Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:14:p6
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 14 (pt 6/9)
Character Range: 2347089–2350188

TDIi = 0.0009 mg/kg/day (=0.003 mg/m3)         TDIi derived on the same basis as the current US EPA RfC (with different uncertainty factors).
RIVM (2001)                                  TDI = 0.05 mg/kg/day                           TDI was derived on the basis of a NOAEL of 4.5 mg/kg/day associated with male reproductive effects from a 90-day rat study with well-soluble NaCN salt (which forms free cyanide readily after ingestion), and a 100-fold uncertainty factor (as considered by WHO 2011). This is rounded to the TDI of 0.05 mg/kg/day.
                                             TC = 0.025 mg/m3                               TC was derived on the basis of a LOAEL (HEC) of 2.5 mg/m3 based on critical effects to the CNS and thyroid in an occupational study of HCN, and a 100-fold uncertainty factor (same study as considered by US EPA).
ATSDR (2006)                                 No chronic MRL                                 Intermediate MRL (exposures up to 1 year) based on same study and approach considered by WHO (2011).
                                             Intermediate MRL = 0.05 mg/kg/day
OEHHA                                        RfC = 0.009 mg/m3                              Value based on same study considered by US EPA with consideration of a 300-fold uncertainty factor (less than adopted by US EPA).
US EPA (2010)                                RfD = 0.0006 mg/kg/day                         RfD based a point of departure (BMDL10) of 1.9 mg/kg/day from a 13-week drinking water study in male rats (NTP 1993) and a 3000-fold uncertainty factor.
                                             RfC = 0.0008 mg/m3                             RfC based on a LOAEL (HEC) of 2.5 mg/kg/day based on CNS and thyroid effects in an occupational study (1975) of HCN and application of a 3000-fold uncertainty factor.

In relation to the evaluations presented above for the assessment of oral exposures, the following can be noted:
    * There are few good oral studies available for the assessment of chronic effects of exposure to cyanide.
    * WHO evaluation considered that, in relation to cyanide exposures and toxicity, it is more relevant to establish a guideline for short-term exposures rather than chronic exposures. Hence the guideline established, from a NOAEL of 4.5 mg/kg/day from the NTP (1993) study was considered relevant to short-term exposures (rather than chronic exposures). The same key study has been considered as the most reliable repeated dose study by NICNAS, RIVM, ATSDR and US EPA, where the NOAEL has been used to derive short-term and chronic toxicity reference values. It is noted that the US EPA review has established a BMDL10 of 1.9 mg/kg/day from the study, rather than use the NOAEL.
    * The study considered in the derivation of the Australian Drinking Water Guideline (also adopted by the UK review), is 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