Chemical antagonists

The risk sununation tecluiiques assume tliat intakes of individual substances are small. They also assume independence of action by the compounds involved (i.e., tliat there are no synergistic or antagonistic chemical interactions and tliat all chemicals produce the same effect, i.e., cancer). If tliese assumptions are incorrect, over- or mider-estimation of tlie actual multiple-substance risk could result. 

Therapeutic Function Anticoagulant, Vitamin K antagonist Chemical Name 3-(Q -acetonyl-p-nitrobenzyl)-4-hydroxycoumarin Common Name Nicoumalone Structural Formula ... 

Schlicker E, Kathmann M, Bitschnau H, Marr I, Reidemeister S, Stark H, Schunack W (1996) Potencies of antagonists chemically related to iodoproxyfan at histamine H3 receptors in mouse brain cortex and guinea-pig ileum evidence for H3 receptor heterogeneity Naunyn-Schmiedeberg s Arch Pharmacol 353 482-488. 

E. M. Krovat, T. Langer. Non-peptide angiotensin II receptor antagonists chemical feature based pharmacophore identification. /. Med. Chem., 46, 716-726, 2003. 

Therapeutic Function Corticosteroid antagonist Chemical Name 2a-Cyano-4a,5a-epoxyandrostan-17 5-ol-3-one Common Name -Structural Formula ... 

Synonyms Benadryl Diphenhist Genahist So-minex Nytol Sleepinal Caladryl Dermarest Chemical/Pharmaceutical/Other Class An etha-nolamine derivative H-1 receptor antagonist Chemical Formula C17H21NO Chemical Structure ... 

Mignani S, Hittinger O, Archard D, Bouchard H, Bouquerel J, Capet M, Grisoni S, Malleron JL (2000) Preparation of l-bis(aryl)methyl-3-(alkylsulfonyl)arylmethyleneazetidines as cannabinoid CBl receptor antagonists. Chemical Abstracts. Aventis Pharma SA, France, p236982s... 

In addition to uncertainty in exposure, dose, and cancer estimations, the possibility of multiple simultaneous exposures to different chemicals needs to be considered. Risks from simultaneous exposure to more than one carcinogenic substance are typically estimated by assuming that the individual risks are additive. This process assumes that intakes of individual substances are relatively small, that there are no synergistic or antagonistic chemical interactions, and that all chemicals produce the same toxic effect (US EPA 1989). However, because health risks from exposures to chemical mixtures are generally based on a combination of upper-bound risks calculated for individual compounds, these risk assessments tend to be overly conservative (Gaylor and Chen 1996 Hwang and Chen 1999 Kodell and Chen 1994). 

Aramaki, Y. et al. (2004) Synthesis of 1-benzothiepine and 1-benzazepine derivatives as orally active CCRS antagonists. Chemical eC Pharmaceutical Bulletin, 52 (2), 254-258. 

Naya, A., Kobayashi, K., Ishikawa, M., Ohwaki, K, Saeki, T. et al. (2003) Structure-activity relationships of 2-(benzofhiazolylthio)acetamide class of CCR3 selective antagonist. Chemical Pharmaceutical Bulletin, 51, 697—701. 

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