Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:3:p4
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 3 (pt 4/6)
Character Range: 2427102–2429963

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
WHO (2011)          No threshold value set   The current WHO DWG (2011) has derived a provisional guideline of 0.009 mg/L based on a US NTP study and a linear multistage model associated with tumour increases and an excess lifetime risk of 10-5 (review unchanged since 1993). It is noted that pentachlorophenol is included in the rolling revisions to the DWG, with no revisions currently available.
WHO (1987)          ADI = 0.003 mg/kg/day    References an ADI derived by the National Academy of Sciences which is based on a NOEL of 3 mg/kg/day from a long-term feeding study in rats, and an uncertainty factor of 1000 (same study as considered in the ADWG).
RIVM (2001)         TDI = 0.003 mg/kg/day    TDI based on a LOAEL of 1 mg/kg/day associated with thyroid effects in mink, and an uncertainty factor of 300.
ATSDR (2001)        MRL = 0.001 mg/kg/day    Oral MRL based on a LOAEL of 1 mg/kg/day associated with thyroid effects in mink, and an uncertainty factor of 1000 (same study as considered by RIVM.
US EPA (IRIS 2012)  RfD = 0.005 mg/kg/day    RfD (reviewed in 2010) based on a LOAEL of 1.5 mg/kg/day associated hepatotoxicity, including dose-related increases in incidence and severity of hepatocellular pigmentation, cytoplasmic vacuolation, and chronic inflammation, and significant increases in relative liver weight and increases in absolute liver weight (significant in females), observed in a chronic oral study in dogs (Mecler 1996). An uncertainty factor of 300 was applied. US EPA has also derived a non-threshold oral slope factor not considered relevant here.

While different key studies were considered by the various agencies noted above, use of these studies has largely resulted in the derivation of oral toxicity reference values that are essentially the same (ranging from 0.001 to 0.005 mg/kg/day). Hence the threshold reference value adopted in the ADWG (NHMRC 2011), which is consistent with that derived by all other agencies, including ATSDR, US EPA and RIVM, is recommended.

No dermal or inhalation specific studies or data are available. For the presence of PCP in soil it is considered appropriate to consider use of the available TDI for all pathways of exposures.

    3.4.3         Recommendation
On the basis of the discussion above, the following toxicity reference values (TRVs) have been adopted for PCP in the derivation of HILs:

3.5              Calculated HILs
On the basis of the above, the following HILs have been derived for PCP (refer to Appendix B for equations used to calculate the HILs and Appendix C for calculations):
HIL