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

Mice exposed to DDVP by inhalation also did not show dominant lethal effects. CF-1 mice were
exposed to DDVP (>97% purity; 30 or 55 ug/L) by inhalation for 16 hours (Dean and Thorpe, 1971a).
There was a significant (p @ 0.05) increase in early fetal death only on week 6 of 8 matings of the 30
ug/L group. This effect was not considered to be compound-related since it was not observed in the
other matings, and no other indications of dominant lethal effects were observed. Multiple exposures
to DDVP (>97% purity; 0, 2.1, or 5.8 ug/L) by inhalation at 23 hours per day for 4 weeks also did not
cause any effects (Dean and Thorpe, 1971b). Both of the studies were unacceptable to DPR because
of inadequacies in the protocol and/or report of the data.
ICR male mice (10/group) was given DDVP (98.09% purity; 0, 12.5, 25, or 50 mg/kg-day) by gavage
for 5 consecutive days (Putman and Shadley, 1992). Bone marrow cells and spermatogonial cells
were collected 24 hours after the last dosing. Cyclophosphamide was the positive control. There was
no increase in the number of aberrations in either the bone marrow or spermatogonial cells of DDVP
treated animals. This study was unacceptable to DPR because bone marrow from only one sex was
examined.
DDVP (purity not specified, 10 mg/kg) was given to male mice (Q strain) by a single intraperitoneal
injection (Degraeve et al., 1984a). After a recovery period of 10 to 15 days, there was no increase in
the number of aberrations in the primary spermatocytes. This study was unacceptable to DPR
because the report was incomplete.
DDVP (99% purity, 2 ppm) was given in the drinking water to male mice for 7 weeks (Degraeve et al.,
1984b). No increase in bone marrow or sperm chromosomal aberrations was detected. This study
was unacceptable to DPR because the report was incomplete.
Other Genotoxic Effects
In an in vivo study, B6C3F1 mice were given DDVP (98.4% purity; 0, 3, 10, or 30 mg/kg-day) by
intraperitoneal injection (Microbiological Associates, Inc. 1985). Sister chromatid exchanges were
scored in cells collected 24 hours after treatment. There was no significant increase in the number of
sister chromatid exchanges in cells treated with DDVP compared to the untreated controls. This study
was acceptable to DPR.
DDVP (purity not specified; 0, 6.5, 65, or 650 mM) was added to human epithelial cells in the absence
of rat liver preparation (Aquilina et al., 1984). A positive, concentration-dependent effect for
unscheduled DNA synthesis was detected for all doses. There was also no induction by DDVP (0,
1.25, 2.5, or 5.0 mM) of ouabain resistant mutations in Chinese hamster cells. This study was
unacceptable to DPR because of inadequacies in the protocol and in the report of data.
Mice were exposed to DDVP resin strips for 80 days before mating (Selby et al., 1982). No fetal
skeletal malformation was observed. This study was unacceptable to DPR because of protocol
inadequacies.
No methylation of tissue DNA, an indicator of mutation, was found from rats exposed to DDVP ( 14 C,
92.5% purity, 0.064 ug/L or equivalent to 31 ug/kg) for 12 hours by nose-only inhalation exposure
(Wooder et al., 1977). However, low levels (8 x 10 -13 mole methyl/g DNA) of alkylation of guanine-N-7
were detected in the DNA of pooled organs (liver, kidney, spleen, heart, brain, lung and testes) from
mice given DDVP ( 14 C, 99% purity, 420 ug/kg) by intraperitoneal administration (Segerback, 1981).
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