2,6-xylidine

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Chemical Mutagenesis Testing in Drosophila . X. Results of 70 Coded Chemicals Tested for the National Toxicology Program

Author:

Foureman P, et al.

Year:

1994

Bibliographic source:

Environ. Mol. Mutagen. 23, 208-227

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)

Principles of method if other than guideline:

Seventy chemicals were tested for the ability to induce sex-linked recessive lethal (SLRL) mutations in postmeiotic and meiotic germ cells of male Drosophila melanogaster.

GLP compliance:

not specified

Type of assay:

Drosophila SLRL assay

Test material

Test material information

Constituent 1

Reference substance name:

2,6-xylidine

EC Number:

201-758-7

EC Name:

2,6-xylidine

Cas Number:

87-62-7

Molecular formula:

C8H11N

IUPAC Name:

2,6-dimethylaniline

Test material form:

liquid

Details on test material:

Name of test material: 2,6-dimethylaniline

Specific details on test material used for the study:

- Name of test material (as cited in study report): Xylidine
- Supplier: Ethyl Corporation,
- purity: 99.1 %
- Batch No.: E121279/01,
- no further data

Test animals

Species:

Drosophila melanogaster

Strain:

other: Canton-S and Basc

Sex:

male

Administration / exposure

Route of administration:

other: feeding and injection

Duration of treatment / exposure:

3 x 2 - 3 days or single injection

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 other: mg/L (feeding)

Doses / concentrations 2

Dose / conc.:

4 000 other: mg/L (injection)

Control animals:

yes, concurrent vehicle

Positive control(s):

A total number of 70 chemicals were included in this study among them a number of test chemicals considered positive in the experiment including 4,4'-methylenedianiline 2HCI, 3-(chloromethyl) pyridine HCI, HC blue 1, maloxon, cis-dichlorodiaminoplatinum, 1,2-pro-dibromoethane, dibromomannitol, 1,2-epoxypropane, glycidol, myleran, toluene diisocyanate.
.

Examinations

Statistics:

For the SLRL assay, a minimum of about 5,000 chromosomes was scored from each of the treated and concurrent control groups unless the mutant frequency exceeded 1 %. If two or more lethals were recovered among the progeny of one male, a Poisson analysis [Owen, 19621 was performed to determine if these were part of a "cluster ." (A cluster is defined as a group of mutated sperm cells derived from a single mutational event occurring in a spermatogonial cell.) Clusters must be spontaneous in origin, because only meiotic and postmeiotic stages of spermatogenesis were treated. Therefore in those cases in which a male was determined to have produced a cluster the lethal and nonlethal tests for that P1 male were removed from the data. The corrected treated and control data were compared using a normal approximation to the binomial distribution, as suggested by Margolin et al. [1983]. In addition, the treated data were compared to the historical control as described by Mason et al. [1992]. For a compound to be considered mutagenic, the mutant frequency in the treated series (treated frequency must exceed 0.15 % with a P value of < 0.05, or the treated frequency exceed 0.10 % with a P value of < 0.01. If the treated frequency is between 0.10 % and 0.15 % and the P value is between 0.1 and 0.01, or if the treated frequency is higher than 0.15 % and the P value is between 0.1 and 0.05, the result is considered equivocal. All other results are considered negative. Translocation data for each treated sample were compared to the historical control data for that laboratory using a conditional binomial test [Kastenbaum and Bowman, 1970]. As a rule, at least two translocations required among about 5,000 tests in the treated series for a compound considered positive. As a comparison, the combined historical translocation rate for three laboratories, including 33.783 new tests is 4/149,946 (0.0027%).

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not examined

Any other information on results incl. tables

Table 1: Summary of results

Dose of 2,6-Xylidine	ROA	% mortality	% sterility	Lethals			Tests			Total lethals	Total tests	% lethals
				BR1	BR2	BR3	BR1	BR2	BR3
100	feeding	5	0	0	2	6	2,211	1,942	1,821	8	5,974	0,13
0				4	2	10	1,934	2,128	2,046	16	6,108	0,26
4000	injection	14	0	4	1	3	1,911	1,793	1,669	8	5,373	0,15
0				0	0	6	1,999	1,821	1,811	6	5,631	0,11

One cluster of 4 lethals in treated injection experiment .

Applicant's summary and conclusion

Conclusions:

Negative: no increase in the frequency of sex-linked recessive lethals was found.