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

FLUSILAZOLE
First draft prepared by
C. Adcock 1 and M. Tasheva 2
1
Health Evaluation Directorate, Pest Management Regulatory Agency,
Health Canada, Canada; and
2
National Center of Public Health Protection, Sofia, Bulgaria
Explanation ...................................................................................................... 317
Evaluation for acceptable daily intake ............................................................. 318
1. Biochemical aspects ........................................................................... 318
1.1 Absorption, distribution and excretion ....................................... 318
1.2 Biotransformation ...................................................................... 319
2. Toxicological studies ......................................................................... 319
2.1 Acute toxicity.............................................................................. 319
(a) Ocular irritation ................................................................ 320
(b) Dermal irritation................................................................ 320
(c) Dermal sensitization ......................................................... 321
2.2 Short-term studies of toxicity ..................................................... 321
(a) Oral administration ........................................................... 321
(b) Dermal application ........................................................... 323
2.3 Long-term studies of toxicity/carcinogenicity ........................... 324
2.4 Genotoxicity................................................................................ 328
2.5 Reproductive toxicity ................................................................. 328
(a) Multigeneration studies ..................................................... 328
(b) Developmental toxicity...................................................... 330
2.6 Special studies ............................................................................ 336
(a) Studies on mechanisms by which Leydig-cell
tumours are induced .......................................................... 336
(b) Study on the mechanism of liver effects in dogs .............. 338
Comments......................................................................................................... 339
Toxicological evaluation................................................................................... 342
References ....................................................................................................... 344
Explanation
Flusilazole is the International Organization for Standardization (ISO) approved name for
1-[[bis(4-fluorophenyl)methyl]silyl]methyl]-1H-1,2,4-triazole (Chemical Abstracts Service, CAS
No. 85509-19-9). It is a broad-spectrum fungicide that belongs to the triazole subclass of ergosterol
biosynthesis inhibitors. Flusilazole was previously evaluated by the Joint Meeting in 1989 (Annex 5,
references 56, 58) and in 1995. An acceptable daily intake (ADI) of 0–0.001 mg/kg bw was allocated
in 1989, based on a no-observed-adverse-effect level (NOAEL) of 0.14 mg/kg bw per day (5 ppm)
for liver toxicity in a 1-year feeding study in dogs. This was confirmed in 1995. The compound was
re-examined by the present Meeting as part of the periodic re-evaluation programme of the Codex
FLUSILAZOLE 317–347 JMPR 2007