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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented and scientifically acceptable - comparable to guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Principles of method if other than guideline:
On each of days 6 to 19 inclusive on pregnancy 25 animals were transferred to exposure chambers and exposed to a an atmosphere of the test material at concentrations of 0, 1, 3, or 9 mg/litre air for 6 hours. All animals were killed on day 20 of pregnancy, 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 distribution 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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: 96.5 %

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

Rats inhaled analyzed o-chlorotoluene concnetrations of 0, 1,100, 3,100, or 9,000 mg/m³ for 
6 hours/day from days 6 to 19 of pregnancy. Animals in the 3,100 mg/m³ group exhibited slight 
ataxia during exposure. Animals in the 9,000 mg/m³ group displayed ataxia, lacrimation and/or 
salivation as well as a brownish discoloration of the fur. Beginning at 3,100 mg/m³, a 
dose-dependent reduction in feed intake and body weight gain was observed, as well as a 
dose-dependent increase in drinking water consumption. No treatment-related effects were seen 
for animals in the 1,100 mg/m³ group. The off-spring of the 1,100 and 3,100 mg/m³ groups did 
not exhibit treatment-related effects. In the 9,000 mg/m³ group, a reduction in fetal and litter 
weights was observed. The incidence of fetal malformations was increased by 6 fetuses 
(distributed among 4 litters), which each exhibited brachdactylia on one of its fore or hind paws. 
5 of these 6 fetuses simultaneously displayed terminal hemorrhaging in the affected paw. In 
correlation to the reduced mean fetal weight, delayed ossification led to an increased occurrence 
of skeletal variations. The incidence of visceral anomalies was unchanged, however.

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 concentrations 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.

Animals in the 3,100 mg/m³ group exhibited slightataxia during exposure. Animals in the 9,000 mg/m³ group displayed ataxia, lacrimation and/orsalivation as well as a brownish discoloration of the fur. Beginning at 3,100 mg/m³, adose-dependent reduction in feed intake and body weight gain was observed, as well as adose-dependent increase in drinking water consumption. No treatment-related effects were seenfor animals in the 1,100 mg/m³ group. The off-spring of the 1,100 and 3,100 mg/m³ groups didnot exhibit treatment-related effects. In the 9,000 mg/m³ group, a reduction in fetal and litterweights was observed. The incidence of fetal malformations was increased by 6 fetuses(distributed among 4 litters), which each exhibited brachdactylia on one of its fore or hind paws.5 of these 6 fetuses simultaneously displayed terminal hemorrhaging in the affected paw. Incorrelation to the reduced mean fetal weight, delayed ossification led to an increased occurenceof skeletal variations. The incidence of visceral anomalies was unchanged, however.

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