Bouchard Michèle, Carrier Gaétan, Brunet Robert C, Dumas Pierre, Noisel Nolwenn
Chaire en Analyse des Risques Toxicologiques Pour la Santé Humaine and Département de Santé Environnementale et Santé au Travail, Faculté de Médecine Université de Montréal, Succursale Centre-ville, Montréal, Québec, Canada.
Ann Occup Hyg. 2006 Jul;50(5):505-15. doi: 10.1093/annhyg/mel005. Epub 2006 Mar 1.
Exposure to selected organophosphorus insecticides (OPs), malathion, diazinon and acephate, was evaluated in a group of horticultural greenhouse workers. This was achieved through measurements of the cumulative urinary excretion time courses of specific and non-specific biomarkers over a 24 h period following the onset of work exposure. For malathion, the absorbed daily doses were estimated from the 24 h cumulative urinary amounts of the specific mono- and di-carboxylic acid metabolites (the sum of MCA and DCA) through the use of a kinetic model. The observed 24 h urinary levels were also compared with a biological reference value (BRV) of 57 nmol kg(-1) of body weight established in a previous work on the basis of a human no-observed-effect level exposure dose. Excretion values were found to be 2.5% or less of the BRV, suggesting a negligible health risk. Both median and 95th percentile concentrations of DCA (n = 57 samples) were, however, slightly higher than the baseline values determined by the Centers for Disease Control and Prevention (CDC) in the US civilian population (MCA was not analyzed by the CDC). The cumulative urinary excretion time course of the methyl phosphoric (MP) derivatives, which are metabolites of malathion but also of several other OPs, was also determined. Though relatively low, the MP levels were from 3 to 31 times higher than would be expected on the basis of the malathion specific MCA and DCA excretions, indicating that MP excretions stem from sources other than malathion exposure. Accordingly, only the time courses of MCA and DCA excretion rate (nmol h(-1)) were compatible with the time of work exposure. Urinary biomarkers of exposure to diazinon and acephate were also measured. Urinary concentrations were essentially below or equal to the analytical limit of detection of 1 microg l(-1) for 2-isopropyl-4-methyl-6-hydroxypyrimidine (n = 54) and of 0.8 microg l(-1) for acephate and methamidophos (n = 59): values within the baseline range of the US civilian population, like the observed phosphoric metabolite concentrations. The workers under study thus appeared to be only slightly more exposed to malathion than the general population. However, their overall exposure to OPs, as measured by non-specific phosphoric metabolites, was similar to that of the general population, whose exposure occurs mainly through the ingestion of contaminated food. These results question the relevance of measuring non-specific phosphoric metabolites when attempting to assess low-dose occupational exposure to a specific OP.
对一组园艺温室工人接触特定有机磷杀虫剂（OPs），即马拉硫磷、二嗪农和乙酰甲胺磷的情况进行了评估。这是通过测量工作暴露开始后24小时内特定和非特定生物标志物的累积尿排泄时间进程来实现的。对于马拉硫磷，通过使用动力学模型，根据特定一元和二元羧酸代谢物（MCA和DCA之和）的24小时累积尿量来估算每日吸收剂量。还将观察到的24小时尿水平与先前工作中基于人体无观察到效应水平暴露剂量确定的57 nmol kg⁻¹体重的生物参考值（BRV）进行了比较。发现排泄值为BRV的2.5%或更低，表明健康风险可忽略不计。然而，DCA的中位数和第95百分位数浓度（n = 57个样本）略高于美国疾病控制与预防中心（CDC）在美国平民人群中测定的基线值（CDC未分析MCA）。还确定了甲基磷酸（MP）衍生物的累积尿排泄时间进程，MP衍生物是马拉硫磷的代谢物，但也是其他几种OPs的代谢物。尽管MP水平相对较低，但比基于马拉硫磷特定的MCA和DCA排泄预期的水平高3至31倍，这表明MP排泄源于马拉硫磷暴露以外的来源。因此，只有MCA和DCA排泄率（nmol h⁻¹）的时间进程与工作暴露时间相符。还测量了接触二嗪农和乙酰甲胺磷的尿生物标志物。对于2-异丙基-4-甲基-6-羟基嘧啶（n = 54），尿浓度基本低于或等于1 μg l⁻¹的分析检测限，对于乙酰甲胺磷和甲胺磷（n = 59），尿浓度基本低于或等于0.8 μg l⁻¹：这些值在美国平民人群的基线范围内，与观察到的磷酸代谢物浓度一样。因此，所研究的工人似乎仅比一般人群稍微多接触了一些马拉硫磷。然而，通过非特定磷酸代谢物测量的他们对OPs的总体暴露与一般人群相似，一般人群的暴露主要通过摄入受污染食物发生。这些结果质疑了在试图评估低剂量职业接触特定OP时测量非特定磷酸代谢物的相关性。
