Adipose tissue chemical residues

Concern for the continued widespread use of chlordane centers on its ability to cause liver cancer in domestic mice. Other adverse effects in mammals, such as elevated tissue residues and growth inhibition, were frequently associated with diets containing between 0.76 and 5.0 mg chlordane/kg feed. Metabolism of technical chlordane by mammals results primarily in oxychlordane, a metabolite that is about 20 times more toxic than the parent compound and the most persistent metabolite stored in adipose tissues. Chlordane interactions with other agricultural chemicals produced significant biological effects in warm-blooded organisms, indicating a need for additional research on this subject. 

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. 

TABLE I. Chemical Residues Measured in Adipose Tissue... 

LeBel GK, Williams DT. 1986. Pesticide and industrial chemical residues Determination of helogenated contaminants in human adipose tissue. J Assoc Off Anal Chem 69 451-458. 

Polybrominated Biphenyls. No studies were located regarding absorption of PBBs in humans or animals after dermal exposure to PBBs. However, absorption of PBBs through the skin in humans can be inferred by the relatively high levels of PBB residues detected in the adipose tissue and seniin of w orkers involved in the manufacturing of these chemicals (Brown etal. 1981 Landrigan et al. 1979 Stress et al. 1981). It is assumed that dermal route predominates, but inhalation and/or oral exposure cannot be ailed out. 

The 1991 National Research Council report Monitoring Human Tissues for Toxic Substances recommended that any new program to assay chemical concentrations in tissues of the U.S. population be based primarily on analysis of blood. The use of blood permits sampling of a wider sector of the population, better comparison of exposed populations with national averages, repeat sampling of persons who have high tissue concentrations, and opportunities to follow chemical clearance with time. The 1991 report also advised analysis of adipose tissue (especially for persistent pesticides) that would provide continuity with previous studies and confirmation that a survey based on blood also detects important tissue residues of persistent chemicals (NRC 1991). 

PCBs are industrial compounds which were widely used as organic diluents, plasticizers, pesticide extenders, adhesives, dust-reducing agents, cutting oils, flame retardants, heat transfer fluids, dielectric fluids for transformers and capacitors, hydraulic lubricants, sealants and in carbonless copy paper. PCBs have entered the environment via multiple pathways and residues of these compounds have been identified in air, water, wildlife and human adipose tissue, serum and milk.89-91 Like many other aromatic hydrocarbons, PCBs are highly lipophilic and chemically stable and this has contributed to their environmental persistence and bioconcentration in the food chain. PCBs were originally... 

Biotransformation of certain chlorinated hydrocarbon insecticides results in their conversion to metabolites which are less polar than the parent chemical. Heptachlor and aldrin are converted to the more lipophilic compounds heptachlor epoxide and dieldrin, respectively, whereas DDT is converted to DDE. The primary residue of DDT, which persists to the present day in animals and humans after exposure over a decade ago, is DDE. Following biotransformation, these compounds distribute to tissues which are higher in neutral lipid content than are the major organs of metabolism and excretion, the liver and kidney. These lipid-rich tissues are relatively, deficient in the so-called mixed-function oxidase (MFO) enzyme systems necessary for biotransformation of the halogenated hydrocarbons to more polar and thus more easily excreted compounds. As a result, these lipophilic chemicals remain unchanged in adipose tissue with only limited amounts returning to the circulation for possible metabolism and excretion. Paradoxically, aldrin and heptachlor metabolism results in an increased rather than reduced body load. This is opposite of the pattern seen for most other pesticide classes. 

Immunoassay Development in Meat. The results presented above clearly indicate that the LLNL-Hept-2 antibody recognized all of the cyclodiene insecticides tested with roughly equal affinity. The next problem that needed to be solved was analyzing for pesticide residues in adipose tissue, the site of accumulation in animals. The heptachlor had to be extracted from the fat sample in a manner that is chemically compatible with an immunoassay. In... 

Accumulation of residues in the Hver and kidneys generally exceeds levels in muscle. Some compounds, such as benzimidazoles, show the highest concentration in the liver, while the majority of antibiotics are located in the highest amounts in the kidney. LipophiHc chemical compounds, such as some organophosphates, accumulate in adipose tissue. 

---