Bruce A. Halley

The environmental impact of the use of ivermectin: environmental effects and fate

Abstract The environmental effects and fate of ivermectin were studied either as the pure compound or in feces. Toxicities to microbes, earthworms, algae, fish, and Daphnia, soil-binding parameters and degradation half-lives were determined.

Environmental effects of the usage of avermectins in livestock.

Abamectin (avermectin B1) and ivermectin (22,23-dihydroavermectin B1) are high molecular weight hydrophobic compounds, active against a variety of animal parasites and insects. Numerous environmental fate and effects studies have been carried out in the development of these two compounds as antiparasitic agents and for abamectin as a crop protection chemical. They were found to be immobile in soil (Koc > or = 4000), rapidly photodegraded in water (degradation half-life (t1/2) in the summer 0.5 days or less) and as thin films on surfaces (t1/2 < 1 day), and aerobically degraded in soil (ivermectin in soil/feces mixtures (t1/2) = 7-14 days; avermectin B1a in soils, t1/2 = 2-8 weeks) to less bioactive compounds. Abamectin is not taken up from the soil by plants, nor is it bioconcentrated by fish (calculated steady-state bioconcentration factor of 52, with rapid depuration). Daphnia magna is the fresh water species found to be most sensitive to ivermectin and abamectin (LC50 values of 0.025 and 0.34 ppb respectively); fish (e.g. rainbow trout) are much less sensitive to these compounds (LC50 values of 3.0 ppb and 3.2 ppb, respectively). In the presence of sediment, toxicity toward Daphnia is significantly reduced. The metabolism and degradation of ivermectin and abamectin result in reduced toxicity to Daphnia. Abamectin and ivermectin possess no significant antibacterial and antifungal activity. They display little toxicity to earthworms (LC50 values of 315 ppm and 28 ppm in soil for ivermectin and abamectin, respectively) or avians (abamectin dietary LC50 values for bobwhite quail and mallard duck of 3102 ppm and 383 ppm, respectively), and no phytotoxicity. Residues of the avermectins in feces of livestock affect some dung-associated insects, especially their larval forms. This does not delay degradation of naturally formed cattle pats under field conditions; however, in some cases, delays have been observed with artificially formed pats. Based on usage patterns, the availability of residue-free dung and insect mobility, overall effects on dung-associated insects will be limited. As abamectin and ivermectin undergo rapid degradation in light and soil, and bind tightly to soil and sediment, they will not accumulate and will not undergo translocation in the environment, minimizing any environmental impact on non-target organisms resulting from their use.

Environmental Aspects of Ivermectin Usage in Livestock: General Considerations

A detailed analysis of ivermectin’s effect on the environment was an integral component of the overall program to develop ivermectin as an antiparasitic drug for food-producing animals. The analytical studies were designed to determine whether using ivermectin in animals would result in any harmful or undesirable effects on the environment. These studies measured ivermectin’s physical properties and its mobility, distribution, and stability in soil and water. Additional studies investigated the drug’s effect on a variety of environmentally important organisms. These studies, combined with the clinical use pattern of ivermectin in cattle, sheep, and swine, provided the means to assess ivermectin’s environmental impact.

The environmental safety of ivermectin: An overview

Abstract The environmental safety of ivermectin is evaluated by comparing residue levels expected in soil from the fertilization with animal manures with data from laboratory and field studies. Under approved use, ivermectin should cause no significant adverse environmental effects.

Identification of cytochrome P4503A as the major enzyme sub-family responsible for the metabolism of 22,23-dihydro-13-O-[(2-methoxyethoxy)methyl]avermectin B1 aglycone by rat liver microsomes

1. Metabolism of 22,23-dihydro-13-O-[(2-methoxyethoxy)methyl]-avermectin B1 aglycone (MEM-H2B1), a new avermectin, by rat liver microsomes has been studied. Metabolites identified were formed by demethylation of the methoxyethoxymethoxy (MEM) side chain, loss of the MEM side chain, partial cleavage and further oxidation of the MEM side chain, and oxidation of the aglycone after cleavage of the MEM side chain. 2. The specific cytochrome P450 isoforms involved in the metabolism of MEM-H2B1 were identified through immunoinhibition studies. Among several antibodies prepared against various cytochrome P450s, only anti-rat P4503A IgG inhibited MEM-H2B1 metabolism by liver microsomes from the untreated rat. Moreover, troleandomycin, a selective suicide inhibitor for enzymes of the cytochrome P4503A family, inhibited the total metabolism by > 80%. These results clearly indicate that cytochrome P4503A is primarily responsible for the metabolism of MEM-H2B1. 3. Secondary metabolism was evident in the metabolism of MEM-H2B1 by dexamethasone and phenobarbital induced liver microsomes, where different isoform(s) of cytochrome P4503A could be involved in these multiple step reactions.