Combined Actions and Interactions of Chemicals in Mixtures

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In practical life an allergen may be tolerated in one situation but not in another where it is in combination with another allergen. The threshold dose for elicitation may be very low for allergens in mixture e.g. fragrances in perfume. A chemical or a physical condition (occlusion, disease) that facilitates penetration of the skin by a contact allergen or have an effect on the skin immune system may enhance the possibility of sensitisation. 130
8 Books, articles and reports Several reference books, review articles and reports have been published on the issue of toxicological effects from combined exposure to chemicals. The more important are: 8.1 Books Multiple Chemical Interactions (Calabrese 1991) by Edward J Calabrese is an exhaustive textbook. It consists of six parts: • General principles, which contain chapters on terminology, analysis of combined effects, and pharmacokinetic and pharmacodynamic foundations of interactions. • Carcinogenesis and teratogenesis. • Interactions by chemical class. • Interactions between medical drugs. • The drug-pollutant interface. • Regulatory perspectives. The main emphasis is related to drug therapy and drug-pollutant interactions. However, other authors often make references to the first chapters of the book. Toxicology of Chemical Mixtures – Case studies, Mechanisms, and Novel Approaches (Yang 1994) edited by Raymond SH Yang is an important work in the field of combination toxicology. The book includes basic concepts and mechanisms of interactions in target organ toxicities and it contains a number of informative case studies on different types of industrial and environmental chemicals, such as pesticides and hazardous waste. In addition, it offers novel approaches in the risk assessment of chemical mixtures. Special attention is paied to low-level, long-term exposures. 8.2 Review articles Recent review articles have been published by Dutch researchers from the TNO Nutrition and Research Institute and The National Institute for Public Health and the Environment, Holland. Toxicological Evaluation and Risk Assessment of Chemical Mixtures was published in Critical Review of Toxicology by Cassee et al. (1998). Toxicology of simple and complex mixtures was published in Trends in Pharmacological Sciences by Groten et al. (2001) and Toxicological evaluation of chemical mixtures was published by Feron and Groten (2002) in Food and Chemical Toxicology. Concepts and perspectives in the area are comprehensively described and illustrated by results of toxicological studies on well-defined chemical mixtures performed by the same research group. A pragmatic approach for the study, hazard identification, and risk assessment of chemical mixtures is offered based on the hypothesis of this group of researchers (around Victor Feron) that exposure to mixtures of chemicals at non-toxic doses of the individual constituents is of no health concern. 131
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Combined Actions and Interactions o
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Contents CONTENTS 3 PREFACE 6 SAMME
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7.2.4 Test systems 85 7.2.5 In vitr
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Sammenfatning og konklusioner Indle
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er ingen viden om, hvorledes den ko
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estemt biologisk respons (ED10, ED2
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vivo. The COMET-assay in vivo and g
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and antagonistic effects may be see
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1 Introduction Prepared by John Chr
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Table 1.3.1: Classification of comb
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Physicochemical interactions will t
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US EPA (1986) applied the concept o
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2.4 Test strategies to assess combi
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Figure 2.4.3.1. Isobologram of two
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CI = d1 /D1 = 1 In this case the is
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2.5 Toxicological test methods When
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3 General concepts in the risk asse
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NOAEL, this indicates that the subs
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of uncertainty i.e. differences in
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describe toxicities that appears to
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should be estimated for all endpoin
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1,2,3,6,7,8-HxCDF 0.1 1,2,3,7,8,9-H
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shows the pronounced influence of t
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Table 4.3.1 Estimates of carcinogen
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Figure 4.4.1.1. Scheme for safety e
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obvious ranking of individual const
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4.5 Approach for assessment of join
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4.6 Approaches currently used by re
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no internationally accepted procedu
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Figure 4.6.3.1 Flow chart of the ri
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octyltin dichloride). A number of a
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stannous chloride and cadmium chlor
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seen in the animals from the 1000x
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c TCTFP = 1,1,2-trichloro-3,3,3-tri
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6 Interactions in toxicokinetics Pr
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once more exposed and the kinetics
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Dermis The dermis consists of a sup
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7.1.3 Ocular irritancy 7.1.3.1 Comp
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Another in vitro test for ocular ir
Page 80 and 81: lipid peroxidation was observed, wh
Page 82 and 83: mixture. These interactions may dev
Page 84 and 85: 0.6% of live births in humans. In s
Page 86 and 87: DNA, and that the cell was capable
Page 88 and 89: (Sorsa et al. 1994, Myslak & Kosmid
Page 90 and 91: Four inhibitors of DNA topoisomeras
Page 92 and 93: cyclophosphamide-metabolising enzym
Page 94 and 95: Nickel compounds are carcinogenic t
Page 96 and 97: 7.2.8 Conclusion As shown in this r
Page 98 and 99: Since no compounds are known to cau
Page 100 and 101: In a more mechanistic sense, promot
Page 102 and 103: Several inhibitors of tumour promot
Page 104 and 105: Table 7.4.1.1 Overview of in vivo t
Page 106 and 107: analysis was used to predict the hi
Page 108 and 109: interaction of TCDD and retinoic ac
Page 110 and 111: and now includes compounds as diver
Page 112 and 113: Furthermore, the estrogenic effects
Page 114 and 115: Dose of A (arbitrary units) 10 8 6
Page 116 and 117: chance or experimental error. One w
Page 118 and 119: 7.6.2.3 Receptors A receptor is a b
Page 120 and 121: 7.6.5.2 Kindling Kindling is the ph
Page 122 and 123: Science Institute (RSI) have conven
Page 124 and 125: eaction with sulfhydryl groups). Th
Page 126 and 127: 7.7.1.3 Mechanisms of immunotoxicit
Page 128 and 129: tested separately. This is a phenom
Page 132 and 133: 8.3 Conference proceedings Proceedi
Page 134 and 135: with combinations of environmental
Page 136 and 137: Boyd MR, Statham CM and Longo NS (1
Page 138 and 139: De Wall EJ, Schuurman HJ and Van Lo
Page 140 and 141: theoretical considerations and a su
Page 142 and 143: Groten JP, Sinkeldam EJ, Muys T, Lu
Page 144 and 145: Howes D, Guy R, Hadgraft J, Heyling
Page 146 and 147: cytochrome P450 1A2 expressed in Am
Page 148 and 149: Lison D, Carbonnelle P, Mollo L, La
Page 150 and 151: Narotsky MG, Weller EA, Chinchilli
Page 152 and 153: Ramsey JC and Andersen ME (1984). A
Page 154 and 155: Silva E, Rajapakse N and Kortenkamp
Page 156 and 157: Leeuwen FXR, Liem AKD, Nolt C, Pete
Page 158: Wlodarczyk B, Biernacki B, Minta M,
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Combined Actions and Interactions of Chemicals in Mixtures

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