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

Acute Toxicity
Inhalation
The critical NOEL for acute inhalation exposure was derived from the two experiments on the
developmental toxicity of rabbits where the does were exposed to DDVP for 23 hours/day (Thorpe et
al., 1971b). The two experiments were considered together to derive the acute NOEL since they were
conducted by the same laboratory with the same protocol. In the first experiment, mortality and
cholinergic signs (16 of 20 does) occurred in the 6.25 ug/L (3.25 mg/kg-day) group after 6 days. The
does were severely intoxicated. In the second experiment, 1 of 20 does in the 2 ug/L (the lowest dose
tested, 1.0 mg/kg-day) group died after 2-3 days. No cholinergic signs were reported. Therefore, the
no effect dose of 1.25 ug/L (0.65 mg/kg-day) from the first experiment may be used as the NOEL with
the LOEL at 2.0 ug/L (1.0 mg/kg-day) determined by the second experiment. These studies were
considered unacceptable to DPR as developmental toxicity studies, but do provide useful information
on acute toxicity. Since there is insufficient information on the potential contribution to the exposure
due to grooming and contamination of food and water by DDVP in the air, the air concentration
provides the only estimate of actual exposure level by inhalation. The adjusted NOEL for risk
assessment was 0.325 mg/kg-day (NOEL of 0.65 mg/kg-day x 0.5) based on a default inhalation
absorption factor of 50% used for worker and residential exposures (Appendix B).
Other acute studies (Table 2) showed rats with mild signs of toxicity (lethargy and pupillary
constriction) after exposure to 90 ug/L for 4 hours (18 mg/kg-day), and the NOEL was 50 ug/L (10
mg/kg-day). Studies conducted with hospital patients showed that exposure to DDVP resin strips for
24 hours resulted in the inhibition of plasma ChE with a NOEL of 0.02 mg/kg-day for men without liver
disease and of 0.014 mg/kg-day for sick children (Cavagna et al., 1969). Since plasma ChE inhibition
is considered an indication of exposure rather than toxicity (USEPA, 1990; Brimijoin, 1992), this study
was not used to determine the critical acute NOEL.
Oral
The critical NOEL for the assessment of acute oral exposure was 0.5 mg/kg-day in the neurotoxicity
studies in rats for cholinergic signs (tremors, salivation, neuromuscular deficits, and others) observed
within 24 hours in both the range finding and definitive studies (Lamb, 1992; and Lamb, 1993a).
In the dog chronic study, soft stools were observed in the first week (Markiewicz, 1990). None were
observed for the control and the 0.05 mg/kg-day group. However, this endpoint was not considered
biologically significant as an acute effect because of the low incidences during the first week and lack
of dose response relationship. In the rat developmental study, the NOEL was 3.0 mg/kg-day for
tremors observed within 10-60 minutes in rats given 21 mg/kg-day by gavage (Tyl et al., 1991a).
Clinical signs were observed in rats 2.5 hours after an oral dose of 21 mg/kg by gavage with a NOEL
of 0.8 mg/kg-day (Cheng 1989 and 1991) or 10-20 minutes after a single dose of 30 mg/kg (Tracy et
al., 1960).
Subchronic toxicity
Inhalation
The critical NOEL for subchronic inhalation toxicity of DDVP was 0.25 ug/L (0.13 mg/kg-day) based on
brain ChE inhibition (Thorpe et al., 1971b). There was a significant (p @ 0.05) and dose-related
inhibition of plasma, erythrocyte, and brain ChE activities in the 1.25 and 6.25 ug/L dams after 29
days of exposure. The inhibition of brain ChE activity was dose-related and statistically significant (p
@ 0.05); and was 44% and 15% of control values for the 1.25 ug/L (0.65 mg/kg-day) and 6.25 ug/L
(3.25 mg/kg-day) groups, respectively. The adjusted NOEL for risk assessment was 0.065 mg/kg-day
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