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

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Bifenazate (lot No. DS042795; purity, 90.4%) was given to groups of five male and five
female young adult Sprague-Dawley rats by gavage (25% w/v in distilled water) as a single dose at
5000 mg/kg bw. Treated rats were subjected to gross necropsy at the end of a 14-day observation
period. This study was conducted in accordance with GLP. There were no mortalities, no treatmentrelated
clinical signs of toxicity, and no necropsy findings or changes in body weight observed during
the 14-day observation period. The LD 50
was greater than 5000 mg/kg bw (Hoffman, 1996c).
(b)
Dermal administration
Groups of five male and five female young adult Sprague-Dawley (Crl:CD BR) rats were
exposed for 24 h to bifenazate (lot No. DS042795; purity, 90.4%) at a dose of 5000 mg/kg bw
moistened in 0.9% saline under an occlusive dressing. After 24 h, the occlusive dressing was
removed and the treated site was wiped free of excess test material with dry gauze. Animals were
observed for clinical signs and mortality for up to 14 days after dosing. This study complied with
GLP. No deaths occurred. There were no treatment-related clinical signs or necropsy findings.
All animals had normal body-weight gains. The dermal LD 50
was greater than 5000 mg/kg bw
(Hoffman, 1996a).
(c)
Inhalation
Groups of five male and five female young adult Sprague-Dawley (Crl:CD BR) rats were
exposed by head-nose only inhalation to bifenazate (lot No. DS042795; purity, 90.4%) as dust for 4 h
at a nominal concentration of 5000 mg/m 3 (actual concentration, 4400 mg/m 3 ). Treated animals and
controls were observed for 14 days and necropsied. This study complied with GLP. No mortalities
occurred. No treatment-related effects were observed on body weights, except that one male and
one female lost weight during the first week. Treatment-related clinical signs including moist rales,
chromodacryorrhoea, and/or red/brown nasal discharge were noted in all rats after the exposure.
All rats recovered by day 9. No abnormalities were noted at gross necropsy. The median lethal
concentration (LC 50
) was greater than 4400 mg/m 3 (Hoffman, 1996b).
(d)
Dermal irritation
In a study of primary dermal irritation, groups of three male and three female young adult New
Zealand White rabbits wereexposed for 4 h to 0.5 g of bifenazate (lot No. DS042795; purity, 90.4%)
moistened with 0.5 ml of 0.9% physiological saline. Animals were then observed for 3 days. Irritation
was scored by the Draize method at 30 min, 24 h, 48 h, and 72 h after removal of the dressing. This
study complied with GLP. No mortalities were observed. Very slight erythema was noted in two out
of six rabbits 30 min after patch removal, with resolution by 24 h. No oedema was noted on any
rabbits. The primary irritation index was 0.1, i.e. bifenazate was minimally irritating to the eye under
the conditions of this study (Hoffman, 1996e).
(e)
Ocular irritation
In a study of primary ocular irritation, 0.1 ml of bifenazate (equivalent to 54 mg; lot
No. DS042795; purity, 90.4%), was instilled into the conjunctival sac of one eye of groups of
three male and three female young adult New Zealand White rabbits. Irritation was scored by the
Draize method at 1 h, 24 h, 48 h, and 72 h after exposure. This study was conducted in accordance
with GLP. No corneal opacity or iritis was found in the treated rabbits. All rabbits exhibited slight
conjuctival irritation for up to 24 h after exposure. Bifenazate was considered minimally irritating
to the eye under the conditions of this study (Hoffman, 1996f).
BIFENAZATE X-X JMPR 2006