Gender differences in the disposition and toxicity of metals

Abstract

There is increasing evidence that health effects of toxic metals differ in prevalence or are manifested differently in men and women. However, the database is small. The present work aims at evaluating gender differences in the health effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher prevalence of nickel-induced allergy and hand eczema in women compared to men, mainly due to differences in exposure. Cadmium retention is generally higher in women than in men, and the severe cadmium-induced Itai-itai disease was mainly a woman's disease. Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring. Men generally have higher blood lead levels than women. Lead accumulates in bone and increased endogenous lead exposure has been demonstrated during periods of increased bone turnover, particularly in women in pregnancy and menopause. Lead and mercury, in the form of mercury vapor and methylmercury, are easily transferred from the pregnant women to the fetus. Recent data indicate that boys are more susceptible to neurotoxic effects of lead and methylmercury following exposure early in life, while experimental data suggest that females are more susceptible to immunotoxic effects of lead. Certain gender differences in the biotransformation of arsenic by methylation have been reported, and men seem to be more affected by arsenic-related skin effect than women. Experimental studies indicate major gender differences in arsenic-induced cancer. Obviously, research on gender-related differences in health effects caused by metals needs considerable more focus in the future.

Introduction

Gender differences in exposure to toxic metals have been reported, and there is increasing evidence that health effects of certain toxic metals are also manifested differently in males and females, due to differences in kinetics, mode of action, or susceptibility. However, the database is small and, with a few exceptions, gender differences in exposure and susceptibility has not been considered in the environmental health risk assessment. As for most other chemicals and environmental pollutants, the health risk assessment on toxic metals have largely been based on data on occupationally exposed men, with the obvious exception of reproductive and developmental effects. Still, the results have been used as if they were representative of the general population, including women, children and the elderly. Even though many epidemiological studies of mixed gender population groups reported data separately for men and women, gender differences were seldom evaluated. In addition, experimental toxicological studies have almost exclusively used male animals. Thus, possible mechanisms, e.g., related to certain hormone interactions, were not detected. A review of recent publications in occupational health epidemiology showed that women are still less often studied than men, and that gender factors are seldom investigated in many mixed studies (Niedhammer et al., 2000).

Based on the more extensive literature on the action and side-effects of therapeutic drugs (Christian, 2001; Gandhi et al., 2004; Miller, 2001), gender-differences in the toxic effect of chemicals that people are exposed to in the working and general environment are to be expected. A meeting under the auspice of the Society for Women's Health Research recently concluded that a greater focus on interdisciplinary, hypothesis-driven research is essential in order to understand potential interactions between sex and environmental exposures on health (Keitt et al., 2004). Research needs to explore sex differences from the molecular and cellular levels to behavioral responses, and should track these effects across multiple generations. Such information is essential for evaluation of mechanisms of action and susceptible groups, and to determine the most effective mitigation measures.

This review focuses on gender differences in health effects of nickel, mercury, lead, cadmium, and arsenic. It serves to provide examples showing the necessity of assessing gender differences in exposures, kinetics and toxicity of chemicals and pollutants.