Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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findings were observed on necropsy at termination. The oral median lethal dose (LD50) values in
mice (with 95% confidence interval, CI) were 4665 (95% CI, 3322–6552) and 5359 (3816–7526)
mg/kg bw for males and females, respectively (Malarkey, 1990).
Rats
Groups of five male and five female young adult Sprague Dawley (COBS CD) rats were given
pyrimethanil (purity, 98.4%) as a single dose at 0, 800, 1600 or 6400 mg/kg bw by gavage in 1%
w/v methyl cellulose in distilled water. Treated rats were subjected to gross necropsy at the end of a
14‐day observation period. Five males and three females at 6400 mg/kg bw were killed in extremis 6
h after dosing. Two surviving females at 6400 mg/kg bw showed slight signs of reduced muscle tone,
body soiling, urogenital soiling and hunched posture until termination. All rats at 3200 mg/kg bw
showed slight signs of reduced activity and muscle tone, ataxia and hunched posture, 1 h after dosing
and recovery was complete after 14 days. At 1600 mg/kg bw, four out of five males and two out
of five females showed slightly reduced muscle tone or reduced activity. Females showed complete
recovery within 24 h, and males within 3 days. At 800 mg/kg bw, one male showed slightly reduced
activity immediately after dosing, but appeared normal within 4 h. No effects on body weights were
observed within 14 days. No abnormal findings were observed on necropsy at termination. The oral
LD 50
values in rats were 4149 (95% CI, 3341–5153) and 5971 (95% CI, 4252–8386) mg/kg bw for
males and females, respectively (Markham, 1989a).
(b)
Dermal irritation
In a study of primary dermal irritation, young adult female New Zealand White rabbits were
dermally exposed to 0.5 g of pyrimethanil (purity, 98.4%), moistened with distilled water, for 4 h. the
rabbits were then observed for 3 days. Irritation was scored by the Draize method at 30–60 min, 24,
48, and 72 h after removal of dressing. No erythema or oedema was noted on any rabbits during the
study. Pyrimethanil was considered to be a non-irritant to the intact rabbit skin (Markham, 1989c).
(c)
Ocular irritation
In a study of primary ocular irritation, 0.1 ml of pyrimethanil (purity, 98.4%), was instilled
into the conjunctival sac of one eye of three male and three female young adult New Zealand White
rabbits. Irritation was scored by the Draize method at 1 h, and 1, 2, 3 and 4 days after exposure. One
rabbit showed very slight redness of the conjunctiva, 1 h after instillation, and recovered within 24 h.
Pyrimethanil was considered to be minimally irritating to the eyes of rabbits under the conditions of
this study (Markham, 1989d).
(d)
Dermal sensitization
In a study of dermal sensitization with pyrimethanil (purity, 99.7%), 10 young female Dunkin
Hartley guinea-pigs were tested using the Buehler method. The main study was conducted using 10
guinea-pigs each in the control and treated group. On the basis of results of the preliminary rangefinding
study, a maximum non-irritant concentration of 60% (w/v) of pyrimethanil in Alembicol D
was selected for the induction and challenge phases. In the treatment group, each guinea-pig received
an induction application of 60% w/v of the test material on the dorsal skin under an occlusive dressing
for 6 h. Another control group of five males and five females received Alembicol D (vehicle) only.
Two further induction applications were made at weekly intervals. Two weeks after the final induction
application, test guinea-pigs were challenged with pyrimethanil at a concentration of 60% w/v under
an occlusive dressing for 6 h. Assessments of the dermal reactions were made 24, 48, and 72 h after
the challenge application. Guinea-pigs in the control group were challenged with the vehicle. One
guinea-pig in the control group was killed in extremis on study day 11. Necropsy findings included
intussusception of the jejunum, with the stomach and duodenum being distended with fluid and gas.
Body weights and body-weight gains were not affected by the treatment. In the induction phase, three
PYRIMETHANIL 445–486 JMPR 2007