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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, 1993, by the National Toxicology Program, U.S.A.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
99.9% sodium cyanide. At a buffered pH of about 7, the CN ion from sodium cyanide is present as HCN.

Method

Target gene:
his
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 from liver of CD rat or Syrian hamster treated with Aroclor 1254
Test concentrations with justification for top dose:
0, 1.0, 3.3, 10.0, 33.0, 100.0 and 333.0 micrograms/plate.
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
2-aminoanthracene for metabolic activation positive conrols. Without activation, controls also included 4-nitro-o-phenylenediamine and 9-aminoacridine.
Details on test system and experimental conditions:
Method of Zeiger, et.al., 1992. In the standard NTP protocol (preincubation) for conducting the Ames assay, a test tube containing a suspension of one strain of Salmonella typhimurium (or E. coli) plus S9 mix or plain buffer without S9, is incubated for 20 minutes at 37º C with the test chemical. Control cultures, with all the same ingredients except the test chemical, are also incubated. In addition, positive control cultures are prepared; these contain the particular bacterial tester strain under investigation, the various culture ingredients, and a positive control chemical. After 20 minutes, agar is added to the cultures and the contents of the tubes are thoroughly mixed and poured onto the surface of Petri dishes containing standard bacterial culture medium. The plates are incubated, and bacterial colonies that do not require an excess of supplemental histidine appear and grow.
Evaluation criteria:
according to Zeiger, et.al, 1992.
Statistics:
according to Zeiger, et.al, 1992. Each trial consisted of triplicate plates of concurrent positive and negative controls and of at least 5 doses of sodium cyanide.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
Hydrogen cyanide, sodium cyanide, potassium cyanide and acetone cyanohydrins and plant-derived cyanogenic glycosides are reviewed together because the cyanide anion (CN-) or HCN is the common toxic species of the reviewed substances. As HCN is a relatively weak acid (dissociation
constant Ka ≈ 10–9), most of the cyanide under physiological and environmental conditions (pH ≈ 5 - 8) will be present as HCN. HCN is a clear, volatile liquid or gas. It completely dissolves in water. NaCN and KCN are water soluble, white crystalline solid salts.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

.

Potassium cyanide and sodium cyanide can be considered as a chemical category, along with hydrogen cyanide (HCN) and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, similar physico-chemical properties and common breakdown/metabolic products in physical and biological systems. Particular attention is paid to the dissociation constant of HCN. 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 result from the activity of this common proximal toxicant, 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 this chemical category. 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 potassium cyanide and sodium cyanide to a chemical category does not result in a less protective regulatory status.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative Non-mutagenic

Sodium cyanide is non-mutagenic in Salmonella typhimurium (strains TA97, TA98, TA100 and TA1535) in the Ames Bacterial Reverse Mutation Assay, with and without metabolic activation.
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 potassium cyanide and sodium cyanide to a chemical category does not result in a less protective regulatory status.