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

Male Fischer 344 rats with leukemia transplants were used to develop a short-term assay for
leukemogenic effects induced by DDVP and other chemicals in chronic toxicity studies (Dieter et al.,
1989). These rats (16/group) were given DDVP (purity not stated; 8 or 16 mg/kg-day) by gavage for 5
days per week for 70 days. Control groups included: untreated, transplant only, and DDVP only. At
70 days, clinical chemistry, body weight, spleen weight, and liver weight were determined. Death
occurred only in the DDVP and transplant group where 3/16 rats died during the last week of dosing.
An acceleration of tumor growth rate as shown by significant increases (p @ 0.05; data presented in
graphs only) in the spleen/body weight ratios and white blood cell counts, as well as decreases in red
blood cell indices and platelet counts was observed in rats of both treatment levels. The changes
were of similar magnitude for both levels. Saturation of metabolic processes was suggested as the
reason for the lack of a dose-response relationship. Histological examination of the spleen and liver
showed increased expression of the mononuclear cell leukemia in rats treated with DDVP. This was a
published study and not reviewed for acceptability.
BD IX/Bln rats (70-100/sex/group; body weight not given) were given DDVP (97% purity; 0.1 mg/rat)
by gavage twice (low dose) or 3 times (high dose) per week for 60 weeks (Horn et al., 1988; WHO,
1993). A control group (60/sex) were gavaged with water 3 times per week. In the high dose males,
there was a statistically significant (p @ 0.05) increase (53% compared to 30% for controls) in the
incidence of bile duct cells and liver oval cells hyperplasia. In females of both DDVP groups, there
was a statistically significant (p @ 0.05) reduction in the incidence of urinary bladder hyperplasia (24-
27% compared to 29% for controls), adrenal gland tumors (37-40% compared to 82% in controls),
and mammary gland tumors (32% compared to 46% in controls). No DDVP-induced neoplasia was
observed. This was a published study and not reviewed for acceptability.
Drinking Water - Rat
F344 rats (60/sex/group) were forced to drink DDVP (purity not specified; 0, 140, or 280 ppm
equivalent to 0, 14 and 28 mg/kg-day) in 10 ml of water daily for 104 weeks (Enomoto, 1978). A slight
reduction in the body weight in the 280 ppm males was observed (estimated from graphed data). The
NOELs for body weight reduction were 140 ppm for the males and 280 ppm for the females. There
was a slight increase in the incidence of mononuclear cell leukemias in the males though the increase
was not statistically significant (p @ 0.05) by pair-wise comparison using the Fisher's Exact test. The
incidences (number of animals affected/examined) were 2/51, 6/48, and 6/48 for the control, 140, and
280 ppm groups, respectively. This study was not acceptable to DPR according to FIFRA guidelines
(inadequate histopathology protocol as not all organs were examined in all animals, dosing procedure
unclear, purity of the test article not given, clinical hematology not performed, quality assurance
program not reported).
Inhalation - Rat
Rats (Carworth Farm E strain, 50/sex/group) were exposed to DDVP (purity not specified; at nominal
concentrations of 0, 0.05, 0.5 or 5.0 ug/L) for 23 hours per day, 7 days per week for 2 years (Blair et
al., 1974). The animals were exposed to DDVP by whole body exposure which included oral ingestion
of DDVP deposited on the fur, food, and water as well as dermal absorption. 1 Using the default
respiration
1/
In the discussion of the published report (Blair et al., 1976), the authors reported that the
retained dose by nose-only exposure to 5.0 ug/L was 5.0 mg/day. The total retained dose
from all routes of exposure was 2 times that by nose-only exposure. However, data were not
presented for evaluation.
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