Spinosad Insecticide: Subchronic and Chronic Toxicity and Lack of Carcinogenicity in CD-1 Mice

Abstract

The potential toxicologic and oncogenic effects of spinosad, a natural fermentation product with insecticidal properties, were investigated. The 13-week toxicity study consisted of groups of 10 CD-1 mice/sex provided diets containing 0, 0.005, 0.015, 0.045, or 0.12% spinosad (Study 1). The 0.12% group was terminated on Test Day 44 due to mortality and overt clinical signs of toxicity. An 18-month chronic oncogenicity study consisted of groups of 50 CD-1 mice/sex provided diets containing 0, 0.0025, 0.008, or 0.036% spinosad (Study 2). Two interim groups of 10 mice/sex/group were terminated after 3 and 12 months. Females given 0.036% were terminated on Day 455 due to markedly lower body weights and feed consumption, as well as excessive mortality. Because of the early termination of the female high-dose group, additional groups of 10 male and female mice (12-month interim necrospy) and 50 male and female mice (18-month necropsy) were provided diets containing 0, 0.0008, or 0.024% spinosad (Study 3) to fully assess potential chronic toxicity and oncogenicity. Standard toxicologic parameters were evaluated consistent with existing regulatory guidelines. The primary effect in the 13-week and 18-month studies was intracellular vacuolation of histiocytic and epithelial cells in numerous tissues and organs at doses of > or = 0.015%. The histological vacuolation corresponded to ultrastructural lysosomal lamellar inclusion bodies. This alteration was consistent with phospholipidosis, a condition that results from accumulation of polar lipids in lysosomes. Lesions with no apparent direct relation to vacuolation were hyperplasia of the glandular mucosa of the stomach, skeletal muscle myopathy, bone marrow necrosis, and anemia with associated splenic hematopoiesis. The incidence of tumors in mice given spinosad was not increased relative to controls at any dose level. The no observed effect level for the 13-week study was 0.005% (6 mg/kg/day) spinosad, and for the chronic toxicity/oncogenicity study was 0.008% (11 mg/kg/day) spinosad for male and female CD-1 mice.

Effect of Spinosad and Imidacloprid on Serum Biochemical Alterations in Male Broilers and Its Amelioration with Vitamin E and Silymarin

“…The observations in group 2 were similar to the results of Siddiqui et al, (2007) and Sasidhar Babu et al, (2014) in birds for a period of 28 and 90 days respectively. The observations in group 3 were in accordance with the results of Stebbins et al, (2002) in experimental mice for a period of 13 weeks.…”

“…The observations in group 2 were in agreement with experimental results of in Kammon et al, (2010) and Mohany et al, (2012) in layer chicken and rats respectively in IM induced studies. Increased levels of ALP in group 3 were in agreement with Stebbins et al, (2002) and Yano et al, (2002). An elevated level of serum ALP in the present study might be due to toxicity of IM, SPD and its combination which triggered the process of inflammation in liver, kidney and other organs which were evidenced histopathologically.…”

Hepato and Nephrotoxicity in Male Albino Rats Exposed to Malathion and Spinosad in Stored Wheat Grains

“…The most notable effect of spinosad after subchronic exposure in rats is vacuolar degeneration [19]. Stebbins et al [38] found that mice given 0.015% spinosad had vacuolation in liver and kidney tissues. In addition, it is possible that malathion and spinosad, like several other insecticides, adversely affect the cytochrome P450 system or the mitochondrial membrane transport system of hepatocytes [17].…”

Cytotoxic effects in mammalian Vero cells exposed to pentachlorophenol

“…It is thought that the myeloid bodies represent an adaptative response lysosomal in origin, usually associated with the binding of cationic amphiphilic drugs (CADs) to phospholipids in cellular membranes (Reasor and Kacew, 2001). Nevertheless, not only the CADs induce phospholipidosis; some authors report that different compounds such as the natural insecticide spinosad (Stebbins et al, 2002) and alkylphenols from Gingko biloba (Hecker et al, 2002) are able to develop this cellular disorder. Although the exact mechanism for the accumulation of the phospholipids in lysosomes is unknown, it may be due to the generation of indigestible drug-lipid complex, inhibition of lysosomal phospholipases or a combination of these possibilities (Halliwell, 1997).…”