Effects of oral domoic acid exposure on maternal reproduction and infant birth characteristics in a preclinical nonhuman primate model

Neurotoxicol Teratol. Mar-Apr 2019;72:10-21. doi: 10.1016/j.ntt.2019.01.001. Epub 2019 Jan 5.

Abstract

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.

Keywords: Domoic acid; Infant; Neurotoxicity; Nonhuman primate; Oral exposure; Prenatal; Reproduction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Drug
  • Female
  • Kainic Acid / administration & dosage
  • Kainic Acid / analogs & derivatives*
  • Kainic Acid / blood
  • Kainic Acid / toxicity
  • Macaca fascicularis
  • Male
  • Maternal Exposure / adverse effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / blood
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Reproduction / drug effects*
  • Water Pollutants, Chemical / administration & dosage
  • Water Pollutants, Chemical / blood
  • Water Pollutants, Chemical / toxicity*

Substances

  • Water Pollutants, Chemical
  • domoic acid
  • Kainic Acid