1-chloro-2-nitrobenzene

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-2-nitrobenzene

EC Number:

201-854-9

EC Name:

1-chloro-2-nitrobenzene

Cas Number:

88-73-3

Molecular formula:

C6H4ClNO2

IUPAC Name:

1-chloro-2-nitrobenzene

Details on test material:

- Name of test material (as cited in study report): 1-chloro-2-nitrobenzene
- Physical state: solid
- Analytical purity: 99.7 %
- Purity test date: 1991-08-03
- Lot/batch No.: 039675-00
- Source: OC-P / UA, Bayer AG

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

5 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 500, 5000 ppm (calc. intake: (m):0,16,167,1120 mg/kg bw; (f):0,24,220,1310 mg/kg bw)
Basis:

No. of animals per sex per dose:

12 mice/sex/group and additional 6 mice/sex/group for the interim sacrifice

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: no

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

ca. 50 ppm

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

except one male in the low dose group no deaths,
5000 ppm(m)/500, 5000 ppm(f): reduced food intake, 
sign. clin. findings only in the male 5000 ppm gr.: narrowed
palpebral fissure and corneal opacity;
500/5000 ppm, m/f: centrilobular hepatocytomegaly
5000 ppm, m/f: reduced body weight gain, increased spleen
weight, discolored spleen, deposition of hemosiderin in the
spleen; increased liver weight (differences up to 89% were
noted in females)
5000 ppm,m: reduced tested weight, decreased urea;

5000 ppm, m/f: 
reduced erythrocyte count(change in morphology:
anisocytosis, poiklocytosis and polychromasie), reduced HK-
and HB-content, increased MetHb (2.8 % f; 1.7% m), MCV, MCH,
MCHC, bilirubin, 

500 and 5000 ppm, 
after 1 week,  m/f:
increased cholesterin content, sign. 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: 
f: 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