Hydrogen cyanide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Experimental data was reviewed by the ECETOC Task Force, author of the 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)”, 2007. The report is a weight of evidence approach to an extensive body of literature, much of which was undertaken prior to development of guidelines. The report was peer reviewed by the scientific non-governmental organization (NGO), which judged the data to be reliable with restrictions.

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2007

Reference 2

Reference Type:

review article or handbook

Title:

The toxicity of atmospheres containing hydrocyanic acid gas.

Author:

Barcroft J.

Year:

1931

Bibliographic source:

Journal of Hygiene 31:1-34

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The ECETOC Task Force has explored in depth the relation between inhaled dose (concentration over time, C × t) and mortality, as promoted in revised OECD Guideline No. 403 in 2009. The basic design of these studies was quite similar in that groups of 2 to 10 animals were exposed to a range of concentrations and exposure periods. The Task Force then addressed the relative sensitivity of animals and humans. The primary reference is Barcroft (1931) which, though dated, is the only paper providing directly comparable information on species sensitivity. The results for rats and rabbits were fully comparable between all studies, allowing the Task Force to concluded that the observation of HCN toxicity in other species as reported by Barcroft (1931) is also of sufficient reliability to be used for estimation of the variability of the interspecies sensitivity. According to Barcroft (1931) and McNamara (1976) the sensitivity of humans is comparable to that of monkeys and goats. The LC50 and the LC01 values of this combined group were estimated.

GLP compliance:

no

Remarks:

Study precedes establishment of GLP protocols

Test type:

other: Extrapolation of standard acute toxicity data

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen cyanide

EC Number:

200-821-6

EC Name:

Hydrogen cyanide

Cas Number:

74-90-8

Molecular formula:

CHN

IUPAC Name:

hydrogen cyanide

Test animals

Species:

other: estimates for humans and large animals

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

not specified

Duration of exposure:

ca. 4 h

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 103 mg/m³ air (nominal)

95% CL:

71 - 170

Exp. duration:

4 h

Remarks on result:

other: This LC50 estimate is made for humans, based on data from large animals.

Any other information on results incl. tables

The ECETOC Task Force has explored in depth the relation between inhaled dose (concentration over time, C × t) and mortality, to gain a better understanding of acute inhalation hazard in humans. Special attention was given to the animal studies of Barcroft (1931), Lapin and Mackay (1981) and Ballantyne (1994b). The basic design of these studies was quite similar in that groups of 2 to 10 animals were exposed to a range of concentrations and exposure periods. During an exposure period, the atmospheric concentration was kept broadly constant. The Task Force then addressed the relative sensitivity of animals and humans with a view to deriving C × t dependent estimates of LC50 and LC01 values for humans. Barcroft (1931), though dated, is the only paper providing directly comparable information on species sensitivity. The results for rats and rabbits were fully comparable between all studies. The Task Force concluded that the observation of HCN toxicity in other species as reported by Barcroft (1931) is also of sufficient reliability to be used for estimation of the variability of the interspecies sensitivity. According to Barcroft (1931) and McNamara (1976) the sensitivity of humans is comparable to that of monkeys and goats. On this basis, the Task Force combined the observations on goats and monkeys into one group. The LC50 and the LC01 values of this combined group were estimated. These values are believed be a good estimate of the sensitivity and variability of the acute inhalation toxicity of HCN to humans. The LC50 estimates fit well with accidental and intentional exposure.

Applicant's summary and conclusion

Interpretation of results:

very toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LC50 for humans is estimated from data on large animals, based on the studies of Barcroft, 1931. The value for a 4 hour exposure is 103 mg/m3.