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

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Explanation
Procymidone is the International Organization for Standardization (ISO) approved name for
N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide (International Union of Pure
and Applied Chemistry, IUPAC), Chemical Abstracts Service, CAS No. 32809-16-8. It is a dicarboximide
fungicide that is used on a range of vegetables, fruits, soya bean, sunflowers, tobacco and
oil seed rape, as well as on ornamental plants and flower bulbs. The mechanism of pesticidal action
involves the inhibition of triglyceride synthesis in fungi.
Procymidone was previously evaluated by JMPR in 1981, 1982 and 1989 (Annex 5, references
37, 39, 58). No acceptable daily intakes (ADIs) were established when procymidone was evaluated
by the JMPR in 1981 and 1982. In 1989, an ADI of 0–0.1 mg/kg bw was established based on the
NOAEL of 12.5 mg/kg bw per day identified in studies of reproductive toxicity in rats. Procymidone
was re-evaluated by the present Meeting as part of the periodic review programme of the Codex Committee
on Pesticude Residues (CCPR). A range of new studies was submitted to the present Meeting;
these studies addressed kinetics, developmental toxicity and hormonal effects in different species.
Many of the conventional studies of toxicity with procymidone were relatively old, were performed
before the widespread use of good laboratory practice (GLP) and some contained relatively
limited information. Overall, the Meeting considered that the database was adequate for the risk
assessment.
Procymidone used in the main studies of toxicity was considered to be representative of current
production material, which is typically of > 99% purity. The Food and Agriculture Organization (FAO)
specification for procymidone specifies a minimum content of 98.5% w/w 1 . Procymidone has also
been known under the development code S7131 or ‘Sumilex’; ‘Sumisclex’ is a 50% formulation.
Evaluation for acceptable daily intake
1. Biochemical aspects
1.1 Absorption, distribution and excretion
(a)
Oral route
Mice
Groups of five male ICR mice were given [phenyl- 14 C]procymidone (radiochemical purity,
> 99%; specific activity, 22.8 mCi/mmol (843.6 MBq/mmol) as a single oral dose at 100 mg/kg bw
in corn oil. Urine and faeces were collected for 7 days from one group of mice. Other groups of mice
were killed 2, 4, 6, 8, 12, 24 and 72 h after dosing and a range of tissues removed for radiochemical
analysis. Rapid elimination was observed, with 92% of the administered dose excreted in the first
24 h, mainly in the urine (73.5%). Over a 7-day period, faeces and urine accounted for 22% and 82%,
respectively, of the administered dose. There was no evidence of tissue accumulation in this study; the
highest concentration of radioactivity (429 μg equivalent/g) was found in fat 2 h after dosing, but the
concentration had declined to low concentrations (2 μg equivalent/g) by the end of the experimental
period. Radioactivity in adrenals, blood, brain, kidneys, liver, prostate, epididymis and testes reached
a maximum 2–8 h after dosing (133, 17, 27, 58, 67, 88, 48 and 17 μg equivalent/g respectively) and
subsequently decreased with a half-life of 4–14 h. This study did not claim to be compliant with GLP
(Kimura et al., 1988).
1
http://www.fao.org/ag/AGP/AGPP/Pesticid/Specs/docs/Pdf/new/procymid.pdf
PROCYMIDONE 349–401 JMPR 2007