Chemico-biological Interactions Research Articles

Human Exposure Estimates for Phthalates

Human Exposure Estimates for Phthalates

Kinetics of chlorambucil in vitro: effects of fluid matrix, human gastric juice, plasma proteins and red cells

The mechanisms involved in the bioavailability of chlorambucil or 4-[ p-(bis[2-hydroxyethyl]amino)phenyl]-butyric acid are poorly understood. The effects of different matrices on the disintegration of chlorambucil were investigated by HPLC, 1H NMR, 31P NMR, and mass spectrometry. Cellular incorporation and protein binding of the drug in vitro was assessed with [ 3H]-chlorambucil. Decomposition of chlorambucil and its major metabolite, phenylacetic acid mustard, to mono- and dihydroxy derivatives, was significantly faster in water than in PBS, (phosphate-buffered saline, pH 7.4). The hydrolysis of chlorambucil was as fast in plasma ultrafiltrate as in PBS; plasma proteins, preferentially albumin, prevented this disintegration. In phosphate-buffered media, two additional stabile hydrolysis products were found which were characterised as the mono- and bis-phosphates of 4-[ p-(bis[2-hydroxyethyl]amino)phenyl] butyric acid, results of the reaction of nucleophilic buffer species with the aziridinium ion intermediates. Chlorambucil bound covalently to plasma proteins and was incorporated into red cells. These interactions are likely to have a significant role in vivo, reducing the bioavailability of the drug. High H + concentration associated with high chloride concentration in human gastric juice had a stabilizing effect on chlorambucil. Incorporation of [ 3H]-chlorambucil into red cells was inhibited in a concentration-dependent fashion by whole human plasma as well as by albumin. We conclude that the chemico-biological interactions demonstrated in the present investigation provide explanations for the remarkable pharmacokinetic differences observed intra- and inter-individually in the clinical use of chlorambucil. The present information is important, when clinical or in vitro evaluation of efficacy and bioavailability of chlorambucil is considered.

Cell type-dependent effect of sodium valproate on human immunodeficiency virus type 1 replication in vitro.

Sodium valproate (VPA), a simple branched-chain fatty acid that has anticonvulsant activity and is used in the treatment of many forms of epilepsy, has been reported to stimulate human immunodeficiency virus (HIV) type 1 replication in acutely infected CEM and chronically infected U1 cells (Chemico-Biological Interactions 1994;91:111-121). When attempting to reproduce and extend these findings, we confirmed that VPA is able to stimulate HIV-1(IIIB) replication in acutely infected CEM and C8166 T lymphocytic cell lines and chronically infected ACH-2 and U937/IIIB/LAI cells in a concentration-dependent manner. The stimulatory effect of VPA on HIV replication in CEM cells was not increased by pretreatment of the cells with VPA for 24 hr before infection. However, we could not detect any stimulatory effect of VPA on HIV-1(IIIB) replication in acutely infected peripheral blood mononuclear cells (PBMCs), MT-4, MT-2, HUT-78, and MOLT-4 (clone 8) cells and in chronically infected HUT-78/IIIB/LAI cells. The stimulatory effect by VPA under certain conditions (see above) may be ascribed to an enhanced HIV transcription, as VPA was found to enhance the HIV long terminal repeat (LTR)-directed expression of beta-galactosidase in transiently transfected HLtat, P4, and COS7 cells. VPA did not enhance beta-galactoside expression mediated by the cytomegalovirus (CMV) promoter. VPA did not affect HIV-induced syncytium formation. Nor had VPA any direct inactivating effect on HIV.

Macromolecule adducts as biomarkers of exposure to environmental mutagens in human populations.

A cancer epidemiologist recently said that "adduct measurement has so far been of little use to epidemiological research." This remark gives us a starting point for the discussion of the purposes of measuring macromolecule adducts that originate from electrophilic compounds or metabolites in humans and animals. Historically, methods for adduct monitoring were developed as a means of determining target doses that, combined with measurements of genotoxic potencies, could be used for risk assessment. With mass spectrometric methods, adducts can be quantified at levels that are thousands of times lower than those in which the cancer incidence associated with this exposure is detectable in disease-epidemiological studies. Furthermore, mass spectrometric techniques permit identification of the chemical structure of the adduct, particularly in the case of hemoglobin adducts. Adduct measurement therefore constitutes not only a means of risk estimation but it may be used as a complement of disease epidemiology in situations in which, for statistical reasons, the risk is too low to be detectable--which does not signify that the risk is acceptably low. It also gives a possibility of identification of the dangerous components in mixed exposures and of the relevant reactive intermediates in cases of complex metabolism.

Comparative QSAR: Toward a Deeper Understanding of Chemicobiological Interactions.

Comparative QSAR: Toward a Deeper Understanding of Chemicobiological Interactions.

Role of Chelating Agents for Prevention, Intervention, and Treatment of Exposures to Toxic Metals

Role of Chelating Agents for Prevention, Intervention, and Treatment of Exposures to Toxic Metals

Optical measurements of activity-dependent membrane recycling in motor nerve terminals of mammalian skeletal muscle

Motor nerve terminals in a variety of rat and mouse skeletal muscles were stained in an activity-dependent fashion using the styryl dyes FM1-43 or FM2-10. Low-light video microscopy and digital image processing techniques were used to evaluate destaining of the preparations during application of depolarizing stimuli. Best results were obtained with the mouse triangularis sterni muscle. Quantitative analysis of the destaining of dye-loaded terminals supports the suggestion that FM1-43 stains a recycling membrane compartment, most probably synaptic vesicles. However, the pattern of staining and destaining were not the same as those reported previously for frog neuromuscular junctions. The pattern of nerve terminal staining was less punctate and the rate and amount of activity-dependent destaining were less than in frog muscle. Part of the explanation may be a more acute susceptibility of mammalian terminals to phototoxicity.

Symposium Overview: Toxicology, Carcinogenesis, and Human Health Aspects of 1,3-Butadiene

ArticlesOpen AccessSymposium Overview: Toxicology, Carcinogenesis, and Human Health Aspects of 1,3-Butadiene Ronald L. Melnick, J. E. Huff, Michael G. Bird, and John F. Acquavella Ronald L. Melnick Search for more papers by this author , J. E. Huff Search for more papers by this author , Michael G. Bird Search for more papers by this author , and John F. Acquavella Search for more papers by this author Published:1 June 1990https://doi.org/10.1289/ehp.90863Cited by:9AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited by Swenberg J, Boysen G, Georgieva N, Bird M and Lewis R (2007) Future directions in butadiene risk assessment and the role of cross-species internal dosimetry, Chemico-Biological Interactions, 10.1016/j.cbi.2007.01.012, 166:1-3, (78-83), Online publication date: 1-Mar-2007. Bird M, Rice J and Bond J (2001) Evaluation of 1,3-butadiene, isoprene and chloroprene health risks, Chemico-Biological Interactions, 10.1016/S0009-2797(01)00233-2, 135-136, (1-7), Online publication date: 1-Jun-2001. Brinkworth M, Anderson D, Hughes J, Jackson L, Yu T and Nieschlag E (1998) Genetic effects of 1,3-butadiene on the mouse testis, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 10.1016/S0027-5107(97)00196-6, 397:1, (67-75), Online publication date: 1-Jan-1998. Himmelstein M, Acquavella J, Recio L, Medinsky M and Bond J (2008) Toxicology and Epidemiology of 1,3-Butadiene, Critical Reviews in Toxicology, 10.3109/10408449709037482, 27:1, (1-108), Online publication date: 1-Jan-1997. Anderson D, Dobrzyńka M, Jackson L, Yu T and Brinkworth M (1997) Somatic and germ cell effects in rats and mice after treatment with 1,3-butadiene and its metabolites, 1,2-epoxybutene and 1,2,3,4-diepoxybutane, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 10.1016/S1383-5718(97)00069-7, 391:3, (233-242), Online publication date: 1-Jul-1997. Tates A, van Dam F, de Zwart F, van Teylingen C and Natarajan A (1994) Development of a cloning assay with high cloning efficiency to detect induction of 6-thioguanine-resistant lymphocytes in spleen of adult mice following in vivo inhalation exposure to 1,3-butadiene, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 10.1016/0027-5107(94)90106-6, 309:2, (299-306), Online publication date: 1-Sep-1994. Melnick R, Shackelford C and Huff J (2018) Carcinogenicity of 1,3-butadiene., Environmental Health Perspectives, 100, (227-236), Online publication date: 1-Apr-1993. Walker B and Burton L (2001) Synthetic Polymers-Olefin, Diene Elastomers, and Vinyl Halides Patty's Toxicology, 10.1002/0471435139.tox089 Walker B and Stokes L (2012) Synthetic Polymers-Olefin, Diene Elastomers, and Vinyl Halides Patty's Toxicology, 10.1002/0471435139.tox089.pub2, (891-916) Vol. 86June 1990Metrics About Article Metrics Publication History Originally published1 June 1990Published in print1 June 1990 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Some concepts in toxicology.

Toxicology seeks to understand and quantify injurious chemico-biological interactions. The application of this understanding is prediction of the likelihood of occurrence of injury to human health or to undesirable alteration of ecological balance. The key to understanding chemical induced biological injury is development of improved methods of measuring changes in cellular function and structure and the application of these methods to elucidate the mechanisms and factors that modulate chemical injuries. The key to application of this understanding is appropriately designed dose-response and time-response studies which will, with appropriate consideration of biological mechanisms, allow prediction of conditions of exposure (and their confidence limits) that represent finite levels of risk of injury. The underlying data base required is extensive and will be drawn from traditional studies as well as new methods of testing and risk assessment.

Chemico-biological interactions in biological purification systems V. Relation between biodegradation rate constants of aliphatic alcohols by activated sludge and their partition coefficients in a 1-octanol-water system

Chemico-biological interactions in biological purification systems V. Relation between biodegradation rate constants of aliphatic alcohols by activated sludge and their partition coefficients in a 1-octanol-water system

Chemico-biological interactions in biological purification systems VI. Relation between biodegradation rate constants of di-n-alkyl phthalate esters and their retention times in reverse phase partition chromatography

Chemico-biological interactions in biological purification systems VI. Relation between biodegradation rate constants of di-n-alkyl phthalate esters and their retention times in reverse phase partition chromatography

Quantitative Structure-Activity-Relationships and Modes of Action of Pesticides

The biological structure-activity relationships can be analyzed by means of a procedure similar to what has been used to elucidate physical organic structure-reactivity relationships. Using the Hammett-Taft substituent parameters such as σ, σ* and ES for electronic and steric factors and the parameter π for hydrophobicity defined from oil/water partition coefficients, structure-activity relationships of a number of series of biologically active compounds including pesticides have been analyzed quantitatively. By means of regression analysis, factors governing the variation in the magnitude of biological response are separated into respective terms of physicochemical parameters. By comparing the relative significance of each of the parameter terms with those observed for standard physical organic reactions and empirical rules accumulated for chemicobiological interactions, (sub) molecular modes of action of biologically active compunds can be delineated including mechanisms in the course of transport as well as those for the interaction with the target site in certain cases. This procedure named after Hansch has been used to such biological activities as nerve blocking of BHC and related compounds and acetylcholinesterase inhibition of phenyl N-methylcarbamate insecticides. The nerve blocking is attributed to nonspecific perturbation of nerve membrane due to hydrophobicity of molecule. The acetylcholinesterase inhibition with N-methylcarbamates is governed by positition-specific substituent effects such as biphasic electronic, hydrophobic and hydrogen bonding besides steric and proximity electronic effects of ortho substituents.

Biochemical significance of the hard and soft acids and bases principle

The hard and soft acids and bases (HSAB) principle, which states that hard acids bind preferentially to hard bases and soft acids to soft bases, may serve to assess specific chemico-biological interactions. As living systems are composed mainly of “hard” elements, molecular events taking place within the cell are dominated by “hard-hard interactions”. On this premise, it becomes likely that extraneous “soft” agents are particularly injurious to life. In the HSAB context a selected number of variegated phenomena are briefly discussed qualitatively; these include biocidal actions, heavy metal poisoning, chemical carcinogenesis, some enzymic reactions, and nucleic acid complexations. Although the HSAB principle cannot be used as a tool for mechanistic explanations of biochemical processes, it may provide clues to likely target molecules and the loci of action.

Species variations in the pathways of drug metabolism.

Research ArticleOpen AccessSpecies variations in the pathways of drug metabolism. R T Williams R T Williams Search for more papers by this author Published:1 February 1978https://doi.org/10.1289/ehp.7822133Cited by:14AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited by Ahmad M, Hassan S, Nisa R, Ayub K, Nadeem M, Nazir S, Ansari F, Qureshi N and Rashid U (2016) Synthesis, in vitro potential and computational studies on 2-amino-1, 4-dihydropyrimidines as multitarget antibacterial ligands, Medicinal Chemistry Research, 10.1007/s00044-016-1613-z, 25:9, (1877-1894), Online publication date: 1-Sep-2016. Jones A (2015) Profiles in drug metabolism and toxicology: Richard Tecwyn Williams (1909–1979), Drug Metabolism Reviews, 10.3109/03602532.2015.1115516, 47:4, (401-405), Online publication date: 2-Oct-2015. Wu Q, Yu X, Wang Y, Gu X, Ma X, Lv W, Chen Z and Yan C (2014) Pressurized CEC coupled with QTOF-MS for urinary metabolomics, ELECTROPHORESIS, 10.1002/elps.201400117, 35:17, (2470-2478), Online publication date: 1-Sep-2014. Dowty M, Messing D, Lai Y and Kirkovsky L (2010) ADME ADMET for Medicinal Chemists, 10.1002/9780470915110.ch4, (145-200) Merrifield C, Lewis M, Claus S, Beckonert O, Dumas M, Duncker S, Kochhar S, Rezzi S, Lindon J, Bailey M, Holmes E and Nicholson J (2011) A metabolic system-wide characterisation of the pig: a model for human physiology, Molecular BioSystems, 10.1039/c1mb05023k, 7:9, (2577), . Toyoda Y, Hagiya Y, Adachi T, Hoshijima K, Kuo M and Ishikawa T (2008) MRP class of human ATP binding cassette (ABC) transporters: historical background and new research directions, Xenobiotica, 10.1080/00498250701883514, 38:7-8, (833-862), Online publication date: 1-Aug-2008. Tyrakowska B, Cnubben N, Soffers A, Wobbes T and Rietjens I (1996) Comparative MO-QSAR studies in various species including man, Chemico-Biological Interactions, 10.1016/0009-2797(96)03699-X, 100:2, (187-201), Online publication date: 1-Mar-1996. Tardiff R and Rodricks J (1987) Comprehensive Risk Assessment Toxic Substances and Human Risk, 10.1007/978-1-4684-5290-7_18, (391-434), . Menzer R (1987) Selection of Animal Models for Data Interpretation Toxic Substances and Human Risk, 10.1007/978-1-4684-5290-7_8, (133-152), . Neis J, Yap S, van Gemert P, Roelofs H, Bos R and Henderson P (1986) Activation of mutagens by hepatocytes and liver 9000 × g supernatant from human origin in the Salmonella typhimurium mutagenicity assay, Mutation Research/Environmental Mutagenesis and Related Subjects, 10.1016/0165-1161(86)90040-3, 164:1, (41-51), Online publication date: 1-Feb-1986. Chadwick R, Copeland M, Wolff C, Cooke N, Whitehouse D and Mole M (2009) Effects of age and obesity on the metabolism of lindane by black a/a , yellow A vy / a , and pseudoagouti A vy / a phenotypes of (ys × vy) f 1 hybrid mice , Journal of Toxicology and Environmental Health, 10.1080/15287398509530788, 16:6, (771-796), Online publication date: 1-Jan-1985. Fishbein L (2016) An Overview of Some Metabolic and Modulating Factors in Toxicity and Chemical Carcinogenesis, Journal of the American College of Toxicology, 10.3109/10915818309140669, 2:1, (63-89), Online publication date: 1-Jan-1983. Doyle E and Chasseaud L (1981) Comparative pharmacokinetics of antipyrine (phenazone) in the baboon, cynomolgus monkey and rhesus monkey, Toxicology, 10.1016/0300-483X(81)90097-4, 19:2, (159-168), Online publication date: 1-Jan-1981. Ira Thabrew M and Bababunmi E (1980) Levels of microsomal drug-metabolizing enzymes in animals which are highly susceptible to aflatoxin carcinogenicity: The case of the duck, Cancer Letters, 10.1016/0304-3835(80)90026-9, 9:4, (333-338), Online publication date: 1-Jun-1980. Vol. 22February 1978Metrics About Article Metrics Publication History Originally published1 February 1978Published in print1 February 1978 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Species Variations in the Pathways of Drug Metabolism

Research ArticleOpen AccessSpecies variations in the pathways of drug metabolism. R T Williams R T Williams Search for more papers by this author Published:1 February 1978https://doi.org/10.1289/ehp.7822133Cited by:14AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited by Ahmad M, Hassan S, Nisa R, Ayub K, Nadeem M, Nazir S, Ansari F, Qureshi N and Rashid U (2016) Synthesis, in vitro potential and computational studies on 2-amino-1, 4-dihydropyrimidines as multitarget antibacterial ligands, Medicinal Chemistry Research, 10.1007/s00044-016-1613-z, 25:9, (1877-1894), Online publication date: 1-Sep-2016. Jones A (2015) Profiles in drug metabolism and toxicology: Richard Tecwyn Williams (1909–1979), Drug Metabolism Reviews, 10.3109/03602532.2015.1115516, 47:4, (401-405), Online publication date: 2-Oct-2015. Wu Q, Yu X, Wang Y, Gu X, Ma X, Lv W, Chen Z and Yan C (2014) Pressurized CEC coupled with QTOF-MS for urinary metabolomics, ELECTROPHORESIS, 10.1002/elps.201400117, 35:17, (2470-2478), Online publication date: 1-Sep-2014. Dowty M, Messing D, Lai Y and Kirkovsky L (2010) ADME ADMET for Medicinal Chemists, 10.1002/9780470915110.ch4, (145-200) Merrifield C, Lewis M, Claus S, Beckonert O, Dumas M, Duncker S, Kochhar S, Rezzi S, Lindon J, Bailey M, Holmes E and Nicholson J (2011) A metabolic system-wide characterisation of the pig: a model for human physiology, Molecular BioSystems, 10.1039/c1mb05023k, 7:9, (2577), . Toyoda Y, Hagiya Y, Adachi T, Hoshijima K, Kuo M and Ishikawa T (2008) MRP class of human ATP binding cassette (ABC) transporters: historical background and new research directions, Xenobiotica, 10.1080/00498250701883514, 38:7-8, (833-862), Online publication date: 1-Aug-2008. Tyrakowska B, Cnubben N, Soffers A, Wobbes T and Rietjens I (1996) Comparative MO-QSAR studies in various species including man, Chemico-Biological Interactions, 10.1016/0009-2797(96)03699-X, 100:2, (187-201), Online publication date: 1-Mar-1996. Tardiff R and Rodricks J (1987) Comprehensive Risk Assessment Toxic Substances and Human Risk, 10.1007/978-1-4684-5290-7_18, (391-434), . Menzer R (1987) Selection of Animal Models for Data Interpretation Toxic Substances and Human Risk, 10.1007/978-1-4684-5290-7_8, (133-152), . Neis J, Yap S, van Gemert P, Roelofs H, Bos R and Henderson P (1986) Activation of mutagens by hepatocytes and liver 9000 × g supernatant from human origin in the Salmonella typhimurium mutagenicity assay, Mutation Research/Environmental Mutagenesis and Related Subjects, 10.1016/0165-1161(86)90040-3, 164:1, (41-51), Online publication date: 1-Feb-1986. Chadwick R, Copeland M, Wolff C, Cooke N, Whitehouse D and Mole M (2009) Effects of age and obesity on the metabolism of lindane by black a/a , yellow A vy / a , and pseudoagouti A vy / a phenotypes of (ys × vy) f 1 hybrid mice , Journal of Toxicology and Environmental Health, 10.1080/15287398509530788, 16:6, (771-796), Online publication date: 1-Jan-1985. Fishbein L (2016) An Overview of Some Metabolic and Modulating Factors in Toxicity and Chemical Carcinogenesis, Journal of the American College of Toxicology, 10.3109/10915818309140669, 2:1, (63-89), Online publication date: 1-Jan-1983. Doyle E and Chasseaud L (1981) Comparative pharmacokinetics of antipyrine (phenazone) in the baboon, cynomolgus monkey and rhesus monkey, Toxicology, 10.1016/0300-483X(81)90097-4, 19:2, (159-168), Online publication date: 1-Jan-1981. Ira Thabrew M and Bababunmi E (1980) Levels of microsomal drug-metabolizing enzymes in animals which are highly susceptible to aflatoxin carcinogenicity: The case of the duck, Cancer Letters, 10.1016/0304-3835(80)90026-9, 9:4, (333-338), Online publication date: 1-Jun-1980. Vol. 22February 1978Metrics About Article Metrics Publication History Originally published1 February 1978Published in print1 February 1978 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Scientific bases of environmental carcinogenesis and cancer prevention: developing an interdisciplinary science and facing its ethical implications.

Two distinct types of toxic effects are defined: (1) terminal toxic effects, characterized by early appearance, direct correlation of the intensity of induced pathology with the intensity of exposure, and manifestation of toxicity due to altered functional products, degeneration, or death of the target cells themselves, and (2) self‐replicating toxic effects, characterized by delayed appearance, direct correlation of the frequency of induced pathology with the intensity of exposure, independence of the intensity of induced pathology from the intensity of exposure, and manifestation of toxicity due to proliferation of a new altered cell population. Traditional toxicology deals with terminal effects, but is inadequate to deal with self‐replicating effects, for which a new toxicology is developing. New knowledge of cellular and molecular mechanisms of self‐replicating toxicity has revolutionary implications for the evaluation of environmental toxicology. The mechanisms of carcinogenesis represent an example at the somatic cell level of the general theory of biological evolution by chance events followed by the necessity of biological expression as outlined by Monod in 1970. The implications of modern biological knowledge were developed by Monod into the ethic of knowledge. The scientific method, based on the postulate of objectivity, rejects any confusion between knowledge and “values.” In toxicology, value judgment on societal consequences of discovering chemicobiological interactions should absolutely not interfere with the objective pursuit of scientific evidence. The relationship between etiology and ethics demands high professional and ethical standards, comparable to those accepted in forensic medicine. High quality standards of scientific methodology, provisions to avoid any conflict of interest, and the establishment of licensed laboratories are recommended.

Chemico-biological interactions in biological purification system. I. Growth inhibition effect of azo compounds on activated sludge microorganisms.

There are enormous discharge of synthetic organic compounds into the environment by industrial production. These compounds give large influences not only in natural ecosystem but directly in humanlife and industrial production itself. Then it is important for maintenance and development of production to clarify those behaviors in the environment and to reduce those discharge into the environment.

Chemico-biological interactions in biological purification system. II. Biodegradation of azocompounds by activated sludge.

Chemico-biological interactions in biological purification system. II. Biodegradation of azocompounds by activated sludge.

Chemicobiological interactions and the use of partition coefficients in their correlation

Using octanol/water partition coefficients as an operational definition of hydrophobicity, 70 examples are given in which the hydrophobic interactions of organic compounds with themselves (in micelles) with macromolecules or with biological systems can be quantitatively correlated by the expression: log RBR = a log P + b. In this expression RBR is a binding constant or a relative biological response, P is the octanol/water partition coefficient and a and b are constants obtained via the method of least squares. These results are strong support for the utility of log P in the correlation of hydrophobic interactions. They also illustrate the extremely wide range of processes in which hydrophobic bonding plays a critical role.

Ultrastructural Changes in Rat Liver Cells Following a Single Oral Dose of TCDD

Ultrastructural Changes in Rat Liver Cells Following a Single Oral Dose of TCDD