Publications by authors named "Larry Holden"

Dow AgroSciences (DAS) markets and sells 1,3-Dichloropropene (1,3-D), the active ingredient in Telone®, which is used as a pre-plant soil fumigant nematicide in economically important crops in California. 1,3-D has been regulated as a "probable human carcinogen" and the California Department of Pesticide Regulation limits use of 1,3-D based on human health risk assessments for bystanders. This paper presents a risk characterization for bystanders based on advances in the assessment of both exposure and hazard.

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A de novo population mobility survey of 800 households (random digit dialing-based phone interviews) was conducted in high demand areas of the agricultural fumigant, 1,3-dichloropropene (1,3-D) in Merced and Ventura counties of California. The survey included approximately 20 questions relating to the length of time individuals had lived in the high demand areas in each county, and also relating to weekly and annual mobility patterns. Lifetime inhalation exposures to 1,3-D are determined, in part, by the number of years individuals spend in an area where the fumigant is used.

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An observational biomonitoring study was conducted involving adults and children in households that purchased and applied a cyphenothrin-containing spot-on product for dogs as part of their normal pet care practices. The 3- to 6-yr-old children had greater exposure than the adult applicators in the same house, 3.8 and 0.

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The natural estrogen 17 beta-estradiol (E2) is a potential environmental contaminant commonly employed as a positive control substance in bioassays involving estrogenic effects. The aquatic anuran Xenopus laevis is a frequent subject of reproductive endocrine disruptor research; however, histopathological investigations have tended to be less than comprehensive. Consequently, a study was designed to characterize gross and microscopic changes in the gonads of X.

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Neurotoxicity and mechanistic data were collected for six alpha-cyano pyrethroids (beta-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and lambda-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and multivariate dissimilarity analysis were employed to evaluate four independent data sets comprised of (1) fifty-six behavioral and physiological parameters from an acute neurotoxicity functional observatory battery (FOB), (2) eight electrophysiological parameters from voltage clamp experiments conducted on the Na(v)1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy, potency and binding calculated for calcium ion influx across neuronal membranes, membrane depolarization and glutamate released from rat brain synaptosomes and (4) changes in chloride channel open state probability using a patch voltage clamp technique for membranes isolated from mouse neuroblastoma cells.

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The potential impact of atrazine (ATZ) on gonadal malformations in larval Xenopus laevis has been controversially discussed, and a hypothesis has been generated that ATZ might induce the estrogen-synthesizing enzyme aromatase, leading to feminization or demasculinization. Recently, extensive long-term studies clearly indicate that no adverse effect of ATZ on larval development and sexual differentiation could be found. Therefore, to determine potential transient impacts of ATZ on sexual differentiation processes, short-term exposures were conducted using tadpoles treated for 4 days with ATZ at 25 microg/L.

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Debate and controversy exists concerning the potential for the herbicide atrazine to cause gonadal malformations in developing Xenopus laevis. Following review of the existing literature the U.S.

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Xenopus laevis has been introduced as a model to study effects of endocrine-active compounds (EAC) on development and sexual differentiation. However, variable and inconsistent data have raised questions about the reliability of the test methods applied. The current study was conducted in two laboratories to develop, refine, and standardize procedures and protocols.

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Passive dosimetry (PD) methods for measuring and estimating exposure to agricultural workers (i.e., persons handling agricultural chemicals and working in treated crops) have been in use since the 1950s.

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The reasons for classifying causes of death into aggregate groups are discussed and the impact of mortality partitions on analyses of mortality is described. Special emphasis is given to a mortality partition that distinguishes between intrinsic causes of death that arise primarily from the failure of biological processes that originate within an organism, and extrinsic causes of death that are primarily imposed on the organism by outside forces. Examples involving mortality data for mice, dogs, and humans are used to illustrate how this mortality partition infuses biological reasoning into mathematical models used to analyze and predict senescent-determined mortality, enhances the information content of the mortality schedules generated from these models, improves mortality comparisons between populations within species separated by time or geographic location, and provides a logical pathology endpoint for making interspecies comparisons of mortality.

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An innovative approach to dose-response modeling provides statistical insight into the relative likelihood of different mechanisms of action in cancer dose-response studies. Two illustrative examples are given based on time-to-tumor data on mammary fibroadenoma and adenocarcinoma in female Sprague-Dawley rats using 34 different dose metrics. The likelihood for the study outcome was calculated for each dose metric and compared with the background likelihood using a likelihood-ratio test.

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The Agricultural Reentry Task Force (ARTF) conducted a study to determine if dislodgeable foliar residues (DFR) are either normally or lognormally distributed. This is important because the data are used with worker exposure data, which generally appear to be lognormally distributed, to calculate transfer coefficients that will be used to assess farm worker re-entry exposure. Two chemicals were used for this study.

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