2,4-dichlorotoluene

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on generations indicated in Effect levels (migrated information)

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

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

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 12.5, 79, 500 mg/kg/day
Basis:
nominal in water

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Increased salivation occurred in the group with 500 mg/kg bw/day. This effect was observed only in females.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

Group with 500 mg/kg bw/day: Only 5/12 females became pregnant. It is unclear whether the decreased fertility is caused by the male or the female.

Effect levels (P0)

1

Dose descriptor:

NOEL

Effect level:

12.5 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: repeated dose toxicity

2

Dose descriptor:

NOEL

Effect level:

79 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Basis for effect: fertility

3

Dose descriptor:

NOEL

Effect level:

79 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Basis for effect: maternal

Results: F1 generation

General toxicity (F1)

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Bodyweight of the offspring was reduced on the day of the birth and on the fourth day after the birth (group with 500 mg/kg/day)

Effect levels (F1)

Dose descriptor:

NOEL

Generation:

F1

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: Basis for effect: Bodyweight of the offspring

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOEL for reproductive/ developmental toxicity for both sexes was considered to be 79 mg/kg/day.

Executive summary:

2,4-Dichlorotoluene was studied for oral toxicity in rats according to the OECD combined repeated dose and reproductive/developmental toxicity test [OECD TG 422] at doses of 0, 12.5, 79, 500 mg/kg/day.

Although this combined study was designed to investigate reproductive capability in parental generation as well as development in F1offspring, parameters to evaluate developmental toxicity were limited to only body weights at day 0 and day 4 after birth, and autopsy findings at day 4. Regarding reproductive ability, all pairs in the 12.5 and 79 mg/kg groups achieved pregnancy. In the 500 mg/kg group, 12 pairs showed evidence of copulation with a sperm positive vaginal smear, however, only 5 pairs out of them achieved pregnancy. In six non-pregnant pairs in the 500 mg/kg group, vaginal plugs were not noted or a few sperm were found in the vaginal smears. This result suggests that the male reproductive organs and secondary reproductive organs had functional disorders. Regarding body weight changes of pups, decreases in liver and body weights were noted in the 500 mg/kg group on day 1 of lactation. For delivery or lactating behaviour of dams, viability, general appearance or autopsy of pups, no effects related to the administration of this chemical was noted. On the basis of above-described effects, the NOEL for reproductive/ developmental toxicity for both sexes was considered to be 79 mg/kg/day.

This was a combined repeated dose and reproductive/developmental toxicity test, see also section 7.5.1.