1-chloro-4-nitrobenzene

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: NTP Reproduction and Fertility Assessment using continuous breeding protocoll with evaluation of fertility of the F1 from the final litter

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study; adopted according to OECD SIDS, peer reviewed data

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

SIDS Initial Assessment Report (SIAR): 1-Chloro-4-nitrobenzene CAS No: 100-00-5

Author:

OECD SIDS

Year:

2003

Bibliographic source:

OECD SIDS, UNEP Publications

Reference 2

Title:

No information

Author:

Chapin R, Gulati D, Mounce R (1997) 4-Chloronitrobenzene.|Environm Health Persp 105 [Suppl.1]: 289-290

Bibliographic source:

(as cited in SIDS)

Reference 3

Title:

No information

Author:

NTP (1991) 4-Chloronitrobenzene Reproduction and Fertility|Assessment in Swiss CD-1|mice when administered via gavage. Final Report, July, 1991

Materials and methods

Principles of method if other than guideline:

Method: other: NTP continuous Breeding Protocol, see also 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:

mouse

Strain:

other: Swiss CD-1

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

Exposure period: see type and remarks
Premating exposure period (males): 7 d
Premating exposure period (females): 7 d
Duration of test: 34 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 62.5, 125 or 250 mg/kg bw/day dissolved in corn oil
Basis:

Control animals:

yes, concurrent vehicle

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Dose descriptor:

other: NOAEL(fertility)

Effect level:

125 mg/kg bw/day

Remarks on result:

other: Generation not specified (migrated information)

2

Dose descriptor:

other: NOAEL (adult general toxicity)

Effect level:

125 mg/kg bw/day

Remarks on result:

other: Generation not specified (migrated information)

3

Dose descriptor:

other: LOAEL (offspring general toxicity)

Effect level:

62.5 mg/kg bw/day

Remarks on result:

other: Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

F0-mice:
mortality: 3,3,1,4 control to high dose, but not evaluated
as treatment related; all groups: body weight gain
throughout the study, reduced water consumption, none of the
mice cyanotic,  high dose: reduced food consumption
F0 fertility:
control, 62.5, 125 mg-pairs:
100 resp. 95 % of the pairs delivered at least four litters 
250 mg-gr.: 100 % of the pairs delivered the 1rst and 93 %
the 2nd litter and only 86 % delivered the 3rd and 79 %
delivered the 4th litter, for the 2nd through the 5th
litters significant dose-dependent decreasing trend of
percent of pairs delivering, proportion of born alive of the
final litter significantly reduced; 
in all groups: average number of live pups per litter was
comparable, sex ratio of pups born alive was not affected
125 mg- and 250 mg-gr.: compared to the control group dam
weights were increased at delivery of the final litter (113%
resp. 110% compared to the control) and 21 days after the
delivery of the final litter (112% resp. 118%). A trend test
was positive. 
F1-pups: 
none of the pups were noted as being cyanotic,
125, 250 mg-gr (male, female and combined), 62.5 mg-gr (male
and combined): reduced live pup weights at birth; 
125, 250 mg-gr.: pup weights adjusted for litter size sign.
reduced, dose-related response, in the final litter of the
continuous breeding phase, the F1 weight gain was adversely
affected
250 mg-gr.: in the final litter of the continuous breeding
phase, the F1 pup survival were adversely affected,
proportion of born pups alive sign. decreased;
F1-adult (control and 250 mg-gr): 
water consumption comparable, at mating most of the 250
mg/kg bw/d group F1 animals  were cyanotic (eyes,skin: blue
tint, urine color: amber); fertility, mating and pregnancy 
indices were comparable, number of live pups delivered by
250 mg-dosed pairs was lower than from conrol pairs, the
proportion of F2 pups born alive and live F2 pups weights at
birth were significantly reduced in the 250 mg-group; 
sperm parameters and vaginal cytology (F1, contr. and 250
mg-gr.):
the average estrous cycle length in the F1 females was
significantly increased whereas epididymal sperm motility,
sperm count and sperm morphology were not affected in the
F1 males by 4-chloronitrobenzene treatment; 
gross pathology, F1, 250 mg-gr.:
in both F1 sexes: at terminal sacrifice, absolute liver
weight and liver-to-body weight ratios were increased and
spleens were extremely enlarged and darkened while body
weights were unchanged; 
in males, absolute seminal vesicle weights were
significantly decreased and seminal vesicle-to-body weight
ratios were similarly affected at 250 mg/kg bw/d; 
there was no evidence of an androgen deficiency lesion in
the testes of 5 high-dose males examined