Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, no restrictions, fully adequate for assessment.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1993
Reference Type:
publication
Title:
2-Chloronitrobenzene
Author:
Chapin R, Gulati D, Grimes L, Barnes L
Year:
1997
Bibliographic source:
Environm. Health Persp. 105 [Suppl 1], p 287
Reference Type:
other: OECD SIDS
Title:
1-Chloro-2-nitrobenzene, CAS: 88-73-3
Author:
OECD SIDS
Year:
2001
Bibliographic source:
SIDS Initial Assessment Report for SIAM 13

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: NTP Continuous Breeding Protocol
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: > 99%

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on mating procedure:
F0:
- Length of cohabitation: 98 days of continious breeding

F1:
Last litter from F0, control and high dose groups were reared, weaned, and kept until mating when achieved sexual maturation.
- M/F ratio per cage: 20/20
- Length of cohabitation: 7 days
- After successful mating each pregnant female was caged (how): singly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
34 weeks
Frequency of treatment:
daily
Details on study schedule:
- F1 parental animals not mated until sexual maturity.
Doses / concentrations
Remarks:
Doses / Concentrations:
40, 80, 160 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
20 pairs/group (test groups)
40 pairs (control group)
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
Clinical signs, body weight gain, water consumption;
F0, F1 males and females: control and 160 mg/kg bw/day group: spleen weight, methemogobin;
F0, F1 males and females: fertility indices;
F1(male): testes,epididymis, F1(female): vaginal cytology
Litter observations:
Clinical signs, body weight gain, water consumption in F1 generation
Postmortem examinations (parental animals):
Control and high dose F1 groups: spleen weight, methaemoglobin
Postmortem examinations (offspring):
Control and high dose F1 groups: spleen weight, methaemoglobin

All F1 males: testes, epididymis
All F1 females: vaginal cytology
Reproductive indices:
Fertility indices

Results and discussion

Results: P0 (first parental animals)

Details on results (P0)

Mortality:
2, 2, 2, 3 from control to high dose group

160 mg/kg bw/day group: increased terminal body weight and spleen weights;

80 mg/kg bw/day group (1 male), 160 mg-group (3 males): hepatocellular degeneration;
160 mg-group: methaemoglobinaemic, during the first 10 days mice were slightly inactive post dosing, 3 lactating females were cyanotic for up to 2 weeks; no other clinical signs.

F0-fertility and reproductive parameters were not affected

Effect levels (P0)

Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
160 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no altered reproductive function

Results: F1 generation

Details on results (F1)

In the final litter of the holding period following the continuous breeding phase, F1 pup weight gain during suckling was lower in all treated groups;
at weaning, F1 pups in the 160 mg/kg bw/d group weighed 10-13% less than controls, all other fertility and reproductive parameters were not affected;

Control and high dose group:
no clinical signs observed,
160 mg/kg bw/day: significantly lowered body weights at weaning but significantly heavier than controls at mating and at terminal necropsy; right epididymis, kidney/adrenals(m), spleen and liver weights increased, seminal vesicle-to-body weight ratio was significantly decreased, significant methaemoglobinaemia; none of the fertility and reproductive parameters examined were affected in F1 mice, i.e., epididymal sperm parameters (motility, count and percentage of abnormal sperms) and estrous cycle length and estrual cyclicity.

Effect levels (F1)

Dose descriptor:
NOAEL
Remarks:
reproduction
Generation:
F1
Effect level:
160 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no altered reproductive function

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion