Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

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Critical end-points for setting guidance values for exposure to haloxyfop (including haloxyfop-R
and haloxyfop-R methyl ester)
Absorption, distribution, excretion and metabolism in mammals
Rate and extent of oral absorption Rapid and extensive
Distribution
Widely distributed with highest levels in liver and kidneys.
Potential for accumulation None
Rate and extent of excretion T ½
= 6.3 days for clearance from plasma to urine (human). Mostly excreted in urine.
Main route of excretion is faeces in mice, male rats and dogs but urine in female
rats, cynomolgus monkeys and men.
Metabolism in mammals
Oral haloxyfop methyl ester rapidly transformed to haloxyfop acid on
absorption. Little primary metabolism, but some conjugation.
Toxicologically significant compounds Haloxyfop
in animals, plants and the environment
Acute toxicity
Rat, LD 50
, oral
300–337 mg/kg bw in males,
545–623 mg/kg bw in females
Rat, LD 50
, dermal
> 2000 mg/kg bw
Rabbit, dermal irritancy
Not irritating
Rabbit, eye irritancy
Not irritating
Guinea-pig, skin sensitization Not sensitizing (Buehler, and Magnusson & Kligman)
Short-term studies of toxicity
Target/critical effect
Liver
Lowest relevant oral NOAEL 0.2 mg/kg bw per day (serum alkaline phosphatase activity in mouse)
Lowest relevant dermal NOAEL < 40 mg/kg bw per day (erythrocytes)
Genotoxicity
Not genotoxic in vitro or in vivo
Long-term studies of toxicity and carcinogenicity
Target/critical effect
None
Lowest relevant NOAEL
0.1 mg/kg bw per day (highest dose tested in male rats)
Carcinogenicity
No carcinogenic potential in the rat. Hepatocellular carcinoma in female mice
associated with peroxisome proliferation (mode of action not relevant to humans)
Reproductive toxicity
Reproductive target/critical effects No reproductive effects
Low pup weight
Lowest relevant reproductive
NOAEL
Developmental target critical effect
Lowest relevant developmental
NOAEL
Neurotoxicity/delayed neurotoxicity
Other toxicological studies
Mechanism studies
Medical data
Parental: 1 mg/kg bw per day (highest dose tested)
Offspring: 0.065 mg/kg bw per day (pup weight)
Delayed ossification, resorptions
Maternal: 7.5 mg/kg bw per day (mortality)
Developmental: 1 mg/kg bw per day (delayed ossification)
No specific study; no findings in other studies
Increased hepatocellular peroxisome proliferation in mice, rats and hepatocytes
from guinea-pigs
No effect on peroxisome proliferation in dogs, monkeys or hepatocytes from humans
No adverse effects on health of manufacturing workers
HALOXYFOP X-X JMPR 2006