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2. Toxicological studies
2.1 Acute toxicity
Results of studies of acute toxicity with pyrimethanil are summarized in Table 5. Young adult
CD-1 mice were given pyrimethanil as a single dose at 0, 1250, 2500 or 5000 mg/kg bw. Two females
and three males at 5000 mg/kg bw were killed in extremis within five h of dosing. One male died on
day 6 after dosing. The death of male on day 6 was attributed to fighting. Rats dosed at 1250 mg/kg bw
and greater generally showed reduced activity, reduced muscle tone, prostration and coolness to the
touch, which were generally observed within about 2 h after dosing. Recovery was complete within 5 h
and within 6 days in the group at the highest dose. Groups of young adult Sprague-Dawley rats were
given pyrimethanil as a single dose at 0, 800, 1600 or 6400 mg/kg bw. Five males and three females
at 6400 mg/kg bw were sacrificed in extremis 6 h after dosing. Some clinical signs such as reduced
activity, reduced muscle tone, body soiling, urogenital soiling, ataxia and hunched posture were seen
within 1 h after dosing and recovery was complete within 4 h at 800 mg/kg bw, and within 14 days
at higher doses. No abnormal findings were observed on necropsy. No clinical signs of toxicity were
observed in the study of toxicity with pyrimethanil delivered by inhalation and also in the studies of
eye and skin irritation.
(a)
Mice
Oral administration
Groups of five male and five female young adult CD-1 mice were given pyrimethanil (purity,
98.4%) as a single dose at 0, 1250, 2500 or 5000 mg/kg bw by gavage in 1% w/v methyl cellulose
in distilled water. Treated mice were subjected to gross necropsy at the end of a 14-day observation
period. Two females and three males at 5000 mg/kg bw were killed in extremis within 5 h after dosing.
One male died on day 6 after dosing. The death of one male on day 6 was attributed to fighting.
Mice at 5000 mg/kg generally showed reduced activity, reduced muscle tone, prostration and coolness
to the touch. Clinical observations were generally observed 2 h after dosing in males and 2–5 h
after dosing in females. The surviving male was recovered by 6 days after dosing. Surviving females
recovered within 5 h after dosing. At 2500 mg/kg bw, reduced activity and reduced muscle tone were
observed within 2 h after dosing and recovery was complete within 5 h. At 1250 mg/kg bw, reduced
activity and reduced muscle tone was observed in four out of five females within 2 h after dosing and
they recovered within 5 h. No effects on body weights were observed within 14 days. No abnormal
Table 5. Results of studies of acute toxicity with pyrimethanil
Species Strain Route Purity (%) LD 50
(mg/kg bw) LC 50
(mg/l air) Reference
Mice
Rat
Rat
Rat
NS, not stated.
CD1, Crl:CD-1-
(ICR)BR
Sprague-Dawley,
COBS CD
Sprague-Dawley,
COBS CD
Sprague-Dawley,
Crl:CD(SD)BR
Oral 98.4 Males: 4665
(range, 3322–6552)
Females: 5359
(range, 3816–7526)
Oral 98.4 Males: 4149
(range, 3341–5153)
Females: 5971
(range, 4252–8386)
Dermal NS > 5000
(males and females)
Inhalation
(4-h, nose only)
NS — > 1.98 (males
and females)
— Malarkey
(1990)
— Markham
(1989a)
— Markham
(1989b)
Jackson &
Hardy (1992)
PYRIMETHANIL 445–486 JMPR 2007