Multiple Chemical Exposures Research Articles

Mortality experience of employees with occupational exposure to DBCP.

Concern about the carcinogenic potential of 1,2-dibromo-3-chloropropane(DBCP) has arisen recently, focusing on six organ sites: stomach, liver, kidney, lung, testes, and skin. To examine the mortality experience of persons potentially exposed, a cohort of 550 employees involved in production and formulation from 1957 to 1976 was defined. A total of 35 deaths was observed through 1979 (39.2 expected). No statistically significant excess was observed for any cause of death. No cancer deaths were noted for five of the hypothesized sites. For the lung cancer category, five deaths were observed (2.7 expected, P greater than .135), two of which occurred in a subgroup directly exposed for at least 1 yr (0.5 expected, P greater than .077). Aside from arsenicals exposure, potential confounding resulting from smoking or multiple chemical exposures could not be evaluated.

General principles in the assessment of toxicity of chemical mixtures.

A toxicological interaction may be defined as a condition in which exposure to two or more chemicals results in a qualitatively or quantitatively altered biological response relative to that predicted from the action of a single chemical. Such multiple-chemical exposures may be simultaneous or sequential in time and the altered response may be greater or smaller in magnitude (1,2). The question of how the risk to health of exposure to a combination of chemicals compares to the estimated risk from exposure to each alone may be approached in several ways. The existing literature may be searched for laboratory, clinical or epidemiological studies that deal specifically with exposures to the combinations of chemicals in question. Laboratory and/or epidemiological studies may be initiated to specifically test for interactive effects of specific combinations of chemicals when and if concern for a specific joint exposure arises. Knowledge of the toxicokinetic and toxicodynamic characteristics of individual chemicals may be used to make judgements of the potential for altered health risk arising from specific combined exposure situations. All three of these have several limitations in any problem area dealing with potential exposures to numerous and diverse chemicals. The number of possible combinations of exposures is multiplicative as the list of individual chemicals of concern grows. Furthermore, the permutation of time considerations (that is; simultaneous, separate but close in time or far in time, repeated or single exposures to multiple chemicals) greatly complicates the design of studies for assessment of interactions. As for the first approach, that of literature search for interaction data, there are few reports of

Psychosocial factors and sudden cardiac death: A pilot study

Despite the fact that virtually all chemicals exposure of humans are to mixtures, and that these mixed exposures occur in the context of numerous other risk modifiers, our current understanding of human health risks is based almost entirely on the evaluation of chemicals studied in isolation. This paper describes findings from our collaborative studies that prompt questions about these approaches in the context of neurotoxicology. The first section describes studies investigating the interactions of maternal Pb exposure with maternal stress. Examined across a range of outcome measures, it shows that maternal Pb can modulate the effects of maternal stress, and, conversely, stress modifies the effects of Pb. Further, effects of Pb + stress could be detected in the absence of an effect of either risk factor alone, and, moreover, the profile of effects of Pb alone differs notably from that of Pb + stress. Collectively, interactions were not systematic, but differed by brain region, gender and outcome measure. A second section describes outcomes of studies examining combined exposures to the pesticides paraquat (PQ) and maneb (MB) during development which likewise reveal potentiated effects of combined exposures. They also demonstrate examples of both progressive and cumulative neurotoxicity, including a marked vulnerability following gestational exposure to MB, to the effects of PQ, a pesticide with no structural relationship to MB. The ability of current hazard identification and risk assessment approaches to adequately identify and encompass such effects remains an important unanswered question. One consideration proposed for further evaluating potential interactions that may be of significance for the nervous system is based on a multi-hit hypothesis. It hypothesizes that the brain may readily compensate for the effects of an individual chemical itself acting on a particular target system, but when multiple target or functional sites within that one system are attacked by different mechanisms (i.e., multiple chemical exposures or chemical exposures combined with other risk factors), homeostatic capabilities may be restricted, thereby leading to sustained or cumulative damage.