Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:2:p3
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 2 (pt 3/5)
Character Range: 2606265–2609085

(most sensitive) is 0.014 µg/kg/day or 0.000014 mg/kg/day. This intake is negligible in comparison with the adopted TRV of 0.01 mg/kg/day.

On the basis of the above, background intakes of 2,4-D have been assumed to be essentially negligible (where 2,4-D is not used).

2.4              Identification of Toxicity Reference Values

2.4.1         Classification
The International Agency for Research on Cancer (IARC 1987) has classified chlorophenoxy herbicides as Group 2B—possibly carcinogenic to humans.

US EPA has not classified 2,4-D.

2.4.2         Review of Available Values/Information
There is limited information on the assessment of carcinogenicity and genotoxicity for 2,4-D from IARC and US EPA. Ibrahim et al. (1991) provided a summary of a review of carcinogenicity of 2,4-D following review by a panel of 13 scientists. Based on a weight-of-evidence approach 2,4-D was considered unlikely to be a genotoxic carcinogen because it has not been shown to be mutagenic in most in vitro and in vivo systems. The predominant opinion from the panel was that the weight of evidence indicates that it is possible that exposure to 2,4-D may cause cancer in humans.

On the basis of the available information, it is considered appropriate that a threshold dose-response approach be adopted for 2,4-D. The following are available from Level 1 Australian and International sources:
Source              Value                    Basis/Comments
Australian
ADWG (NHMRC 2011)   TDI = 0.01 mg/kg/day     Current ADWG (NHMRC 2011) of 0.03 mg/L based on 10% intake from drinking water. Based on equations presented in the ADWG, the TDI considered in this derivation is equal to 0.009 mg/kg/day, which can be rounded to 0.01 mg/kg/day, essentially equivalent to the ADI available from the OCS.
OCS (2012)          ADI = 0.01 mg/kg/day     The ADI is noted to have been last reviewed in June 2006 and is based on a NOEL of 1 mg/kg/day associated with abnormal renal morphology in a 2-year rat study, supported by the same NOELs (based on kidney effects) in a 2-year mouse and 1-year dog study.
International
WHO (2011)          ADI = 0.01 mg/kg/day     ADI, used in the derivation of the current WHO DWG (2011), was established by JMPR (FAO/WHO 1997) for 2,4-D and its salts and esters on the basis of a NOAEL of 1 mg/kg/day in a 1-year toxicity study in dogs and 2-year study in rats, and an uncertainty factor of 100-fold.
ATSDR               No evaluation available
US EPA (IRIS 2012)  RfD = 0.01 mg/kg/day     US EPA has derived an oral RfD of 0.01 mg/kg/day. The value was last reviewed in 1986 and is derived based on a LOAEL of 1 mg/kg/day associated with abnormal renal morphology from a 90-day rat bioassay and a 1-year interim report from a 2 year rat study, and an uncertainty factor of 100.

Based on the available