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

AZINPHOS-METHYL
First draft prepared by
U. Mueller 1 and A. Moretto 2
1
Food Standards Australia New Zealand, Canberra, ACT, Australia; and
2
Department of Occupational Medicine and Public Health, University of Milan,
ICPS Ospedale Sacco, Milan, Italy
Explanation ...................................................................................................... 139
Evaluation for acceptable daily intake ............................................................. 140
1. Biochemical aspects ........................................................................... 140
1.1 Absorption, distribution and excretion ....................................... 140
1.2 Biotransformation ...................................................................... 140
1.3 Effect on enzymes and other biochemical parameters ............... 141
2. Toxicological studies ......................................................................... 141
2.1 Acute oral toxicity ...................................................................... 141
2.2 Short-term studies of toxicity ..................................................... 141
2.3 Long-term studies of toxicity and carcinogenicity ..................... 145
2.4 Reproductive toxicity ................................................................. 148
(a) Multigeneration studies ...................................................... 148
(b) Developmental toxicity ....................................................... 151
2.5 Special studies: neurotoxicity .................................................... 156
3. Observations in humans ..................................................................... 160
Comments ........................................................................................................ 163
Toxicological evaluation .................................................................................. 165
References ....................................................................................................... 168
Explanation
Azinphos-methyl is the International Organization for Standardization (ISO) approved
common name for S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl O,O-dimethyl phosphorodithioate
(International Union of Pure and Applied Chemistry, IUPAC) or O,O-dimethyl S-[(4-oxo-
1,2,3-benzotriazin-3(4H)-yl)methyl] phosphorodithioate (Chemical Abstracts Service, CAS; CAS
No. 86-50-0). It is a broad-spectrum organophosphorus pesticide. Its toxicity was first evaluated by
the 1965 JMPR, when an acceptable daily intake (ADI) of 0–0.0025 mg/kg bw was established based
on a no-observed-adverse-effect level (NOAEL) of 0.25 mg/kg bw per day for inhibition of cholinesterase
activity in serum and erythrocytes in a repeat-dose study in rats. The 1968 JMPR considered
a number of additional studies that were not available to the Meeting in 1965. The ADI established
in 1965 was confirmed. The 1973 JMPR considered new studies that involved human volunteers
but, owing to the absence of sufficient information on the conduct of these studies in humans, the
existing ADI was re-affirmed. In 1991, the ADI was increased to 0−0.005 mg/kg bw on the basis
of reduced body-weight gain and fertility observed in the multigeneration study in rats. Azinphosmethyl
was reviewed by the present Meeting within the periodic review programme of the Codex
Committee on Pesticide Residues (CCPR). All studies previously submitted to JMPR were available
AZINPHOS-METHYL 139–172 JMPR 2007