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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study precedes the establishment of, but is similar to, OECD Guideline protocol for the in vivo Micronucleus assay.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.5385 (In Vivo Mammalian Cytogenetics Tests: Bone Marrow Chromosomal Analysis)
Principles of method if other than guideline:
Other: U.S. EPA Health Effects guidelines
EPA Report 560/5-83-001
GLP compliance:
yes
Type of assay:
other: cytogenetics chromosomes aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID 4 Test Substance: as prescribed by 1.1-1.4

98.5% Acetone cyanohydrin. Certificate of Analysis

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
approximates the LD 50 of 17 mg/kg bw, from previous studies with rats.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1.5 & 15mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
6

Results and discussion

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

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Six animals per sex per group were administered ACH at dosages of 1.5 & 15 mg/kg bw, and were sacrificed at 6, 12, 24 and 48 hours
after dosing. Body weights recorded before dosing and at 24 and 48 hr time points. Bone marrow cells were processed
according to the modified techniques described by Evans (1977).

Animals were observed for general appearance, behaviour, toxic and pharmacological effects twice daily or prior to sacrifice. The concentrations tested were approximately to the established LD50 of acetone cyanohydrin in the rat, 17 mg/kg bw, from a previous study to approximate the oral LD50. No gross signs of toxicity were apparent in this study. Acetone cyanohydrin demonstrates a steep dose response curve for acute toxicity with little or no signs of toxicity at sub-lethal doses. There was no statistically significant increase in the frequency of chromosomal aberrations compared withcontrols at any dose level. Acetone cyanohydrin is considered non-clastogenic and non-genotoxic.