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

404
Explanation
Profenofos is the International Organization for Standardization (ISO) approved name for
(RS)-O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate (International Union of Pure
and Applied Chemistry, IUPAC). The Chemical Abstracts Service (CAS) chemical name for profenofos
is O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate (CAS No. 41198-08-7).
It is a broad-spectrum organophosphorus insecticide that is used to control insect pests in cotton,
maize, sugar beet, soya bean, potato, vegetables and other crops. Its mode of action is by inhibition of
acetylcholinesterase activity. Profenofos is a racemic mixture of the two optical isomers at the chiral
phosphorus atom. The S (−) isomer is a markedly more potent inhibitor of acetylcholinesterase in
vitro than the R (+) isomer.
Profenofos was previously evaluated by JMPR in 1990 (Annex 5, reference 171) and an acceptable
daily intake (ADI) of 0–0.01 mg/kg bw per day was established. The ADI was based on the
no-observed-adverse-effect level (NOAEL) of 20 ppm, equal to 1.0 mg/kg bw per day, the highest
dose tested, in a three-generation study of reproduction in rats.
Profenofos was re-evaluated by the present meeting within the periodic review programme of
the Codex Committee on Pesticide Residues (CCPR). All pivotal studies with profenofos were certified
as complying with good laboratory practice (GLP).
Evaluation for acceptable daily intake
1. Biochemical aspects
1.1 Absorption, distribution and excretion
RAI rats (four males and three females) received a single oral dose (gavage) of ring-labelled
[ 14 C]profenofos (specific activity, 9.79 μCi/mg (362.23 kBq/mg) at approximately 4.8 mg/kg bw
in ethanol : polyethylene glycol 200 : water (25 : 25 : 50). Urine and faeces were collected for 6
days after dosing and selected tissues were removed at necropsy. Essentially all the administered
radioactivity was eliminated in the urine (males, 81.8%; and females, 96.4%) and faeces (males,
15.7%; and females, 2.5%) within 6 days. Most of the urinary and faecal excretion occurred within
the first 24 h after dosing. The elimination half-life for excretion was less than 8 h for both sexes.
Only minor amounts of 14 CO 2
were eliminated in expired air (males, 0.08%; and females, 0.07% ).
When the rats were killed 6 days after dosing, detectable amounts of radioactivity were present
only in the liver (males, 0.013 μg equivalent/g; and females, 0.023 μg equivalent/g) and kidneys
(males, 0.007 μg equivalent/g; and females, 0.008 μg equivalent/g). The concentration of radioactivity
in blood, fat, muscle, testis, ovary and brain was below the limit of quantification (for blood) or
d etection (I fflaender & Mücke, 1974).
Figure 1. Chemical structure of profenofos
PROFENOFOS 403–443 JMPR 2007