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

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very low. Total residues excluding the carcass (which accounted for < 3% of the administered dose)
were < 0.2% (Cheng, 1986).
1.2 Biotransformation
[ 14 C]Flusilazole was extensively metabolized when administered orally to Charles River CD
rats. Recovered parent compound accounted for only 2–11% of the administered dose in all groups
regardless of dose (low/high) or preconditioning (with/without), found predominantly in faeces; urinary
levels were < 1% of the administered dose. After absorption, flusilazole was cleaved at the triazole
ring. With phenyl-labelled test material, the major faecal metabolites identified were: (i) [bis(4-fluorophenyl)methyl]
silanol (approximately 30% of the administered dose in males, approximately
19% in females); (ii) [bis(4-fluorophenyl)methylsilyl] methanol (approximately 9% of the administered
dose in both sexes); (iii) the fatty acid conjugates of [bis(4-fluorophenyl)methylsilyl] methanol
(19% of the administered dose in males, 10% in females); and (iv) disiloxane (approximately 11%
in males, approximately 7% in females). Except for the fatty acid conjugates, the same metabolites
were found in the urine. In males, all three urinary metabolites were < 1% of the administered dose;
in females, [bis(4-fluorophenyl)methyl] silanol, [bis(4-fluorophenyl)methylsilyl] methanol and siloxane
accounted for 7.5%, 2.2% and 1.9% of the administered dose, respectively. With triazole-labelled
material, the main metabolite identified was 1H-1,2,4-triazole, which was found predominantly in the
urine (63.8% of the administered dose in males, 51.6% in females). Faeces contained only a minor
amount of the metabolite (4% of the administered dose in males, 17% in females). On the basis of
these results, a metabolic pathway for flusilazole in the rat was proposed (Anderson, 1986).
2. Toxicological studies
2.1 Acute toxicity
The results of studies of acute toxicity with flusilazole technical are summarized in Table 1. All
studies complied with GLP.
Flusilazole is slightly to moderately toxic in rats when given as a single dose via the oral route;
and minimally toxic in rats and rabbits when administered acutely via the dermal or inhalation route.
Symptoms of toxicity after oral administration included weight loss, weakness, lethargy and at higher
doses, prostration, salivation, laboured breathing, convulsions and loss of righting reflex. Dermal
administration resulted only in mild erythema at site of application. Inhalation effects were mainly
laboured breathing and lung sounds.
Table 1. Results of studies of acute toxicity with flusilazole
Species Strain Sex Route LD 50
(mg/kg bw)
LC 50
(mg/l air)
Purity (%)
Reference
Rat Crl:CD Males
Females
Crl:CD(SD)IGC BR Males
Females
Crl:CD(SD)BR Males &
females
Rabbit New Zealand White Males &
females
Oral 1110
674
— > 92.7 Wylie et al. (1984a)
Oral 1216 — > 92.7 Finlay (2000)
672
Inhalation — 6.8–7.7 > 92.7 Turner et al. (1985)
Dermal > 2000 — > 92.7 Gargus & Sutherland
(1983)
FLUSILAZOLE 317–347 JMPR 2007