reaction products of acetic anhydride and adipic acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Non GLP. Near-guideline study. Published in peer reviewed literature. Minor restrictions in design and/or reporting but otherwise adequate for assessment. Read-across justification: The available toxicological data for the target and source substances is outlined in the data matrix (Annex I). The toxicological properties of the target substance are related mainly to acetic acid/acetate since the anhydride components of the substance are hydrolytically unstable. When the target substance comes in contact with water or moisture a complete hydrolysis will take place to form no other hydrolysis products than acetic acid/acetate and adipic acid. Thus, the use of data from acetic acid and adipic acid is justified to evaluate toxicological properties of the target substance. Furthermore, data from acetic anhydride is used in the assessment. Experimental data obtained with the source substances indicate that the substances has low oral (LD50 > 1780 – 3310 mg/kg bw) and inhalation (LC50 1680 - 7700 mg/m3) acute toxicity. Furthermore, the acetic acid and acetic anhydride are irritating to skin at concentration < 25% and corrosive to skin at ≥ 25%. Acetic anhydride and acetic acid are not tested for sensitisation due corrosive properties; adipic acid did not show any evidence of sensitising in an animal study. The source substances did not show positive response in genetic toxicity studies available. Repeated toxicity studies via oral route conducted for acetic acid showed NOAEL values ≥ 210 mg kg bw/day and via inhalation route for acetic anhydride 4.2 mg/m3.. Reproduction toxicity studies conducted for acetic acid did not show any adverse effects on reproduction at the highest concentration tested (1600 mg/kg bw/day).

Data source

Reference

Reference Type:

publication

Title:

Evaluation of modified methods for determining skin irritation

Author:

Nixon GA, Bannan EA, Gaynor TW, Johnston DH & Griffith JF

Year:

1990

Bibliographic source:

Regul. Toxicol. Pharmacol. Vol 12, pp 127-136

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

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
- Substance type: 3.3% and 10% aqueous solutions
- Physical state: liquid
- Analytical purity: not reported
- Stability under test conditions: not reported
- Storage condition of test material: not reported
- No further details

Test animals

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS - no further details reported

ENVIRONMENTAL CONDITIONS - no details reported

IN-LIFE DATES: Not reported

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 3.3% and 10%

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: not reported
- % coverage: not reported
- Type of wrap if used: gauze patches

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h

SCORING SYSTEM:
Sites were graded for erythema and oedema at 4, 24, 48 and 72 h using the Draize scale.

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 72 h

Score:

0.5 - 1.1

Remarks on result:

other: scores for 3.3 % and 10%, acetic acid, respectively

Other effects:

No other effects reported

Any other information on results incl. tables

Table 1  Primary Irritation Indices (PII) in rabbits

Acetic acid %	3.3	10
PII	0.5	1.1

Sites were graded for erythema and oedema at 4, 14, 48 and 72 h. PII was calculated by averaging the scores for all test sites.

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information

Conclusions:

Acetic acid, as a 3.3% or a 10% aqueous solution, was slightly irritating to rabbit skin.

Executive summary:

In a study with rabbits, acetic acid was applied to shaved, intact skin using gauze pads for 4 h and the sites graded for erythema and oedema at 4, 24, 48 and 72 h. Primary Irritation Indices (PII) were calculated by averaging the scores for all test sites. The PII for a 3.3% aqueous solution of acetic acid was 0.5 and for a 10% aqueous solution was 1.1. Thus acetic acid was considered to be slightly irritating to rabbit skin at concentrations of 3.3 and 10%.