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

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are caused by the higher incidence of uterine adenocarcinoma. The combined incidences of uterine
adenoma and adenocarcinoma at 25 and 50 ppm were lower than the incidence in controls.
The NOAEL for systemic toxicity was 25 ppm, equal to 1.2 and 1.6 mg/kg bw per day in
males and females, respectively, on the basis of liver toxicity (increased mixed eosinophilicclear
cell foci) and thyroid effects (follicular epithelial hypertrophy) at 50 ppm and greater. The
NOAEL for oncogenicity was 50 ppm, equal to 2.5 and 3.3 mg/kg bw per day in males and females,
respectively, on the basis of increased incidences of thyroid follicular cell adenoma in males and
uterine adenocarcinoma in females at 500 ppm and greater (Bomhard et al., 1998).
2.4 Genotoxicity
In vitro
The mutagenic potential of thiacloprid (purity, 97.2%; dissolved in dimethylsulfoxide [DMSO])
was investigated in a test for reverse mutation in Salmonella typhimurium (TA1535, TA100, TA1537 and
TA98). 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). A
slight bacteriotoxic effect was noted at the highest concentration. Tests were performed with quadruplicate
plating at each concentration using the plate incorporation method, and results were confirmed in an
independently repeated assay using the preincubation method. No biologically or statistically significant
increase in the number of revertant colonies was seen in any strain at any concentration. The positive
controls (sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine and 2-aminoanthracene) produced
significant increases in the frequency of revertant colonies (Herbold, 1995a).
The mutagenic potential of thiacloprid (purity, 96.8%; dissolved in DMSO) was investigated
in a test for reverse mutation in Salmonella typhimurium (TA98, TA100, TA1535 and TA1537) and
Escherichia coli (WP2 uvrA). The study complied with test guideline OECD 471. Five concentrations
of up to 5000 μg/plate were used in the presence and absence of a metabolic activation system
(phenobarbital- and 5,6-benzoflavone-induced rat liver S9). Precipitation of the test material was seen
at the highest concentration used in this study. Tests were performed with triplicate plating at each
concentration using the preincubation method and results were confirmed in an independently repeated
assay. No biologically or statistically significant increase in the number of revertant colonies was seen at
any concentration or in any strain. The positive controls (furylfuramide, sodium azide, 9-aminoacridine
and 2-aminoanthracene) produced significant increases in the number of revertant colonies (Ohta, 1995).
The mutagenic potential of thiacloprid (purity, 96.8–97.2%; dissolved in DMSO) was tested
in a test for HPRT locus mutation in mammalian cells in vitro in Chinese hamster V79 cells. The
study complied with test guideline OECD 476. Six concentrations of up to 500 μg/ml were used
in the presence and absence of a metabolic activation system (Aroclor 1254-induced rat liver S9).
No cytotoxicity was observed at concentrations up to 1000 μg/ml; precipitation of the test material
was seen at concentrations of 500 μg/ml and greater. Cells were exposed to thiacloprid for 5 h and
cultured for an additional 4 days and 7 days before subculturing in selective medium. Duplicate
cultures were used at each concentration and results were confirmed in independently repeated assays.
There was no significant dose-related or reproducible increase in the frequency of mutants above that
of the negative controls. The positive controls (ethylmethanesulfonate and dimethylbenzanthracene)
produced significant increases in the frequency of mutants (Brendler-Schwaab, 1996a).
The clastogenic potential of thiacloprid (purity, 96.8–97.2%; dissolved in DMSO) was tested
in a test chromosome aberration in Chinese hamster V79 cells in vitro. The study complied with test
guideline OECD 473. Cells were exposed for 4 h to thiacloprid at a concentration of 0, 75, 300 or
750 μg/ml in the presence and absence of a metabolic activation system (Aroclor 1254-induced rat liver
THIACLOPRID X-X JMPR 2006