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

G. DEVELOPMENTAL TOXICITY
Summary: DDVP, given by oral or inhalation routes, was not teratogenic in rats, mice, or rabbits.
Cholinergic signs (tremors, ataxia, diarrhea, and other effects) were observed in the pregnant rats and
rabbits. Selected studies are presented in Table 13.
Gavage - Rat
DDVP (97% purity; 0, 0.1, 3.0, or 21.0 mg/kg-day) was given to Sprague-Dawley pregnant rats
(25/group) by gavage once daily from gestational days 6 to 15 (Tyl et al., 1991a). Systemic toxicity
was observed only in the high dose group. There was a significant (p @ 0.05) reduction in the
maternal body weight as the mean maternal weight gain was 66% of control value during the
treatment period. Cholinergic signs observed were tremors and excitability. Tremors were observed
in the 21.0 mg/kg-day group with the onset within 10-60 minutes after each daily dosing. Other signs
of toxicity included prone positioning, hindlimb splay, circling, vocalization, hypoactivity, labored
respiration, ear shaking, and coprophagia. Examination of the fetuses showed no significant
increases in the incidence of gestational parameters and of individual or pooled external, visceral,
skeletal, or total fetal malformations or variations. The incidence (18 fetuses/8 litters) of enlarged
lateral ventricles of the cerebrum in the fetuses of the 21.0 mg/kg-day was slightly higher, though not
statistically significant, than that (9 fetuses/5 litters) for the control group. The NOELs were 3.0
mg/kg-day for maternal toxicity and greater than 21.0 mg/kg-day for developmental toxicity. This
study was considered acceptable to DPR according to FIFRA guidelines.
Intraperitoneal - Rat
Pregnant Sherman rats (6/group) were given a single dose of DDVP (purity not stated, 15 mg/kg) by
intraperitoneal injection on day 11 after insemination (Kimbrough and Gaines, 1968). On day 20 of
pregnancy, the fetuses were examined. Of the 41 fetuses examined, omphalocele was noted in 3
fetuses. There were no significant differences in the average weight gain of the dams, average
number of fetuses per litter, average number of resorptions, average weight of fetuses, and average
weight of placenta. The report noted that a dose of 20 mg/kg DDVP was lethal to pregnant rats.
Except for lethality and dam body weights, the report did not include clinical observations.
Inhalation - Rat
Female rats (Carworth Farm E strain, 9-10/treated group) were exposed to DDVP (>97% purity; at
nominal concentrations of 0, 0.25, 1.25, or 6.25 ug/L equivalent to 0, 0.23, 1.15, or 5.75 mg/kg-day)
for 23 hours daily by inhalation (Thorpe et al., 1971a). They were treated from day 1 of insemination
(pregnancy) to gestation day 20. At the end of the experiment, plasma, erythrocyte, and brain ChE
activities of the 1.25 ug/L group were significantly (p