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Toxicological information

Acute Toxicity: inhalation

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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

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2007
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

Reference
Name:
Unnamed
Type:
Constituent

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.