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

hematocrit) in rats. From studies with lactating rats and milk cows after oral subchronic dosing, ChE
activity depression and cholinergic signs were noted in the dams, but not in the offspring.
Chronic Toxicity and Oncogenicity- DDVP caused the inhibition of plasma, erythrocyte, and brain
ChE activities. Other non-oncogenic effects included hepatocellular lesions (vacuoles in the
cytoplasm, cell swelling, prominence of cell membranes), reduced body weight, emesis, salivation,
and ataxia. Oncogenic effects observed in rats and mice were pancreatic adenoma; mononuclear
leukemia; mammary gland carcinoma, fibroadenoma, and adenoma; forestomach papillomas and
carcinomas; and pituitary adenomas. DDVP also increased tumor growth rate in rats given leukemia
transplant.
Genotoxicity- DDVP was genotoxic in some in vitro systems, including assays with Salmonella TA
100 strain and Schizosaccharomyces pombe, mouse lymphoma forward mutation assay, and
unscheduled DNA synthesis assay using human epithelial cells. However, DDVP was not genotoxic
in the micronucleus, dominant lethal, in vivo chromosomal aberrations, and in vivo sister chromatid
exchange assays. Studies conducted in the presence and absence of a liver preparation (S-9
fraction) showed that the decrease in genotoxicity in the presence of the preparation may be due to
the inactivation of DDVP by liver esterases. Methylated DNA was detected in tissues of mice given
DDVP by intraperitoneal injection, but not in rat tissues when DDVP was given by inhalation.
Reproductive Toxicity- Exposure of rats to DDVP in the water 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. Remating
of the F 1 females after the F 2 generation showed that 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.
Developmental Toxicity- 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.
Neurotoxicity- Possible adverse effects of nerve fiber degeneration and spinal cord degeneration
were observed in chickens treated with DDVP. No acute delayed neurotoxicity in hens was reported,
except at lethal doses. Acute neurotoxicity study in the rat given DDVP by gavage resulted in
cholinergic effects which included gait alteration, constricted pupils, tremors, and salivation.
RISK ASSESSMENT
Hazard Identification- The no-observed-effects levels (NOELs) from both inhalation and oral studies,
and oncogenic risk from an oral study were used to evaluate the health hazards from potential
exposure by workers and the general population to DDVP. For non-oncogenic endpoints, acute and
chronic inhalation and dietary exposures were considered. For oncogenic endpoints, inhalation and
dietary exposures to DDVP were assessed.
For acute inhalation exposure, the definitive NOEL was 1.25 ug/L or 0.65 mg/kg-day (NOEL adjusted
for exposure duration and respiration rate). The NOEL was based on death in pregnant rabbits after 2
days of inhalation exposure to a LOEL of 2 ug/L DDVP.
The NOEL for acute oral exposure was 0.5 mg/kg-day based on tremors, salivation, neuromuscular
deficits, and other cholinergic signs observed in rats within 1 day after a single dose by gavage.
The NOELs for chronic toxicity were based on the inhibition of brain ChE activity in a one-year dog
oral study and a two-year rat inhalation study. The adjusted NOELs for inhalation and oral routes
were 0.025 mg/kg-day, and 0.05 mg/kg-day, respectively.
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