草甘膦除草剂(GBHs)是世界上使用最广泛的农药,草甘膦是这种除草剂的活性成分,包括被称为农达的配方。GBHs的大量和越来越多的使用不仅导致了全球职业暴露的负担,但也增加了对普通人群的暴露。当前的试点研究代表了我们在未来5年内对GBH进行的长期调查的第一阶段。在本文中,我们提出了研究设计,首次评估体内参数并测定尿液中草甘膦及其主要代谢产物氨甲基膦酸(AMPA)。
我们通过饮用水将Sprague-Dawley(SD)大鼠口服暴露于相当于美国可接受的每日摄入量(USADI)1.75mg/kgbw/天的草甘膦剂量,定义为美国EPA确定的慢性参考剂量(cRfD),从产前生活开始,即母亲的妊娠日(GD)6。一个队列连续给药直到性成熟(6周队列),另一个队列连续给药直到成年(13周队列)。在这里,我们提供了有关草甘膦及其主要代谢产物AMPA的一般毒性和尿中浓度的数据。
生存,体重,动物的食物和水消耗不受草甘膦或农达治疗的影响。在用草甘膦处理的SD大鼠的尿液中检测到的草甘膦和AMPA的浓度与在用农达处理的动物中观察到的浓度相当,随着治疗持续时间的增加。大多数草甘膦未改变地排泄。母体化合物的尿液水平,草甘膦,比其代谢物的水平高100倍左右,AMPA.
尿液中的草甘膦浓度表明,在草甘膦和农达暴露后,大部分给药剂量作为不变的母体化合物排泄,与治疗持续时间相关的草甘膦在尿液中排泄的模式增加。农达中存在的佐剂和其他物质似乎对草甘膦的吸收和排泄没有重大影响。我们的结果表明,在啮齿动物模型中,尿草甘膦是比AMPA更相关的暴露标志物。
Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine.
We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA.
Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA.
Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.