Human exposure adipose tissue

Distribution. Quantitative inhalation, oral, or dermal distribution studies in humans are not available for 1,4-dichlorobenzene. 1,4-Dichlorobenzene has been detected in human blood, adipose tissue, and breast milk after an assumed inhalation exposure in Tokyo residents (Morita and Ohi 1975 Morita et al. 1975), as well as people in some parts of the United States (EPA 1983b, 1986). The available data indicate that after inhalation, oral, and subcutaneous exposure, 1,4-dichlorobenzene preferentially distributes to the fat tissue and organ-specific sites within the body (Hawkins et al. 1980), following the order adipose > kidney > liver > blood (Charboimeau et al. 1989b Hawkins et al. 1980). Although... 

DEHP is lipophilic and tends to migrate into adipose deposits. Since it is cleared from these deposits slowly, analysis of fat tissues probably provides the best test for previous exposure to this plasticizer. Analysis of human abdominal adipose tissues from accident victims indicated that DEHP was present in these tissues at a concentration of 0.3-1.0 ppm (Mes et al. 1974). DEHP was also identified in 48% of the adipose tissue specimens from cadavers autopsied in 1982 as part of the Human Adipose Tissue Survey from the National Human Monitoring Program (EPA 1989b). Neither study contained data on DEHP exposure history of the subjects, however, and there is no information regarding correlation of adipose tissue concentrations with DEHP exposure concentration and duration. 

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. 

GC/MS has been employed by Demeter et al. (1978) to quantitatively detect low-ppb levels of a- and P-endosulfan in human serum, urine, and liver. This technique could not separate a- and P-isomers, and limited sensitivity confined its use to toxicological analysis following exposures to high levels of endosulfan. More recently, Le Bel and Williams (1986) and Williams et al. (1988) employed GC/MS to confirm qualitatively the presence of a-endosulfan in adipose tissue previously analyzed quantitatively by GC/ECD. These studies indicate that GC/MS is not as sensitive as GC/ECD. Mariani et al. (1995) have used GC in conjunction with negative ion chemical ionization mass spectrometry to determine alpha- and beta-endosulfan in plasma and brain samples with limits of detection reported to be 5 ppb in each matrix. Details of commonly used analytical methods for several types of biological media are presented in Table 6-1. 

Following inhalation exposure to trichloroethylene in humans, the unmetabolized parent compound is exhaled, whereas its metabolites are primarily eliminated in the urine. Excretion of trichloroethylene in the bile apparently represents a minor pathway of elimination. Balance studies in humans have shown that following single or sequential daily exposures of 50-380 ppm trichloroethylene, 11% and 2% of the dose was eliminated unchanged and as trichloroethanol, respectively, in the lungs 58% was eliminated as urinary metabolites and approximately 30% was unaccounted for (Monster et al. 1976, 1979). Exhaled air contained notable concentrations of trichloroethylene 18 hours after exposure ended because of the relatively long half-life for elimination of trichloroethylene from the adipose tissue (i.e., 3.5-5 hours) compared to other tissues (Fernandez et al. 1977 Monster et al. 1979). 

Exposure Levels in Humans. Metabolism of endrin in humans is relatively rapid compared with other organochlorine pesticides. Thus, levels in human blood and tissue may not be reliable estimates of exposure except after very high occupational exposures or acute poisonings (Runhaar et al. 1985). Endrin was not found in adipose tissue samples of the general U.S. population (Stanley 1986), or in adipose breast tissue from breast cancer patients in the United States (Djordjevic et al. 1994). Endrin has been detected in the milk of lactating women (Alawi et al. 1992 Bordet et al. 1993 Dewailly et al. 1993), but no data from the United States could be located. Data on the concentrations of endrin in breast milk from U.S. women would be useful. No information was found on levels of endrin, endrin aldehyde, or endrin ketone in blood and other tissues of people near hazardous waste sites. This information is necessary for assessing the need to conduct health studies on these populations. 

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). 

Anderson HA. 1985. Utilization of adipose tissue biopsy in characterizing human halogenated hydrocarbon exposure. Environ Health Perspect60 127-131. 

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. 

Detection of heptachlor epoxide may indicate either recent or past exposure. This compound has a long half-life, particularly in adipose tissue, because it is very lipophilic. Because of its highly lipophilic nature, heptachlor epoxide remains accumulated in adipose tissue for months to years. However, it is eventually mobilized into the serum and subsequently to the liver for further breakdown. Blood serum levels are often taken to indicate a recent exposure. Following long-term exposure, the level in the blood may be very low, but because of an equilibrium between fat and blood, it can be used to detect exposure to heptachlor epoxide. Thirty-five human adipose tissue samples were obtained during autopsy between 1987 and 1988 from residents of North Texas (Adeshina and Todd 1990). In 97% of these samples, there were measurable levels of heptachlor... 

Biomarkers of Exposure and Effect. Exposure to heptachlor and heptachlor epoxide is currently measured by determining the level of these chemicals in the blood or adipose tissue in living organisms (Curley et al. 1969 Klemmer et al. 1977 Radomski et al. 1968). This measure is specific for both heptachlor and heptachlor epoxide. Heptachlor epoxide is also a metabolite of chlordane, and thus its presence is not specific for exposure to heptachlor alone. However, in the absence of stable chlordane residues (e.g., nonachlor and oxychlordane), the heptachlor epoxide would most likely have been derived from heptachlor. Because heptachlor is believed to be converted rapidly in the body to heptachlor epoxide, it is impossible to determine whether the exposure was to one or the other of these two compounds. Heptachlor and heptachlor epoxide accumulate in adipose tissue and are released slowly over long periods of time. Therefore, it is not possible to accurately identify whether the exposure was recent or what the duration of exposure was. However, the ratio of heptachlor epoxide to heptachlor increases over time and therefore may be used as a biomarker of possible exposure to heptachlor. The sensitivity of the methods for identifying these compounds in human tissue appears to be only sufficient to measure background levels of heptachlor epoxide in the population. Additional biomarkers of exposure to heptachlor would be helpful at this time. 

Exposure Levels in Humans. Heptachlor epoxide has been detected in human blood, tissues (including adipose tissue), and breast milk (Al-Omar et al. 1986 Holt et al. 1986 Larsen et al. 1971 Savage et al. 1981). The presence of heptachlor epoxide is used as an indicator of exposure to heptachlor. Current monitoring studies of heptachlor epoxide in these tissues and fluids would be helpful in assessing the extent to which populations, particularly in the vicinity of hazardous waste sites, have been exposed to heptachlor. 

Analytical methods exist for measuring heptachlor, heptachlor epoxide, and/or their metabolites in various tissues (including adipose tissue), blood, human milk, urine, and feces. The common method used is gas chromatography (GC) coupled with electron capture detection (ECD) followed by identification using GC/mass spectrometry (MS). Since evidence indicates that heptachlor is metabolized to heptachlor epoxide in mammals, exposure to heptachlor is usually measured by determining levels of heptachlor epoxide in biological media. A summary of the detection methods used for various biological media is presented in Table 6-1. 

D5 has slightly different properties than D4, and it does not have any estrogenic activity [289]. It does, however, also have adverse effects on the reproductive system, much like D4, but also on the adipose tissue, bile production, and even immune system due to D5 s effect of reducing the prolactin levels [291]. In addition, it was determined that D5 causes a significant increase in uterine tumors in rats after a 160 ppm exposure. However, it is proposed that the tumors occur in rats through a mechanism that would not affect humans [291]. D5 also acts as a dopamine agonist and it can cause adverse effects on the nervous system in humans [291]. For exposures to D6 in rats, an increase in liver and thyroid mass and reproductive effects were observed [292]. 

XZ/N VI RON MENTAL APPLICATIONS OF CHEMOMETRics are of interest because of the concern about the effects of chemicals on humans. The symposium upon which this book is based served as an important milestone in a process we, the editors, initiated in 1982. As members of the Environmental Protection Agency s Office of Toxic Substances (OTS), we have responsibilities for the acquisition and analysis of human and environmental exposure data in support of the Toxic Substances Control Act. OTS exposure studies invariably are complex and range from evaluating human body burden data (polychlorinated biphenyls in adipose tissue, for example) to documenting airborne asbestos levels in schools. 

No studies were located regarding the tissue distribution of 1,4-dichlorobenzene in humans after inhalation exposure to 1,4-dichlorobenzene. The compound has been found, however, in human blood, fatty tissue, and breast milk, presumably as a result of exposure via inhalation. In a study of Tokyo residents, detectable levels of 1,4-dichlorobenzene were found in all of 34 adipose tissue samples and all of 16 blood samples tested (Morita and Ohi 1975 Morita et al. 1975). In a national survey of various volatile organic compounds (VOC) found in composites of human adipose tissue, samples were collected from persons living in the nine geographic areas that comprise the United States (within this survey). 

Exposure Levels in Humans. Detection of 1,4-dichlorobenzene in breath, adipose tissue, breast milk, and blood, can be used as indicators of human exposure (Ashley et al. 1994, 1995 EPA 1989d Erickson et al. 1980 Hill et al. 1995 Pellizzari et al. 1982 Stanley 1986 Wallace et al. 1986). Levels of... 

There is no information on in utero developmental effects in humans exposed to HCB, but oral exposure of young children has caused small or atrophied hands, short stature, pinched facies, osteoporosis of the carpal, metacarpal, and phalangeal bones, and painless arthritic changes. HCB has been demonstrated to cross the placenta in humans and in rodents. HCB residues have been detected in human milk and adipose tissue and in the blood of the umbilical cord of newborn infants and their mothers. Teratogenic effects were not... 

Hexachlorobutadiene has been identified in samples of human adipose tissue (Mes et al. 1985). The tissue samples were obtained from cadavers and, thus, no data were available pertaining to the route of exposure. 

No studies were located regarding distribution in humans after oral exposure to hexachlorobutadiene. In animals, 5-14% of ( C) radiolabeled hexachlorobutadiene was retained in the tissues and carcass 72 hours after compound administration (Dekant et al. 1988a Reichert et al. 1985). The kidney (outer medulla), liver, and adipose tissue appeared to concentrate hexachlorobutadiene label when single doses of up to 200 mg/kg ( C) hexachlorobutadiene in corn oil were administered by gavage (Dekant et al. 1988a Nash et al. 1984 Reichert et al. 1985). In one report, the brain was also determined to contain a relatively high concentration of label 72 hours after exposure (Reichert et al. 1985). Label in the kidney 72 hours after exposure was more extensively covalently bound to proteins than that in the liver (Reichert et al. 1985). 

Hexachlorobutadiene has been detected in human adipose tissue and blood samples. These data indicate that exposure to hexachlorobutadiene does occur in humans, however route-specific estimates of hexachlorobutadiene exposure were not located. Based on monitoring data, individuals who work in hexachlorobutadiene-producing facilities, live at or near hazardous waste facilities, or consume large amounts of hexachlorobutadiene-contaminated fish may have above-average exposures to hexachlorobutadiene. 

Exposure Levels in Humans. Flexachlorobutadiene has been detected in human adipose tissues and blood (Bristol et al. 1982 Mes et al. 1985). Studies which establish a correlation between exposure levels in environmental media and the resulting levels in human tissues and excreta would be valuable in predicting exposures and corresponding health risks in humans who live at or near hazardous waste sites and who are likely to be exposed to hexachlorobutadiene. 

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