Human exposure tissue

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste sites) based on the results of studies where doses were higher or were administered in different species. Figure 3-4 shows a conceptualized representation of a PBPK model. 

With respect to sampling, sufficient numbers of environmental samples should be obtained to permit reliable statistical and biologic Interpretation of results. At the same time, the samples collected should be from environmental locations where human exposure Is most likely to occur (or did occur. If questions of past exposures require assessment). They should also be targeted for those environmental media which can be expected to have the greatest potential for human exposure and absorption. Finally, the samples must be obtained and preserved so that the chemicals which pose the greatest threat for human health In terms of toxicity and tissue persistence can be accurately measured. 

The USTUR proposed modifications to the ICRP americium model, based on post-mortem americium measurements in human exposure cases (Kathren 1994). The major modifications are 1) the initial deposition fraction is assumed to be skeleton 45%, liver 25%, muscle 20%, other tissues 10% 2) the half-... 

Studies using radioactivity-labeled acrylonitrile indicate that acrylonitrile or its metabolites form covalent adducts with cellular macromolecules in most tissues. Studies to develop chemical or immunological methods for measuring these adducts would be especially valuable in detecting and perhaps even quantifying human exposure to acrylonitrile. Adverse health effects demonstrated following exposure to acrylonitrile, particularly acute exposures, were characteristic of cyanide toxicity. Because these effects are also indicative of exposure to many other toxicants, additional methods are needed for more specific biomarkers of effects of acrylonitrile exposure. 

Perbellini L, Mozzo P, Brugnone F, et al. 1986. Physiologicomathematical model for studying human exposure to organic solvents Kinetics of blood/tissue -hexane concentrations and of 2,5-hexanedione in urine. Brit J Ind Med 43(11) 760-768. 

Mirex has been found in human adipose tissue (Burse et al. 1989 Kutz et al. 1974). Although the route of exposure was not specified, exposure was probably via the inhalation, oral, and dermal routes. Levels of 0.16-5.94 ppm and 0.3-1.13 ppm in males and females, respectively, were found in tissue samples taken either from postmortem examinations or during surgery (Kutz et al. 1974). The adipose tissue samples came from individuals who lived in areas in which mirex was used extensively in a program to control fire ants. Adipose tissue levels of mirex ranging from 0.03 to 3.72 ppm have been found in residents living near a dump site in Tennessee (Burse et al. 1989). 

Phillips LJ, Birchard GF. 1991a. Regional variations in human toxics exposure in the USA An analysis based on the national human adipose tissue survey. Arch Environ Contam Toxicol 21 (2) 159-168. 

Exposure Levels in Humans. This information is necessary for assessing the need to conduct health studies on these populations. Di- -oclylphthalatc has historically been reported to have been found in human adipose tissue (EPA 1986d). However, more recent information indicates that the compound detected was actually the branched di(2-ethylhexyl) isomer (EPA 1989b). Additional information on the concentrations of di-n-octylphthalate in human tissues and fluids, particularly for populations living near hazardous waste sites, is needed to assess potential human exposure to the compound. 

Exposure Levels in Humans. 1,2-Dibromoethane can be measured in blood and metabolites can be detected in urine (Letz et al. 1984 Nachtomi et al. 1965). However, since the compound is rapidly and extensively metabolized in mammals, and 1,2-dibromoethane metabolites do not persist in tissues, these biomarkers have not been useful in identifying or quantifying human exposure to the compound. 

---