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

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3.8 Other modes of action
Genotoxicity is always one possible mode of action to consider, but no genotoxic potential was
demonstrated for thiacloprid in the following tests:
• Mutation in four strains of Salmonella typhimurium;
• Mutation at the Hprt locus of Chinese hamster V79 cells;
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Chromosomal aberration in Chinese hamster V79 cells;
Unscheduled DNA synthesis induction in primary rat hepatocytes; and
Micronucleus induction in bone-marrow cells of mice treated in vivo.
Therefore, the available evidence indicates that genotoxicity is not an alternative mode of
action for thiacloprid.
3.9 Uncertainties, inconsistencies, and data gaps
No inconsistencies were identified in the database for thiacloprid with regard to the postulated
mode of action for ovarian luteomas in mice. However, there appears to be a lack of data for increases
of serum estradiol and/or prolactin levels, since these endpoints have not been investigated at
appropriate sampling times.
3.10 Assessment of postulated mode of action
The data presented are considered, with a moderate degree of confidence, to be adequate to
explain that thiacloprid exerts its carcinogenic effect on the mouse ovaries secondary to induction of
hepatic aromatase activity leading to increased serum estradiol and prolactin levels and prolonged
stimulation of ovarian tissues.
3.11 Conclusion
There is experimental evidence that thiacloprid induces ovarian luteomas in mice by a
process including induction of hepatic aromatase and prolonged stimulation of the ovarian tissues
by increased serum estrogen and prolactin levels. Although the postulated mode of action could
theoretically operate in humans, the available information allows for the conclusion that induction
of ovarian luteomas in mice by thiacloprid is exclusively a high dose phenomenon not relevant for
human exposure at levels of residues in food.
THIACLOPRID X-X JMPR 2006