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 3/6)
Character Range: 2424334–2427376

used in Australia and while it is persistent, background levels are expected to be low. Dietary intakes are expected to be the most significant background source (ATSDR 2001). Total intakes of PCP (dominated by food intakes) have been estimated to be between 0.1 and 6 µg/day (equal to 1.480 ng/kg/day) (WHO 1987) and 535 µg/day (70500 ng/kg/day) (WHO 2011), though these estimates are based on older data.

ATSDR (2001) notes that intakes estimated from a US total diet survey (19821984) suggested intakes for 2-year-old children were up to 48.5 ng/kg/day (about 0.6 µg/day). Estimates from a later total diet survey (19861991) suggested lower intakes by children aged 2 years of 1.4 ng/kg/day (about 20 ng/day). Intakes from the later study are consistent with background intakes estimated by RIVM (2001). These intakes are essentially negligible compared with the recommended oral TRV. Hence intakes from other sources have been considered to be negligible.

3.4              Identification of Toxicity Reference Values

    3.4.1         Classification
The International Agency for Research on Cancer (IARC 1991) has classified PCP as Group 2B—possibly carcinogenic to humans.

It is also noted that US EPA has classified PCP as Group B2—probable human carcinogen.

    3.4.2         Review of Available Values/Information
Studies on experimental animals have shown some carcinogenic potential associated with oral exposures to technical grade and mixtures of PCP. However PCP has not demonstrated genotoxicity in in vitro and in vivo test systems and in occupationally exposed humans (RIVM 2001 and NHMRC 2010). Review by ATSDR (2001) and IARC (1991) suggests PCP may exhibit weak clastogenic effects.

Review by MfE (2011) suggested that the data on the genotoxicity of PCP is equivocal, with the strongest indication of genotoxicity (chromosomal effects) occurring in assays with rat microsomal protein (S9). The primary rodent metabolite, tetrahydrochloroquinone (TeHQ), is unambiguously genotoxic. TeHQ does not appear to be a major metabolite of PCP in humans. Furthermore, the majority of PCP appears to be excreted unchanged (ATSDR 2001).

On the basis of the available information, it is considered appropriate that a threshold doseresponse approach be adopted for PCP.

Few quantitative toxicity values are available; however the following threshold values are available from Level 1 Australian and International sources:
Source              Value                    Basis/Comments
Australian
ADWG (NHMRC 2011)   TDI = 0.003 mg/kg/day    The current ADWG (NHMRC 2011) has derived a health-based guideline of 0.01 mg/L, based on a TDI of 0.003 mg/kg/day, noted to be based on a NOEL of 3 mg/kg/day from a 2-year rat study, and an uncertainty factor of 1000 (10 for interspecies extrapolation, 10 for intraspecies variability extrapolation and an additional safety factor of 10 due to the limitations of the toxicological data available at the time the ADI was set).
OCS (2012)          No evaluation available
International