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Toxicological information

Toxicity to reproduction

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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

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2003
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)
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

Constituent 1
Chemical structure
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)

open allclose all
Dose descriptor:
other: NOAEL(fertility)
Effect level:
125 mg/kg bw/day
Remarks on result:
other: Generation not specified (migrated information)
Dose descriptor:
other: NOAEL (adult general toxicity)
Effect level:
125 mg/kg bw/day
Remarks on result:
other: Generation not specified (migrated information)
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

Applicant's summary and conclusion