Registration Dossier

Administrative data

Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non- GLP, non- guideline study, published in peer reviewed literature. No restrictions, fully adequate for assessment.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Acetic acid, a potent stimulator of mouse epidermal macromolecular synthesis and hyperplasia but with weak tumour-promoting ability
Author:
Slaga T, Bowden G & Boutwell R
Year:
1975
Bibliographic source:
Nat. Cancer Inst., Vol 55, pp 983-987

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Acetic acid was used as a promotor for tumour development in mice initiated with DMBA or β-PL and was applied dermally 1-3 times per week (at doses of 1-40 mg/animal) for 32 weeks. Control animals received acetic acid dermally once per week. The incidence of papillomas and carcinomas was recorded and they were removed at random for histological verification.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Acetic acid
EC Number:
200-580-7
EC Name:
Acetic acid
Cas Number:
64-19-7
Molecular formula:
C2H4O2
IUPAC Name:
acetic acid
Details on test material:
- Name of test material (as cited in study report): Acetic acid
- Analytical purity: Not reported
- No details reported

Test animals

Species:
mouse
Strain:
CD-1
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Mouse Farms, North Wilmington, Massachusetts, USA
- Age at study initiation: 7-12 weeks old
- Weight at study initiation: not reported
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported

Administration / exposure

Type of coverage:
not specified
Vehicle:
acetone
Details on exposure:
TEST SITE
- Area of exposure: No details reported
- % coverage: No details reported
- Type of wrap if used: No details reported
- Time intervals for shavings or clippings: shaved 2 days before exposure

REMOVAL OF TEST SUBSTANCE
- no details reported

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2 mL in acetone
- Concentration (if solution): 33, 167, 333, 500, 667, 833 or 1000 μmoles/animal
- Constant volume or concentration used: yes

VEHICLE
- Justification for use and choice of vehicle (if other than water): No details reported
- Amount(s) applied (volume or weight with unit): 0.2 mL

USE OF RESTRAINERS FOR PREVENTING INGESTION: no details
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
32 weeks

Frequency of treatment:
1-3 times per week.
Controls dosed once per week.

Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 1. 2, 10, 20, 40 mg/animal
Basis:

Remarks:
Doses / Concentrations:
0, 17, 33, 167, 333, 667 μmoles
Basis:

No. of animals per sex per dose:
20-30

Control animals:
yes, sham-exposed
Positive control:
0.25% croton oil

Examinations

Observations and examinations performed and frequency:
The animals were observed and the incidence of papillomas and carcinomas was recorded weekly
Sacrifice and pathology:
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes - during the 32 week study, papillomas and carcinomas were removed for histological verification at random

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Details on results:
Mortality:
- A single dermal application of acetic acid at doses of up to 40 mg/animal, in mice initiated with ß-PL or DMBA did not induce excessive mortality. However, more than one weekly application of 10-40 mg acetic acid caused excessive mortality. 33% of mice died when 10 mg acetic acid/animal was applied dermally 3 times per week and approximately 50% of mice died when 20 mg was applied twice a week.


Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
toxicity
Effect level:
30 other: mg/animal
Sex:
female
Basis for effect level:
other: No deaths when applied dermally once per week for 32 weeks
Dose descriptor:
LOAEL
Remarks:
toxicity
Effect level:
10 other: mg/animal
Sex:
female
Basis for effect level:
other: Mortality (33%) when applied dermally 3 times per week.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

Acetic acid was used as a promotor for tumour development in mice initiated with DMBA or β-PL and was applied dermally 1-3 times per week (at doses of 1-40 mg/animal) for 32 weeks. Control animals received acetic acid dermally once per week.

A single dermal application of acetic acid at doses of up to 40 mg/animal, in mice initiated with ß-PL or DMBA did not induce excessive mortality. However, more than one weekly application of 10 -40 mg acetic acid caused excessive mortality. 33% of mice died when 10 mg acetic acid/animal was applied dermally 3 times per week and approximately 50% of mice died when 20 mg was applied twice a week.