CRC Critical Reviews in Toxicology

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ISSN : 0045-6446
Published by: Informa UK Limited (10.3109)
Total articles ≅ 194
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James L. Schardein, Kit A. Keller, B. A. Schwetz
CRC Critical Reviews in Toxicology, Volume 19, pp 251-339; https://doi.org/10.3109/10408448909037473

Abstract:
Some 50 chemicals have been identified from environmental, occupational, or therapeutic exposure data as being potential developmental toxicants in humans. The toxicity pattern of these chemicals in humans has been characterized and correlated with developmental toxicity end points in laboratory animal models in order to determine the relevance and predictiveness of the results of testing in animals in extrapolation to human data. In general, animal developmental toxicity data closely paralleled human outcomes, and while humans in most cases were more sensitive than animals, the data support the concept that, imperfections aside, studies in animals serve a vital role in the hazard identification process.
Timothy P. Coogan, Dorothy M. Latta, Elizabeth T. Snow, Max Costa, A. Lawrence
CRC Critical Reviews in Toxicology, Volume 19, pp 341-384; https://doi.org/10.3109/10408448909029327

Abstract:
The toxicity and carcinogenicity of nickel compounds are considered in three broad categories: (1) systemic toxicology, (2) molecular toxicology, and (3) carcinogenicity. The systemic toxicity of nickel compounds is examined based upon human and animal studies. The major organs affected are discussed in three categories: (1) kidney, (2) immune system, and (3) other organs. The second area of concentration is molecular toxicology, which will include a discussion of the chemistry of nickel, its binding to small and large molecular weight ligands, and, finally, its cellular effects. The third major area involves a discussion of the carcinogenicity and genotoxicity of nickel compounds. This section focuses on mechanisms, using studies conducted in vivo and in vitro. It also includes a discussion of the assessment of the carcinogenicity of nickel compounds.
Corwin Hansch, Donbosco Kim, Albert J. Leo, , Carlo Silipo, Antonio Vittoria, James A. Bond, Rogene F. Henderson
CRC Critical Reviews in Toxicology, Volume 19, pp 185-226; https://doi.org/10.3109/10408448909037471

Abstract:
Correlation equations between logP (P = octanol water partition coefficient) and the biological activity of alcohols has been derived for 101 examples on all sorts of systems, from simple proteins to whole animals. This provides an overview of the toxic nature of hydrophobic compounds which can be used as a basis for comparison of more complex chemicals. About 100 examples of the hydrophobic effects of chemicals, other than alcohols, to various living systems or their parts are presented for comparison. It is clear that hydrophobic xenobiotics are toxic to almost every form of life, including humans (or parts there of).
Nobuyuki Ito, Katsumi Imaida, Ryohei Hasegawa, Hiroyuki Tsuda, Samuel M. Cohen
CRC Critical Reviews in Toxicology, Volume 19, pp 385-415; https://doi.org/10.3109/10408448909029328

Abstract:
It is very important to detect environmental carcinogens in a short period. For this purpose, a rapid bioassay system based on two-step hepatocarcinogenesis has been developed in our laboratory. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and, starting 2 weeks later, were treated with test compounds for 6 weeks and then sacrificed, all rats being subjected to a two thirds partial hepatectomy at week 3. Carcinogenic potential was scored by comparing the glutathione S-transferase placental form-positive foci in the liver with those of the corresponding control. More than 90% of hepatocarcinogens showed positivity, and none of the compounds reported as noncarcinogenic demonstrated positivity. Furthermore, this system also detected inhibitory effects. In order to detect nonhepatocarcinogens, other appropriate systems also have been developed, for example, using methylnitrosourea or other multispectrum carcinogens. These rapid bioassay systems are particularly useful for the screening of environmental carcinogens.
James A. Bond, Hermann M. Bolt
CRC Critical Reviews in Toxicology, Volume 19, pp 227-249; https://doi.org/10.3109/10408448909037472

Abstract:
Styrene is used in the production of plastics and resins, which include polystyrene resins, acrylonitrile-butadiene-styrene resins, styrene-acrylonitrile resins, styrene-butadiene copolymer resins, styrene-butadiene rubber, and unsaturated polyester resins. In 1985, styrene ranked in the top ten of synthetic organic chemicals produced in the U.S. This review focuses on various aspects of styrene toxicology including acute and chronic toxicity, carcinogenicity, genotoxicity, pharmacokinetics, effects on hepatic and extrahepatic xenobiotic-metabolizing enzymes, pharmacokinetic modeling, and covalent interactions with macromolecules. There appear to be many similarities between the toxicity and metabolism of styrene in rodents and humans. Needed areas of future research on styrene include studies on the molecular dosimetry of styrene in terms of both hemoglobin and DNA adducts. The results of such research should improve our ability to assess the relationship between exposure to styrene and surrogate measures of "effective dose", thereby improving our ability to estimate the effects of low-level human exposures.
Anna Maria H. Seppäläinen, Philip J. Landrigan
CRC Critical Reviews in Toxicology, Volume 18, pp 245-298; https://doi.org/10.3109/10408448809037468

Abstract:
Various neurophysiological methods, including electroencephalography, electromyography, nerve conduction velocities, and evoked potential techniques, have been used to detect early signs of neurotoxicity in humans. These methods have been applied to groups of occupationally exposed workers and their referents in epidemiologic studies, to patients with suspected or proven diseases after long-term work in toxic environment, and to human subjects during or after experimental exposure. The main body of knowledge arises from epidemiologic studies of occupationally exposed subjects, and several chemicals widely used in industry have been shown to be neurotoxic. Of these, e.g., lead causing peripheral neuropathy, some solvents like carbon disulfide, n-hexane, and methyl n-butyl ketone also causing neuropathy and at times central nervous system effects as well as acryl amide have been studied using neurophysiological approaches. Several other solvents including toluene, xylene, and various mixtures of organic solvents have been suspected to be neurotoxic, and nervous system effects have been ascribed to those in several neurophysiological studies. Some studies have elucidated acute nervous system effects of ethyl alcohol or industrial solvents in experimental situations applying, for example, evoked potential techniques or electroencephalography.
M. W. Anders, , Wolfgang Dekant, Adnan A. Elfarra, David R. Dohn, Donald J. Reed
CRC Critical Reviews in Toxicology, Volume 18, pp 311-341; https://doi.org/10.3109/10408448809037470

Abstract:
The material presented in this review deals with the hypothesis that the nephrotoxicity of certain halogenated alkanes and alkenes is associated with hepatic biosynthesis of glutathione S-conjugates, which are further metabolized to the corresponding cysteine S-conjugates. Some glutathione or cysteine S-conjugates may be direct-acting nephrotoxins, but most cysteine S-conjugates require bioactivation by renal, pyridoxal phosphate-dependent enzymes, such as cysteine conjugate beta-lyase (beta-lyase). The biosynthesis of glutathione S-conjugates is catalyzed by both the cytosolic and the microsomal glutathione S-transferases, although the latter enzyme is a better catalyst for the reaction of haloalkenes with glutathione. When glutathione S-conjugate formation yields sulfur mustards, as occurs with vicinal-dihaloethanes, the S-conjugates are direct-acting toxins. In contrast, the S-conjugates formed from fluoro- and chloroalkenes yield S-alkyl- or S-vinyl glutathione conjugates, respectively, which are metabolized to the corresponding cysteine S-conjugates by gamma-glutamyltransferase and dipeptidases; inhibition of these enzymes blocks the toxicity of the glutathione S-conjugates. The cysteine S-conjugates must be metabolized by beta-lyase for the expression of toxicity; the beta-lyase inhibitor aminooxyacetic acid blocks the toxicity of cysteine S-conjugates, and the corresponding alpha-methyl cysteine S-conjugates, which cannot be metabolized by beta-lyase, are not toxic. Moreover, probenecid, an inhibitor of renal anion transport system, blocks the toxicity of cysteine S-conjugates, which cannot be metabolized by beta-lyase, are not toxic. Moreover, probenecid, an inhibitor of renal anion transport system, blocks the toxicity of cysteine S-conjugates. Homocysteine S-conjugates are also potent cyto- and nephrotoxins. The high renal content of gamma-glutamyltransferase and the renal anion transport system are probably determinants of kidney tissue as a target site. Biochemical studies indicate that renal mitochondrial dysfunction is produced by the cysteine S-conjugates. Finally, some of the glutathione and cysteine conjugates are mutagenic in the Ames test, and reactive intermediates formed by the action of beta-lyase may contribute to the nephrocarcinogenicity of certain chloroalkenes.
B. C. Das, A. T. Natarajan
CRC Critical Reviews in Toxicology, Volume 19, pp 43-86; https://doi.org/10.3109/10408448809040817

Abstract:
Sister chromatid exchange (SCE) reflects an interchange of DNA sequences between helices in a replicating chromosome. This was initially accomplished by Taylor and colleagues (1957) using tritiated thymidine incorporation followed by autoradiography. The development of an elegant technique for differential staining of sister chromatids by incorporating a thymidine analog, 5-bromodeoxyuridine (BrdU) has greatly simplified the detection of SCEs in metaphase chromosomes. In recent years, the analysis of SCE has been considered to be a highly sensitive and additional (i.e., with chromosome aberrations) end point for measuring mutagenic/carcinogenic potential of various environmental agents and is increasingly being used to detect and differentiate among chromosome fragility human diseases that predispose to neoplasia. Attention has been focused to see if the induction of SCEs in lymphocyte cultures can be used as a reliable "biological dosimeter" for genetic risk assessment and to monitor the exposed populations. Several physical or preparatory as well as biological factors that modify the response and formation of SCEs make the monitoring difficult. The purpose of this article is to review and analyze these factors to facilitate an effective development of a standard protocol for SCE testing and for appropriate evaluation of test results. This may also provide clues to understand the yet unknown molecular mechanism(s) and biological significance of SCE formation.
John D. Groopman, Lawrence G. Cain, Thomas W. Kensler, Curtis C. Harris
CRC Critical Reviews in Toxicology, Volume 19, pp 113-145; https://doi.org/10.3109/10408448809014902

Philippe Grandjean, Clair C. Patterson
CRC Critical Reviews in Toxicology, Volume 19, pp 11-21; https://doi.org/10.3109/10408448809040815

Abstract:
Lead is stored in calcified tissues, and the lead levels in human remains will therefore reflect in vivo exposures in the past, provided that postmortem contamination can be ruled out or successfully removed. Reliable chemical testimonies from archeological finds indicate that prepollution exposures to lead were of the order of 1% of current-day exposures in industrialized countries. Examination of these silent witnesses of past times has also shown that lead exposures during recent historical periods were much higher than today. Studies in this area provide a framework for evaluation of lead exposures. The results would suggest that an ideal control group should not be exposed to lead levels any higher than the low, prepollution levels.
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