Undecanedioic acid

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Peer-reviewed database (OECD SIDS); comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Mutagenic Evaluation of Compound FDA 71- 50, Adipic Acid

Author:

Litton Bionetics, Inc.

Year:

2001

Bibliographic source:

cited in: OECD SIDS, dicarboxylic acid category, 2001 / Litton Bionetics, Inc. (1974). Mutagenic Evaluation of Compound FDA 71-50, Adipic Acid, Report No. FDABF-GRAS-310. PB-245466, 1-138, December 9, 1974.

Materials and methods

Principles of method if other than guideline:

In vivo cytogenetic test in rats with oral application by gavage. Groups of 5 treated and 3 control animals were used. Acute study (single dosing) and subacute study (treatment once a day for 5 consecutive days). Doses upt to 5000 mg/kg (acute study) or up to 2500 mg/kg/d (subacute study) were administered.

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Adipic acid

EC Number:

204-673-3

EC Name:

Adipic acid

Cas Number:

124-04-9

IUPAC Name:

adipic acid

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

Acute study: single dosing
Subacute study: once a day for 5 consecutive days

Frequency of treatment:

Acute study: single dosing
Subacute study: once a day for 5 consecutive days

Post exposure period:

Animals were killed 6, 24 and 48 hours after a single administration in the acute study. In the subacute study 5 doses, 24 hours apart, were administered and animals were killed 6 hours after the last dose.

Doses / concentrations

Remarks:

Doses / Concentrations:
Test 1: acute and subacute: 3.75, 37.5, 375 mg/kg bw/day; Test 2: acute 5000 mg/kg bw and subacute 2500 mg/kg bw/day
Basis:

No. of animals per sex per dose:

Groups of 5 treated and 3 control male animals were used.

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine

Examinations

Tissues and cell types examined:

bone marrow

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Test I (3.75, 37.5 and 375 mg/kg bw/day dosing):

Acute study: The negative control group cells contained no aberrations. The compound produced no aberrations except for one cell containing a break in the 6-hour sample of the intermediate dose level. The expected severe chromosomal damage was observed for the positive control group (triethylenemelamine treated animals). The mitotic indices were within normal limits. Negative and positive controls were functional.

Subacute study (5 days): The negative control group and the low level test group contained no aberration. The intermediate level contained one cell with a reunion and one cell that was polyploid. The highest level contained three cells with breaks and one fragment. These were considered to be within the normal limits of the historical negative controls of the laboratory. Negative control was functional, no positive control.

Test 2:

Acute study: Adipic acid was administered at a single dose of 5000 mg/kg bw. The compound produced no aberrations except for 3 cells with polyploidy (2 in the 6-hour sample and 1 in the 24-hour). Neither the variety nor the number of these aberrations differed significantly from the negative controls (polyploidy observed in 4 cells). Negative and positive controls were functional.

Subacute study (5 days, 2500 mg/kg bw/day). Only 218 metaphases have been evaluated. The compound produced no aberrations except for 1 cell with polyploidy. Polyploidy was also observed in the negative control group. These are considered to be within the normal limits of the historical negative controls. Negative control was functional, no positive control.

In summary, adipic acid can be considered non-mutagenic as measured by the cytogenetic test.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Adipic acid was not mutagenic in in vivo cytogenetic studies. Based on a read across (category approach), undecanedioic acid is expected to be as well non mutagenic.