Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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:
Unnamed
Year:
1987

Materials and methods

Principles of method if other than guideline:
A facial skin formulation containing 5.0% test material was applied shaved dorsal skin of 15 female rats in a 13 wk dermal toxicity study.
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): Stearic acid

Test animals

Species:
rat
Strain:
other: Crl:COBS CD(SD)BR
Sex:
female
Details on test animals and environmental conditions:
No reported

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.0 mL/kg product
- Concentration (if solution): 5.0% (200 mg/kg bw/day)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 wk
Frequency of treatment:
Daily, 5 times per wk (total of 65 applications)
Doses / concentrations
Remarks:
Doses / Concentrations:
4.0 mL formulation (5%)/kg bw
Basis:
no data
No. of animals per sex per dose:
15
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale:The treatment was estimated to provide a dose 100-fold greater than the daily exposure to human
Positive control:
No

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

DERMAL IRRITATION (if dermal study): Yes

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes

URINALYSIS: Yes
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
CLINICAL SIGNS AND MORTALITY: None

HAEMATOLOGY: Statistically significant decrease was observed of the hemoglobine and hematokrit

CLINICAL CHEMISTRY: Statistically significant decrease was observed for glucose and increase serum glutamic-pyruvic transaminase concentrations during the 7th wk and drecreased mean corpuscular volume and total erythrocryte count during the 13th wk.

URINALYSIS: Were in normal values

ORGAN WEIGHTS: Increase in absolute weights of the liver, heart, kidneys and adrenals and in liver/body weight ratios were statistically significant

HISTOPATHOLOGY: NON-NEOPLASTIC: Subclinical bronchitis and 'focal interstitial mononuclear cell infiltration into the kidneys, liver and heart' were noted in an unspecified numbers of rats. Grade 1 hyperkeratosis was observed in 5 of 15 treated rats.

OTHER: Minimal to moderate skin irritation was observed throughout the study

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 200 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The apparent statistical significance between hematologica, biochemical and organ weight values of treated and control groups was within normal limits.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, a NOAEL for the formulation containing stearic acid was determined to be >200 mg/kg bw/day.
Executive summary:

A 13 week repeated toxicity study was conducted to evaluate the dermal toxicity of stearic acid to rat.

A facial skin formulation containing 5.0% test material was applied shaved dorsal skin of 15 female rats in a 13 wk dermal toxicity study.

No mortality was observed. Minimal to moderate skin irritation was observed throughout the study. The apparent statistical significance between hematologica, biochemical and organ weight values of treated and control groups was within normal limits.

Under the test conditions, a NOAEL for the formulation containing stearic acid was determined to be >200 mg/kg bw/day.