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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在临床前非人类灵长类动物模型中，口服海藻酸暴露对母亲生殖和婴儿出生特征的影响。

海藻酸（DA）是海洋藻类产生的一种自然存在的兴奋性毒素，可以在贝类和有鳍鱼中生物富集。食用被DA污染的海鲜会导致胃肠道疾病，在高DA暴露的情况下，可能演变成一系列反应，从躁动到幻觉，记忆力减退，癫痫发作和昏迷。由于产生DA的藻华正变得越来越普遍，并且对长期低剂量暴露的危险知之甚少，因此我们开展了一项临床前研究，重点研究非人灵长类动物模型中DA的生殖和发育作用。为此，每天32只成年雌性猕猴在怀孕前和怀孕期间每天口服0、0.075或0.15 mg / kg /天的DA。将雌性繁殖给未暴露的雄性，并在出生时对婴儿进行评估。这项研究的结果没有提供证据表明慢性暴露会使DA血浆浓度发生变化。DA暴露与生殖毒性或新生儿生理特征的不利变化无关。然而，在一项意料之外的发现中，我们的临床观察表明，在成年女性中，以故意震颤的形式存在着微妙的神经系统作用。虽然两个剂量组中的女性均表现出增加的震颤，但该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，慢性，