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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Documentation suffers from deficiencies mainly because of limited documentation.

Data source

Reference
Reference Type:
publication
Title:
Hygienic standard for 3,4-dichloronitrobenzene vapor in the air of working premises.
Author:
Belyaev VA and Kuznetsov AV
Year:
1969
Bibliographic source:
Hyg Sanit 34: 211 - 214

Materials and methods

Principles of method if other than guideline:
Method: other: see freetext ME
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID4 Test substance: other TS: 1,2-dichloro-4-nitrobenzene, no data on purity but melting point: 43°C

Test animals

Species:
other: rats or mice
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
other: migrated dataset
Vehicle:
other: migrated dataset
Remarks on MMAD:
MMAD / GSD: migrated dataset
Duration of treatment / exposure:
4 months
Frequency of treatment:
4 hrs/d
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.4, 3.6, 10 mg/m3
Basis:

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

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Effect level:
0.4 mg/m³ air
Sex:
not specified
Basis for effect level:
other: based on significant changes in the hematological parameters from 3.6 mg/m³ onwards including methemoglobinemia and Heinz bodies

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
RATS and MICE :
No effects on behaviour and body weights.
RATS and MICE:
Blood counts and biochemical tests revealed significant changes, mainly among animals treated with a concentration of 10 mg/m³
e.g. RATS:
0.4 mg/m3:
no adverse effects were reported;
3.6 mg/m3:
increase in Heinz bodies (up to 7 %) and
reticulocytes (up to 19.6 %); significantly increased activity of liver catalase (35.6 versus 26.5[catalase numbers] of control);
10 mg/m3:
significant changes in blood counts and biochemical tests: decrease in RBC of 10% towards the 18th day of treatment, decreased haemoglobin levels from 15.1g% to 12.2 g%, neutrophilic leucocytosis, pronounced reticulocytosis, increase in Heinz bodies and in methaemoglobin levels (up to 7.6 %);
significantly (sig.) increased activities of serum transaminases (Glutamic-alanine-transa.: 35.4 versus 28.9 [extinction units] of controls; Glutamatic-aspartic-transa.: 141.5 versus 121.8 [extinction units] of controls), sig. liver catalase (47.6 versus 26.5 [cataslase numbers] of controls), sig. liver diaminooxidase (56.8 versus 41.4 [ug/g tissue] of controls), sig. increased levels of bilirubin in blood (6.03 versus 2.0 [mg%] of controls), sig. increased cholesterol level in adrenals (4.7 versus 3.7 [mg/100 g tissue] of controls);
histological examination:
10 mg/m³: morphological changes of the brain (cells with hyperchromic nuclei most commonly in the subcortical ganglia).

Applicant's summary and conclusion

Executive summary:

Inhalation exposure of rats for 4 months against 0.4 to 10 mg/m³ 1,2 -dichloro-4-nitrobenzene yielded a NOAEC of 0.4 mg/m³ based on significant changes in the hematological parameters from 3.6 mg/m³ onwards including methemoglobinemia and Heinz bodies