Oxalonitrile

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

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: see 'Remark'

Remarks:

While this is not a guideline study, these data are generated by one of the premier experts in the toxicology of cyanides, Dr. Brian Ballantyne, author of "Clinical and Experimental Toxicology of Cyanides", 1987. This data was reviewed by and found to be valid by the ECETOC Task Force on Cyanides, who authored the ECETOC JACC No. 53 report.

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 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2007

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1987

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Installation of single doses of cyanide salt in conjunctival sac

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium cyanide

EC Number:

205-599-4

EC Name:

Sodium cyanide

Cas Number:

143-33-9

Molecular formula:

CNNa

IUPAC Name:

sodium cyanide

Test animals

Species:

rabbit

Sex:

female

Administration / exposure

Route of administration:

other: intraocular

Vehicle:

unchanged (no vehicle)

Details on exposure:

Sodium cyanide was administered into the eye as either a solution or a solid powder.

Control animals:

no

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

5.06 mg/kg bw

95% CL:

> 4.44 - < 6.1

Remarks on result:

other: Solution; equivalent to 0.121 mmol/kg

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

4.47 mg/kg bw

95% CL:

3.47 - 5.93

Remarks on result:

other: Solid; equivalent to 0.090 mmol/kg

Mortality:

Mortality was observed in the LD50 study.

Clinical signs:

Signs include rapid breathing, weak and ataxic movements, convulsions, tonic spasms, irregular and shallow breathing, coma and cessation of breathing.

Body weight:

not applicable.

Gross pathology:

Animals dying after conjunctival instillation of cyanide had high concentrations of cyanide in blood, serum, myocardium, lung and brain, with the highest concentrations being measured in HCN-exposed animals. These results indicate that following instillation into the conjunctival sac, the material is readily absorbed and distributed by the systemic circulation. Cyanide irritation induces a conjunctival hyperaemia, which facilitates the absorption of the material.

Other findings:

The corresponding time to death was 2-3 min. Times to death among all cyanide compounds were 2-12 min post-instillation, with the time being generally longer for NaCN than for hydrogen cyanide.

Any other information on results incl. tables

Additionally, drainage into the nasal cavity may occur through the nasolachrimal duct and allow cyanide to be absorbed across the nasal mucosa. A further determinant of the toxicity of cyanide by contamination of the eye is that material passes intot he systemic circulation without a first-pass hepatic detoxification.

Applicant's summary and conclusion

Conclusions:

Sodium cyanide, when administered as a powder into the conjunctival sac of the eye of the rabbit, results in death with a LD50 of 4.47 mg/kg bw. When administered as a NaCN solution, it has an LD50 of 5.06 mg/kg bw.