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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with minor deviations. (No positive control.)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
No positive control.
Qualifier:
according to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Qualifier:
according to
Guideline:
EPA OPP 84-2
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ziram technical
- Lot no.: 8331 AA
- Purity: 98.8%

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River, USA
- Age at study initiation: 5-6 weeks
- Weight at study initiation: no data

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
89 days
Frequency of treatment:
daily
Post exposure period:
none
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 25, 75, 225 and 675 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes, plain diet

Examinations

Tissues and cell types examined:
Peripheral blood
Details of tissue and slide preparation:
Peripheral blood smears were prepared from 5 male and 5 female animals in each group. The smears were stained using Giemsa then examined by light microscopy for the presence of micronuclei in normochromatic and polychromatic erythrocytes (1000 cells of each type were examined from each animal). The ratio of polychromatic to normochromatic erythrocytes was assessed by examination of at least 1000 erythrocytes from each animal.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined

Any other information on results incl. tables

Dose level [ppm]

Ration p/n (mean)

Incidence mnp (mean)

Incidence mnn (mean)

Control

0.108

0.9

1.1

25*

0.143

0.6

1.7

75**

0.124

1.2

2.0

225

0.095

0.8

0.7

675

0.135

0.5

1.2

p/n Ratio of polychromatic to normochromatic erythrocytes

mnp No. of micronucleated cells observed per 1000 polychromatic erythrocytes

mnn No. of micronucleated cells observed per 1000 normochromatic erythrocytes

* Prepared at 29 ppm initially to allow for loss during storage

** Prepared at 83 ppm initially to allow for loss during storage

Applicant's summary and conclusion