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

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pound and the equitoxic mixtures was essentially the same. The compounds were suspended in aqueous
carboxymethyl cellulose and given to groups of five male and five female Tif-RAIf (SPF) rats that were
then observed for 14 days. None of the studies were conducted to GLP or to any regulatory guideline.
No potentiation effects were found when mixtures of profenofos with methidathion (GS
13’005), methacrifos (CGA 20’168) or diazinon (G 24’480) were given to rats in equitoxic doses
(Sachsse & Bathe, 1977, Sachsse & Bathe, 1978). In contrast to this, a potentiation experiment with
profenofos Q (active ingredient of higher purity; from the toxicological point of view regarded as
equivalent to CGA 15’324) and malathion showed a strong potentiation of the acute oral toxicity.
The experimental LD 50
values of the single compounds were 377 (range, 282–545) mg/kg bw
for profenofos (purity, 96.3%) and 4658 (3320–8504) mg/kg bw for malathion (purity not stated). The
equitoxic mixture led to an experimental LD 50
of 76 (range, 45–125) mg/kg bw, while the t heoretical
(calculated) LD 50
was 2517 mg/kg bw (Sarasin, 1981).
Profenofos (purity, > 95%) at doses of 0.5 to 5.0 mg/kg bw given intraperitoneally to mice
strongly inhibited the liver microsomal esterase(s) responsible for the hydrolysis of trans-permethrin.
At an intraperitoneal dose of 25 mg/kg bw, profenofos increased the toxicity of fenvalerate by more
than 25-fold, and that of malathion by more than 100-fold. This potentiation did not occur with transpermethrin
(Gaughan et al., 1980).
3. Studies on metabolites
No studies have been conducted with metabolites of profenofos. However, studies conducted in
1981 with analogous alkyl phosphate metabolites in vitro demonstrated a complete lack of anticholinesterase
activity (Chukwudebe et al., 1984).
4. Observations in humans
Workers engaged in the manufacture of profenofos were given a medical examination annually
between 1980 and 1998. No health effects related to exposure to profenofos were identified (Novartis
Crop Protection AG Assessment, 1998).
In a biological monitoring study, cotton was sprayed with different formulations of profenofos,
using manual equipment. Six workers in Multan, Central Pakistan, were monitored daily during a
4-day spraying campaign. Cholinesterase activities were determined in whole blood and were found
to be slightly below the values determined before exposure. Individual cholinesterase activities declined
from 100% (pre-test) to an average of 81%, with a lowest value of 73%. None exceeded the
threshold of 30% inhibition that was considered to be biologically significant. The handling of the
active ingredient and of its formulations is subject to the usual precautionary measures recommended
for the handling of insecticidal organophosphates (Loosli, 1989).
There are seven reports of effects after exposure to profenofos during application of the product.
In one, considered of moderate severity, the operator used only marginally protective equipment.
He was given atropine and fully recovered. The other six reports described adverse incidents that
were of minor severity and also involved people using the product without protective equipment or
with marginally protective equipment. The symptoms were transient and resolved spontaneously. The
exposed persons fully recovered.
Finally, one accidental exposure had been notified. This involved a child (bystander) who inhaled
spray mist. Again the symptoms were transient, the effects disappeared without the need for
treatment and the child fully recovered.
PROFENOFOS 403–443 JMPR 2007