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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: peer-reviewed data

Data source

Reference
Reference Type:
other: database
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Standard NTP Protocol for in-vivo toxicology study
Deviations:
no
Principles of method if other than guideline:
The National Toxicology Program, USA (NTP) routinely conducts peripheral blood micronucleus tests on mice that are treated in the 13-week toxicity studies as part of the bioassay program. At the end of the 13-week exposure period (routes of exposure: inhalation, dosed-feed, drinking water, oral gavage, skin painting), a blood sample is obtained from male and female mice in each dose group (usually 10 animals per treatment group per sex) and slides are prepared, fixed and stained as for the bone marrow studies. Sample collection time is typically between 0 (in the case of continuous exposures) and 24 hours (in the case of single daily exposures). 1,000 to 10,000 mature erythrocytes (normochromatic erythrocytes or NCEs) are scored per animal for presence of micronuclei. These mature erythrocytes represent about 95% or more of the circulating erythrocytes. The percent PCE is determined in the blood as a measure of chemical-induced toxicity to the bone marrow. All data are analyzed separately for male and female mice.
The acridine orange staining procedure that is used for micronucleus slides allows the scorer to differentiate between the recently formed, immature erythrocytes (polychromatic or PCE) that are less than 48 hr old, and mature erythrocytes 2-35 days old (normochromatic or NCE) based on their staining characteristics. PCE contain residual RNA and thus they stain differently than the NCE that no longer have residual RNA. MN in PCEs arise from damage that occurred recently (within the past 48 hr) and the NCE population shows the result of damage accumulated over the past month, with the NCE population being in steady state equilibrium in the peripheral blood (newly damaged or undamaged erythrocytes are moving from bone marrow to blood at the same rate as old erythrocytes -- the NCEs-- are being removed from the blood). Thus, for longer-term peripheral blood MN studies, it is usually more appropriate to score MN in the NCE population. The mouse spleen is inefficient in removing damaged erythrocytes from circulation (thus permitting the achievement of steady state), but the rat spleen quickly eliminates micronucleated erythrocytes from circulation. Therefore, only mice can be used in a longer-term peripheral blood MN test that analyzes the NCE population. For acute studies, particularly those in which bone marrow tissue is analyzed, PCEs are scored.
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
five times per week
Post exposure period:
10 to 14 days
No. of animals per sex per dose:
usually 10 animals per treatment group per sex

Examinations

Tissues and cell types examined:
erythrocytes

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Under the conditions employed in the assay described in this report, the data suggest that the test article allyl alcohol shows no genetic toxicity.

Interpretation of results: negative.