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

F. REPRODUCTIVE TOXICITY
Summary: Exposure of rats to DDVP during reproduction resulted in the inhibition of plasma,
erythrocyte, and brain ChE. Clinical signs were observed in both parents and offsprings. Other
toxicity included decreased body weights and decreased water consumption. Re-mating of the F 1
females after the F 2 generation showed decreased estrous cycling and increased incidence of
abnormal estrus cycling. Mice exposed to DDVP containing resin strips showed only plasma ChE
depression and no effect on reproduction. A summary of selected studies reviewed is listed in Table
12.
Dietary - Rat
DDVP (93% purity; 0, 0.1, 1.0, 10, 100, or 500 ppm) in the diet was fed daily to CD rats (15/sex/group)
for 3 generations (Witherup et al., 1965). The progenitor rats were dosed for 6 weeks before the first
mating. No compound related effects in fertility, relative number of the progeny in each generation, or
anatomical abnormalities were observed. The NOEL was greater than or equal to 500 ppm. The
dosages were not estimated and body weight data were not included in the report. This study was
unacceptable to DPR according to FIFRA guidelines (the diet was prepared once a week instead of
daily, no individual data or histopathology data).
Drinking water - Rat
In a range-finding study for a two-generation reproductive toxicity study, Sprague-Dawley rats
(10/sex/group) were given DDVP (purity not specified; 0, 20, 80, 200, or 400 ppm) in the drinking
water (Tyl, 1990). The reported mean dosages were 0, 3, 12, 24, and 41 mg/kg-day from days 0 to
14 for both sexes during premating period. During gestation (days 0-20), the reported mean dosages
were 0, 3, 11.3, 22.1, and 47.9 mg/kg-day. During lactation (days 0-21), the mean dosages were 5.2,
17.4, 44.4, and 77.3 mg/kg-day. Cholinergic signs were observed during all stages of reproduction in
the parents and F 1 off-spring. At 400 ppm (48 mg/kg-day), tremors were first observed in the F 0
females on day 7 of premating. At 200 ppm, tremors, rough coat, and lethargy were first observed in
the F 1 off-spring on postnatal day 26. No observations were reported for the 400 ppm pups due to
early sacrifices of moribund pups and high mortality. The plasma, erythrocyte, and brain ChE
activities measured after pre-mating and mating exposure were reduced in a dose-related manner for
all treated groups. At 20 ppm, the plasma, erythrocyte, and brain ChE activities for male-female were
48-66%, 58-61%, and 54-93% of control values, respectively. Body weights, water intake, and food
consumption when measured from premating to lactation were reduced, frequently statistically
significant (p @ 0.05) for the dams in the 200 and 400 ppm groups and the NOEL was 80 ppm (11-17
mg/kg-day for premating to lactation dosages). In addition to cholinergic signs, the food and water
consumption, and average body weights were reduced in the 200 ppm pups. The fetal NOEL was 80
ppm (11 mg/kg-day based on gestation dosages). The recommended doses for the definitive study
were 0, 5, 20, and 80 ppm.
In the definitive study, Sprague-Dawley rats (30/sex/group) were given DDVP (98.1% purity; 0, 5, 20,
or 80 ppm) in the drinking water 24 hours daily (Tyl et al., 1992). The reported dosages for each
group are listed in Table 11. Rats of both sexes were treated for 10 and 11 weeks during the
premating period, respectively, for the F 0 and F 1 animals and were then allowed to mate for 3 weeks.
Selected F 1 offspring were either necropsied or maintained to breed for the F 2 generation.
Cholinesterase activities of the plasma, erythrocyte, and brain were determined after mating for the
males, and after lactation for the females. Because of low reproductive performance, F 1 males were
subjected to detailed reproductive assessment, and the F 1 females were studied for estrous cyclicity
as well as mated with untreated males for the F 2 b generation. Decreased water consumption in both
generations and reduced body weight in the F 1 parents were observed in the 80 ppm group.
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