Spinosad insecticide: subchronic and chronic toxicity and lack of carcinogenicity in Fischer 344 rats.

Spinosad is an insecticide derived from a naturally occurring bacterium via fermentation. The toxicity of spinosad was characterized in subchronic and chronic toxicity/oncogenicity studies conducted according to standard toxicology regulatory guidelines. Subchronic toxicity was evaluated in groups of 10 Fischer 344 rats/sex given feed containing 0, 0.05, 0.1, 0.2, or 0.4% spinosad (Study 1) or 0, 0.003, 0.006, 0.012, or 0.06% spinosad (Study 2) for 13 weeks. Lower body weights and increased mortality occurred in rats given 0.4% spinosad. Microscopic effects were observed in the adrenal glands, liver, lymphoid cells, reproductive tissues, kidney, thyroid, stomach, lung, and skeletal muscle of rats given > or = 0.05% spinosad, and consisted primarily of vacuolation of cells; however, degenerative, regenerative, and/or inflammatory changes were also noted in some tissues. Vacuolation within a number of tissues was ultrastructurally characterized by an increase in size and number of lysosomes that contained extensive membranous whorls consistent with phospholipidosis. The no observed effect level (NOEL) in the 13-week studies was 0.012% (24 mg/kg/day) spinosad. Chronic toxicity and oncogenicity were evaluated in groups of 60 Fischer 344 rats/sex given feed containing 0, 0.005, 0.02, 0.05, or 0.1% spinosad for up to 2 years. Rats given 0.1% spinosad for 1 year had microscopic effects similar to those observed in the subchronic studies. Vacuolation and inflammation of the thyroid gland also occurred in rats given 0.05% spinosad for 1 year. Excessive mortality occurred in rats from the oncogenicity study given 0.1% spinosad by 21 months, and surviving rats were euthanized because the maximum tolerated dose had been exceeded. Rats given 0.05% spinosad for 2 years had vacuolation and/or inflammation involving the thyroid, lymphoid tissue, and lung. Rats given 0.05% spinosad had similar numbers of neoplasms as control rats, indicating that spinosad was not carcinogenic at dose levels up to 0.05%. The NOEL at 2 years was 0.005% (2.4 mg/kg/day) spinosad.