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

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Thiacloprid did not cause any specific neurobehavioural or neuropathological effects in the
offspring when administered to the dams during gestation and lactation at dietary concentrations of up
to 500 ppm. Non-specific signs of general toxicity, including decreased body-weight gains and delayed
sexual maturation, were observed in the offspring at dietary concentrations of 300 ppm and higher.
The NOAEL for maternal toxicity was 50 ppm, equal to 4.4 mg/kg bw per day, on the basis
of reduced body weights and feed consumption at 300 ppm and higher. The NOAEL for toxicity
to offspring was 50 ppm on the basis of reduced body weights in both sexes and delayed sexual
maturation (preputial separation) in males at 300 ppm and higher, and delayed sexual maturation
(vaginal patency) in females at 500 ppm (Hoberman, 2001).
(b)
Studies on metabolites
(i) Thiacloprid-amide (KKO 2254)
In a study of acute oral toxicity, five male and five female non-fasted Wistar (Hsd/Cpb:WU)
rats were given KKO 2254 (purity, 98.8%) as a single dose at 2000 mg/kg bw in demineralized water
with 2% v/v Cremophor by gavage. In addition, five males were dosed with 500 mg/kg bw. The
study complied with test guideline OECD 401. A single female died in the group at the highest dose.
Clinical signs of toxicity were observed in both sexes and included piloerection, decreased motility,
spastic and uncoordinated gait, tachypnea, laboured breathing, narrowed palpebral fissure, poor
reflexes and spontaneous vocalization. These overt signs were evident between 3–6 h after treatment
and lasted for up to 2 days in males and 3 days in females. No gross treatment-related findings were
detected at necropsy. The LD 50
value for the test material was greater than 2000 mg/kg bw for both
sexes (Kroetlinger, 1995c).
The mutagenic potential of KKO 2254 (purity, 98.8%; dissolved in DMSO) was investigated in a
test for reverse mutation in Salmonella typhimurium (TA1535, TA100, TA1537, TA98 and TA102). The
study complied with test guideline OECD 471. Six concentrations of up to 5000 μg/plate were used in
the presence and absence of a metabolic activation system (Aroclor 1254-induced rat liver S9). The initial
test was performed in triplicate using the plate incorporation procedure, and the results were confirmed
in an independent assay using the preincubation (20 min) method. No biologically or statistically
significant increase in the number of revertant colonies was seen in any strain at any concentration.
No bacteriotoxicity was observed. Appropriate positive controls (sodium azide, nitrofurantoin, 4-nitro-
1,2-phenylene diamine, cumene hydroperoxide and 2-aminoanthracene) produced significant increases
in revertant colonies (Herbold, 1995d).
(ii) Thiacloprid-sulfonic acid Na-salt (WAK 6999)
In a study of acute oral toxicity, five male and five female non-fasted Wistar (Hsd/Cpb:WU) rats
were administered WAK 6999 (purity, 95.7%) as a single dose at 2000 mg/kg bw in demineralized
water with 2% v/v Cremophor by gavage. The study complied with test guideline OECD 401. No
deaths occurred during the study. Clinical signs were observed 4 h after treatment and included
diarrhoea and lack of faeces. All overt signs had resolved within 2 days of treatment. No gross
treatment-related findings were detected at necropsy. The LD 50
value for the test material was greater
than 2000 mg/kg bw for both sexes (Kroetlinger, 1996d).
The mutagenic potential of WAK 6999 (purity, 95.7%; dissolved in deionized water) was
investigated in a test for reverse mutation in Salmonella typhimurium (TA1535, TA100, TA1537,
TA98 and TA102). The study complied with test guideline OECD 471. Six concentrations of
up to 5000 μg/plate were used in the presence and absence of a metabolic activation system
(Aroclor 1254-induced rat liver S9). The initial test was performed in triplicate using the
THIACLOPRID X-X JMPR 2006