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

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Rabbits
Groups of two male and two female Russian-breed rabbits were given profenofos (purity unknown)
as a single dose at 100, 600, 1000 or 2150 mg/kg bw in 2% aqueous carboxymethyl cellulose
by oral intubation. Rabbits were observed for only 7 days. The study was not conducted in accordance
with GLP regulations. Within 24 h, all rabbits at 2150 mg/kg bw and one male and two females at
600 mg/kg bw had died; only one male at 600 mg/kg bw died at 48 h after dosing. None of the rabbits
in the group at the lowest dose (100 mg/kg bw) died or showed any signs of toxicity. In other groups,
within 2–3 h after dosing, rabbits showed salivation, ataxia, exophthalmus, lateral position and sedation,
these being more accentuated in groups at higher doses. No other details of clinical signs (incidence
and observation duration) were provided in the study report. The surviving rabbits recovered
within 4–12 days. Necropsy of these animals revealed no gross changes to organs; congested organs
were noted in rabbits that died during the study. The oral LD50 for male and female rabbits was calculated
to be approximately 700 mg/kg bw (95% confidence interval undefined) (Sachsse, 1974a).
(b)
Rats
Dermal administration
Groups of three male and three female Tif:RAI rats received a single application of profenofos
(purity unknown) at a dose of 2150, 2780 or 3170 mg/kg bw. Profenofos was applied as a concentrate
under occlusive conditions (with a plaster and aluminium foil) to the shaved back of the rat. After
24 h, the plaster and aluminium foil were peeled off and the skin was washed with warm water. Rats
were observed for clinical signs and mortality for 14 days. This study was not conducted in accordance
with GLP regulations. Two male rats at the highest dose died within 7 days after application
of the substance. There were no deaths in other groups. Within 24 h after treatment, rats at all doses
showed sedation, dyspnoea, loss of postural tone, and ruffled fur. In the group at the highest dose,
slight erythema was observed. Surviving rats recovered within 5–8 days. At necropsy, no substancerelated
gross changes to organs were seen. The dermal LD 50
was calculated to be approximately
3300 mg/kg bw in males and females (Bathe, 1974c).
In two more recent studies, groups of five male and five female Sprague-Dawley rats were
given profenofos (two batches; purity, 92.1%; and purity, 89.0%) at a dose of 2000 mg/kg bw applied
once to the skin for 24 h. These studies were conducted in accordance with GLP regulations. In the
first study, there were no signs of toxicity or dermal irritation and no treatment-related gross abnormalities
were noted in any rat at necropsy 14 days after treatment (Merkel, 2004b). All rats gained
weight during the observation period. Similar results were obtained in the second study except that
dermal irritation (erythema and oedema) was noted in four of the female rats 1 and 2 days after treatment.
Neither the severity of irritation nor the scoring method was given in the study report. In the
second study, the lot number and purity of profenofos was different to that used in the first study. The
dermal LD 50
was > 2000 mg/kg bw in male and female rats (Durando, 2005b).
Rabbits
Dermal toxicity was investigated in mixed-breed rabbits. Groups of three male and three female
rabbits were given profenofos (purity unknown) as a single dose at 215, 464 and 1000 mg/kg bw. The
test substance was applied as a concentrate under occlusive conditions (plaster and aluminium foil) to
the shaved back of the rats for 24 h. After 24 h, the plaster and aluminium foil were peeled off and the
skin was washed with warm water. Rabbits were observed for 14 days. The study was not conducted
in accordance with GLP regulations. Three males and two females at the highest dose (1000 mg/kg
bw) and two males and two females at the intermediate dose (464 mg/kg bw) died within 7 days after
application of the substance. Twenty-four hours after treatment, rabbits at the intermediate and highest
dose showed ataxia, tremor, salivation, loss of postural tone, and sedation. Surviving rabbits recovered
PROFENOFOS 403–443 JMPR 2007