Stone DL

References (3)

Title : Notes from the field: acute illness associated with use of pest strips - seven u.s. States and Canada, 2000-2013 - Tsai_2014_MMWR.Morb.Mortal.Wkly.Rep_63_42
Author(s) : Tsai RJ , Sievert J , Prado J , Buhl K , Stone DL , Forrester M , Higgins S , Mitchell Y , Schwartz A , Calvert GM
Ref : MMWR Morb Mortal Wkly Rep , 63 :42 , 2014
Abstract : Dichlorvos-impregnated resin strips (DDVP pest strips) are among the few organophosphate products still available for indoor residential use. The residential uses for most other organophosphate products, including most DDVP products, were canceled because they posed unreasonable risks to children. DDVP pest strips act by inhibiting acetylcholinesterase activity in the brain and nerves of insect pests and are designed to gradually release DDVP vapor for up to 4 months. Acute illnesses in humans associated with nonlethal acute exposures usually resolve completely, but recovery is not always rapid. To assess the frequency of acute illnesses associated with DDVP pest strips, cases from 2000 through June 2013 were sought from the 12 states that participate in the Sentinel Event Notification System for Occupational Risks (SENSOR)-Pesticides Program, the National Pesticide Information Center (NPIC), and Health Canada.* A total of 31 acute DDVP pest strip-related illness cases were identified in seven U.S. states and Canada. The majority of these illnesses resulted from use of the product in commonly occupied living areas (e.g., kitchens and bedrooms), in violation of label directions. Although 26 of the 31 cases involved mild health effects of short duration, five persons had moderate health effects. Illnesses caused by excess exposure to DDVP pest strips can be reduced by educating the public about the proper usage of DDVP pest strips and with improvements in label directions.
ESTHER : Tsai_2014_MMWR.Morb.Mortal.Wkly.Rep_63_42
PubMedSearch : Tsai_2014_MMWR.Morb.Mortal.Wkly.Rep_63_42
PubMedID: 24430101

Title : Dialkyl phosphates as biomarkers of organophosphates: the current divide between epidemiology and clinical toxicology - Sudakin_2011_Clin.Toxicol.(Phila)_49_771
Author(s) : Sudakin DL , Stone DL
Ref : Clinical Toxicology (Phila) , 49 :771 , 2011
Abstract : CONTEXT: Organophosphate insecticides are widely utilized throughout the world. The cholinergic toxidrome, resulting from cholinesterase inhibition, is the clinically relevant endpoint in organophosphate poisoning. In recent years, urinary dialkyl phosphates (DAPs) have emerged as a common method of assessing exposure to organophosphates in epidemiological investigations. Using dialkyl phosphates as biomarkers of exposure to organophosphates, several recent epidemiological studies have reported associations with adverse health outcomes. The purpose of this article is to review the application and limitations of urinary DAPs as biomarkers of exposure to organophosphate insecticides. METHODS: A literature search was conducted of the PubMed database, using keywords "dialkylphosphate" and "dialkyl phosphate." The scientific literature was reviewed to identify sources of dialkyl phosphate metabolites from in vivo metabolism of organophosphates, and as environmental degradation products. Epidemiological investigations were reviewed to summarize the use of use of DAPs as biomarkers in cross-sectional studies, occupational exposures, acute poisonings, and in health outcome studies. Emphasis was placed on the assessment of DAPs in the context of existing biomarker frameworks, as defined by the National Research Council. Studies were assessed for concurrent use of cholinesterase activity as a biomarker of effect, and whether a dose-response relationship could be determined between DAPs and cholinesterase depression or cholinergic effects. RESULTS: Over 184 publications were identified, describing dialkyl phosphates and their use as biomarkers of exposure. The in vivo metabolism of organophosphates yields different DAPs, depending upon whether they undergo bioactivation or detoxification. The detection of urinary DAPs does not provide specificity with respect to the organophosphate from which they were derived, or their toxicological potency. Several recent studies documented the common presence of DAPs in residential environments and foods. Experimental studies support that DAPs have significant oral bioavailability, and undergo little to no metabolism prior to urinary excretion. Cross-sectional studies in multiple countries confirm that urinary DAPs are commonly detectable in the general population. No occupational studies were identified supporting a dose-response relationship between DAPs and significant cholinesterase inhibition. No occupational studies were identified supporting evidence of a threshold level of DAPs excretion at which clinical cholinergic signs or symptoms have been observed. Recent prospective epidemiological studies using DAPs as biomarkers have not concurrently assessed effects on cholinesterase activity, or conducted analyses that distinguish different DAPs that reflect bioactivation versus detoxification pathways. DISCUSSION: There are numerous limitations to the use of DAPs as biomarkers of exposure. These include a lack of specificity with respect to the organophosphate from which they were derived, and a growing body of evidence that toxicologically irrelevant DAPs are commonly encountered in food and the environment. Substantial intra- and inter-day variability has been reported for dialkyl phosphate excretion in humans, which is problematic for studies that rely on single measurements to assess exposure. The toxicological distinction between different DAPs reflecting biomarkers of activation and detoxification processes has not been considered in some prospective epidemiological studies. A relationship between DAPs as biomarkers of exposure and the critical biomarker of effect, cholinesterase activity, has not been established. CONCLUSIONS: The science of exposure assessment using DAPs as biomarkers is not advancing, and this complicates the interpretation of epidemiological studies. At the current time, DAPs have very limited utility in clinical toxicology or in the risk assessment process for organophosphates. Until these limitations are addressed, the appropriate role of DAPs in the assessment of human health risks from organophosphates is unclear.
ESTHER : Sudakin_2011_Clin.Toxicol.(Phila)_49_771
PubMedSearch : Sudakin_2011_Clin.Toxicol.(Phila)_49_771
PubMedID: 22077242

Title : Longitudinal trends in organophosphate incidents reported to the National Pesticide Information Center, 1995-2007 - Stone_2009_Environ.Health_8_18
Author(s) : Stone DL , Sudakin DL , Jenkins JJ
Ref : Environ Health , 8 :18 , 2009
Abstract : BACKGROUND: Regulatory decisions to phase-out the availability and use of common organophosphate pesticides among the general public were announced in 2000 and continued through 2004. Based on revised risk assessments, chlorpyrifos and diazinon were determined to pose unacceptable risks. To determine the impact of these decisions, organophosphate (OP) exposure incidents reported to the National Pesticide Information Center (NPIC) were analyzed for longitudinal trends.
METHODS: Non-occupational human exposure incidents reported to NPIC were grouped into pre- (1995-2000) and post-announcement periods (2001-2007). The number of total OP exposure incidents, as well as reports for chlorpyrifos, diazinon and malathion, were analyzed for significant differences between these two periods. The number of informational inquiries from the general public was analyzed over time as well.
RESULTS: The number of average annual OP-related exposure incidents reported to NPIC decreased significantly between the pre- and post-announcement periods (p < 0.001). A significant decrease in the number of chlorpyrifos and diazinon reports was observed over time (p < 0.001). No significant difference in the number of incident reports for malathion was observed (p = 0.4), which was not phased-out of residential use. Similar to exposure incidents, the number of informational inquiries received by NPIC declined over time following the phase-out announcement. CONCLUSION: Consistent with other findings, the number of chlorpyrifos and diazinon exposure incidents reported to NPIC significantly decreased following public announcement and targeted regulatory action.
ESTHER : Stone_2009_Environ.Health_8_18
PubMedSearch : Stone_2009_Environ.Health_8_18
PubMedID: 19379510