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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
adopted according to OECD SIDS, peer reviewed data

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2003
Reference Type:
study report
Title:
Unnamed
Year:
1981

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
no
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: 99.12 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
90 d
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 3, 10 or 30 mg/kg bw/day dissolved in corn oil
Basis:

Control animals:
yes
Details on study design:
Post-exposure period: no data

Examinations

Statistics:
Dunnett's and Bartlett's test,modified Mann-Witney test(Bonferroni inequality), Kolmogorov-Smirnov one-tailed test

Results and discussion

Effect levels

Dose descriptor:
LOAEL
Effect level:
ca. 3 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other:  increased methemoglobin levels

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

one control female died due to physical trauma during dosing.

clinical observation: 30 mg-group, males and females, 10 mg-group, females: general paleness immediately after dosing, no statistically significant differences in body weight gain when compared to control rats, food consumption was sign. higher: females: mid dose, 1 of 13 w, high dose, 5 of 13 w, males: mid dose, 9 of 13 w, high dose, 10 of 13 w hematological changes:  significant increased methemoglobin levels at 3, 10, 30 mg/kg bw: male/female: day 45: 4.2/4.6, 7.8/9.2, 15.0/18.1 %, resp., versus 0.5/0.9 % of controls and day 90: 4.5/4.9, 9.0/9.8, 14.2/18.2 % resp., versus 0.9/1.0 % in controls;
dose-related increase in WBC in males and females (d 45): up to 44.21 % versus 11.67 %(control), (d 90): up to 12.95 %
(control 10.24 %); dose related increase in reticulocyte count in males and females: (d 90): up to 39.8 % versus 0.6
% in controls, and in MCV, MCH values in males and females; significant dose related decrease in erythrocyte count
(d45): up to 5.51 versus 8.49 (control),(d 90): up to 5.58  versus 9.07 in controls, in HGB up to 14.45 % versus 18.78 %
in controls and in HCT, and MCHC values in males and females clinical chemistry: total protein sign. reduced with increasing dosing d45: females 10 and 30 mg/kg bw; d90: males 10 and 30 mg/kg bw 
and SGPT reduced: males 30 mg/kg bw

urinalysis: At week 13 (= d 90) qualitative increases in levels of
urinary urobilinogen were found in all male and female rats receiving TS.
gross and histopathology:
spleen:  (both sexes, all dosages, dose dependent in incidence and severity): abnormal coloration, enlargement 
increased relative and/or absolute spleen weights, excessive hemosiderin, excessive hemopoiesis, congestion,
vacuolization of the congested red pulp liver: male and female, 30 mg: enlargement, hemosiderosis
and excessive hemopoiesis kidneys: both sexes, dose-dependent: discoloration,
enlargement, hemosiderosis in kidney tubules 30 mg-group: enlargement of the hearts in females, in both
sexes: hyperplasia of bone marrow

Applicant's summary and conclusion