2,4-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:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

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:

Benzene, 2,4-dichloro-1-methyl-

IUPAC Name:

Benzene, 2,4-dichloro-1-methyl-

Constituent 2

Reference substance name:

2,4-dichlorotoluene

EC Number:

202-445-8

EC Name:

2,4-dichlorotoluene

Cas Number:

95-73-8

Molecular formula:

C7H6Cl2

IUPAC Name:

2,4-dichloro-1-methylbenzene

Details on test material:

Purity: 98,96 %

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Duration of treatment / exposure:

Male: 46 days,
female: from 14 days before mating to day 3 of lactation

Control animals:

yes

Results and discussion

Results of examinations

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight gain was reduced in 500 mg/kg females in the pregnancy and lactation periods

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption was decreased in the 500 mg/kg group on day 2 of administration in males and on day 10 of administration and day 3 of pregnancy in females.

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

On the haematological and blood chemical analyses, the 500 mg/kg males exhibited decreased numbers of platelets and increased cholinesterase values.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Increases in relative organ weights were seen for the livers of males and females, and kidneys of males at 500 mg/kg. On gross necropsy, dark brown discoloration of the liver was observed in 9/12 males receiving 500 mg/kg.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Hypertrophy of hepatocytes in the centrilobular zones of the livers: 500 mg/kg males and 2/12 79 mg/kg males. Atrophy and regeneration of kidney tubular epithelium and dilation of tubules: 2/12 males and 1/12 females 500 mg/kg, and 1/12 79 mg/kg males.

Effect levels

1

Dose descriptor:

NOEL

Remarks:

for P generation

Effect level:

12.5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: repeated dose toxicity

2

Dose descriptor:

NOEL

Remarks:

for P generation

Effect level:

79 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Basis for effect: fertility

3

Dose descriptor:

NOEL

Remarks:

for P generation

Effect level:

79 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Basis for effect: maternal

4

Dose descriptor:

NOEL

Remarks:

for F1 generation

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: Bodyweight of the offspring

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

This was a combined repeated dose and reproductive/developmental toxicity test, see also section 7.8.1.

Applicant's summary and conclusion

Conclusions:

Repeat dose toxicity
NOEL: 12.5 mg/kg/day
Reproductive and developmental toxicity
NOEL for P generation: 79 mg/kg/day
NOEL for F1 generation: 500 mg/kg/day