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

395
Toxicologically significant compounds in animals,
plants and the environment
Acute toxicity
Rat, LD 50
, oral
Rat, LD 50
, dermal
Rat, LC 50
, inhalation
Rabbit, skin irritation
Rabbit, eye irritation
Guinea-pig, skin sensitization (test method used)
Short-term studies of toxicity
Target/critical effect
Lowest relevant oral NOAEL
Lowest relevant dermal NOAEL
Lowest relevant inhalation NOAEC
Genotoxicity
Long-term studies of toxicity and carcinogenicity
Target/critical effect
Lowest relevant NOAEL
Carcinogenicity
Reproductive toxicity
Reproduction target/critical effect
Lowest relevant reproductive NOAEL
Developmental target/critical effect
Lowest relevant developmental NOAEL
Neurotoxicity/delayed neurotoxicity
Special studies
Medical data
Procymidone, hydroxyprocymidone
> 5000 mg/kg bw
> 2500 mg/kg bw
> 1.5 mg/l
Slight transient irritant
Not irritating
Negative (Magnusson & Kligman maximization test)
Decreased body-weight gain, liver effects, testes
25 mg/kg bw per day
1000 mg/kg bw per day
No data
Not genotoxic
Body weight, liver effects
14 mg/kg bw per day (rat)
Liver tumours in mice; testes tumours in rats.
Hypospadias; altered testes and epididymis weight
12.5 mg/kg bw per day
Hypospadias (rat)
12.5 mg/kg bw per day
No evidence in conventional studies
Kinetic and metabolism studies in rats, monkeys, rabbits,
mice and with human tissues showed differences between
species. Rats having a relatively high area-under-the curve
and a low capability to metabolize procymidone and
hydroxyprocymidone.
Receptor-binding assays showed that procymidone and
hydroxyprocymidone could bind to rat and human androgen
receptors. Both procymidone and hydroxyprocymidone were
extensively bound (≥ 77%) to plasma proteins.
Procymidone produced increases in luteinizing hormone and
human chorionic gonadotrophin-stimulated production of
testosterone in rats at 6000 ppm and ≥ 700 ppm respectively.
Ejaculate mass was reduced in monkeys exposed to
procymidone for 13 weeks at ≥ 100 mg/kg bw per day.
NOAEL was 30 mg/kg bw per day
Hydroxyprocymidone induced hypospadias in rats
at ≥ 62.5 mg/kg bw per day; BMDL 10
was 43.8 mg/kg bw
per day.
No adverse findings reported
PROCYMIDONE 349–401 JMPR 2007