Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

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The metabolites of cyfluthrin studied (both confirmed and hypothetical) exhibit weak to moderate
toxicity after oral administration to the rat and after intraperitoneal administration to the mouse. The
data indicate that their acute toxicity is lower than that of the parent compound (see Table 2). No
evidence of mutagenic potential was found for any of the metabolites studied.
Comments
Biochemical aspects
In rats, cyfluthrin is rapidly absorbed and distributed. Peak concentrations in the blood were
reached after 1 or 6 h, depending on the vehicle used. About 98% of the radiolabel was eliminated in
the urine and faeces within 48 h after oral administration, with an initial half-life of about 3 h. Similar
amounts were eliminated after intravenous administration. The ratio of excretion in urine : faeces was
higher in males (3 : 1) than in females (3 : 2). About one third of the administered dose was excreted
in bile. The highest concentrations of radiolabel were found in fat, ovaries, adrenal, liver and spleen.
Repeat-dosing experiments yielded similar results. In rats, the major metabolic transformation is ester
hydrolysis to a 3-phenoxy-4-fluorobenzyl alcohol intermediate and a permethric acid moiety. After
ester hydrolysis, the benzyl alcohol moiety is oxidized to the free 3-phenoxy-4-fluorobenzoic acid
metabolite, which can either be conjugated with glycine or oxidized to give 4’-hydroxy-3-phenoxy-
4-fluorobenzoic acid.
Toxicological data
The acute oral LD 50
values of cyfluthrin and beta-cyfluthrin in rats ranged from 11 to
> 1000 mg/kg bw, depending on the vehicle used and the feeding status of the animals. The
observed clinical signs (increased salivation, uncoordinated movements, increased activity and
vocalization, and reduced, laboured breathing, apathy, straddle-legged gait (mostly in the rear
legs), and reduced sensitivity to external stimuli) are typical of this class of pyrethroids. In rats,
the inhalation LC 50
values ranged from 0.047 to > 1 mg/l, and the dermal LD 50
values were
> 5000 mg/kg bw. Cyfluthrin is not irritating to the skin, is slightly irritating to the eyes and is
not a skin sensitizer.
The critical end-points induced by cyfluthrin and beta-cyfluthrin are neurotoxicity and reduction
in body weight.
Several short-term studies of oral toxicity with cyfluthrin were available for mice, rats and dogs.
In a 4-week study in mice, the NOAEL was 300 ppm (equal to 43.1 mg/kg bw per day) on the basis
of histological changes in the liver and the submaxillary gland. In one 4-week dietary study and two
3-month dietary studies, the overall NOAEL was 100 ppm (equal to 8.3 mg/kg bw per day) on the basis
of a reduction in blood glucose concentration. In a 4-week gavage study, the NOAEL was 20 mg/kg bw
per day on the basis of mortality, reduced body weight, increased liver and adrenal weight and clinical
signs. In one 6-month study and two 12-month studies in dogs, the overall NOAEL was 200 ppm (equal
to 6.5 mg/kg bw per day) on the basis of clinical signs and reductions in body-weight gain.
The effects of short-term oral exposure to beta-cyfluthrin were assessed in rats and dogs. In
a 4-week gavage study in rats, the NOAEL was 1 mg/kg bw per day on the basis of clinical signs
(increased motility, grooming and digging movements) at 4 mg/kg bw per day, which had already
been observed on the first day of administration. In a 13-week dietary study in rats, the NOAEL was
125 ppm (equal to 9.5 mg/kg bw per day) on the basis of clinical signs, and reductions in bodyweight
gain, food and water consumption. In a 13-week dietary study in dogs, the NOAEL was
60 ppm (equal to 1.3 mg/kg bw per day) on the basis of clinical signs.
CYFLUTHRIN AND BETA-CYFLUTHRIN X-X JMPR 2006