4-chlorotoluene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: secondary literature - comparable to guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

On each of days 6 to 19 inclusive on preganancy 25 animals were transferred to exposure chambers and exposed to a an atmosphere of the test material at concnetrations of 0, 1, 3, or 9 mg/litre air for 6 hours. All animals were killed on day 20 of preganancy, dissected and examined for abnormalities and changes in maternal organs. The ovaries and uteri were examined to determine number of corpora lutea, number of distribution of live young, number and ditribution of embryonic/foetal deaths, individual foetal weight, gross foetal abnormalities. half of the pups in each litter were preserved for subsequent sectioning to discover visceral abnormalities; the remainder were fixed for skeletal examination.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-chlorotoluene

EC Number:

202-424-3

EC Name:

2-chlorotoluene

Cas Number:

95-49-8

Molecular formula:

C7H7Cl

IUPAC Name:

1-chloro-2-methylbenzene

Details on test material:

purity: 96.5 % o-chlorotoluene, 3.4 % p-chlorotoluene, 0.1 % toluene

Test animals

Species:

rat

Strain:

other: CrL : COBS CD (SD) BR

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

not applicable

Duration of treatment / exposure:

days 6-19 of gestation

Frequency of treatment:

6 h/d

Duration of test:

days 6-19 of gestation

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1.1, 3.1 or 9.0 mg/l
Basis:
analytical conc.

No. of animals per sex per dose:

25

Control animals:

yes, concurrent no treatment

Details on study design:

Sex: female
Duration of test: on day 20 of gestation the dams were killed

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEC

Effect level:

1.1 mg/L air

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Effect levels (fetuses)

Dose descriptor:

NOAEC

Effect level:

3.1 mg/L air

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

1.1 mg/l: 
no maternal effects being obviously attributable to treatment
fetal effects:  4 malformed fetus compared to 3 in the control group. One showing brachygnathia, one showing retro-oesophageal aortic arch, one showing cardiac ventricular septal defect and one showing brachydactyly  and bachymelia of all four limbs. The last malformation was similiar   with the observed  malformation of six fetuses at 9 mg/l
3.1 mg/l: maternal effects: slight ataxia observable during the exposure periods
fetal effects: no notable or significant deviations from control values  among litter parameters and among indices of malformations, anomalies and  skeletal variants of the offspring   
3.1 and 9 mg/l: maternal effects: dosage-related reduction in food consumption and in bodyweight gain and dosage-related increase in  water consumption
9 mg/l: maternal effects: ataxia, lachrymation and/or salivation among occasional animals during exposure, and brown
fur staining; 
fetal effects: mean values for litter and mean fetal weight
significantly reduced; increase in the incidence of fetal
malformations mainly due to the occurrence of six fetuses
(distributed among four litters) showing brachydactyly of a
single fore- or hindpaw; for five of the 6 fetuses the
brachydactyly was associated with a terminal haemorrhagic
area on the affected paw; 3 other malformations (1 microphthalmia,1  anophthalmia amd 1 cardiac ventricular septal defect); correlating with  the lower mean fetal weight, reduced skeletal ossification observable,
providing an increased incidence of fetuses with sternebral variants and contributing to a significant increase in fetuses with skeletal anomaly; incidence of visceral anomalies unaffected

Applicant's summary and conclusion

Executive summary:

On each of days 6 to 19 inclusive on preganancy 25 animals were transferred to exposure chambers and exposed to a an atmosphere of the test material at concnetrations of 0, 1, 3, or 9 mg/litre air for 6 hours. All animals were killed on day 20 of preganancy, dissected and examined for abnormalities and changes in maternal organs. The ovaries and uteri were examined to determine number of corpora lutea, number of distribution of live young, number and ditribution of embryonic/foetal deaths, individual foetal weight, gross foetal abnormalities. half of the pups in each litter were preserved for subsequent sectioning to discover visceral abnormalities; the remainder were fixed for skeletal examination.

The NOAEL for maternal toxicity is 1.1 mg/litre, the NOAEL for teratogenicity is 3.1 mg/litre.