In vitro and in vivo assessment of the effect of impurities and chirality on methamidophos-induced neuropathy target esterase aging.

In vitro and in vivo studies evaluated neuropathy target esterase (NTE) inhibition and aging (i.e., loss of reactivation potential) by analytical and technical grade racemic and resolved L-(-) and D-(+) isomers of methamidophos (O,S-dimethyl phosphoramidothioate). For studies in vitro, microsomal protein from phenobarbital-induced livers was isolated from chick embryos and NTE inhibition assays were performed using chick embryo brain homogenate treated with 1 or 5 mM methamidophos (with and without metabolic enzymes); for studies in vivo, hens received 30 to 35 mg/kg methamidophos injected into the pectoral muscle. NTE aging in hens was assessed 24 h later or after 30 min to 1 h incubation in vitro using solutions of potassium fluoride (KF) reactivator. Technical methamidophos produced significantly higher levels of aged-inhibited NTE than analytical methamidophos or isolated optical isomers. In vivo, technical methamidophos produced 61% total NTE inhibition with 18% aged and 43% unaged NTE; hens receiving analytical grade averaged 6% aged, 52% unaged, and 58% total NTE inhibition. Results for 1 mM analytical methamidophos in vitro were 5% aged, 54% unaged, and 59% total inhibition; for 1 mM technical methamidophos, values averaged 11% aged, 50% unaged, and 60% total NTE inhibition. The degree of NTE aging obtained both in vivo and in vitro for the isolated D-(+) and L-(-) isomers never exceeded that obtained using analytical grade. These data indicate that impurities in methamidophos could contribute to OPIDN potential. The in vitro methodology described could be applied to first tier screening for detection of NTE inhibition and aging, thus reducing the need for whole-animal testing for OPIDN.

Assessment of azinphosmethyl exposure in California peach harvest workers.

We compared measurements of urinary alkylphosphate metabolites and oxime-induced reactivation of plasma cholinesterase (P-ChE) and erythrocyte acetylcholinesterase (RBC-AChE) with measurements of foliar residues, skin and clothing contamination, and P-ChE and RBC-AChE activities among 20 Northern California peach orchard workers exposed to the organophosphate agent azinphosmethyl (Guthion). Subjects entered orchards treated 30 d previously with azinphosmethyl and worked 21 d in treated fields during the ensuing 6 wk. Dislodgeable foliar residues ranged from 0.32-0.96 micrograms/cm2. Median reduction in RBC-AChE activity was 7% (p < .001) over the initial 3-d period of exposure and 19% (p < .01) over the 6-wk season. Urinary metabolites were the most sensitive indicator of recent exposure and correlated moderately with dermal and clothing levels (rs = +0.31-(+)0.55); urinary metabolites correlated well with RBC-AChE drawn 3 d after exposure began (rs = -0.77). No significant oxime-induced reactivation was found.

Years of potential life lost (YPLL)--what does it measure?

The concept of years of potential life lost (YPLL) involves estimating the average time a person would have lived had he or she not died prematurely. This measure is used to help quantify social and economic loss owing to premature death, and it has been promoted to emphasize specific causes of death affecting younger age groups. YPLL inherently incorporates age at death, and its calculation mathematically weights the total deaths by applying values to death at each age. The method of calculating YPLL varies from author to author, each producing different rankings of leading causes of premature death. One can choose between heart disease, cancer, or accidents as the leading cause of premature death, depending on which method is used. Confusion in the use of this measure stems from a misunderstanding of the value system inherent in the calculation, as well as from differing views as to values that should be applied to each age at death.