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

LAMBDA-CYHALOTHRIN
First draft prepared by
G. Wolterink 1 & D. Ray 2
1
Centre for Substances and Integrated Risk Assessment,
National Institute for Public Health and the Environment,
Bilthoven, Netherlands; and
2
Medical Research Council Applied Neuroscience Group, Biomedical Sciences,
University of Nottingham, Queens Medical Centre
Nottingham, England
Explanation ...................................................................................................... 173
Evaluation for acceptable daily intake ............................................................. 174
1. Biochemical aspects ........................................................................... 174
1.1 Absorption, distribution and excretion ....................................... 174
1.2 Biotransformation ...................................................................... 177
(a) In vivo ............................................................................... 177
2. Toxicological studies ......................................................................... 180
2.1 Acute toxicity.............................................................................. 180
2.2 Short-term studies of toxicity...................................................... 181
2.3 Long-term studies of toxicity and carcinogenicity...................... 184
2.4 Reproductive toxicity ................................................................. 186
(a) Multigeneration studies ..................................................... 186
(b) Developmental toxicity...................................................... 187
2.5 Genotoxicity................................................................................ 188
2.6 Special studies: neurotoxicity..................................................... 188
3. Observations in humans ..................................................................... 191
Comments ........................................................................................................ 193
Toxicological evaluation................................................................................... 195
References ....................................................................................................... 198
Explanation
Lambda-cyhalothrin, the International Organization for Standardization (ISO) approved common
name for (R)-cyano(3-phenoxyphenyl)methyl (1S,3S)-rel-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-
propenyl]-2,2-dimethylcyclopropanecarboxylate is a synthetic cyano-containing type II pyrethroid
insecticide (Chemical Abstracts Service, CAS No. 91465-08-6).
Cyhalothrin (CAS No. 68085-85-8) was evaluated by the JMPR in 1984, when an acceptable
daily intake (ADI) of 0–0.02 mg/kg bw was established based on a no-observed-adverse-effect level
(NOAEL) of 20 ppm, equal to 2 mg/kg bw per day, identified on the basis of clinical signs in a 2-year
study in mice; a NOAEL of 30 ppm, equal to 1.5 mg/kg bw per day, identified on the basis of decreased
body-weight gain in a three-generation study in rats; and a NOAEL of 2.5 mg/kg bw per day, identified
on the basis of neurotoxicity in a 6-month study in dogs, and using a safety factor of 100.
LAMBDA-CYHALOTHRIN 173–200 JMPR 2007