Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Not reported
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary literature source (documentation insufficient for assessment).
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
review article or handbook
Title:
Amended final report on the safety assessessment of hydroxystearic acid (Reviewed by the Cosmetic Ingredient Review Expert Panel).
Author:
Cosmetic Ingredient Review (CIR) Panel
Year:
1999
Bibliographic source:
Int. J. of Toxicol. 18 (Suppl. 1): 1-10

Materials and methods

Principles of method if other than guideline:
The test substance was applied to dorsal skin of 30 mated female rats. Applications were made on gestation Days 6 through 15, once daily, and left on for 6 h each day. The control article was similarly applied to an additional group of rats of the same strain. All surviving animals were killed on Day 20 of gestation. Following parameters were evaluated: implantations, postimplantations losses, corporea lutea, fetal sex ratio, mean fetal body weight or uterine weight, malformations and developmental variations.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Two antiperspirant prototype formulations containing 7% of hydroxystearic acid
- Physical state: Off-white solids
- Composition of test material, percentage of components: 7% hydroxystearic acid

Test animals

Species:
rat
Strain:
other: Charles River Crl:CV VAF/Plus
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: International Research and Development Corporation)
- Age at study initiation: 12.5 wk old
- Weight at study initiation: 211-289 g

Administration / exposure

Route of administration:
dermal
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: To dorsal skin (clipped free of hair)
- Type of wrap if used: Wrap was used but not further specified

USE OF RESTRAINERS FOR PREVENTING INGESTION: No (the test sites were covered, but not occluded, to prevent ingestion during the study)
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data
Duration of treatment / exposure:
From gestation Days 6 through 15
Frequency of treatment:
One time per d (and left on for 6 h)
Duration of test:
Until Day 20 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
7%
Basis:
no data
No. of animals per sex per dose:
2 x 30 mice
Control animals:
yes
Details on study design:
- Other: Two groups of 30 mated Charles River Crl:CD VAF/Plus female rats were tested in this study. An additional group of 30 rats, of the same strain, was used as a control.

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: No data

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


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

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: Ovary

OTHER: Following additional parameters were evaluated: Implantations, postimplantations losses, corporea lutea, fetal sex ratio, mean fetal body weight or uterine weight, malformations and developmental variations.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
Fetal examinations:
- External examinations: Yes
- Soft tissue examinations: No data
- Skeletal examinations: No data
- Head examinations: No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Clinical and necropsy observation:
No deaths were reported during the study. There were no significant differences in clinical or necropsy observation between experimental and control groups.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEC
Effect level:
>= 7 other: %
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
>= 7 other: %
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no significant difference between experimental and control groups with respect to implantations, postimplantations losses, corporea lutea, fetal sex ratio, mean fetal body weight or uterine weight. The incidence of implantation losses/resoptions was 14 of 325 viable fetuses in the first experimental group and 20 of 316 viable fetuses in the second experimental group.

Regarding the incidence of fetal malformations, there were no test article-related or statistically significant differences between experimental and control groups. The incidence of malformations was 2 of 325 viable fetuses in the first experimental group and 1 of 316 viable fetuses in the second group.

The incidence of developmental variations was 88 of 325 viable fetuses in the first experimental group and 80 of 316 viable fetuses in the second group.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Under the test conditions, no maternal or developmental toxicity was observed after repeated application of hydroxystearic acid on rat. Therefore, the NOEL value of the test substance for maternal and developmental toxicity was determined to be equal or more than 7%.
Executive summary:

A study was conducted to evaluate the teratogenicity effects of the test substance on Charles River Crl:CD VAF/Plus female rats.

The test substance was applied to dorsal skin of two groups of 30 mated female rats. Applications were made on gestation Days 6 through 15, once daily, and left on for 6 h each day. The control article was similarly applied to an additional group of rats of the same strain. All surviving animals were killed on Day 20 of gestation. Following additional parameters were evaluated: implantations, postimplantation losses, corporea lutea, fetal sex ratio, mean fetal body weight or uterine weight, malformations and developmental variations.

There were no significant differences in clinical or necropsy observation between experimental and control groups.

There were no test-article related or statistically significant differences in the incidence of of fetal malformations or fetal developmental variations between experimental and control groups.

Under the test conditions, no maternal or developmental toxicity was observed after repeated application of hydroxystearic acid on rat. Therefore, the NOEL value of the test substance for maternal and developmental toxicity was determined to be equal or more than 7%.