reaction products of acetic anhydride and adipic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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:

Near guideline study, GLP status unknown, 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:

Assay of 855 test chemicals in ten tester strains using a new modification of the Ames test for bacterial mutagens

Author:

McMahon RE, Cline JC and Thompson CZ

Year:

1979

Bibliographic source:

Cancer Research 39, 682-693

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

assessment of mutagenic potential in 8 histidine auxotrophs of S. typhimurium and 2 trytophan auxotrophs of E. coli over a 10000-fold concentration range using a gradient plate method.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Acetic anhydride

EC Number:

203-564-8

EC Name:

Acetic anhydride

Cas Number:

108-24-7

Molecular formula:

C4H6O3

IUPAC Name:

acetic anhydride

Method

Species / strain

Species / strain / cell type:

other: S. typhimurium LT-2, TA1535, TA100, C3076, TA1537, D3052, TA1538, TA98. E. coli WP2 and WP2 uvrA-

Metabolic activation:

with and without

Metabolic activation system:

S9 from Arochlor induced rat liver

Test concentrations with justification for top dose:

Approximately 0.1 - 1.0, 1-10, 10-100 and 100-1000 µg/mL using concentration gradient plates.

Vehicle / solvent:

dimethyl sulfoxide.

Controls

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

other: streptozotocin (mutagenic - activation) and 2-acetylaminofluorene (mutagenic + activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation using gradient plates)

DURATION
- Exposure duration: 48 hours at 37°C

NUMBER OF REPLICATIONS: Not reported

Evaluation criteria:

The concentration range over which chemically induced mutant colonies are present was recorded. when the plates are read the operator has a series of 4 plates covering a 10,000-fold concentration range on which to base his judgment. If the test chemical is toxic to the auxotroph, minimal inhibitory concentrations can be observed as clear zones and were also recorded.

Results and discussion

Test results

Species / strain:

other: S. typhimurium LT-2, TA1535, TA100, C3076, TA1537, D3052, TA1538, TA98. E. coli WP2 and WP2 uvrA-

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

In a modified Ames test, acetic anhydride, at concentrations of up to 1000 µg/mL, was negative, ie non-mutagenic

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

In a modified Ames test using a gradient plate method, acetic anhydride, at concentrations of up to 1000 µg/mL, was negative, ie non-mutagenic

Executive summary:

In a modified Ames test using a gradient plate method, acetic anhydride, at concentrations of up to 1000 µg/mL, was negative, ie non-mutagenic