12-hydroxystearic acid

Repeated dose toxicity: dermal

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Stearic acid

EC Number:

200-313-4

EC Name:

Stearic acid

Cas Number:

57-11-4

Molecular formula:

C18H36O2

IUPAC Name:

Octadecanoic Acid

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 or test system 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.