2,6-xylidine

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

The in vivo effect of 2,6-xylidine on induction of micronuclei in mouse bone marrow cells

Author:

Parton JW, et al.

Year:

1988

Bibliographic source:

Mutat. Res. 206, 281-283

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The ability of 2 .6-xylidine to produce chromosome breakage and/or spindle malformation in vivo was evaluated by an assessment of the capacity of the compound to induce micronuclei in bone marrow polychromatic erythrocytes.

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): 2,6-xylidine
- Aldrich Chemical Co.. Milwaukee, WI
- no further data

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan - Sprague-Dawley, Indianapolis IN
- Weight at study initiation: 28-32 g
- Assigned to test groups randomly: yes
- Fasting period before study: none
- Housing: groups of 5
- Diet Purma pelleted rodent chow (No . 5002) ad libitum
- Water ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: 10 % acacia

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: 2,6-xylidine was diluted in 10 % acacia

Duration of treatment / exposure:

not applicable due to single oral application

Frequency of treatment:

single treatment

Post exposure period:

72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
87.5, 175, or 350 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

5 animals

Control animals:

yes

Positive control(s):

cyclophosphamide;
- Route of administration: oral (gavage)
- Doses / concentrations: 100 mg/kg

Examinations

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
highest dose represents 50 % of the oral LD50

TREATMENT AND SAMPLING TIMES:
24, 48, 72 hours

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The oral administration of up to 350 mg/kg of 2,6-xylidine did not result in the induction of micronuclei in bone marrow of male ICR mice either at 24, 48 or 72 h after dosing. Furthermore, no decrease in the PCE/NCE ratio observed in any animal treated with the test article. In contrast, the administration of 100 mg/kg cyclophosphamide produced a significant induction of micronucleated PCE and confirmed sensitivity of the system for the identification of genotoxins.

Any other information on results incl. tables

 

Treatment (mg/kg)	Harvest time (h)	PCE/NCE ratio	MPCE/1000 PCE
350	24	0.9 ± 0.1	1.6 ± 1.5
	48	1.1 ± 0.4	2.2 ± 0.8
	72	1.1 ± 0.4	1.2 ± 1.3
175	24	0.9 ± 0.5	1.2 ± 1.1
	48	1.1 ± 0.2	0.8 ± 1.1
	72	1.5 ± 0.2	1.3 ± 1.0
87.5	24	1.0 ± 0.3	0.8 ± 1.1
	48	1.0 ± 0.1	1.2 ± 0.8
	72	1.0 ± 0.6	1.3 ± 1.3
control	24	1.0 ± 0.2	1.4 ± 0.9
	48	1.0 ± 0.0	1.0 ± 0.7
	72	1.3 ± 0.4	0.8 ± 1.1
100 cyclophosphamide	24	1.0 ± 0.5	46.2 ± 10.7
	48	severe bone marrow toxicity
	72	severe bone marrow

 

The negative results obtained in this study are in contrast to the positive findings for the in vitro induction of SCE and chromosome aberrations reported by other authors. Such discordant cytogenetic observations are not unprecedented. In vitro systems do not duplicate the possible detoxification, distribution and excretion mechanisms that exist in vivo which can prevent chemicals from reaching a target population, in this case the bone marrow . The absence of an effect on the PCE/NCE ratio in suggests that 2,6-xylidine or an active metabolite may not have been present in bone marrow in sufficient concentration to induce micronuclei. On the other hand, the high dose in this was equivalent to 50% of the LD50 and this should have been more than adequate to evaluate the intrinsic genotoxic potential of the test compound.