Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:3:p3
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 3 (pt 3/5)
Character Range: 2494201–2497106

Review of Available Values/Information
As chlordane has been banned from use in a number of countries, there are few recent studies/reviews available. Review of chlordane by the European Food Safety Committee (EFSA 2007) provided a review of long-term toxicity studies, carcinogenicity and genotoxicity for chlordane. Long-term oral studies with the nervous system and liver were shown to be the most significant target organs. Data on genotoxicity is limited and conflicting, however overall chlordane was not mutagenic in vivo and not or only weakly mutagenic in a few tests in vitro. On the basis of the weight of evidence, chlordane is not considered to be genotoxic. Chlordane causes liver tumours in mice via a non-genotoxic mechanism and is classified by IARC as possibly carcinogenic to humans.

On the basis of the available information, it is considered appropriate that a threshold doseresponse approach be adopted for chlordane. The following are available from Level 1 Australian and International sources:

Source              Value                           Basis/Comments
Australian
ADWG (NHMRC 2011)   ADI = 0.00045 mg/kg/day         Current ADWG (NHMRC 2011) of 0.001 mg/L based on 10% intake from drinking water, a NOEL of 0.045 mg/kg/day based on a long-term (30 week) dietary study in rats, and a 100-fold uncertainty factor. This is consistent with the PTDI used in the current WHO DWG, as well as OCS (2012).
OCS (2012)          TDI = 0.0005 mg/kg/day          TDI was set in 2003, no study referenced. This value is noted to be based on the JMPR evaluation from 1994. The TDI is noted to be retained for comparison against dietary intakes only as these compounds are no longer used in agricultural practice. The TDI listed is also adopted by FSANZ.
International
WHO (2011)          PTDI = 0.0005 mg/kg/day         Provisional TDI based on a NOAEL of 0.05 mg/kg/day for increased liver weights, serum bilirubin levels and hepatocellular swelling from a long term study in rats (same study as considered in the ADWG), and a 100-fold uncertainty factor.
ATSDR (1994)        Oral MRL = 0.0006 mg/kg/day     Chronic oral MRL based on liver hypertrophy in a 30-month rat study.
                    Inhalation MRL = 0.00002 mg/m3  Chronic inhalation MRL based on hepatic effects in a 90-day subchronic rat study. The study used to derive the inhalation MRL is the same as that used by the US EPA in the derivation of the RfC. The application of uncertainty factors differs between the organisations.
US EPA (IRIS 2012)  RfD = 0.0005 mg/kg/day          Oral RfD based on a NOAEL of 0.15 mg/kg/day associated with hepatic necrosis in a 104-week mouse study, and 300-fold uncertainty factor.
                    RfC = 0.0007 mg/m3              RfC based on hepatic effects in a subchronic rat inhalation study. The evaluation was last reviewed in 1998. In addition, US EPA has also derived