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Male and female F344 rats but not B6C3F1 mice exposed for 104 weeks to propiverine hydrochloride (1-methylpiperid-4-yl 2,2-diphenyl-2-(1-propoxy)acetate hydrochloride), used for treatment of patients with neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), presented with an accumulation of proteins in the cytosol and nuclei of renal proximal tubule epithelial cells, yet despite this, no increased renal tumor incidence was observed. In order to provide an improved interpretation of these findings and a better basis for human health risk assessment, male and female F344 rats were exposed for 16 weeks to 1000 ppm propiverine in the diet, the accumulating protein was isolated from the kidneys via cytosolic and nuclear preparations or laser-capture microdissection and analyzed using molecular weight determination and mass spectrometry. The accumulating protein was found to be d-amino acid oxidase (DAAO), an enzyme involved in amino and fatty acid metabolism. Subsequent reanalysis of kidney homogenate and nuclear samples as well as tissue sections using western blot and DAAO-immunohistochemistry, confirmed the presence and localization of DAAO in propiverine-treated male and female F344 rats. The accumulation of DAAO only in rats, and the limited similarity of rat DAAO with other species, including humans, suggests a rat-specific mechanism underlying the drug-induced renal DAAO accumulation with little relevance for patients chronically treated with propiverine.

The acute toxicities of 6 insecticides deriving from 5 different insecticide classes were assessed in laboratory tests with Micromus tasmaniae (Walker) after different post treatment periods (1.5-360 h). The aim was to determine optimal test durations for the calculation of stable (i.e., no further change over time) LC 50 and LC 90 estimates. In addition, the responses of M. tasmaniae to the above insecticides were compared with those for Chrysoperla carnea (Stephens). In short-term evaluations (≤24 h), methyl-parathion caused the highest mortality in M. tasmaniae. The toxicity of methyl-parathion did not change significantly over time; however, the toxicity of azinphos-methyl, cypermethrin, fenoxycarb, and diflubenzuron did. Minimum posttreatment periods of 48, 72, 120, and 360 h were necessary before stable lethal concentrations estimates could be determined for azinphos-methyl, cypermethrin, fenoxycarb, and diflubenzuron, respectively. At the point of stable LC 50 and LC 90 , the latter compounds were more toxic to M. tasmaniae than methyl-parathion. Tebufenozide did not cause any mortality in either lacewing species. Comparisons between the 2 lacewings species showed that M. tasmaniae was more sensitive to methyl-parathion, azinphos-methyl, and cypermethrin than C. carnea, whereas the toxicity offenoxycarb and diflubenzuron was similar to both species. The results demonstrate the importance of carrying out acute toxicity studies to an adequate posttreatment period to avoid underestimating the toxicities of insecticides. In addition, the comparisons with C. carnea demonstrated that the results of toxicity studies cannot be extrapolated to closely related families.

Specific activities of head acetylcholinesterase (AChE) and whole body glutathione-S-transferase (CST) were assayed as biomarkers of sublethal exposure to insecticides in larvae of 2 lacewing species, the Chrysopid Chrysoperla carnea Stephens and the Hemerobiid Micromus tasmaniae Walker. When M. tasmaniae was exposed to the organophosphates methyl-parathion or azinphos-methyl, the rate of AChE-inhibition was toxin-specific, exponentially dose-dependent, and increased within 24 h of exposure. Activity of AChE was less inhibited in C. carnea larvae, which reflected its higher tolerance to organophosphates in mortality tests. No inhibition of AChE activity (e.g., resulting from nonspecific binding to the enzyme) was observed following treatment with the pyrethroid cypermethrin and the insect-growth regulators fenoxycarb, diflubenzuron, and tebufenozide. The activity of GST increased significantly in M. tasmaniae larvae treated with sublethal doses of cypermethrin and decreased significantly in larvae treated with fenoxycarb. In contrast, no changes in GST activity were observed in C. carnea larvae for any of the compounds tested. Inhibition of AChE in lacewings proved a useful tool to study the impact of different organophosphates used in integrated pest management. However, further investigations are necessary to evaluate the potential applicability of GST activity as a biomarker in lacewings as different results are likely for different lacewing species, varying exposure times, repeated dose levels, different-aged larvae, and different substrates for the enzyme reaction.

Effects of 3 conventional insecticides (methyl parathion, azinphos-methyl, cyper­ methrin) and 3 insect growth regulators (fenoxycarb, diflubenzuron, and tebufenozide) on life-table parameters of Micromus tasmaniae Walker were determined in adults derived from insecticide-treated larvae. The following parameters were compared with the control: sex ratio, longevity, sterility, and fecundity. Power analysis was used to increase the efficiency and the predictability of the life-table test. Diflubenzuron resulted in a higher proportion female lacewings. Longevity was reduced for females emerging from fenoxycarb- and diflubenzuron­ treated larvae. Total number of eggs was reduced for diflubenzuron- and fenoxycarb-treated lacewings, as weIl as the following generation oftebufenozide-exposed lacewings. Daily number of eggs was reduced for the diflubenzuron treatment. Peak egg production was increased for lacewings exposed to azinphos-methyl and was decreased for the following generation of tebufenozide-exposed lacewings. Diflubenzuron treatment resulted in an extended preovipo­ sition period. Oviposition periods were reduced for lacewings treated with fenoxycarb, di­ flubenzuron or azinphos-methyl as weIl as for the following generation of the tebufenozide treatment. The time to peak egg production was similar for all treatments. Methyl parathion, cypermethrin, and tebufenozide treatments showed no differences in any ofthe tested life-table parameters in the 1st generation. In summary, the insect growth regulators fenoxycarb and diflubenzuron had a more severe impact on life-table parameters than the 2 organophosphates and the pyrethroid. In future research, increased attention should be paid to long-term (e.g., the following generation) effects on life-table parameters.