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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from peer-reviewed journal

Data source

Reference
Reference Type:
publication
Title:
A toxicologic and dermatologic assessment of cinnamyl alcohol, cinnamaldehyde and cinnamic acid when used as fragrance ingredients
Author:
D. Bickers, P. Calow, H. Greim, J.M. Hanifin, A.E. Rogers, J.H. Saurat, I.G. Sipes, R.L. Smith, H. Tagami
Year:
2005
Bibliographic source:
Food and Chemical Toxicology 43 (2005) 799–836

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Equivalent or similar to OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Oily liquid
Details on test material:
- Name of test material (as cited in study report): Cinnamyl alcohol
- Substance type: Organic
- Physical state: liquid

Test animals

Species:
rat
Strain:
not specified

Administration / exposure

Route of administration:
oral: unspecified
Details on exposure:
No data available
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data available
Duration of treatment / exposure:
Entire course of pregnancy (days 22–23 of gestation)
Frequency of treatment:
Once Daily
Duration of test:
No Data Available
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
5.35 mg/kg bw/day
Dose / conc.:
53.5 mg/kg bw/day
No. of animals per sex per dose:
0 mg/kg bodyweight : 14–15 female rats
5.35 mg/kg bodyweight: 14–15 female rats
53.5 mg/kg bodyweight: 14–15 female rats
Control animals:
yes, concurrent vehicle
Details on study design:
No data available

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

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

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- 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

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:No data

POST-MORTEM EXAMINATIONS: Yes
- On day 20 of gestation, 6–9 rats from each group were sacrificed and the fetuses removed for examination.
- Organs examined: Fetuses were examined.

OTHER
The remaining animals delivered normally on days 22–23 of gestation.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: No data
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: No data
- Number of early resorptions: No data
- Number of late resorptions: No data
Fetal examinations:
- External examinations: No data
- Soft tissue examinations: No data
- Skeletal examinations: No data
- Head examinations: No data
Statistics:
No data available
Indices:
No data available
Historical control data:
No data available

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:
not specified
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:
not specified
Early or late resorptions:
not specified
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:
53.5 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: No toxic effects were observed
Remarks on result:
other: No toxic effects were observed

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
not specified
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
not specified
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
no effects observed
Description (incidence and severity):
Measurements of general development at birth and at one month following birth revealed no significant differences between test and control animals.
Details on embryotoxic / teratogenic effects:
Measurements of offspring bodyweight, size, survival number and general development at birth and at one month following birth revealed no significant differences between test and control animals.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
53.5 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Measurements of offspring bodyweight, size, survival number and general development at birth and at one month following birth revealed no significant differences between test and control animals.
Remarks on result:
other: No developmental toxic effects were observed

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
Based on all the available data, it was concluded that under the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 53.5 mg/kg bw/day.
Executive summary:

The present study was conducted to determine the developmental toxicity potential of test chemical when administered orally to rats. Groups of 14–15 female rats were orally administered either 0, 5.35 or 53.5 mg/kg body weight test chemical once daily for the entire course of pregnancy. On day 20 of gestation, 6–9 rats from each group were sacrificed and the fetuses removed for examination. The remaining animals delivered normally on days 22–23 of gestation. Measurements of offspring bodyweight, size, survival number and general development at birth and at one month following birth revealed no significant differences between test and control animals. Therefore, Based on all the available data, it was concluded that under the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be  53.5 mg/kg bw/day.