1-chloro-2-nitrobenzene

Toxicity to reproduction

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1997

Reference 3

Reference Type:

other: OECD SIDS

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

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 generation)

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