Oxalonitrile

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

read-across based on grouping of substances (category approach)

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.

Justification for type of information:

Ethanedinitrile, hydrogen cyanide (HCN), potassium cyanide and sodium cyanide can be considered as a chemical category, along with and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, common breakdown/metabolic products in physical and biological systems, and similar physico-chemical properties. Particular attention is paid to the dissociation constant of HCN. Ethanedinitrile breaks down in aqueous solution into cyanide ion (CN-) and cyanate ion (OCN-) (Cotton and Wilkinson 1980). Ethanedinitrile due to its low log Kow (0.07) and relatively high solubility in water (2.34 g/L) needs to get dissolved in aqueous solutions in lungs to enter the body. The rate of hydrolysis of ethanedinitrile is very fast (Ajwa 2015). Also, in the vast majority of environmental and physiologic conditions, the cyanide salts will dissolve in water to form hydrogen cyanide. The physico-chemical hazards and toxicity therefore result from the activity of HCN. An ECETOC Task Force, in the 2007 ECETOC Joint Assessment of Commodity Chemicals (JACC) Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)” supports the development of the chemical category inclusive hydrogen cyanide, sodium and potassium cyanides. Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI, Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of ethanedinitrile to a chemical category does not result in a less protective regulatory status.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1984

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)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

acetone cyanohydrin

Cas Number:

75-86-5

Molecular formula:

(CH3)2C(OH)CN

IUPAC Name:

acetone cyanohydrin

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Details on exposure:

approximates the LD 50 of 17 mg/kg bw, from previous studies with rats.

Duration of treatment / exposure:

single dose

Frequency of treatment:

single dose

Post exposure period:

6, 12, and 24h post-administration

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1.5 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

5 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

15 mg/kg bw/day (nominal)

No. of animals per sex per dose:

24 male
24 female

Control animals:

yes

Examinations

Tissues and cell types examined:

bone marrow cells

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Additional information on results:

No statistically significant increases in the frequency of chromosomal aberrations or changes in mitotic index compared with control values were found in bone marrow cells from four groups of 24 male and 24 female Sprague-Dawley rats administered a single dose of acetone cyanhydrin by oral gavage at levels of 0, 1.5, 5, or 15 mg/kg body weight with preparation intervals of 6, 12, and 24h post-administration.

Applicant's summary and conclusion

Conclusions:

No statistically significant increases in the frequency of chromosomal aberrations or changes in mitotic index compared with control values were found in bone marrow cells from four groups of 24 male and 24 female Sprague-Dawley rats administered a single dose of acetone cyanhydrin by oral gavage at levels of 0, 1.5, 5, or 15 mg/kg body weight with preparation intervals of 6, 12, and 24h post-administration.

Executive summary:

No statistically significant increases in the frequency of chromosomal aberrations or changes in mitotic index compared with control values were found in bone marrow cells from four groups of 24 male and 24 female Sprague-Dawley rats administered a single dose of acetone cyanhydrin by oral gavage at levels of 0, 1.5, 5, or 15 mg/kg body weight with preparation intervals of 6, 12, and 24h post-administration.