Potentiation of 2,6‐dinitrotoluene genotoxicity in fischer 344 rats by pretreatment with coal tar creosote

Chadwick, Robert W.; George, S. Elizabeth; Kohan, Michael J.; Rt, Williams; Allison, J. C.; Talley, Detra L.; Hayes, Y. O.; Chang, Jer Jang

doi:10.1080/15287399509531962

Cited by 10 publications

(4 citation statements)

References 19 publications

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“…A metabolite, 2-amino-6-nitrotoluene, gave the same adducts as 2,6-DNT, but at 30-fold lower levels (158). Intestinal microflora were important in activating 2,6-DNT to mutagenic metabolites (159), and the genotoxicity was increased by pretreating the rats with the enzyme inducers Aroclor 1254 or creosote (160,161 …”

Section: Toxic Effectsmentioning

confidence: 86%

Aromatic Nitro and Amino Compounds

Bingham¹,

McGowan²

2012

Patty's Toxicology

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Logically, aromatic nitro and amino compounds should be discussed together because their toxic responses are often similar due to a common metabolic intermediate. Synthetically, amines are generally derived from nitro compounds, but in some cases nitro compounds can be prepared through amines when other methods fail to afford specific compounds. There are good and bad attributes to these types of compounds. Some act as sensitizers and contingent on physical properties may be absorbed through the skin or mucous membranes. They may also cause methemoglobinemia, depending on such factors as the structure and the particular organism. Some members of this class are known as animal and human carcinogens; for humans, the urinary bladder is the most prominent target organ. Nevertheless, these compounds and their derivatives have enlivened our world through their use as dyestuff intermediates or as photographic chemicals, they alleviate pain as components of widely used analgesics, and they cushion or insulate us through their use in flexible and rigid foams. Other important uses include production of pesticides, including herbicides and fungicides, as ingredients in adhesives, paints and coatings, antioxidants, explosives, optical brighteners, rubber ingredients, and as intermediates in many other products.

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Section: Toxic Effectsmentioning

confidence: 86%

Aromatic Nitro and Amino Compounds

Bingham¹,

McGowan²

2012

Patty's Toxicology

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“…Activation of the hepatocarcinogen 2,6 dinitrotoluene (DNT) is a process involving both hepatic and intestinal enzymes (Chadwick 1995). Pre-treatment of Fischer 344 rats with Aroclor 1254 or creosote (a complex mixture of PAH, phenols and heterocyclic compounds), potentiate the genotoxic effect of DNT, measured as hepatic DNA adduct formation.…”

Section: Biotransformationmentioning

confidence: 99%

Environmental Chemicals

Hileman¹

2003

Chem. Eng. News Archive

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Hazard index (HI) 4.2.2 Point of Departure Index (PODI) 4.2.3 Toxicity equivalency factors (TEF) 4.2.4 Margin of exposure (MOE) 4.2.5 Cumulative risk index (CRI) 4.3 USE OF RESPONSE ADDITION (SIMPLE DISSIMILAR ACTION) IN THE RISK ASSESSMENT OF MIXTURES OF POLYCYCLIC AROMATIC HYDROCARBONS (PAH).45 4.4 APPROACH TO ASSESS SIMPLE AND COMPLEX MICTURES SUGGESTED BY THE DUTCH GROUP 4.4.1 Simple mixtures 4.4.2 Complex mixtures 4.5 APPROCH FOR ASSESSMENT OF JOINT TOXIC ACTION OF CHEMICAL MIXTURES SUGGESTED BY ATSDR 4.5.1 ATSDR strategy for noncarcinogenic effects 4.5.2 ATSDR strategy for carcinogenic effects 4.6 APPROACHES CURRENTLY USED BY REGULATORY AGENCIES IN DENMARK 4.6.1 Danish Working Environment Authority 4.6.2 The Danish Environmental Protection Agency 4.6.3 The Danish Veterinary and Food Administration 5 EXPERIMENTAL STUDIES USING SIMPLE, WELL-DEFINED MIXTURES 5.1 7.2.4 Test systems 7.2.5 In vitro assays 7.2.6 In vivo assays 7.2.7 Interactions between genotoxic substances 7.2.8 Conclusion 7.3 CARCINOGENICITY 7.3.1 Introduction 7.3.2 Combination effects in initiation 7.3.3 Combination effects in promotion 7.3.4 Combination effect at later stages 7.3.5 Anticarcinogenesis 7.3.6 Conclusions: Over-all effects and complex mixtures 7.4 REPRODUCTIVE TOXICITY 7.4.1 Introduction 7.4.2 In vitro studies for testing interaction of teratogenic compounds 7.4.3 Examples of interaction of reproductive toxicants in vivo 7.4.4 Evaluation of the in vivo studies 7.4.5 Conclusions 7.5 ENDOCRINE DISRUPTING CHEMICALS 7.5.1 Introduction 7.5.2 Examples of studies on interaction of endocrine disrupting chemicals (EDCs) 7.5.3 Comments on studies dealing with interactions of EDCs 7.5.4 The isobole method -a practical approach 7.5.5 Conclusion 7

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“…Mammalian liver enzymes (cytochromes P-450 and epoxide hydrolase) oxidize certain PAHs to fjord-and bay-region diolepoxides (2,11,17,29,30); these moieties form covalent adducts with DNA (17,28). Therefore, many PAHs are genotoxic and/or carcinogenic (1, 2, 8, 14, 23) and promote similar effects of other compounds (6). Thus, a total of 16 PAHs have been included on the U.S. Environmental Protection Agency (EPA)'s priority pollutant list (13).…”

Section: Appendix -Publicationmentioning

confidence: 99%