2,6-dichlorotoluene

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,6-dichlorotoluene

EC Number:

204-269-7

EC Name:

2,6-dichlorotoluene

Cas Number:

118-69-4

Molecular formula:

C7H6Cl2

IUPAC Name:

1,3-dichloro-2-methylbenzene

Details on test material:

- Analytical purity: 99.2%

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

For 2 weeks prior to mating and 2 weeks of mating. Further for 2 weeks after mating in males and throughout pregnancy up till day 3 post partum in females.

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
30mg/kg/day
Basis:
other: in corn oil

Doses / concentrations 2

Remarks:

Doses / Concentrations:
100mg/kg/day
Basis:
other: in corn oil

Doses / concentrations 3

Remarks:

Doses / Concentrations:
300mg/kg/day
Basis:
other: in corn oil

Doses / concentrations 4

Remarks:

Doses / Concentrations:
1000mg/kg/day
Basis:
other: in corn oil

No. of animals per sex per dose:

Males, 13; females, 13

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

1

Dose descriptor:

NOEL

Effect level:

30 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

2

Dose descriptor:

NOEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

1. Males: Decrease in locomotor activity was observed in one animal in the 300 mg/kg group, as well as decrease in locomotor activity (9 animals) and adoption of a prone position (2 animals) in the 1000 mg/kg group. Body weight gain was suppressed in the 300 and 1000 mg/kg groups. Autopsy following treatment for 42 days demonstrated increases in the relative kidney weights in the 300 and 1000 mg/kg groups and the relative liver weights in the 1000 mg/kg group. As histopathological findings, increase in eosinophilic bodies in the kidneys was observed in the groups receiving 100 mg/kg or more, and centrilobular hypertrophy and ground glass appearance of the hepatocytes were observed in those with 300 mg/kg and more. Decrease in the concentration of glucose was determined in the 300 and 1000 mg/kg groups. No effects of 2,6-dichlorotoluene were observed on food consumption and hematology.

2. Females: Decrease in locomotor activity (all animals tested), adoption of a prone position (10 animals) and incomplete eyelid opening (6 animals) were observed in the 1000 mg/kg group. Food consumption was decreased as well as suppression of body weight gain in the 1000 mg/kg group. At autopsy on postpartum day 4, increases in the relative kidney weight and relative liver weight were found in the 1000 mg/kg group. As histopathological findings, vacuolar and fatty degeneration in the proximal kidney tubules and centrilobular hypertrophy of the hepatocytes were observed in the 300 and 1000 mg/kg groups. In addition, decreases in the relative thymus weight and atrophy of the thymus were observed in the 300 mg/kg and more groups. No effects of 2,6-dichlorotoluene were observed on urinalysis.

Applicant's summary and conclusion

Conclusions:

NOELs for repeated dose toxicity of 2,6-dichlorotoluene are considered to be 30 mg/kg/day in males and 100 mg/kg/day in females.