Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:6:p3
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 6 (pt 3/5)
Character Range: 2529334–2532292

to adopt for establishing an HIL. The available data (most recently reviewed by WHO 2006) does not suggest that heptachlor is genotoxic and hence a threshold approach is considered appropriate for the derivation of an HIL. Further review of heptachlor by WHO (2006) identified that non-carcinogenic (non-neoplastic) effects were observed at doses 1/20th of those where carcinogenic (neoplastic) effects were observed. Hence, use of a threshold based on non-carcinogenic effects is adequately protective of all effects (including carcinogenicity).

The following are available from Level 1 Australian and International sources:

Source              Value                       Basis/Comments
Australian
ADWG (NHMRC 2011)   ADI = 0.0001 mg/kg/day      ADI referenced from JMPR evaluation (1991) and noted to be based on a NOEL of 0.025 mg/kg/day associated with liver effects from two studies using dogs, and an uncertainty factor of 200 (10 for interspecies variation, 10 for intraspecies variation and 2 for inadequacies in data base).
OCS (2012)          TDI = 0.0005 mg/kg/day      TDI (changed from ADI of same value in 2003) provided as heptachlor no longer in use in Australia. TDI adopted derived from earlier JMPR evaluation (since updated as noted below).
International
JMPR                ADI/PTDI =0.0001 mg/kg/day  An ADI of 0.0005 mg/kg/day was estimated for heptachlor by JMPR in 1970. Review of heptachlor by JMPR in 1991 revised the ADI to 0.0001 mg/kg/day based on the level that caused no toxicological effects in studies in rats and dogs (reproduction study and 2-year dog study, NOEL of 0.025 mg/kg/day, and uncertainty factor of 200). In 1994 the JMPR converted the ADI to a PTDI with the same value.
WHO (2011)          PTDI =0.0001 mg/kg/day      No guideline has been established by WHO as concentrations of heptachlor occur in drinking water well below those of health concern. However the review notes that a health-based value of 0.03 µg/L can be derived on the basis of a provisional TDI of 0.1 µg/kg/day, based on a NOAEL of 0.025 mg/kg/day, and uncertainty factor of 200 (as adopted in the ADWG). The review notes that water concentrations below 0.1 µg/L are generally not achievable.
WHO (2006)          TDI = 0.0001 mg/kg/day      Based on lowest NOAEL of 0.025 mg/kg/day for histopathological liver changes from dog studies and a LOAEL/NOAEL of 0.03 mg/kg/day associated with developmental neurotoxicity and immunotoxicological studies in rats (more recent study than in dogs), and an uncertainty factor of 200.
ATSDR (2007)        No chronic value derived    No chronic MRL was derived, however an intermediate MRL of 0.0001 mg/kg/day was derived on the basis of a LOAEL of 0.03 mg/kg/day associated with developmental immunological and neurological effects in rats (study also considered by WHO 2006), and an uncertainty factor of 300.
US EPA (IRIS 2012)  RfD = 0.0005 mg/kg/day      Oral RfD (last reviewed in 1987) based