1-chloro-4-nitrobenzene

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: adopted according to OECD SIDS, peer reviewed data

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2003

Reference 2

Reference Type:

study report

Title:

Unnamed

Reference 3

Reference Type:

publication

Title:

No information

Author:

Nair RS, Johannsen FR, Schroeder RE (1985) Evaluation of|Teratogenic Potential of Para-Nitroaniline and|Para-Nitrochlorobenzene in Rats and Rabbits. In: Toxicity of|Nitroaromatic Compounds (Rickert, D.E. ed.): pp. 61-85,|Hemisphere Publishing Corporation, New York

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

Method: other: according to OECD Guide-line 414: 24 mated rats per group, see also freetoxt ME

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-4-nitrobenzene

EC Number:

202-809-6

EC Name:

1-chloro-4-nitrobenzene

Cas Number:

100-00-5

Molecular formula:

C6H4ClNO2

IUPAC Name:

1-chloro-4-nitrobenzene

Details on test material:

- Name of test material (as cited in study report): 1-chloro-4-nitrobenzene
- Analytical purity: > 99 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

days 6-19 of gestation

Frequency of treatment:

daily

Control animals:

yes, concurrent vehicle

Details on study design:

Sex: female

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

LOAEL

Effect level:

ca. 5 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

ca. 15 mg/kg bw/day

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

Maternal data:
Pregnancy rates were similar between the groups. No
mortality occurred in the control or treated groups during
d6-20. Terminal body weight and body weight gain (d6-20) was
comparable between control, low-  and mid-dose females, but
sign. reduced in high-dose females (71 g versus 118 g of
controls). Several high-dose females were reported to have
pale eye color during dosing interval. Comparable between
control, low-  mid- and high-dose groups were the mean
numbers of implantations (13.3,13.9,14.1,13.6), but mean
number of resorptions were sign. increased in the high-dose
group: 5.6 versus 0.5 in controls and mean number of live
fetuses were significant decreased (8.0 versus 12.8 in
controls) in this dose-group, 7/22 high-dose females (31.8%)
had uterine implantation sites comprised entirely  of
resorption sites. 
Maternal gross postmortem observations: mean spleen weights
sign. higher than control in each treated group, mean spleen
to body weight ratio higher in all treated groups, sign. in
the mid- and high-dose group (dose-related increase), from
low-dose onwards significant  dose-dependent lesions of the
spleen: enlargement (up to 4 x normal size in high-dosed
females), dark coloration and/or pitted surface.
Fetal data: 
The mean number of male and female fetuses and mean fetal
weights were comparable between the control, low- and
mid-dose groups. In the high dose group, the mean number of
male and female fetuses (male: 4.2 versus 6.2 in control,
female 3.8 versus 5.5 in contr.) and the respective mean
weights (male: 3.33 g versus 3.95 g, female: 3.11 g versus
3.76 g in contr.) were markedly lowered. In this dose-group
the incidence of ossification variations (i.e.,
assymetrical/unossified sternebrae, incompletely ossified
cervical vertebral transverse processes, rudimentary
structures) was sign. increased when compared to controls
(95.7 % versus 85.5 % in contr.). 
Fetal evaluations at low- and mid-dose levels did not reveal
a teratogenic response. At high-dose level, a significant
increase in the incidence of skeletal malformations (30.4 %
versus 1.3 % in controls), predominantly angulated ribs
alone or associated with misshapen and/or shortend bones of
the forelimbs (i.e. humerus, radius, ulna) was noted.