions, pre implantation loss, did not show any statistically significant difference in the treated groups as compared with vehicle control.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
body weight and weight gain

Results (fetuses)

Description (incidence and severity):
Total placenta weight, did not show any statistically significant difference in the treated groups as compared with vehicle control. Whereas, statistical significance decrease in male and female combined fetuses weight, male fetuses weight and female fetus weight in G2 and increase in anogenital distance (AGD) in male and female pups in G2 group as compared with vehicle control G1. Although statistically significant, above these parameters did not correlate with any other parameters/observations. Therefore, these significances have been considered as spontaneous/ incidental findings unrelated with the test item treatment as compared to control group G1.
Details on embryotoxic / teratogenic effects:
There was no treatment related external, visceral, head- razor and skeletal abnormalities in the pups from the test item, Dimethyl Benzyl Carbinyl Acetate in control and treated groups. The abnormalities showed in the male and female pups were incidental and comparable.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
To conclude, based on overall observations and under the circumstances of the present study, the test item, Dimethyl Benzyl Carbinyl Acetate when administered at 0, and 1000 mg/kg body weight by oral gavage route in Sprague Dawley rats for (GD 5-19) days did not produce any treatment related effects on the body weights or body weight gain/loss, feed consumption and fetal abnormalities. There were no treatment related clinical signs noticed in females all the dose levels. Based on the above observations, the dose of 1000 mg/kg body weight has been considered as No Observed Adverse Effect Level (NOAEL) for maternal toxicity and embryo fetal toxicity of the test item, Dimethyl Benzyl Carbinyl Acetate in Sprague Dawley rats.