Dichlorvos (DDVP) Risk Characterization Document - California ...

Potency values were estimated by fitting the Global 86 model to the incidences of pancreatic
adenoma, mononuclear leukemia, and forestomach papilloma or carcinoma identified in the NTP
study (Chan, 1989) and are listed in Table 15 (Appendix E). The potency values estimated from
experimental animals were extrapolated to humans assuming the interspecies dose equivalence
based on the body weight to the 3/4 power (see Equation 4 in Appendix D). Using this assumption, a
factor of 1/4 power of the human-to-animal body weight ratio was applied.
In this document, the theoretical cancer risk associated with the use of DDVP was assessed based on
the incidence of mononuclear cell leukemias found in rats (Chan, 1989). This endpoint was chosen
because it was a systemic effect and the result was statistically significant for both the Trend Test and
the Fisher's Exact Test. The finding of pancreatic adenoma was not used because of the possible
influence of corn oil in the induction and the lack of evidence for malignancy. The finding of
forestomach tumors in mice was also not used in this assessment because the human equivalent
potency factor was 5-fold lower than that for mononuclear cell leukemias in the rat. While there is no
direct counterpart to the rodent forestomach, the human esophagus and possibly the squamous
epithelium at the squamocolumnar junction of the cardiac portion of the stomach may be a site for
either squamous cell carcinoma or adenocarcinoma (Huff, 1992).
Table 15.
The maximum likelihood estimates and 95% upper confidence limit for tumors in
rodents treated with DDVP a .
Maximum
Tumor type likelihood estimate (q 1 ) 95% upper confidence limit (q 1 *)
animal human b animal human b
Pancreatic adenoma 0.097 0.33 0.15 0.52 mg/kg-day -1
Mononuclear leukemia 0.058 0.20 0.10 0.35 mg/kg-day -1
Forestomach papilloma 0.000 0.00 0.011 0.073 mg/kg-day -1
or carcinoma
a/ Data were from Chan, 1989.
b/ The human equivalent q 1 and q 1 * were calculated by (Appendix D Equation 4 for derivation):
q 1 human = q 1 animal x (human body weight/animal body weight) ¼
where the human body weight = 70 kg, rat body weight = 0.5 kg, and
mouse body weight = 0.037 kg.
For example: for pancreatic adenoma: q 1 human = 0.097 x (70/0.5) ¼ = 0.33
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