Epidemiological studies of neurotoxic, reproductive, and carcinogenic effects of complex mixtures.

Abstract

Neurotoxic, reproductive, and carcinogenic effects are potentially important health end points in epidemiological studies of complex mixtures, particularly when such mixtures contain volatile organic compounds or trace metals. Epidemiological studies of neurotoxicity often will require direct clinical, behavioral, and/or physiological testing of study subjects, because these effects are likely to be subtle and not identifiable as clearly defined diseases. Peripheral nervous system toxicity can be assessed by clinical neurologic examinations, by electrophysiological tests of nerve conduction, and by physiological tests of thresholds for neurosensory perception, though these tests require considerable standardization for use outside the clinical setting, and most of the available tests have not been assessed for their utility in detecting effects of neurotoxic exposures. Neurobehavioral effects of exposures to solvents, as examples of complex mixtures, have been studied widely; but batteries of tests are often used, and these have not been well standardized and are generally unfamiliar to most research investigators in this area. Recently standardized neurobehavioral test systems developed by the World Health Organization and by a U.S. group for use in field studies, show promise in detecting neurobehavioral effects at relatively low environmental exposures. Similarly, new and sensitive measures of disturbed reproductive function, such as time-to-conception and biochemical indices of early pregnancy loss, are affected by some low-concentration environmental agents; but those measures have not yet been applied to studies of complex mixtures. Because of the long latency problem and small expected relative risks, population-or community-based studies of the carcinogenic effects of complex mixtures are unlikely to yield data of adequate quality to justify more than exploratory studies of carcinogens in ambient air.

Urinary delta-ALA: A potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese

“…The onset of neurotoxic effects is largely subtle, insidiously manifested and unidentifiable as a clearly defined disease (Shy, 1993). Accordingly, biomarkers (BMs), as observable endpoints in a continuum of events from exposure to disease, have become increasingly important for the detection and diagnosis of early poisoning (Kakkar and Jaffery, 2005; Scherer, 2005).…”

Multimetal exposure: Challenges in diagnostics, prevention, and treatment

“…Neurotoxicity is one of the most potential health outcomes of the complex mixtures as evident from the epidemiological studies. [ 14 ] Metal mixtures are generally responsible for increased risk of neurotoxicity due to synergism. For instance, sub‐chronic treatment with a mixture of Pb, Cd, and As interacted synergistically to exert neurodevelopmental disorders in albino rats.…”