Dose-response assessment for impaired memory from chronic exposure to domoic acid among native American consumers of razor clams.

Domoic acid (DA) is a marine neurotoxin that accumulates in filtering shellfish during harmful algal blooms. A health protection limit of 20 ppm DA in razor clams (RC) has been set based principally upon an episode of acute DA toxicity in humans that included Amnesic Shellfish Poisoning among survivors. The objective of this study was to determine the dose-response relationship between estimated DA exposure through RC consumption and memory loss in Washington state Native Americans from 2005 to 2015. Results from total learning recall (TLR) memory scores were compared before and after the highest DA exposures. A decrease in TLR was related to DA dose (p < 0.01) regardless whether the effect was assumed to be transient or lasting, and whether the dose was expressed as an average daily dose or an average dose per meal. Benchmark dose modeling identified BMDL10 values of 167 ng/kg-day and 2740 ng/kg-meal assuming a transient effect, and 196 ng/kg-day and 2980 ng/kg-meal assuming no recovery of function occurs. These DA dose thresholds for a measurable memory function reduction observed in this study of clam consumers are well below the safe acute dose underpinning the current regulatory DA limit of 20 ppm (ca. 60 µg/kg).

Perception of risk for domoic acid related health problems: A cross-cultural study.

Risk perception is a complex process that refers to the way people approach, think about, and interpret risks in their environment. An important element of risk perception is that it is culturally situated. Since HABs can present a health risk in many places around the world, looking at cultural parameters for understanding and interpreting risks is important. This study examined how two different groups of people perceive the potential health risks of low-level exposure to domoic acid (DA) through razor clam consumption. The risk perceptions of Washington State, USA coastal dwelling Native American nations (NA) were compared to that of a community sample of recreational razor clam harvesters (CRH). Overall, the findings support the hypothesis that cultural and community specific contexts impact the perception of risk of a DA related illness. Specifically, the NA sample was distinguished from the CRH group in particular, by their worries about ocean pollution, attribution of DA risks to climate change, concerns about the potential impact of DA on future generations, and feeling of being better informed than the CRH group. The CRH group was more likely to attribute the DA problem to anthropogenic or industrial causes and view the risk of health problems from DA as lower than those associated with smoking, high cholesterol, anxiety or depression, alcoholism, high blood pressure or obesity. The CRH group was also more likely to turn to the media for DA-related information. Both groups trusted the decisions of state and tribe health and natural resources officials, and demonstrated a complex pattern of findings that involved gender. In summary, risk communication and outreach activities should be designed to take into consideration the specific factors that are unique to each cultural community.

Sex differences in effects of low level domoic acid exposure.

Consumption of seafood containing the phytoplankton-derived toxin domoic acid (DOM) causes neurotoxicity in humans and in animals. It has been reported that DOM-induced symptoms may be more severe in men than women, but to date the effect of sex on DOM-induced effects in adults is not known. We investigated sex differences in DOM-induced effects in adult rats. Since low level exposure is of greatest relevance to human health (due to DOM regulatory limit), we examined the effects of low level exposure. Adult male and female Sprague Dawley rats were administered a single intraperitoneal injection of DOM (0, 1.0, 1.8 mg/kg). Behaviour was monitored for 3h and immunohistochemistry in the dorsal hippocampus and olfactory bulb was also examined. DOM increased locomotor and grooming activity, compared to vehicle group. DOM exposure also significantly increased stereotypic behaviours and decreased phosphorylated cAMP response element-binding protein immunoreactivity (pCREB-IR). There was no effect of sex on the magnitude of the behavioural responses, but the onset of DOM-induced locomotor activity and ear scratches was quicker in females than in males. Mixed effect modelling revealed the predicted peak in locomotor activity in response to DOM was also quicker in females than in males. Severe toxicity was evident in 2/7 male rats and 0/8 female rats dosed with 1.8 mg/kg DOM. These data suggest that males exposed to low level DOM may be more susceptible to severe neurotoxicity, whereas females are affected more quickly. Understanding sex differences in DOM-induced neurotoxicity may contribute to future protective strategies and treatments.