Indole

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer-reviewed journal

Justification for type of information:

Data is from peer-reviewed journal

Data source

Reference

Reference Type:

publication

Title:

FURTHER STUDIES ON INCOMPLETE CARCINOGENESIS: TRIETHYLENE MELAMINE (T.E.M.), 1,2-BENZANTHRACENE AND ,3-PROPIOLACTONE, AS INITIATORS OF SKIN TUMOUR FORMATION IN THE MOUSE.

Author:

F. J. C. ROE AND M. H. SALAMAN.

Year:

1954

Bibliographic source:

Cancer Research Department, London Hospital Medical College, London, E.1. December 18, 1954.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below mentioned

Principles of method if other than guideline:

Subchronic repeated dermal toxicity study was conducted to determine the toxicity of test substance in male mice.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl formate

EC Number:

203-721-0

EC Name:

Ethyl formate

Cas Number:

109-94-4

Molecular formula:

C3H6O2

IUPAC Name:

Ethyl formate

Details on test material:

- Name of test material (as cited in study report): Ethyl frmate
- Molecular formula (if other than submission substance): C3H6O2
- Molecular weight (if other than submission substance): 74.0784 g/mole
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): No data

Test animals

Species:

mouse

Strain:

other: Stock albino of the " S " strain

Sex:

male

Details on test animals or test system and environmental conditions:

Details on test animal
- Age at study initiation: 7-9 weeks old.
- Diet :fed on cubes prepared according to the Rowett Institute plus fresh greenstuff twice a week formula
- Water : ad libitum
- Acclimation period:

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: Acetone

Details on exposure:

Details on dermal exposure
PREPARATION OF DOSING SOLUTIONS:
All solutions were prepared weight per total volume in the solvent. The preparation of glycine ethyl ester from the hydrochloride is described in the experimental section. The podophyllin extract used was prepared from the crude resin by extraction with acetone. Dosage was calculated on the dry weight of the extract after filtration and evaporation.
positive control: croton oil


TEST SITE
- Area of exposure: whole back, from forelimbs to tail.

The hair was clipped from the whole back, from forelimbs to tail, before treatment and at intervals when necessary. Solutions were delivered from calibrated pipettes, care being taken that they spread as evenly as possible over the whole
clipped area. A glass spreader was used for solutions which did not otherwise spread easily.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

10 weeks

Frequency of treatment:

10 weekly applications of 0.3ml neat agent

Doses / concentrations

Dose / conc.:

2 760 mg/kg bw/day

No. of animals per sex per dose:

No data

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

No data

Sacrifice and pathology:

HISTOPATHOLOGY: Yes

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

not specified

Dermal irritation:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Specimens of skin from mice additional to each group were removed under ether anaesthesia three days after one and/or two applications of the test substance. Mice which died during or were killed at the end of the tests were examined post mortem for lung adenomata and other abnormalities. Specimens for histological examination were fixed in Zenker's fluid, embedded in paraffin wax, and stained with haematoxylin and eosin-Biebrich scarlet.

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

NOEL

Effect level:

2 760 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

histopathology: non-neoplastic

Remarks on result:

other: No Epidermal hyperplasia observed.

Target system / organ toxicity

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 2760 mg/kg bw/day when male “s” strain mice were treated by test substance for 10 weeks dermally.

Executive summary:

10 weeks repeated dermal study was conducted for test substance on male “s” strain mice with the dose concentration of 2760 mg/kg bw/day (0.3ml in acetone applied) and the histopathologic analysis is done to determine the toxic effects. No significant activity was observed In terms of epidermal hyperplasia. Therefore, NOAEL was considered to be 2760 mg/kg bw/day for test substance when male “s” strain mice were treated for 10 weeks