[No public or meaningful name is available]

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study and GLP

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

1,4-Dichloro-2-nitrobenzene: Preliminary Reproductive/Developmental toxicity study

Author:

MHLW (Ministry of Health, Labour and Welfare)

Year:

1996

Bibliographic source:

Chemical Investigation Promotion Council Vol 3. 111-115, 117-127, 470-473

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 421

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dichloro-2-nitrobenzene

EC Number:

201-923-3

EC Name:

1,4-dichloro-2-nitrobenzene

Cas Number:

89-61-2

Molecular formula:

C6H3Cl2NO2

IUPAC Name:

1,4-dichloro-2-nitrobenzene

Test material form:

other: solid

Details on test material:

content: > 99.5 %

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Details on test animals or test system and environmental conditions:

standart conditions

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

The test substance was administered in graduated doses to several groups of males and females. males are dosed during two weeks before mating; females of the parenteral generation are dosed for two weeks; then the animals are mated and the test substance is administered to both sexes throughout the mating.period and pregnancy and up to day 4 of lactation when all aninals including offspring are killed

Details on analytical verification of doses or concentrations:

no details

Details on mating procedure:

1.1 (one male to one female)

Duration of treatment / exposure:

52 days

Frequency of treatment:

once daily

Duration of test:

52 days

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

for general toxicity see section 7.5.1
oestrous cyclicity and reproductive performace was determined
copulation index, fertility index, implantation index, gestation index, delivery index, live birth index

Ovaries and uterine content:

no

Fetal examinations:

viability index, external anomalies

Statistics:

yes when appropriate

Indices:

copulation index, fertility index, implantation index, gestation index, delivery index, live birth index, viability index,

Historical control data:

no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
oestrous cyclicity was not disturbed, Copulation index was not impaired,
fertility index was not affected
no relevant difference to controls was shown in implantation index, ingestation index, in delivery index, live birth index
however:
one dam receiving 60 mg/kg bw delivered only dead pups
in the 200 mg/kg bw group,
one dam died on day 20 of pregnancy, one during the delivery period and 4 during the lactaion period
lack of care behavior in 7 dams
at 60 mg/kg and more
dams are affected during the perinatal perieod by the test substance (no further details)

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

20 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

60 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
With the pups of the 200 mg/kg bw/day group, reduced body weight values were obtained for both sexes on days 0 and 4 of lactation and the indication that the test substance affected the growth of the newborn pups at 200 mg/kg bw/day, No external malformations were seen

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

1,4- Dichloro-2 -nitrobenzene was studied for its oral toxicity in rats in an OECD preliminary reproduction toxicity screening test at doses of 0, 6, 20, 60. and 200 mg/kg bw/day. Based on general toxic effects the NOAEL was 60 mg/kg bw/day. With the pups of the 200 mg/kg bw/day group, reduced body weight values were obtained for both sexes on days 0 and 4 of lactation and the indication that the test substance affected the growth of the newborn pups at 200 mg/kg bw/day the NOAEL for development of pups in terms of reprocuctive developmental toxicological effects is considered to be 60 mg/kg bw/day