Registration Dossier

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable publication

Data source

Reference
Reference Type:
publication
Title:
Micronucleus tests in mice on four chrome-containing pigments.
Author:
Odagiri Y et al.
Year:
1989
Bibliographic source:
Jpn J Ind Health 31: 438-439

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Mouse bone marrow micronucleus test
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): chrome Yellow
- Molecular formula (if other than submission substance): PbCrO4
- Analytical purity: not specified
- Impurities (identity and concentrations): not specified

Test animals

Species:
mouse
Strain:
ICL-ICR
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not specified
- Age at study initiation: 9 weeks
- Diet (e.g. ad libitum): basal diet (pellet CE-2, Clea Japan)
- Water (e.g. ad libitum): not specified

ENVIRONMENTAL CONDITIONS
no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: olive oil
- Justification for choice of solvent/vehicle: solubility
- Concentration of test material in vehicle: not specified
Duration of treatment / exposure:
once or 2 days
Frequency of treatment:
once in each 25, 50, 100 and 100 mg/kg bw dose groups and twice in one group receiving 100 mg/kg bw (second treatment 24 hours after the first one)
Post exposure period:
animals were examined 24 hours after the single injection, or 6 hours after the second injection in the multiple treatments
Doses / concentrations
Remarks:
Doses / Concentrations:
25, 50, 100 and 2x 100 mg/kg bw
Basis:
other: actual injected (ip)
No. of animals per sex per dose:
4
Control animals:
yes, concurrent vehicle
Positive control(s):
mitomycin C
- Route of administration: ip
- Doses / concentrations: 2.5 mg/kg bw

Examinations

Tissues and cell types examined:
bone marrow polychromatic erythrocytes (PCEs)
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
maximum tolerated dose and its dilutions

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
for sampling, the animals were killed by cervical dislocation 24 h or 6 h after treatments

DETAILS OF SLIDE PREPARATION:
the bone marrow smear preparations were made according to Schmid (1975), Mutat Res 31: 9-15

METHOD OF ANALYSIS:
1000 PCEs per mouse were examined and the number containing micronuclei was scored.
Statistics:
Statistical analysis was carried out by the binominal distribution test

Results and discussion

Test results
Sex:
female
Genotoxicity:
negative
Remarks:
No significant induction of micronuclei was observed in bone marrow erythrocytes of mice treated with any of the pigments (Table 1). In contrast, the animals treated with sodium dichromate showed a significantly increased number MNPCEs
Toxicity:
no effects
Remarks:
the compounds, ZPC (zinc potassium chromate) and ZTO (zinc tetroxychromate), also examined in the study showed cytotoxicity at the highest dose levels as evidenced by the significant reduction in PCEs frequency.
Vehicle controls validity:
valid
Negative controls validity:
other: some of the chemicals tested also shwon negative results
Positive controls validity:
valid

Any other information on results incl. tables

CONCLUSION:

It is concluded that the negative results in the micronucleus test of chrome yellow and molybdenum red, all of which presented a very low water solubility (1%; as opposed to 6-8% for zinc potassium chromate or to 2380 g/l for sodium dichromate), are likely not reliable, because the treatment with either chemicals did not show evidence for absorption and transport of these compounds to bone marrow, as evidenced by a lack of reduction in PCEs frequency.

Applicant's summary and conclusion