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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, TS technical grade

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Principles of method if other than guideline:
Method: other: according to Evans HJ (1976) Cytological methods for detecting chemical mutagens. In: Hollaender A (ed.) Plenum Press, NY and Killian DJ et al. (1977) Handbook of mutagen testing. Elsevier, Amsterdam. see also freetext TC
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID4 Test substance: other TS: technical grade: 85 % 3,4-dichloronitrobenzene and 15 % 2,3-dichloronitrobenzene, assumed purity: 100 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: approximately 50 days
- Weight at study initiation:
- Assigned to test groups randomly: yes
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 69-78
- Humidity (%): 54-76
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
- Purity: 100 %
Details on exposure:
no further details
Duration of treatment / exposure:
single application
Frequency of treatment:
once
Post exposure period:
6, 12, 24, 48 hrs
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 75, 250 or 750 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
24
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide;
- Route of administration: i.p.
- Doses / concentrations: 40 mg/kg

Examinations

Tissues and cell types examined:
bone marrow
Details of tissue and slide preparation:
according to the modified technics described by Evans (1969) and Kilian et al (1977); Giemsa stain
Evaluation criteria:
according to statistical evaluation
Statistics:
Kruskal-Wallis nonparametric analysis of variance nonparametric pairwise group comparison (KW-ANOVA) Analysis of covariance (ANOVA)

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes

Any other information on results incl. tables

    

RS-Freetext:
Clinical observations:
no rat died
all test groups: signs of intoxication included red stains on nose and/or eyes,

depression, soft feces, rough coat and urine stains. The number and severity increased with increased dose
250 or 750 mg/kg bw-group: significantly reduced body weight gain in rats of both sexes 24 and 48 hours post treatment.
cytogenetic analysis:
---modal number: the average number of chromosomes in the examined metaphases was determined for each animal and all test groups and revealed no statistically significant difference between test and control animals.
---mitotic incices( number of cells undergoing mitosis per 500 cells counted) of the test groups compared to vehicle control revealed no statistically significant differences.
---chromosomal aberrations were not statistically significant increased when compared to the vehicle controls.
---the positive control cyclophosphamide was functional.

Applicant's summary and conclusion

Executive summary:

1,2-dichloro-4 -nitrobenzene technical grade showed no clastogenic activity in vivo in a chromosomal aberration test in bone marrow of rats (Monsanto Co 1983)