This article reviews the present state of the art regarding the toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). The absorption, body distribution, and metabolism can vary greatly between species and also may depend on the congener and dose. In biota, the 2,3,7,8-substituted PCDDs and PCDFs are almost exclusively retained in all tissue types, preferably liver and fat. This selective tissue retention and bioaccumulation are caused by a reduced rate of biotransformation and subsequent elimination of congeners with chlorine substitution at the 2,3,7, and 8 positions. 2,3,7,8-Substituted PCDDs and PCDFs also have the greatest toxic and biological activity and affinity for the cytosolic arylhydrocarbon (Ah)-receptor protein. The parent compound is the causal agent for Ah-receptor-mediated toxic and biological effects, with metabolism and subsequent elimination of 2,3,7,8- substituted congeners representing a detoxification process. Congener-specific affinity of PCDDs and PCDFs for the Ah-receptor, the genetic events following receptor binding, and toxicokinetics are factors that contribute to the relative in vivo potency of an individual PCDD or PCDF in a given species. Limited human data indicate that marked species differences exist in the toxicokinetics of these compounds. Thus, human risk assessment for PCDDs and PCDFs needs to consider species-, congener-, and dose-specific toxicokinetic data. In addition, exposure to complex mixtures, including PCBs, has the potential to alter the toxicokinetics of individual compounds. These alterations in toxicokinetics may be involved in some of the nonadditive toxic or biological effects that are observed after exposure to mixtures of PCDDs or PCDFs with PCBs.

The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity.

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Toxicological profile for polybrominated biphenyls and polybrominated diphenyl ethers

Data on two classes of brominated polyaromatic flame retardants are reviewed with emphasis on analytical aspects, occurrence, fate, and toxicity in the environment. Concentrations of brominated fire retardants are quantified as equivalents of commercial mixtures. Because different congeners behave differently in the environment and show large differences in toxicity, future studies would benefit from the availability of analytical standards of individual congeners. The main environmental properties and mechanisms of toxicity of the PBBs and PBDEs are similar to those of the structurally related PCBs and dibenzodioxins. Although the present concentrations of brominated fire retardants do not yet appear to represent a major environmental risk in marine food chains, their replacement by environmentally less harmful alternatives is recommended.

Polybrominated biphenyl and diphenylether flame retardants: analysis, toxicity, and environmental occurrence.

Polybrominated biphenyls (PBB) were used as a fire retardant. In common with other halogenated hydrocarbons, PBBs are lipophilic and resistant to chemical and metabolic degradation. Cattle on about 25 Michigan farms were exposed to as much as 250 g per head of PBB when it was accidentally mixed in cattle feed in 1973 to 1974. Livestock exposures several orders of magnitude lower occurred on several hundred other farms because of carryover and equipment contamination in feed mills. Approximately 85% of the Michigan population received some exposure to PBB because dairy product marketing involves mixing milk from many farms. A few cases of high human exposure, which may have been as great as 10 g, occurred when residents of the more highly exposed farms consumed their own products. Although numerous clinical signs and pathological changes were reported in exposed cattle, only anorexia, lacrimation, emaciation, hyperkeratosis, and kidney damage were confirmed in controlled studies. The acute toxicity of PBB in laboratory animals is low, but a variety of subacute effects have been reported. Induction of microsomal enzymes, enlargement and histopathological changes of the liver, fetotoxicity, and immunosuppression are among the more significant. Epidemiological studies of exposed humans have revealed no pattern ofmore » clinical signs or symptoms that were related to PBB exposure. A complete evaluation of the human consequences of exposure to PBB await the conclusion of long-term epidemiological studies. 84 references.« less

The PBB episode in Michigan: an overall appraisal.

Endosulfan is an insecticide possessing a relatively broad spectrum of activity ; as a cyclic sulfite ester, it differs from the chlorinated hydrocarbons of the cyclodiene group by its physiological properties and behavior in the organism as well as by its extremely sparing action on beneficial insects. The technical active substance consists of two isomers, α- and β-endosulfan, which both possess similar insecticidal properties. Endosulfan was synthesized at Hoechst Aktiengesellschaft by Frensch and Goebel (1954 and 1954 a), the insecticidal effect of which was discovered by Frensch et al. (1954 b), and brought onto the market under the registered trade name Thiodan®.

Properties, Effects, Residues, and Analytics of the insecticide Endosulfan

A method for the determination of polybrominated biphenyls (PBBs) in dairy products is described. Fat is extracted from the products by the official AOAC method. The PBB residues are separated from the fatty material by gel permeation chromatography prior to gas-liquid chromatographic (GLC) quantitation. An additional cleanup using petroleum ether elution through a miniature Florisil column is necessary for thin layer chromatographic (TLC) confirmation. Recoveries of PBBs from samples fortified at levels from 0.1 to 0.5 ppm ranged from 94 to 104% with an average of 99%. GLC sensitivity permits the estimation of PBB residue levels as low as 0.007 ppm. Routine TLC confirmation is limited by sensitivity to greater than or equal to 0.2 ppm.

Determination of polybrominated biphenyl residues in dairy products.

Survey of 2,3,7,8-tetrachlorodibenzo-p-dioxin in fish from the Great Lakes and selected Michigan rivers

A new procedure is described for the determination of polybrominated biphenyls (PBBs) in dry animal feeds and developmental results are discussed. Finely ground feed is packed into a chromatographic column containing Celite and then eluted with methylene chloride. The concentrated extract is cleaned up by elution with petroleum ether through Florisil before gas-liquid chromatographic quantitation. Chromatograms thus obtained were essentially free of the interfering peaks encountered when using AOAC methods for pesticide residues in dry products. Results of feed analyses by the proposed procedure averaged 30% higher than those obtained by AOAC procedures. Recoveries of PBBs from samples fortified at levels of 0.04 to 0.4 ppm ranged from 90 to 104%, with an average of 98%.

Determination of polybrominated biphenyl residues in dry animal feeds.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in the edible portion of fish and shellfish from various U.S. waterways has been monitored since 1979. Analytical results for the period 1979-1994 are reported. Extracts obtained after column chromatographic and liquid chromatographic cleanup were examined by electron capture detection-gas chromatography (GC), and final quantitation and confirmation were performed by GC/mass spectrometry with multiple ion detection. Analyses of 1623 test samples indicated that TCDD residues in fish and shellfish were not widespread but rather were localized in areas near waste sites, chlorophenol manufacturers, and pulp and paper mills. Analytical results indicated that levels in aquatic species from these sites have been declining steadily. No TCDD (limit of detection and confirmation, 1-2 ppt) has been found in recent years in aquatic species from most Atlantic, Pacific, and Gulf of Mexico sites and Great Lakes other than Lake Ontario and Saginaw Bay (Lake Huron).

Norbert V Fehringer

Papers

Determination of polybrominated biphenyl residues in dairy products.

Survey of 2,3,7,8-tetrachlorodibenzo-p-dioxin in fish from the Great Lakes and selected Michigan rivers

Determination of polybrominated biphenyl residues in dry animal feeds.

TCDD residues in fish and shellfish from U.S. waterways.

HRGC‐FPD and HRGC/MS‐ITD characterozation of pentyl derivatives of the phenyl‐ and cyclohexyl‐tin pesticides and their metabolites