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Spinosad is a bacterially derived insect control agent consisting of two active compounds, spinosyns A and D. The objective of this paper is to describe the environmental fate of spinosad in aquatic systems. To this end, several studies performed to meet regulatory requirements are used to study the fate and degradation in individual environmental media. Specifically, investigations of abiotic (hydrolysis and photolysis) and biotic (aerobic and anaerobic aquatic) processes are described. Understanding developed from the laboratory-based studies has been tested and augmented by an outdoor microcosm study. Understanding of aquatic fate is a building block for a complete environmental safety assessment of spinosad products (Cleveland, C. B.; Mayes, M. A.; Cryer, S. A. Pest Manag. Sci. 2001, 58, 70-84). From individual investigations, the following understanding of dissipation emerges: (1) Aqueous photolysis of spinosad is rapid (observed half-lives of <1 up to 2 days in summer sunlight) and will be the primary route of degradation in aquatic systems exposed to sunlight. (2) Biotic transformations contribute to spinosad's dissipation, but less so than photolysis; they will be of primary importance only in the absence of light. (3) Spinosad partitions rapidly (within a few days) from water to organic matter and soil/sediment in aquatic systems but not so rapidly as to replace sunlight as the primary route of dissipation. (4) Abiotic hydrolysis is relatively unimportant compared to other dissipation routes, except under highly basic (artificial) conditions and even then observed half-lives are approximately 8 months. Degradation pathways are understood are follows: (1) Degradation primarily proceeds by loss of the forosamine sugar and reduction of the 13,14-bond on the macrolide ring under aqueous photolytic conditions. (2) Degradation to several other compounds occurs through biotic degradation. Degradation under anaerobic conditions primarily involves changes and substitutions in the rhamnose ring, eventually followed by complete loss of the rhamnose ring. Degradation under aerobic conditions was more extensive (to smaller compounds) with the loss of both the forosamine and rhamnose sugars to diketone spinosyn aglycon degradates. (3) Hydrolytic degradation involves loss of the forosamine sugar and water and reduction on the macrolide ring to a double bond at the 16,17-position.

In order to better understand the potential toxicity of diethanolamine (DEA) and preparatory to physiologically-based pharmacokinetic model development, the pharmacokinetics of DEA at high and low internal dose through 96-h post-dosing were determined in female Sprague-Dawley rats administered 10 or 100 mg/kg uniformly labeled 14C-DEA via intravenous injection. Clearance of DEA from blood was calculated to be approximately 84 ml/h/kg at the low dose, increasing to approximately 242 ml/h/kg at the high dose. The primary route of excretion of administered radioactivity, approximately 25-36%, was via the urine as parent compound. A majority of the administered radioactivity was recovered in the tissues of treated rats, especially in the liver and kidneys, suggesting a propensity of DEA or its metabolites for bioaccumulation. An accumulation of radioactivity also occurred gradually in the red blood cells from about 6-96 h post-dosing. Some evidence of dose dependency in the fate of iv-administered DEA was observed, suggesting that saturation of the bioaccumulation process(es) occurred at a dose level of 100 mg/kg.

A sensitive gas chromatographic-mass spectrometric method was developed to quantitate total o-phenylphenol (OPP) (free plus conjugates) in human urine. Conjugates of OPP were acid-hydrolyzed to free OPP, derivatized to the pentafluorobenzoyl ester derivative and analyzed via negative-ion chemical ionization gas chromatography-mass spectrometry. Two stable isotope analogs of OPP were shown to be suitable as internal standards for this method (D2-phenol ring, 13C6-phenyl ring). A synthetic method is presented for the preparation of the D2-OPP internal standard. The 13C6-OPP analog was also shown to be useful as an alternate test material for laboratory-based exposure studies. The limit of quantitation for this method was 1 ng OPP/ml urine. Calibration curves were linear for the analyte over the concentration range of 0.5-1117 ng OPP/ml urine. Relative recovery of OPP from urine ranged from 97.0 to 104.7%. Low levels of OPP (mean=6+/-7 ng/ml; n=22) were found in control human urine samples. The method was validated with urine samples obtained from human volunteers undergoing a dermal exposure study with 12C-/13C6-/14C-OPP. This method was developed to aid in assessments of human exposure to OPP during a variety of uses of the compound.

A sensitive and selective gas chromatographic-negative-ion chemical ionization mass spectrometric method was developed to simultaneously quantitate 2-butoxyethanol (BE) and butoxyacetic acid (BAA) in rat and human blood at low ng/g levels as pentafluorobenzoyl and pentafluorobenzyl derivatives, respectively. Analysis of 13C-labeled analogs of BE and BAA were found to improve the limits of quantitation to below 2 ng/g. Deuterium-labeled BE and BAA were used as internal standards. Calibration curves were generally linear over three orders of magnitude, with limits of quantitation of 16-18 ng/g for both BE and BAA, and 1.5 and 0.4 ng/g for [13C2]BE and [13C2]BAA, respectively, in human blood. Linearity in rat blood was similar, with limits of quantitation of 22 ng/g for BE and 5 ng/g for BAA. This method was developed for the support of mammalian metabolism studies and human biomonitoring studies involving exposure to BE or [13C2]BE.

A physiologically based pharmacokinetic model was developed to describe the disposition of 2-butoxyethanol (CAS 111-76-2) and its major metabolite, 2-butoxyacetic acid, in rats and humans. A previous human inhalation model by Johanson (Toxicol. Lett. 34, 23 (1986)) was expanded to include additional routes of exposure, physiological descriptions for rats, competing pathways for metabolism of 2-butoxyethanol, and measured partition coefficients for 2-butoxyethanol and 2-butoxyacetic acid. Simulations were compared to data gathered from rats following either intravenous infusion or oral or inhalation exposure and from humans following either inhalation or dermal exposure to 2-butoxyethanol. It was necessary to add equations for both protein binding of 2-butoxyacetic acid in blood and saturable elimination of 2-butoxyacetic acid by the kidneys to consistently describe the data. While the model predicted that rats metabolize 2-butoxyethanol and eliminate the acid metabolite faster per kilogram body weight than humans, the balance of these two processes in addition to physiological differences between species resulted in higher predicted peak blood concentrations as well as total areas under the blood concentration time curves for 2-butoxyacetic acid for rats versus humans. These species differences in kinetics coupled with the fact that human blood is significantly less susceptible than rat blood to the hemolytic effects of 2-butoxyacetic acid indicate that there is considerably less risk for hemolysis in humans as a result of exposure to 2-butoxyethanol than would have been predicted solely from standard toxicity studies with rats.