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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
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other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993
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:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
According to OECD Guideline 407, 1981; 12 mice/sex/group and additional 6 mice/sex/group for the interim sacrifice.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
5 weeks
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 50, 500 and 5000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 16, 167, 1120 mg/kg bw/day (males); 0, 24, 220, 1310 mg/kg bw/day (females)
Basis:
actual ingested
No. of animals per sex per dose:
12 mice/sex/dose treated for 5 weeks and an additional 6 mice/sex/dose sacrificed after 1 week of treatment
Control animals:
yes, concurrent no treatment

Results and discussion

Results of examinations

Details on results:
Mortality: no treatment-related mortality (one low-dose male died intercurrently).
Clinical signs: narrowed palpebral fissure and corneal opacity at 5000 ppm in males.
Body weight gain: reduced in both sexes at 5000 ppm.
Food intake: reduced at 5000 ppm(male)/500, 5000 ppm(female).

500/5000 ppm, male/female: centrilobular hepatocytomegaly.
5000 ppm, male/female: increased spleen weight, discolored spleen, deposition of hemosiderin in the spleen; increased liver weight (differences up to 89% were noted in females);
5000 ppm, male: reduced tested weight, decreased urea;
5000 ppm, male/female: reduced erythrocyte count (change in morphology:anisocytosis, poiklocytosis and polychromasie), reduced haematocrit and
haemoglobin, increased MetHb (2.8 % f; 1.7% m), MCV, MCH, MCHC, bilirubin;
500 and 5000 ppm, after 1 week, male/female: increased blood cholesterol, significant changes in the activity of cytochrome 450-dependent EOD (7-Ethoxycoumarin deethylase), EH (Epoxide Hydroxylase) and ALD (Aldrin epoxidase) and Phase II enzymes: GSH-T(Glutathion-S-transferase), GLU-T (UDP-Glucuronyltransferase), and decreased gluconeogenesis and glycogen;
After 5 weeks:
females: normal ALD activity, increased activity of EOR, EH, Glu-T, slight increase in EOD, strong increase in GSH-T activity; m: increased activities of EOD, EOR, GLU-T, ALD,GSH-T, EH.
5000 ppm: increased activity of ASAT, ALAT, alkaline phosphatase(m), activated pentose phosphate cycle, increased glycolysis.
No signs of nephrotoxicity.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 16 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Dose descriptor:
NOAEL
Effect level:
24 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion