Development of a consumer product ingredient database for chemical exposure screening and prioritization.

Consumer products are a primary source of chemical exposures, yet little structured information is available on the chemical ingredients of these products and the concentrations at which ingredients are present. To address this data gap, we created a database of chemicals in consumer products using product Material Safety Data Sheets (MSDSs) publicly provided by a large retailer. The resulting database represents 1797 unique chemicals mapped to 8921 consumer products and a hierarchy of 353 consumer product "use categories" within a total of 15 top-level categories. We examine the utility of this database and discuss ways in which it will support (i) exposure screening and prioritization, (ii) generic or framework formulations for several indoor/consumer product exposure modeling initiatives, (iii) candidate chemical selection for monitoring near field exposure from proximal sources, and (iv) as activity tracers or ubiquitous exposure sources using "chemical space" map analyses. Chemicals present at high concentrations and across multiple consumer products and use categories that hold high exposure potential are identified. Our database is publicly available to serve regulators, retailers, manufacturers, and the public for predictive screening of chemicals in new and existing consumer products on the basis of exposure and risk.

Differential evolution and neofunctionalization of snake venom metalloprotease domains.

Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteine-rich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type natriuretic peptide instead of the SVMP. The results of this study reinforce the value of studying obscure venoms for biodiscovery of novel investigational ligands.

Predicting pesticide emissions and downwind concentrations using correlations with estimated vapor pressures.

Pesticide emissions to air have been shown to correlate with compound vapor pressure values taken from the published literature. In the present study, emissions correlations based on vapor pressures derived from chemical property estimation methods are formulated and compared with correlations based on the literature data. Comparison was made by using the two types of correlations to estimate emission rates for five herbicides, a fungicide, and an insecticide, for which field-measured emission rates from treated soil, foliage, and water were available. In addition, downwind concentrations were estimated for two herbicides, three fungicides, four insecticides, and two fumigants, for which concentration measurements had been made near treated sources. The comparison results demonstrated that correlations based on vapor pressures derived from chemical property estimation methods were essentially equivalent to correlations based on literature data. The estimation approach for vapor pressures is a viable alternative to the inherently more subjective process of selecting literature values.

Chemomorphic analysis of malathion in skin layers of the rat: implications for the use of dermatopharmacokinetic tape stripping in exposure assessment to pesticides.

The dermatopharmacokinetic (DPK) method of dermal tape stripping may prove to be a valuable addition to risk assessment protocols for toxic substances as it has been for the assessment of bioequivalence and bioavailability of topical dermatologic drugs. The measurement of drug penetration into stratum corneum (SC) with respect to time is thought to be comparable with drug distribution in underlying tissues. To examine this possibility, the dermal penetration and absorption characteristics of [(14)C]malathion in the Sprague-Dawley rat was examined by three analytical techniques. [(14)C]Malathion was applied in different vehicles for 30-min and 1-h periods of exposure. Penetration into the SC was assessed by tape stripping followed by instant electronic autoradiography (IEA). Also, the (14)C activity retained in three successive 16 microm sections of the skin application site was determined by IEA and malathion was identified by Fourier transform infrared microscopy (FTIR microscopy). Absorbed [(14)C]malathion was measured in selected tissues, organs, and the residual carcass by liquid scintillation counting (LSC). Penetration into the SC followed a linear trend. The capacity of the SC reservoir for malathion amounted to approximately 1% of the dermal dose, while approximately 6% of the dose was absorbed. Results from this study support the view that LSC remains the method of choice to efficiently and reliably quantify absorption of a radiolabeled test substance. IEA offers the ability of the user to visualize the extent and profile of dermal absorption. When IEA is combined with FTIR microscopy, an effectual tool for studying the penetration of chemicals into layers of the skin emerges. The combined use of the three analytical techniques can be used to test the validity of the DPK method in hazard evaluation and exposure assessment of the organophosphorus insecticides.

Long-term follow-up of Vena Tech-LGM filter: predictors and frequency of caval occlusion.

PURPOSE: To report the frequency of caval occlusion after Vena Tech-LGM filter placement and identify related factors and their potential clinical significance. MATERIALS AND METHODS: The filter was inserted into 243 patients, 142 of whom met inclusion criteria for this prospective study. Follow-up examinations performed every 2 years included clinical evaluation, plain frontal radiography of the abdomen, duplex scanning of the inferior vena cava (IVC), and/or phlebocavography. RESULTS: A progressive decrease in IVC patency was observed, reaching 66.8% at 9 years of follow-up. Complete caval occlusion occurred in 28 patients and was significantly (P < 10(-6)) associated with retraction in 24 cases. Caval occlusion was not related to age, sex, pulmonary embolism (PE), deep venous thrombosis level, underlying conditions predisposing to a thromboembolic disease before filter insertion, the level of filter placement, use of anticoagulant therapy, and death during follow-up. PE with anticoagulation failure was a predictive factor (P = .016) of subsequent filter occlusion during follow-up as compared to all other clinical indications for filter placement. Filter patency at 9 years of follow-up was 35.2% in the PE group with anticoagulation failure and 80% for other patients (odds ratio, 2.5; 95% confidence interval 1.16-5.4). CONCLUSION: PE with anticoagulation failure was the only factor predictive of subsequent caval occlusion observed in patients after Vena Tech-LGM filter placement. Caval occlusion was also related to Vena Tech-LGM filter retraction, which usually occurred at the time of occlusion.

Determination of the distribution of malathion in rats following various routes of administration by whole-body electronic autoradiography.

The distribution of [14C]-malathion, an organophosphorus pesticide, in rats after intravenous, oral and dermal administration was carried out using electronic autoradiography of whole body sections of treated animals. The study indicated that a major difference in the disposition of [14C]-malathion occurred following various routes of administration to rats. Following intravenous administration, the liver and kidney accumulated extremely high levels of the chemical. After oral administration, [14C]-malathion absorption from the stomach was slow and its excretion followed mostly the fecal route. Dermal application of [14C]-malathion may represent a high risk for exposure to the organophosphorus pesticide where the entire skin, not only the site of application, may act as reservoir for the compound.

Malathion disposition in dermally and orally treated rats and its impact on the blood serum acetylcholine esterase and protein profile.

14C-methoxy-malathion with either pure or 50% E.C. formulated malathion were applied orally or dermally at one tenth of their LD50 to two batches of male albino rats. More than 90% of 14C was released with urine after 24 hours. The rest of 14C was detected in the feces, blood, intestines, liver and kidney in a descending order. No significant 14C was detected in other organs. Comparing the oral pure and formulated malathion treatments, there was no significant variation in the rate of disposition or excretion of 14C-malathion. However, the dermal treatment revealed that the 14C-formulated malathion was released faster than the pure one in urine in the first 24 hours; while the 14C-pure malathion showed relatively higher levels in the feces and blood in the first 24 hours. In a third batch of male albino rats, the effect of the same level of dermal treatment by either pure or 50% E.C. formulated malathion on serum acetylcholine-esterase (A. Ch. E.) activity and serum protein profile was studied. The serum A. Ch. E. activity was found to be inhibited to 40% activity after 6 to 24 hours for both treatments. However, after 96 hours the serum of the pure malathion treated rats showed full recovery of A.Ch.E. activity, while the formulated malathion treated showed only 60% activity. The SDS-PAGE analysis showed a differentiation in the serum protein bands of the 48 hours exposed rats to formulated malathion which was confirmed by the scanned gel profile. The FPLC integrated chromatograms proved an initiation of a new protein band accompanied with rearrangement of the albumin and pre-albumin bands. Thus it can be concluded that, the impact on the blood serum protein profile and A. Ch. E. activity can be used as reliable criteria to detect acute toxicity of malathion and other choline-esterase inhibitors in exposed field workers. Further research is needed to elucidate the specificity and sensitivity of such criteria as biomarkers for human exposure.

Structural and statistical object recognition in medical images.

Comparative results for LV identification are shown in Fig. 7, from which the following conclusions can be drawn: 1) success rate almost double when BOS are used. LV is finally found and correctly classified in 90% of cases, 2) a first class of error consists of undetected LVs. Since the process is aware of its failure, this is considered as a minor error. It happens with atypical images for which either the description is unadapted (4.7%) or some new BOSes (not encountered in the learning set) occur (2.7%). The latter case can be solved by updating the graph, contrarily to the first one, 3) a second class of error consists in misclassification. This is considered as a major error since the process is not aware of its failure. Such errors are due to either poor statistical classification (1.4%) or unmodelled BOSes (1.4%). The first case can be solved by improving the classification technique which is quite (too ?) simple in our work, while updating the graph should solve the second one.

Bioelectrical activity of isolated ventral nerve cords of the cockroach, Periplaneta americana L., treated with toxaphene.

Effects of toxaphene were studied with the ventral nerve cord (VNC) of the cockroach, Periplaneta americana (L). Intense forms of activity were observed in isolated nerve preparations treated with toxaphene. Latent periods between introduction of toxaphene and onset of intense activity decreased as the concentrations were increased.