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

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Table 31. Metabolite concentrations (μg equivalent/g) in plasma and tissues from female rats
(n = 3) receiving procymidone metabolites at 62.5 mg/kg bw
Metabolite
Concentration of metabolite (μg equivalent/g)
Plasma Liver Kidney Ovary
Six h after dosing with PCM-CH 2
OH
PCM-CH 2
OH 2.9 33.8 20.9 16.8
PCM-COOH 7.3 3.0 15.1 1.8
PA-CH 2
OH 12.9 6.0 6.2 3.1
PA-COOH 2.3 1.4 2.8 0.5
Others 3.1 1.4 2.6 0.6
Four h after dosing with PCM-CH 2
OH
PCM-CH 2
OH 0.6 16.4 12.7 10.6
PCM-COOH 2.7 5.1 10.4 2.0
PA-CH 2
OH 12.8 2.0 5.4 0.5
PA-COOH 3.0 2.9 3.8 0.7
Others 4.2 0.6 1.3 0.3
From Tarui (2005a)
PA, procymidone acid; PA-CH 2
OH, hydroxyprocymidone acid; PA-COOH, carboxyprocymidone acid; PCM,
procymidone; PCM-CH 2
OH, hydroxyprocymidone; PCM-NH-COOH, carboxyprocymidone.
examination records were checked for 1991–2000 for adverse effects on body weight, vital capacity,
hearing acuity, chest X-ray, blood pressure, urine analysis, haematology and clinical biochemistry.
An annual questionnaire that was completed at the time of the medical examination was also examined.
This recorded headaches, dizziness, irritability, restlessness, fatigue, loss of appetite, full stomach,
diarrhoea, cough, dyspnoea, hearing problems, tinnitus, abnormal taste, gastroenteric problems
or any other abnormalities.
The number of hours spent packing ranged from 10 to 83 per year. Four of the workers had
been engaged in packing for 10 years or more, four for between 5 and 9 years and seven for less
than 4 years. Five of the workers were aged at least 50 years, two were aged between 40 and 49, five
were aged between 30 and 39 and three were aged less than 29 years. All workers wore protective
equipment consisting of long-sleeved cotton clothes, plastic helmets, masks, glasses and gloves. No
abnormalities were apparent from the medical records that could be related to the manufacture or
handling of technical-grade procymidone (Kurihara, 2001). A similar study in 2007 confirmed that
there were no adverse health effects in the monitored workforce (Kumagai, 2007).
The sponsor reported there were no documented cases of intoxication with procymidone and
no information on effects of exposure of the general population to procymidone.
Comments
Biochemical aspects
Studies with 14 C-labelled procymidone showed that radiolabel was rapidly absorbed (C max
,
2–8 h) and rapidly eliminated (> 80% in 24 h) in mice and rats. Absorption was extensive, as shown
by the high level of urinary excretion (> 80% of the administered dose), with similar results obtained
in mice and rats receiving doses of up to 100 mg/kg bw. At higher doses, the proportion of the administered
dose excreted in the faeces increased: at 250 mg/kg bw, 24–33% was eliminated by that route
after 168 h; the increase in faecal radioactivity was mainly attributable to an increase in unabsorbed
PROCYMIDONE 349–401 JMPR 2007