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

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Table 17. Results of studies of acute toxicity and irritation with CGA 71019 (1,2,4-triazole)
Study Species Results Reference
Acute oral LD 50
Rats 500 < LD 50
< 5000 mg/kg bw Procopio & Hamilton (1992)
LD 50
= 1650 and 1648 mg/kg bw for males
and females, respectively.
Acute dermal LD 50
Rats LD 50
= 4200 and 3129 mg/kg bw for males
and females, respectively
Thyssen & Kimmerle (1976)
Thyssen & Kimmerle (1976)
Rabbits 200 < LD 50
< 2000 mg/kg bw Procopio & Hamilton (1992)
Acute inhalation LC 50
(4 h) Rats Exposure to the test article not demonstrated Thyssen & Kimmerle (1976)
Acute inhalation LC 50
(6 h) Mice Exposure to the test article not demonstrated Thyssen & Kimmerle (1976)
Acute skin irritation Rabbits Not irritating Procopio & Hamilton
(1992); Thyssen & Kimmerle
(1976)
Acute eye irritation Rabbits Irritating Procopio & Hamilton
(1992); Thyssen & Kimmerle
(1976)
Skin sensitization
(maximization test)
Guinea-pigs Not ssensitizing Frosch (1998)
males and 234 mg/kg bw per day in females) and at 1000/4000 ppm (210 mg/kg bw per day in males;
275 mg/kg bw per day in females). At these doses, degenerative lesions were seen in the cerebellum,
the lumbar dorsal root ganglion and other peripheral nerves. The brain lesions were limited to the anterior,
dorsal cerebellum and were coded overall as an increased incidence of cellular degenerations
and necrosis. Findings were characterized by extensive loss of Purkinje cells, variable white matter
degeneration and gliosis. Subtle atrophy of the molecular layer, primarily at the cerebellar surface,
or loss of granule cells was occasionally present. The effects tended to be slightly more prominent in
males. Individual nerve-fibre degeneration, which is frequently seen in healthy rats of this age, was
increased in incidence and severity in the peripheral nerves (sciatic, tibial, sural). Additionally, minimal
to mild neuronal chromatolysis and vacuolation of the lumbar dorsal root ganglia was observed
at ≥ 3000 ppm, but no similar change was seen in the cervical dorsal root ganglia. The NOAEL for
general effects and effects on the nervous system in rats was 500 ppm (33 mg/kg per day in males
and 41 mg/kg per day in females).
In comparison to rats, mice proved to be less sensitive to 1,2,4-triazole. In a 13-week dietary
study in mice, clinical symptoms were found only at 6000 ppm (988 mg/kg bw per day in males
and 1346 mg/kg bw per day in females). Body-weight gain was decreased at this dose in males and
females and at 3000 ppm in males (487 mg/kg bw per day). In mice treated for 13 weeks, the central
nervous system was established as a target organ for 1,2,4-triazole, albeit only near or above the limit
dose of 1000 mg/kg bw per day (6000 ppm). In histopathology, a minimal to mild loss of Purkinje
cells was seen in the cerebellum at the end of the 13-week exposure period in mice at 6000 ppm, with
no effects on the peripheral nervous system. Lower absolute brain weights were observed in males
at 3000 ppm and males and females at 6000 ppm; however, no histopathological effects on the brain
were observed at 3000 ppm. In a separate 28-day dietary study in mice, no effects on the nervous
system were observed at doses of up to 2000 ppm (356 mg/kg bw per day in males and 479 mg/kg
bw per day in females).
In the 28-day study in mice, effects on the testes and epididymides were observed at the highest
dose only (2000 ppm). Similar effects on the testes were observed in a dose–responsive manner at
3000 and 6000 ppm (487 and 988 mg/kg bw per day) in the 13-week study in mice. This effect on the
testes was related to increased incidence and severity (minimal to slight) of certain findings that also
DIFENOCONAZOLE 201–272 JMPR 2007