Hydrogen cyanide

Genetic toxicity: in vivo

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

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

Test material information

Constituent 1

Reference substance name:

2-hydroxy-2-methylpropionitrile

EC Number:

200-909-4

EC Name:

2-hydroxy-2-methylpropionitrile

Cas Number:

75-86-5

Molecular formula:

C4H7NO

IUPAC Name:

2-hydroxy-2-methylpropanenitrile

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.