Acute Inhalation Toxicity in Quantitative Risk Assessment – Methods and Procedures

In the Netherlands, quantitative risk assessment (QRA) is used for land-use planning purposes for external safety. Under Dutch legislation, the individual risk and societal risk of activities involving hazardous substances must be calculated using a standardized method. One of the effects considered in the QRA method is acute inhalation toxicity. In order to estimate the number of deaths as a result of acute exposure to toxic chemicals, probit functions are used. A lethality probit function describes the lethality rate in an exposed population as a function of any combination of the exposure concentration and exposure duration. Probit functions are derived from animal studies according to a specified method. In 2008, the Dutch Ministry of Environment commissioned a 5-member scientific expert panel, charged with (1) reviewing newly derived or revised probit functions and (2) developing and maintaining robust protocols and criteria necessary to produce these probit functions. After scientific approval by the expert panel, the Ministry will decide whether or not a probit function will be formally implemented for use in QRAs. This decision is primarily based on the results of an analysis of the consequences (in terms of individual and societal risk) of implementation. Between 2008 and 2012, the existing method for derivation of probit functions was thoroughly revised by the expert panel. Major revisions include higher demands on the quality of inhalation toxicological data, and the consideration of data on (non-)lethal effects in humans, if these are available. Since its inception in 2008, the expert panel has reviewed probit functions for 46 substances, including 37 new and 9 revised. As part of the standard procedure, draft probit documents are published for public review before being discussed by the expert panel. On some occasions this has resulted in discussion between the expert panel and third parties. In general, the revised method yields slightly more conservative probit functions than the former method, but the implementation of a revised probit function will have significant consequences in QRAs for a limited number of substances only. As of January 2013, no new or revised probit functions have been formally implemented. However, new probit functions that have been approved by the expert panel are used in QRAs.