Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:14:p7
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 14 (pt 7/9)
Character Range: 2349967–2352761

based on a study (Jackson et al. 1986 and Jackson 1988) that has been considered to be deficient, though the NOEL of 1.2 mg/kg/day established is slightly lower than but similar to (in the same order of magnitude) as that established on the NTP (1993) study (noted above).
    * Toxicity reference values established on the basis of the above studies have primarily incorporated uncertainty factors of 100-fold (10 for interspecies variations and 10 for intraspecies variations), with the exception of the US EPA review.
    * The most recent detailed review by US EPA has considered all the available studies, including a range of  end points determined in the NTP (1993) study, Jackson et al. (1988), Kamalu (1993) and more recent study by Manzano et al. (2007). The point of departure from these studies ranged from 0.714.6 mg/kg/day, with the NTP (1993) study identified as the most appropriate for establishing a toxicity reference value. This is consistent with reviews of other organisations.
    * The key difference with the US EPA review (from reviews by other organisations) is the use of a significantly larger uncertainty factor of 3000 (10 for interspecies, 10 for intraspecies, 10 for extrapolating sub-chronic to chronic and 3-fold for database deficiencies). The use of uncertainty factors is based on expert judgement and differs from organisation to organisation. Review by WHO (2011) indicated that the use of a sub-chronic study to establish a short-term guideline is adequately protective of the chronic effects of oral exposures to cyanide. Hence use of the additional 10-fold sub-chronic to chronic uncertainty factor is not considered warranted. Consideration of database deficiencies is relevant as the available studies for cyanide toxicity are limited. Hence use of a factor of 3-fold is appropriate. On this basis, it is reasonable that a 300-fold uncertainty factor be applied to the point of departure from the NTP (1993) study. If the BMDL10 established by the US EPA were considered (1.9 mg/kg/day), this would result in an oral toxicity reference value of 0.006 mg/kg/day. This value is the same as the toxicity reference value adopted in the derivation of the Australian Drinking Water Guidelines of 0.012 mg/kg/day if an additional 2-fold factor were adopted to account for the limitations with the study.
    * Consideration of use of an oral toxicity reference value of 0.006 mg/kg/day results in the derivation of an HIL A value of 200 mg/kg. This value is similar to (20% lower than) the existing HIL A of 250 mg/kg/day. Review of the available information in relation to cyanide does not indicate that the available science supports a change to the existing HIL, Hence the existing HIL A should be retained.
With respect to inhalation exposures to HCN,