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

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Estimate of acceptable daily intake for humans
0–0.01 mg/kg bw
Estimate of acute reference dose
0.3 mg/kg bw
Information that would be useful for the continued evaluation of the compound
Results from epidemiological, occupational health and other such observational studies of
h uman exposure
Critical end-points for setting guidance values for exposure to difenoconazole
Absorption, distribution, excretion and metabolism
Rate and extent of oral absorption High, but incomplete (rats)
Dermal absorption
Approximately 8% (rats)
Distribution
Distributed throughout the body; higher concentrations in liver and
g astrointestinal tract
Potential for accumulation
Rate and extent of excretion
Metabolism in animals
Toxicologically significant compounds
in animals, plants and environment
Low, no evidence of accumulation
High; essentially 100% excretion in bile and urine within 7 days
Extensive; a small number (< 10) of metabolites; little parent compound
remaining
Parent, 1,2,4-triazole
Acute toxicity
Rat, LD 50
, oral
1453 mg/kg bw
Rat, LC 50
, inhalation 3.3 mg/l (4 h)
Rabbit, LD 50
, dermal
2010 mg/kg bw
Rabbit, skin irritation
Very slightly and transiently irritating
Rabbit, eye irritation
Moderately and transiently irritating
Guinea-pig, skin sensitization Not sensitizing (modified Buehler test)
Short-term studies of toxicity
Target/critical effect
Lowest relevant oral NOAEL
Lowest relevant dermal NOAEL
Lowest relevant inhalation NOAEC
Genotoxicity
Liver; body weight
3.6 mg/kg bw per day (12-month study in dogs)
100 mg/kg bw per day (4-week study in rats)
No data
Not genotoxic
Long-term studies of toxicity and carcinogenicity
Target/critical effect
Liver; body weight
Lowest relevant NOAEL
1.0 mg/kg bw per day (24-month study in rats)
Carcinogenicity
Not carcinogenic at levels below those causing changes in the liver
Reproductive toxicity
Reproductive target/critical effect
Lowest relevant reproductive NOAEL
Developmental target/critical effect
None
132 mg/kg bw per day
Not teratogenic; reduced fetal body weight, delayed ossifications in rats, but
not in rabbits
DIFENOCONAZOLE 201–272 JMPR 2007