Controlled human exposures

A controlled human exposure study provided information regarding non-lethal effects following acute (head-only) exposure to monomethylhydrazine... 

Golz HH Controlled human exposures to malathion aerosols. AMA Arch Ind Health 19 516-523, 1959... 

Studies which involved controlled human exposure to volatile organic compounds (VOCs) combined with repeated blood sampling have enabled researchers to evaluate the utility of PBPK models for interpreting biomonitoring results taken under non-steady-state conditions (Canuel et al. 2000 Tan et al. 2005 Sohn et al. 2004). 

Dinitrophenols (as alkali salts or aliphatic amine salts) have long been used in weed control. Human exposure to these compounds has led to nausea, gastric upset, rapid breathing, tachycardia (rapid heartbeat), cyanosis, and ultimately coma. Death or recovery occurs within 24 hours. 

Considerable weight has been given to occupational exposure information, which used longer term, substantively higher sulfur dioxide exposures than were used in many of the controlled human exposure studies. The occupational data are considered particularly valuable in providing practical information about the relationships of concentration and time course, tolerance, and acclimation to irritant effects caused by sulfur dioxide exposures in a healthy human population—as would be more closely representative of the population found in a submarine. 

The database on chlorine is robust. The irritant properties and toxicity of chlorine have been studied with controlled human exposures as well as with multiple species of laboratory animals. Exposure durations range from acute to chronic. Subjects with rhinitis or asthma appear to be more sensitive to the irritant effects of chlorine than healthy individuals. Thus, risk assessment addresses the potential for greater effects in these sensitive populations. 

In rats, MTBE did not seem to be a strong sensory irritant, in terms of inhibiting respiratory function. Such inhibition was noted after exposure to 8000 ppm, but not at lower concentrations. On the basis of this information and the Alarie model, a level for sensory irritation in humans was estimated to be 140 ppm MTBE. Consistent with the study in rats showing that MTBE alone is a weak respiratory irritant, the controlled human exposure studies failed to document significant sensory irritation - either subjective or objective - from MTBE alone. 

Fiedler N, Kelly-McNeil K, Mohr S, et al. Controlled human exposure to methyl tertiary butyl ether in gasoline Symptoms, psychophysiologic and neurobehavioral responses of self-reported sensitive persons. Environ Health Perspectl000 108(8) 753 63. 

Hepatic Effects. Although there were no indications of liver effects in studies of controlled human exposure to 1,1,1-trichloroethane, data from case reports of overexposed humans suggest that this chemical may produce mild hepatic effects in humans exposed to high levels. 

Prah JD, Goldstein CM, Devlin R, Otto D, Ashley D, House D, Cohen KL, Gerrity T (1994) Sensory, symptomatic, inflammatory, and ocular responses to and the metabolism of methyl tertiary butyl ether in a controlled human exposure experiment. Inhal Toxicol 6 521-538... 

Removal of the decomposition products from the work environment is one of the most important actions taken to reduce and control human exposure. Even at room temperature, small amounts of trapped monomers or other gases can diffuse out of the resin particles. It is a good practice to open the fluoropolymer container in a well-ventilated area. All processing equipment should be ventilated by local exhaust ventilation schemes. 

However, the controlled human exposure studies are few, and the results have not been confirmed. Also, the results of epidemiological studies are inconsistent. Therefore, is it not possible today to conclude whether or not sensory irritation is associated with the sum of mass concentrations of VOCs at the low exposure levels typically encountered in nonindustrial indoor air. Thus, at present, no precise guidance can be given on which levels of TVOC are of concern from a health and comfort point of view, and the magnitude of protection margins needed cannot be estimated. 

Controlled human exposure studies are essential to establish the health consequences of PM exposures. These studies are typically designed to study inhalation of size-defined PM under highly controlled conditions that will allow the characterization of exposure-response relationships. Since humans are exposed to the pollutant of interest, specifically size-fractionated PM, causahty can be established easily and the confounding effects of other pollutants can be minimized (Devlin et al. 2005). Another advantage of such clinical studies is the abihty to select subjects with a known clinical status (i.e., healthy vs. a specific disease, typically cardiovascular or pulmonary disease) and observe the pathophysiological responses of interest. However, controlled human exposures have some limitations (Utell and Frampton 2000). For both practical and ethical reasons, clinical studies are restricted to exposure concentrations and durations that will only ehcit transient responses in human subjects. These studies involve a small number of sample subjects, which excludes susceptible populations at higher risk. Chronic exposure or high PM concentration related health effects are not attainable by the clinical studies. These experiments are also very costly to perform. 

Uich B, Silverman F, Corey P et al (2005) Acute blood pressure responses in healthy adults during controlled air pollution exposures. Environ Health Perspect 113 1052-1055 Utell MJ, Frampton MW (2000) Toxicologic methods controlled human exposures. Environ Health Perspect 108 605-613... 

In addition to field studies, controlled human exposures to PERC have been reported. In this type of studies, subjects were exposed to various constant levels of PERC for different lengths of time with or without exercise. Samples of blood, exhaled air and urine were collected according to a variety of schedules both during exposure and for varying lengths... 

Experimental data were used in a model, which divided the body into four tissue compartments vessel rich group, muscle group, fat group and liver. Metabolism was assumed to take place in die Ever as a combination of a linear metabolic component and a Mi-chaelis-Menten component. Metabolic parameters and partition coefficients determined for rats were scaled for body weight and were used in fitting results for humans. The model fit very well the data reported from other controlled human exposure studies. - - ... 

Liu, L., B. Urch, R. Boon, M. Szyszkowicz, M. Speck, D. R. Gold, A. J. Wheeler, et al. Effects of Ambient Coarse, Eine, and Ultrafine Particles and Their Biological Constiments on Systemic Biomarkers A Controlled Human Exposure Smdy Environmental Health Perspectives 123 (2015) 534-40. doi 10.1289/ehp. 1408387. 

Punte, C.L., Owens, E.J., Gutentag, P.J., 1963. Exposures to orthochlorobenzylidene malononitrile. Controlled human exposures. Arch. Environ. Health 6,366-374. 

The model fit very well the data reported from other controlled human exposure stud-... 

Research into mechanisms of the adverse health effects of PMio mass concentrations observed in recent epidemiological studies needs to be undertaken in controlled exposure studies of humans and animals. It is only through integration of the complementary evidence from laboratory animal and controlled human exposure studies with the results from epidemiological studies that the risk of particle exposures can be fully evaluated. Nevertheless, these recent epidemiological studies implicate particulate air pollution as contributing to respiratory morbidity and mortality, even at exposure levels below the current ambient air quality standards in the United States and in Europe. 

---