Toxicology design

QSAR in Drug Design and Toxicology D. Fladzi, B. Jennan-Blazic, Eds., Elsevier, Amsterdam (1987). 

TOPI-CAT toxicology prediction tool Health Designs Inc. (HDI)... 

During the design, conducting, and evaluation of toxicology studies, there is a constant need to be aware of the numerous factors that may influence the nature, severity, and probabiUty of induction of toxic injury. Some of the more important are Hsted below. 

Typical events that are considered are fire, explosion, ship collision, and the failure of pressurized storage vessels for which historical data established the failure frequencies. Assessment of consequences was based partly on conservative treatment of past experience. For example ilic assessment of the number of casualties from the release of a toxic material was based on past histoiy conditioned by knowledge of the toxicology and the prevailing weather conditions. An altemati. e used fault trees to estimate probabilities and identify the consequences. Credit is taken in this process for preventative measures in design, operation, and maintenance procedures. Historical data provide reliability expected from plant components and humans. 

Since the OELs provide the basis for ventilation requirements, an astute designer tries to find out how secure the OELs of the chemicals which will be used in the plant he or she is planning. Some of the chemicals used may totally lack OELs. Therefore, it is advisable to become familiar with the relevant literature, preferably together with a specialist. It is clear that the ventilation engineer needs to be aware of the possible significance of toxicology for industrial ventilation construction. 

Even though environmental toxicology could have profound effects on the HS response, there are other considerations where manipulation of the HS response could be beneficial. For example, constitutive induction of the HS response in bacteria could be a potential means to develop super-microbes which could withstand harsh environments while engaging in their genetically-designed function such as scouring oil spills and enzymatically converting toxins into harmless substances. 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate information on the health effects of methyl parathion is available. Where adequate information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the initiation of a program of research designed to determine the health effects (and techniques for developing methods to determine such health effects) of methyl parathion. 

This chapter provides a health effects summary based on evaluations of existing toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weight-of-evidence discussions for human health end points by addressing the following questions. 

Kedwards, T.J., Maund, S.J., and Chapman, PE. (1999a and 1999b). Community level analysis of ecotoxicological field studies 1 Biological Monitoring and 11 Replicated design studies. Environmental Toxicology and Chemistry 18, 149-157 and 158-166. 

Matthews EJ, Benz RD, Contrera JF. Use of toxicological information in drug design. J Mol Graph Modell 2000 18 605-15. 

---