Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Does not meet important criteria of todays stadard methods (test material part of a mixture (containing only 1% test substance), analytical purity of test substance not provided, only 9 female animals/test group, limited documentation).

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Final Report on the Safety Assessment of Sorbitan Stearate, Sorbitan Laurate, Sorbitan Sesquioleate, Sorbitan Oleate, Sorbitan Tristearate, Sorbitan Palmitate, and Sorbitan Triolate
Author:
Elder, R.L., ed.
Year:
1985
Bibliographic source:
Journal of the American College of Toxicology 4(3): 465-121
Reference Type:
secondary source
Title:
Final Report on the Safety Assessment of Sorbitan Caprylate, Sorbitan Cocoate, Sorbitan Diisostearate, Sorbitan Dioleate, Sorbitan Distearate, Sorbitan Isostearate, Sorbitan Olivate, Sorbitan Sesquiisostearate, Sorbitan Sesquistearate, and Sorbitan Tri...
Author:
Lanigan RS, Yamarik TA; Cosmetic Ingredient Review Expert Panel
Year:
2002
Bibliographic source:
International Journal of Toxicology 21(suppl. 1): 93-112
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Principles of method if other than guideline:
13 weeks dermal toxicity study, where 9 female rabbits received an application of 0.3, 3, and 30 mg/kg bw respectively, of a hormone cream containing 2% test substance. An additional group was treated with 30 mg/kg of the same cosmetic without hormone.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
female

Administration / exposure

Details on exposure:
TEST SITE
- Area of exposure: back
- Preparation of test site: clipped

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30, 300, and 3000 mg/kg bw
- Concentration (if solution): 1% in technical product
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily, 5 days/week, for a total of 65 treatments
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
30, 300, 3000 mg product/kg bw/day
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
0.3, 3, 30 mg/kg bw/day (the product contained 1% of the test substance)
Basis:
nominal per unit body weight
No. of animals per sex per dose:
9 females
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DERMAL IRRITATION (if dermal study): Yes

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes
- Time schedule: before the first application and then at weeks 4, 7 and 13

URINALYSIS: Yes
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
- Organ weights of brain, heart, liver, kidney, spleen, adrenals were taken.
HISTOPATHOLOGY: Yes
- Examinations of brain, liver, kidney, heart, spleen, lung, pancreas, adrenals, spleen, ovaries, uterus, stomach, large and small intestine, bone marrow, skin

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
one animal died and two were killed due to non-product-related diseases (group membership not given)
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
minimal to slight skin irritation in all dose groups
Mortality:
mortality observed, treatment-related
Description (incidence):
one animal died and two were killed due to non-product-related diseases (group membership not given)
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
One animal died and two were killed due to non-product-related diseases (group membership not given). The skin from the application sites had no irritation in the untreated group, minimal irritation (slight irritation or slight desquamation) in the low dose group, minimal or negligible irritation in the mid dose group, slight irritation beginning in the fifth test week in the high dose group, and slight irritation beginning in the fourth test week in the high dose group without the hormone.

BODY WEIGHT
No substance-related effects noted.

HAEMATOLOGY
No substance-related effects noted.

CLINICAL CHEMISTRY
No substance-related effects noted.

URINALYSIS
No substance-related effects noted.

ORGAN WEIGHTS
A dose-related increase in uterine weight was observed of rabbits topically exposed to 0.3, 3, and 30 mg/kg bw/day of the product and also in splenic weight in animals receiving 3 and 30 mg/kg bw. Liver weights were decreased in animals given 3 and 30 mg/kg bw. It was assumed that the effect on organ weights was caused by the estrogenic hormone rather than the by the test substance.

GROSS PATHOLOGY
No substance-related effects noted.

HISTOPATHOLOGY
No substance-related effects noted.


Effect levels

Dose descriptor:
NOEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No systemic effects were noted.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion