Fatty acids, lanolin, iso-Pr esters

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Insufficient for assessment (only a 5% formulation tested, test substance purity not specified, limited documentation, no ophthalmoscopic and neurobehavioural examination).

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Reference 2

Reference Type:

secondary source

Title:

Final report of the safety assessment for Isopropyl Lanolate.

Author:

CIR

Year:

1980

Bibliographic source:

Journal of environmental pathology, toxicology and oncology;4/4, 121-132, 1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)

Deviations:

yes

Remarks:

only a 5% formulation tested, test substance purity not specified, limited documentation, no ophthalmoscopic and neurobehavioural examination

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, lanolin, iso-Pr esters

EC Number:

264-119-1

EC Name:

Fatty acids, lanolin, iso-Pr esters

Cas Number:

63393-93-1

Molecular formula:

UVCB

IUPAC Name:

Fatty acids, lanolin, isopropyl esters

Details on test material:

- Name of test material (as cited in study report): isopropyl lanolate
- Physical state: yellow buttery solid
- Analytical purity: no data
- Composition of test material, percentage of components: 5% isopropyl lanolate and 3% glycol stearate in a liquid foundation

Test animals

Species:

rat

Strain:

other: COBS CD (BR)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, In., Wilmington, Massachusetts
- Housing: Animals were individually housed in wire-mesh, stainless steel cages
- Diet: Teklad Mouse and Rat Died, ad libitum
- Water: tap water, ad libitum

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: 5% isopropyl lanolate and 3% glycol stearate in a liquid foundation

Details on exposure:

TEST SITE
- Time intervals for shavings or clipplings: Each rat was clipped weekly to remove dorsal hair.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks (animals received 65 applications in total)

Frequency of treatment:

once daily, 5 days a week

Doses / concentrations

Remarks:

Doses / Concentrations:
100 mg/kg bw
Basis:
nominal per unit body weight

No. of animals per sex per dose:

15

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily

BODY WEIGHT: Yes
- Time schedule for examinations: initially and weekly thereafter and on the day of necropsy

HAEMATOLOGY: Yes
- Time schedule for collection of blood: One week prior to the termination of the study, animals were fasted over night (16 hours).
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 15 animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: One week prior to the termination of the study, animals were fasted over night (16 hours).
- Animals fasted: Yes
- How many animals: 15 animals

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, at the end of the test, all animals were dissected, with a macroscopic assessment of the internal organs, these being weighed and preserved for histological investigations. The following organs were analyzed: thymus, trachea, esophagus, stomach, pancreas, small intestine, large intestine, ovary and bladder.

ORGAN WEIGHTS: Yes, brain, lung, heart, liver, spleen, kidney, adrenals and uterus

HISTOPATHOLOGY: Yes, tissues were subjected to histopathologic examination by A.A. Stein, M.D., Microscopy for Biological Research, Ltd., Albany, New York. The following organs were analyzed: bone marrow, liver, spleen, kidney, skin, brain, heart, lung and uterus.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

non adverse

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

non adverse

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:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

non adverse

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
All animals survived for the duration of the study.
External appearance of the skin at sites of application of the test substance was not different from that of control. All groups exhibited slight to moderate erythema and drying intermittently throughout the study.
During the period of application and at the end of the test, all animals were free from other symptoms.

BODY WEIGHT AND WEIGHT GAIN
The dose group exhibited higher body weights compared to the control group. After 14 days no significant differences were observed. Therefore, this finding was not believed to be compound-related.

HAEMATOLOGY
No deviations in comparison with the control animals.

CLINICAL CHEMISTRY
No deviations in comparison with the control animals.

ORGAN WEIGHTS
The kidney weight for the dose group was higher compared to the control value. The histopathology showed no deviations in comparison with the control anaimals. Therefore, this observation was not believed to be compound-related. All other organ weights were within the normal range.

GROSS PATHOLOGY
No deviations in comparison with the control animals.

HISTOPATHOLOGY: NON-NEOPLASTIC
No deviations in comparison with the control animals.

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 100 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

female

Basis for effect level:

other: clinical observations, body weight gains, hematology, clinical chemistry, organ weights, histopathology

Target system / organ toxicity

Critical effects observed:

not specified