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

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Declaration of Helsinki (Cristie, 2000) or equivalent statements prepared for use by national and/or
multinational authorities.
1. Toxicological studies
1.1 Acute toxicity
(a)
Results of studies of acute toxicity
The results of studies of acute toxicity are summarized in Table 1. Clinical signs of acute
toxicity are consistent with those caused by organophosphates, including decrease of spontaneous
activity, sedation, dyspnoea, ataxia, tremors, convulsions, lacrimation and diarrhoea. The symptoms
were reversible in surviving animals.
Table 1. Results of studies of acute toxicity with diazinon (technical material)
Species Sex Route LD 50
(mg/kg bw) LC 50
(mg/m 3 ) Purity (%) Reference
Mouse Males and Oral 187 — NS Bathe (1972a)
females
Rat
Males and Oral 422 — 97.1 Bathe (1980)
females
1350 (males) — 87.9 Kuhn (1989)
1160 (females)
300 — 95.7 Piccirillo
(1978)
1031 (males) — 96.1 Schoch (1985)
870 (females)
> 2150
— NS Bathe (1972b)
(no deaths)
Inhalation — > 2327
(no deaths)
87.9 Holbert (1989)
LC 50
; median lethal concentration; LD 50
, median lethal dose; NS, not stated.
(b)
Time-course of acute inhibition of cholinesterase activity
Rats
Groups of 15 male and 15 female Hsd:Sprague-Dawley rats were given single doses of
diazinon (purity, 88%) at a dose of 0, 2.5, 150, 300 or 600 mg/kg bw by gavage. Of the 15 rats, 10
were used for neurological testing and 5 for measurement of cholinesterase activity. Dose selection
was based on the results of three studies of median lethal doses that revealed the lowest lethal
dose to be 750 mg/kg bw and the highest non-lethal dose to be 500 mg/kg bw. Hence, at the
highest selected dose of 600 mg/kg bw, significant neurotoxic effects were anticipated. The selected
intermediate doses (150 and 300 mg/kg bw) were reducing multiples of the highest dose and so were
anticipated to give intermediate or minimal effects, while a previous investigation (Glaza, 1993) had
indicated that no reduction in cholinesterase activity in erythrocytes and brain was evident at the
lowest dose of 2.5 mg/kg bw. Groups of 10 male and 10 female rats were given triadimefon (purity,
99%) at a dose of 150 mg/kg bw by gavage as a positive control for neurological effects. On the day
of treatment, all rats were observed before and after dosing and twice daily thereafter for general
DIAZINON X-X JMPR 2006