Domoic Acid (DA) is a naturally-occurring excitotoxin, produced by marine algae, which can bioaccumulate in shellfish and finfish. The consumption of seafood contaminated with DA is associated with gastrointestinal illness that, in the case of high DA exposure, can evolve into a spectrum of responses ranging from agitation to hallucinations, memory loss, seizures and coma. Because algal blooms that produce DA are becoming more widespread and very little is known about the dangers of chronic, low-dose exposure, we initiated a preclinical study focused on the reproductive and developmental effects of DA in a nonhuman primate model. To this end, 32 adult female Macaca fascicularis monkeys were orally exposed to 0, 0.075 or 0.15 mg/kg/day DA on a daily basis, prior to and during pregnancy. Females were bred to non-exposed males and infants were evaluated at birth. Results from this study provided no evidence of changes in DA plasma concentrations with chronic exposure. DA exposure was not associated with reproductive toxicity or adverse changes in the physical characteristics of newborns. However, in an unanticipated finding, our clinical observations revealed the presence of subtle neurological effects in the form of intentional tremors in the exposed adult females. While females in both dose groups displayed increased tremoring, the effect was dose-dependent and observed at a higher rate in females exposed to 0.15 mg/kg/day. These results demonstrate that chronic, low-level exposure to DA is associated with injury to the adult CNS and suggest that current regulatory guidelines designed to protect human health may not be adequate for high-frequency shellfish consumers.

中文翻译：

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口服软骨藻酸暴露对临床前非人灵长类动物模型中母体生殖和婴儿出生特征的影响。


软骨藻酸 (DA) 是一种天然存在的兴奋性毒素，由海洋藻类产生，可在贝类和鱼类中生物累积。食用受 DA 污染的海鲜与胃肠道疾病有关，在接触大量 DA 的情况下，胃肠道疾病可能会演变成一系列反应，包括烦躁、幻觉、记忆丧失、癫痫发作和昏迷。由于产生 DA 的藻华正在变得越来越普遍，而且人们对长期、低剂量接触的危险知之甚少，因此我们启动了一项临床前研究，重点关注 DA 在非人类灵长类动物模型中的生殖和发育影响。为此，32只成年雌性食蟹猴在怀孕前和怀孕期间每天口服暴露于0、0.075或0.15mg/kg/天的DA。雌性与未暴露的雄性交配，婴儿在出生时接受评估。这项研究的结果没有提供证据表明长期接触 DA 血浆浓度会发生变化。 DA 暴露与生殖毒性或新生儿身体特征的不良变化无关。然而，在一个意想不到的发现中，我们的临床观察揭示了暴露的成年雌性中存在以故意震颤形式出现的微妙的神经系统影响。虽然两个剂量组中的女性都表现出震颤增加，但这种效应是剂量依赖性的，并且在暴露于 0.15 mg/kg/天的女性中观察到的发生率更高。这些结果表明，长期、低水平接触 DA 与成人中枢神经系统损伤有关，并表明当前旨在保护人类健康的监管指南可能不足以满足高频贝类消费者的需求。