Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:14:p5
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 14 (pt 5/9)
Character Range: 2344214–2347379

factor. The cyanide species is not stated in the guidance provided. Review of the study by NICNAS (2010) and WHO (2004) suggested it was not appropriate as the test animals were experimentally compromised.
NICNAS (2010)                                No ADI recommended                             No ADI or TDI has been recommended. The review has identified that the most reliable repeated dose study available is from NTP (1993) where a NOAEL of 4.5 mg/kg/day was determined (same study as considered in the WHO (2011) review).
International
JECFA (WHO 1965)                             TDI = 0.05 mg/kg/day                           ADI adopted for intakes of cyanide arising from the fumigation of food with HCN. Values derived on the same study as noted by US EPA (IRIS 2012) with consideration of a different uncertainty factor. The value was established in 1965 and has not been replaced.
WHO (2004)                                   No values derived                              Review of hydrogen cyanide and cyanides by WHO indicated a number of limitations with the available data (particularly with respect to chronic assessments) were identified. A chronic inhalation TC could not be derived due to inadequate data.
WHO (2011)                                   TDI = 0.045 mg/kg/day for short term exposure  No drinking water guideline is established by WHO (2011) as cyanide is considered to occur in drinking water at concentrations well below those of health concern.
                                                                                            However WHO has identified that cyanide is highly acutely toxic, where they note the following: 'It is detoxified in the liver by first-pass metabolism following oral exposure. As a consequence, exposure to a dose spread over a longer period, for example through a day, will result in lower toxicity, or higher tolerance, than the same dose given in a single bolus dose. Exposure to high doses can give rise to thyroid toxicity as a secondary effect of exposure due to the inhibition of iodine uptake from the thiocyanate generated through the detoxifying action of rhodanese.' Hence it is appropriate to establish a short-term guideline rather than a chronic guideline. The review has noted data on acute exposures to cyanide is not suitable for the derivation of a short-term guideline due a high level of uncertainty. However a short-term guideline of 0.5 mg/L has been derived on the basis of NOAEL associated with reproductive effects of 4.5 mg/kg/day from a 90-day (13-week) drinking water study in male rats (NTP 1993), and an uncertainty factor of 100.
 DEFRA & EA (2002)                           TDIo = 0.012 mg/kg/day                         TDIo derived on the basis of the former WHO DWG, as currently referenced in the ADWG (NHMRC 2011).
                                             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