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The marked species differences in short-term toxicity (30-day LD50) of ca. 10,000 (LD50: guinea pigs ca. 1 microgram/kg body wt and Han/Wistar Kuopio rats more than 9600 micrograms/kg body wt) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the central issues of the controversies that have developed on the validity of risk assessment strategies for TCDD and related compounds. One of the most challenging issues that toxicologists face today is the identification of genes that contribute to or are responsible for increased resistance or sensitivity to TCDD and related compounds. It is assumed that most, if not all, toxic effects of TCDD are mediated more or less through the binding affinity to the Ah receptor. This hypothesis was extended and tries to explain the differences in sensitivity/resistance of animals including humans to TCDD by their total fat (lipid) content. In this respect the gene or genes which is or are responsible for obesity of mammals including humans are of great interest. An obvious linear positive logarithmic relationship between the oral 30-day LD50 (microgram/kg) of TCDD in different species and strains of mammals and their total body fat content (TBF%) was found: log LD50 = 5.30 x log (TBF)-3.22, or LD50 = 0.000603 x (TBF)5.30. By means of this regression the toxicity of TCDD in mammals including humans of different age and/or body weight can be predicted if their total body fat content is known. Examples of single-gene and polygenic disease models in different mammals, such as nonobese diabetic, diabetic, viable yellow, obese, and fat mice, as well as transgenic mice, and other suitable animal models, such as fatty Zucker rats, Han/Wistar (Kuopio) rats, and minipigs, are discussed, and predicted LD50 values of TCDD in these animals and humans are presented.

The acute toxicity (48-hr LC50) of lindane (gamma-HCH) to 16 fish species, belonging to eight families, ranges from 22 to 900 micrograms/liter (mean: 150 micrograms/liter). A significant positive linear relationship between the lipid content (% on a wet weight basis) of the fishes and their toxicity to gamma-HCH was found. If the toxicity is referred to 1% lipid, 48-hr LC50 values range between 13.2 and 32 micrograms/liter, and thus the coefficient of variation of the mean is reduced from 139 to 22%. It is concluded that the lipids of aquatic organisms serve as a protective reservoir against the toxic effects of lindane and other lipophilic, relatively persistent organic chemicals, because they are bioconcentrated mainly in the body lipids. Therefore, in organisms with high lipid content, only a relatively small fraction of the hydrophobic chemical can reach target organs (nerves, liver, etc.) and/or receptors. For comparing toxicity data of organic chemicals to aquatic organisms, the total lipid content of the organisms must be considered. The results of this investigation are important in comparative environmental toxicology for risk assessment of freshwater and marine organisms.

This paper provides an explanation for a 40-fold difference in the acute toxicity (LC50) of gamma-hexachlorocyclohexane (gamma-HCH, Lindane) in 14 different fish species, based on well recognized principles of toxicokinetics and toxicodynamics in combination with a compilation of data from the literature and some original data. The 48-h median lethal concentration (48-h LC50) of gamma-HCH in 14 fish species, belonging to 6 families, range from 22 to 900 micrograms/l. A significant positive linear relationship was found between lipid content (% of wet weight) and the 48-h LC50 of gamma-HCH in these fish species, revealing that the toxicity of gamma-HCH in various fish species is decreasing with increasing total lipid content. If median lethal concentrations are normalized for 1% lipid content, then the range of 48-h LC50s is reduced to between 18 and 32 micrograms/l. It is concluded that lipids of aquatic organisms can serve (among other functions) as a protective storage site against the toxic effects of gamma-HCH and, possibly, of other lipophilic, persistent organic chemicals which are bioconcentrated in body lipids. Therefore, in organisms with higher lipid content, a smaller fraction of a lipophilic chemical will reach target organs (liver, lung, central and peripheral nerves, etc.) to cause adverse effects. Results suggest that this correlation can be used to extrapolate the acute toxicity (48-h LC50) of gamma-HCH to other fish species if their lipid content is known. Furthermore, the data generated by extrapolation of this correlation could be useful in the environmental risk assessment of freshwater and marine organisms.

Lipophilic chemicals such as chlorinated hydrocarbon insecticides and other persistent chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are fat soluble chemicals and are readily bioconcentrated in animal fat depots. The modifying role of the body fat content in the toxicity of chlorinated cyclodiene insecticides to insects and in the toxicity of TCDD to different mammals was investigated. The single oral acute 30-day LD50 data of TCDD in different mammals are presented and correlated with their total body fat content. A two linear regression equation with log/log values was obtained. It is concluded that the storage of TCDD and other related lipophilic and persistent chemicals in lipids of organisms is, in a sense, a detoxication mechanism by which the compounds are removed from sites of action and/or receptors. Therefore, terrestrial organisms such as insects and mammals with higher total body fat content can accumulate and tolerate higher chlorinated hydrocarbon insecticide and TCDD doses than organisms with lower fat content. The different sensitivity of mammals of various species, strains, body weight, sex, age, etc. to acute toxicity of TCDD and related lipophilic persistent chemicals can mainly be explained by differences in total body fat content.

Prediction of the bioconcentration of organic chemicals from water by aquatic organisms has important applications in the management of hazardous chemicals. This study gives a compilation of bioconcentration factors on a wet weight basis (BCFw) of 52 organic chemicals by Daphnia magna from aqueous solution. The bioconcentration factors for the chemicals in Daphnia were successfully correlated with their n-octanol/water partition coefficients (log Kow) using a linear regression analysis. In addition to the ordinary least-square regression technique, the geometric mean regression technique is also used because this takes into account deviations in Kow values. Both results show that the Kow value of a chemical is a good predictor of the BCF in Daphnia. The BCF-Kow relationships between Daphnia, algae (Chlorella), and mussels (Mytilus edulis) are compared with each other.

Single oral 30-day LD50s of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were correlated with total body fat (TBF) content in various species and strains of laboratory mammals. LD50 values and TBF contents were either obtained from the literature or determined by experiments. A log (LD50) vs. log (TBF) plot yielded a highly significant linear regression equation (r2 = 0.834, P less than 0.001, n = 20). It is suggested that this correlation exists for at least two reasons: (1) increasing TBF content in organisms represents an enhanced capacity to remove TCDD from the systemic circulation and (2) different TBF content reflects a differential role and regulation of fat metabolism for various organisms. Extrapolation of this correlation to man suggests that adult humans are among the less sensitive species to the acute toxicity of TCDD.