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

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Table 19. Results of studies of acute toxicity and short-term studies of toxicity with 1,2,4-triazolyl
alanine
Study Species Dose LD 50
(mg/
kg bw)
NOAEL (mg/
kg bw per day)
Adverse effect
Reference
Acute toxicity
Oral Rat, mouse — > 5000 — — Mihail (1982)
Oral Rat — > 2000 — — Henderson
& Parkinson
(1980)
Intraperitoneal Rat — > 5000 — — Mihail (1982)
Short-term studies of toxicity
Twenty-eightday,
gavage
Rat 0, 25, 100 or
400 mg/kg bw
per day
— 400 mg/kg bw
per day
None observed Mihail & Vogel
(1983)
Ninety-day,
feeding
Ninety-day,
feeding
Rat 0, 1250, 5 000
and 20 000 ppm
Dog 0, 3 200, 8 000
and 20 000 ppm
— 5000 ppm,
equivalent to
500 mg/kg bw
per day
— 8000 ppm
equivalent to
200 mg/kg bw
per day
Reduced bodyweight
gains in
males at 20 000 ppm
Reduced food intake
and body-weight
gains in females at
20 000 ppm
Maruhn &
Bomhard
(1984)
von Keutz
& Gröning
(1984)
500 mg/kg bw per day, and the NOAEL for fetal toxicity of 2000 ppm, equivalent to 100 mg/kg bw
per day, on the basis of reduced birth weights at 10 000 ppm, equivalent to 500 mg/kg bw per day
(Table 21).
(iii) Toxicology of 1,2,4-triazolyl acetic acid
1,2,4-Triazolyl acetic acid (Figure 6) is a significant residue in plants treated with
d ifenoconazole.
The metabolism and pharmacokinetics of 1,2,4-triazolyl acetic acid have been evaluated in
rats (Lai & Simoneax; 1986b, 1986c). In a repeat-dose study, oral administration of radiolabelled
1,2,4-triazolyl acetic acid resulted in negligible tissue residue with no unusual accumulation in any
tissue or organ. Recovery of the administered dose was high and elimination was rapid, with 66–75%
of the administered dose being excreted via the urine and 11–32% via the faeces. In all cases, only
unchanged 1,2,4-triazolyl acetic acid was excreted.
A balance study to further refine the uptake and rates of excretion of 1,2,4-triazolyl acetic acid
after oral administration again confirmed that the primary route of excretion was via the urine. No
significant differences were observed in excretion patterns between males and females. Excretion of
radioactivity during the first 48 h after administration accounted for > 90% of the total activity at all
three doses used, indicating that clearance was not saturable at the doses tested.
The toxicity of 1,2,4-triazolyl acetic acid has been studied much less extensively than that of
1,2,4-triazolyl alanine. At a dose of 5000 mg/kg bw, no mortality was observed in rats given 1,2,4-
triazolyl acetic acid as a single oral dose and after a 14-day observation period. The LD50 was > 5000
mg/kg bw (Thevenaz, 1984).
In a 14-day dietary study, male and female rats were given diets containing 1,2,4-triazolyl
acetic acid at a concentration of 0, 100, 1000 or 8000 ppm, equal to 0, 11, 103 and 788 mg/kg bw
per day in males and 0, 10, 97 and 704 mg/kg bw per day in females. No mortality occurred in the
study, nor were there any clinical signs of systemic toxicity. Ophthalmic and auditory examinations
revealed no treatment-related reactions. The mean body-weight values and mean food and water
DIFENOCONAZOLE 201–272 JMPR 2007