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

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Explanation
Dimethomorph is a cinnamic acid derivative for which the chemical name is (E,Z)-4-[3-(4-
chlorophenyl)-3-(3,4-dimethoxyphenyl)acryloyl]morpholine or (EZ)-4-[3-(4-chlorophenyl)-3-(3,4-
dimethoxyphenyl)-1-oxo-2-propenyl]morpholine, according to International Union of Pure and
Applied Chemistry (IUPAC) and Chemical Abstract Service (CAS) nomenclatures respectively
(CAS No. 110488-70-5). Dimethomorph is a mixture of E and Z isomers in the ratio of approximately
1 : 1.
Dimethomorph is a fungicide that disrupts fungal cell-wall formation. Fungicidal activity is
primarily associated with the Z isomer.
Dimethomorph has not been evaluated previously by the JMPR and was reviewed at the present
Meeting at the request of the Codex Committee on Pesticide Residues (CCPR). All pivotal studies
with dimethomorph were certified as complying with good laboratory practice (GLP).
Evaluation for acceptable daily intake
1. Biochemical aspects
1.1 Absorption, distribution, metabolism and excretion
Absorption, distribution, metabolism and excretion of [ 14 C]dimethomorph was studied in male
and female Sprague-Dawley CD rats. [ 14 C]Dimethomorph labelled uniformly on the chlorophenyl
ring (radiochemical purity, 98.5%) had a specific activity of 0.647 GBq/mmol and the E : Z isomer
ratio was 44–47 : 56–53. Non-labelled dimethomorph had a purity of 99.2% and the isomer ratio was
virtually 50 : 50.
Figure 1. E- and Z-isomers of dimethomorph
O
O
O
O
O
N
O
O
N
O
Cl
Cl
(Z)-
(E)-
Table 1. Dosing regimen for a study in rats treated with [ 14 C]dimethomorph
Group No. of rats of each sex Dose (mg/kg bw) Remark
A 1 500 Single dose, expired air
B 5 10 Single dose
C 5 10 Repeated doses of non-labelled dimethomorph for
14 days, followed by a single radiolabelled dose
D 5 500 Single dose
E 5 10 Repeated doses of radiolabelled dimethomorph for
7 consecutive days
From Schluter (1990)
DIMETHOMORPH 273–315 JMPR 2007