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

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(j)
Cardiovascular, respiratory and nictitating membrane alterations in cat
Three anaesthetized cats were surgically prepared to measure blood pressure, heart rates, electrocardiogram,
respiration and electrical stimulation of nictitating membrane after intravenous application
of dimethomorph at a dose of 0.01, 0.03 or 0.1 mg/kg bw. The only effect different from
vehicle control injection (dimethylformamide) was a small increase in heart rates at 0.1 mg/kg bw
(Ainsworth & Wright, 1991c).
(k)
Effect on the spontaneous motility of isolated rabbit ileum
Acetylcholine-induced contraction forces of ileum preparations from rabbits were reproducibly
increased; this effect could be inhibited by adrenaline. Dimethomorph at concentrations of up to
30 μg/ml had no significant direct effects on ileum contractions and did not interfere with the cholinergic
and adrenergic receptor dependant reactions (Ainsworth & Wright, 1991l).
(l)
Effect on the isolated guinea-pig ileum and action on four agonists
Acetylcholine, histamine, 5-hydroxytryptamine and BaCl 2
induced contractions of ileum
preparations from guinea-pigs; this effect could be inhibited by atropine. Dimethomorph at concentrations
of up to 30 μg/ml had no significant direct effects on ileum contractions but inhibited the
effects of all four compounds almost completely. Unfortunately, dimethylformamide as vehicle also
significantly inhibited the four contraction agonists (Ainsworth & Wright, 1991m).
(m)
Surface anaesthetic activity in the guinea- pig
In male guinea-pigs, 1% dimethomorph as a dermal injection of 0.1 ml did not have a local
anaesthetic effect (Ainsworth & Wright, 1991h).
3 Observations in humans
In a plant producing dimethomorph in Brazil, no health effects due to possible exposure to
dimethomorph in 75 workers from the start of production on 1 October 1996 until 1 April 1999 were
reported (Milanez, 1999; Milanez et al., 2000).
Comments
Biochemical aspects
In most studies, the batch of dimethomorph used consisted of mixtures of the E and Z isomers
in approximately equal amounts. It was reported that the two isomers can interconvert on exposure
to light.
In several studies, the absorption, distribution, metabolism and excretion of dimethomorph
were investigated in rats treated orally. After single oral doses of 10 or 500 mg/kg bw administered
by gavage to male and female rats, more than 90% of the lower dose was absorbed and excreted
via bile and 7% via urine. At 500 mg/kg bw, absorption decreased to 65% in males and 40% in
females. Pre-treatment of the animals with nonlabelled dimethomorph at the lower dose did not
influence the pattern of excretion. At 10 mg/kg bw, t max
for total radioactivity was reached after
1.4–2.8 h and excretion was virtually complete after 48 h. After 24 h, up to 10% of the administered
dose was found in the gastrointestinal tract (including contents, 0.4–1% in the gastrointestinal
tract only). Less than 1% of the administered dose was found in the carcass and in liver, and
DIMETHOMORPH 273–315 JMPR 2007