Human volunteer studies, data source

There are clear ethical constraints that prevent human research that could definitively answer the questions of concern regarding the military operational and civilian health risks of exposure to low-levels of chemical warfare nerve agents. Only three sources of relevant human data are available for analysis. These data are from either past human volunteer studies, reports based on accidental exposures, or reports of the consequences of malicious releases of the agents. While these sources are valuable, the data have some limitations for deriving dose-response relationships because of inferior analytical and clinical methods or the lack of precise estimates of exposure. 

Data sources regarding the toxicity of chlorine include experimental studies with human volunteers and animals accidentally exposed cohorts of workers, communities, or individuals warfare studies and epidemiologic occupational investigations. Each of these data sources is reviewed below and summarized in... 

Reentry intervals are now established on the basis of (1) data on dermal absorption or dermal dose response (2) inhalation, dermal, and oral acute toxicity studies in animal models (3) foliar and soil residue dissipation data and, (4) available human exposure data. CDFA recommends several sources as useful guides for determining residues of pesticides on soil and leaf surfaces (dislodgeable residue) and conducting field reentry studies involving human volunteers (1-5). Human exposure studies may not be required if adequate animal data from (1) through (3) above are... 

Positive effects seen in either humans or animals will normally justify classification. Evidence from animal studies is usually much more reliable than evidence from human exposure. However, in cases where evidence is available from both sources, and there is conflict between the results, the quality and reliability of the evidence from both sources must be assessed in order to resolve the question of classification on a case-by-case basis. Normally, human data are not generated in controlled experiments with volunteers for the purpose of hazard classification but rather as part of risk assessment to confirm lack of effects seen in animal tests. Consequently, positive human data on contact sensitization are usually derived from case-control or other, less defined studies. Evaluation of human data must therefore be carried out with caution as the frequency of cases reflect, in addition to the inherent properties of the substances, factors such as the exposure situation, bioavailability, individual predisposition and preventive measures taken. Negative human data should not normally be used to negate positive results from animal studies. 

Human experience. Human experience is often regarded as the most useful and the most relevant source of information, but does vary considerably in both quality and quantity. For some solvents which have been in use in large quantities for many years, extensive studies of workplace health (known as epidemiology ) may have been carried out. These studies may either have identified adverse effects or have shown the absence of such effects. A shortcoming is often the extent and quality of exposure estimation, absence of which considerably reduces the value of the study. Useful human data may also be available from studies in volunteers exposed to low levels. Individual case reports of adverse effects are of limited value, but may well indicate the need for further more detailed study. 

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