α,2-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

Study period:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

other: testing report

Title:

Unnamed

Year:

1999

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:

α,2-dichlorotoluene

EC Number:

210-258-8

EC Name:

α,2-dichlorotoluene

Cas Number:

611-19-8

Molecular formula:

C7H6Cl2

IUPAC Name:

1-chloro-2-(chloromethyl)benzene

Constituent 2

Reference substance name:

alpha,2-dichlorotoluene

IUPAC Name:

alpha,2-dichlorotoluene

Details on test material:

Source: Ihara Chemical Industry Co., Ltd.-Lot
No.T7030-Purity: 99.65%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

male: 45 days, female: 41-48 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
2, 10, 50 mg/kg/day
Basis:

Control animals:

yes

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

2 other: mg/kg bw/day

Sex:

male

2

Dose descriptor:

NOAEL

Effect level:

10 other: mg/kg bw/day

Sex:

female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Suppression of body weight gain and decrease in food
consumption were observed in both sexes in the early period
of administration at 50 mg/kg/day. At necropsy, thickening
of the forestomach wall was observed in males of 10
mg/kg/day and both sexes of 50 mg/kg/day. The relative liver weight was  increased and absolute liver weight tended to be increased in females of  50 mg/kg/day. Histopathological examination revealed squamous epithelium  hyperplasia, erosion and ulceration in the forestomach in males of 10  mg/kg/day and both sexes of 50 mg/kg/day. These changes observed in the  forestomach were considered to be related to the irritancy of test  substance. In addition, the increase of hyaline droplets in the proximal  tubular epithelium, eosinophilic bodies, granular casts and basophilic  tubule were observed in the kidneys of males of 50 mg/kg/day. There were  no effects on hematological and clinical examination or organ weights in  males. In this experiment, the no observed effect level (NOEL) was  considered to be 2 mg/kg/day for male and 10 mg/kg/day for female.

Table 1. Absolute and relative liver weights in rats treated orally with  OCBC(a)
=======================================================
Dose (mg/kg)        
0                2                10                50
-------------------------------------------------------
[Male]
No. of animals        
12              12                12                12

Body weight (g)        
464+/-30        478+/-27        457+/-19        461+/-27

Liver, absolute (g)
12.2+/-1.4      12.6+/-1.1       11.7+/-1.0      12.4+/-1.5

Liver, relative (g%)
2.62+/-0.19      2.64+/-0.12      2.55+/-0.17     2.69+/-0.20

----------------------------------------------------------
[Female]
No. of animals
12                11                11                11

Body weight (g)
324+/-26        314+/-29        302+/-25        313+/-15

Liver, absolute. (g)
13.6+/-1.7       13.9+/-1.5      13.2 +/-1.6      14.6+/-1.0

Liver, relative (g%)
4.21+/-0.32      4.43+/-0.34      4.37+/-0.28      4.67+/-0.23**
=======================================================
Values are expressed as Mean+/-S.D.
Significantly different from control;**: P<0.01
(a)No significant change was observed in absolute nor
relative weights of the following organs; thymus, spleen,
kidneys, adrenals, testes, and epididymis.

Applicant's summary and conclusion

Executive summary:

The repeated dose oral toxicity study in rats was conducted according to OECD TG 422. Rats (12 animals/sex/group) were given o-Chlorobenzylchloride by gavage at doses of 2, 10 and 50 mg/kg bw/day. Male rats were dosed from 14 days before mating to the day before scheduled sacrifice through the mating period (total 45 days). Female rats were dosed from 14 days before mating to 4 days after delivery through the mating and gestation periods (total 41-48 days). Suppression of body weight gain and a decrease in food consumption were observed in the early period of administration in male and female rats at 50 mg/kg bw/day. Increases in the relative and absolute liver weights were also observed in females at this dose. At scheduled sacrifice, thickening of the forestomach wall was observed in males at 10 mg/kg bw/day and both sexes at 50 mg/kg bw/day. Histopathological examination revealed squamous epithelium hyperplasia, erosion and ulceration in the forestomach in males at 10 mg/kg bw/day and both sexes at 50 mg/kg bw/day. The changes observed in the forestomach were considered due to the irritating property of o-Chlorobenzylchloride. In addition, increases in the numbers of hyaline droplets in the proximal tubular epithelium, eosinophilic bodies, granular casts and basophilic tubules were observed in the kidneys of males at 50 mg/kg bw/day. There was no effect on hematological and clinical examinations and organ weights in male rats in the substance-treated groups. Based on these observations, the NOAEL for oral repeated dose toxicity was considered to be 2 mg/kg/day in male rats and 10 mg/kg/day in female rats.