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

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The increased incidence of malformations observed in a study of developmental toxicity in
rats treated with cyfluthrin by inhalation was considered to be secondary to effects on pulmonary
function.
In a study of developmental toxicity in rats treated with beta-cyfluthrin by gavage, the NOAEL
for maternal toxicity was 9.4 mg/kg bw per day on the basis of a reduction in body-weight gain,
clinical signs and mortality. The NOAEL for embryo/fetotoxicity was 9.4 mg/kg bw per day on the
basis of reduced fetal weight and retarded ossification.
Cyfluthrin did not cause delayed neurotoxicity in hens. In a study of acute neurotoxicity in
rats treated by gavage, the NOAEL was 1 mg/kg bw per day on the basis of mild clinical signs of
toxicity (shaking) observed in one and two animals at 2.5 and 3 mg/kg bw, respectively. A range of
additional studies of neurotoxicity with repeated high doses of cyfluthrin (30–80 mg/kg bw per day)
administered by gavage also demonstrated clinical signs of (neuro-) toxicity, including disturbed gait,
salivation, tremor and apathy.
Occasionally, in some of the short-term studies of toxicity and studies of neurotoxicity
in rats, marked acute toxicity induced by high doses of cyfluthrin was accompanied by limited
swelling and fragmentation of myelin, which was reversed within 1–3 months after cessation
of treatment. The Meeting concluded that cyfluthrin does not cause irreversible neurological
damage.
The (developmental) neurotoxicity of beta-cyfluthrin was investigated in rats. In a study in
which single doses were administered by gavage, the NOAEL was 0.5 mg/kg bw per day on the basis
of perianal staining, effects in the functional observational battery (decreased approach response
in both sexes, oral staining in males and a decreased activity in females) and decreased motor and
locomotor activities in females. In a 13-week dietary study, the NOAEL was 30 ppm (equal to
2.3 mg/kg bw per day) on the basis of reductions in body-weight gain and food consumption in
females.
In a study of developmental neurotoxicity in rats, the NOAEL for maternal toxicity
was 133 ppm (equal to 11 mg/kg bw per day) on the basis of reduced body weight and food
consumption. The NOAEL for offspring toxicity was 133 ppm (equal to 11 mg/kg bw per day)
on the basis of reduced body-weight gain during lactation and reduced startle habituation at
postnatal day 22.
A number of pharmacological studies with cyfluthrin were considered not to be useful for the
purpose of dietary risk assessment.
A limited number of studies of acute toxicity and genotoxicity with some metabolites 3 of
cyfluthrin were performed. The acute toxicity of the metabolites studied was lower than that of
the parent compound. No evidence of mutagenic potential was found for any of the metabolites
investigated.
Cyfluthrin caused a topical skin effect, characterized by a stinging sensation in the affected
areas in laboratory workers. The areas most commonly affected were the face and mucosal
tissues. Annual medical examinations of factory workers revealed no effects on body weights,
haematological and urine analysis parameters, ALT and GGT activities and thoracic organs, as
examined by X-rays.
3
Metabolite 1: +,-(R,S)-α-Carboxy-[3-phenoxy-4-fluoro]benzyl-1-(R,S)-trans-3-(2´,2´-dichloroethen-1´-yl)-
2,2-dimethylcyclo-propanecarboxylic acid ester
Metabolite 2: +,-(R,S)-α-Carboxamido-[3-phenoxy-4-fluoro]benzyl-1-(R,S)-trans-3-(2,2-dichloroethen-1-yl)-
2,2-dimethyl-cyclopropanecarboxylic acid ester
Metabolite 3: cis-3-(2´,2´-Dichloroethen-1´-yl)-2,2-dimethyl-cyclopropanecarboxylic acid
Metabolite 4: trans-3-(2´,2´-Dichloroethen-1´-yl)-2,2-dimethyl-cyclopropanecarboxylic acid
CYFLUTHRIN AND BETA-CYFLUTHRIN X-X JMPR 2006