Opportunities in Applied Environmental Research and Development (1991) / Chapter Skim
Currently Skimming:
Appendix C: Research to Improve Predictions of Long-Term Chemical Toxicity
Appendix C: Research to Improve Predictions of Long-Term Chemical Toxicity
Pages 127-152
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 127... ...
Spends C Reset lo -~ Precook of -Tea Beach ~
|
From page 129... ...
investigation of the importance of tile physical-e helical properties of substances In SAR models; e) studies to e~l~ the molecular mechanisms underlying SAR; and If)
|
From page 130... ...
International cooperation to Spirit research opportunities arising out of accidental, occupational, or other types of high-level human exposures wherever they may occur in the world; c) research to improve short term follow-up and hypot:hes}s generation, ~ human ensure assessment, through governments vers~ty-pr~vate sector collaboration, computer linkage of poison control centers and occupational health clinics population registries, repositories for storage of appropriate biologic specimens, studies of pertinent pha~macoldnetics, and evaln~tion of relevant biological markers; cI)
|
From page 131... ...
Several workshop participants believe there is strong reason for a new look at the problems reed in the report and the recommendations made in it. The specific considerations and suggestions from workshop pa~apants are given below.
|
From page 132... ...
Once the methodologies have matured and have been validated, this could be done Decently for a large number of chemicals, at reduced expense and without the need to sacrifice a large number of animals, thus making testing goal-onented and cost-effective. Uses of SAR over the next 5 years call for progressive improvements driven by increased efficiency, lowered computer costs, improved models, and a greater range of biological effects for which structural relationships ~ be identified Workshop participants medicated that this approach could lead to greater a~e.ptance, better understanding of the uses and limitations of the models, and increased confidence In their applications, not only to carc~nogen~city but also to other areas of toxicology, during tile new 5 years.
|
From page 133... ...
Inasmuch as chemicals are not usually tested In Focal sets, these participants believe it is deswable to use SAR models to identify chemical moieties that need to be tested to fill In gaps In toxicological knowledge. Treatment of PhysicochemicaI Properties in Models of Long-Term Tot ty Most SAR models of long-te~m to=mty, m~UCliDg models of carcmoge~c~ty, have used descriptors of Chemical structure to explain the toxicological end points.
|
From page 134... ...
Workshop participants believe new approaches must be evaluated and encouraged and funding developed to bang new talent into tbis area. Research proposals submitted to granting agencies often are too narrowly focused to be funded.
|
From page 135... ...
In addition, workshop participants believe that the effectiveness of a test for discam~nating between toxic and nontoxic chemicals could be determined, and the results of the validation studies published the snendfic literature. One important finding of the validation process might be that a test were accurate for some chemical classes and not for others.
|
From page 136... ...
, Chemical Abstracts Services Re~try Numbers, structures of test chemicals, and the source and purity of the chemicals tested. Extrapolation to Humans Research Is needed on methodologies to emapolate from ~ tro to In nvo effects In laboratory animals and In humans without Evolving the unnecessary exposure of humans to potentially toxic materials.
|
From page 137... ...
rid The chemical bank Is designed to address problems that retard test development and would be a repository for chemicals that coadd be used by research laboratones and reference laboratories to validate methods. Chemises would be designated for different methodologies related to particular toxicities or pathologies (e.g., neuroto~c~ty, hepatoto~aaty, and caranogen~c~ty for validation and for castration A toasty testing data bank coed collect and catalog data for methodology validation.
|
From page 138... ...
138 y hi m LU A: C' UJ _ IU C' Z Al G 1 Y Z m C} c i)
|
From page 139... ...
For ad end points, intact animal studies coupled with available human data were considered to surpass the degree of predictive confidence generated by SAR and In vitro sways. The only area participants believed that SAR and ~ tro Whys resulted In greater Ohm a 25% reduction in uncertainty was ~ determining potential carc~nogewc'~.
|
From page 140... ...
Human observations aisoa2Iow laboratory animal models with the closest correspondence to human metabolism to be assigned to further ~nvesUgations. Accidental exposures also provide an opportunity to gather applicable human data With the decrease in emergency response time, several workshop participants believe that the scientific community should be prepared to collect crumples from emergency incidents.
|
From page 141... ...
Second, bio~ays are ea~pe~ve. If results from testing one or a few compound could be applied to an entire class, some workshop participants believe this would enhance the cost-effectiveness of testing and might provide a stronger basis for develops SAR prediction systems.
|
From page 142... ...
Exposure may at times need to be estimated from knowledge of levels in food, ah, and water from direct chemical measurement or Tom use of biological markers. In some circumstances, validation of the results of animal experiments by comparison with effects on humar s may not be possible Men current experimental procedures.
|
From page 143... ...
Such a network/=n1ple storage program could be used to develop information in humans on: pharmaco~netics (metabolism, deposition, and tissue distribution) of an agent; biological markers of e~osl}}e; and biological markers of effect.
|
From page 144... ...
Molecular Approaches Workshop participants believe molecular techniques must be developed for extension to epidemiological studies. As new molecular techniques become available for asse~g health effects, they should be implemented in epidemiolo~cal studies.
|
From page 145... ...
fining Progress ~ improving predictions of long-term chemical toxicity, as wed as related environmental and toxicological issues, will be seriously slowed according to some workshop participants as long as there remand a dearth of scientists with relevant Interdisciplinary training. To illustrate, a review of the Biogenetic literature suggests that ~togenetic~sts often lack epidem~olog~cal training.
|
From page 146... ...
Whole-animal tests are burdensome, and consideration should be given to the possibilities for optimmng bioassay test designs (even more than they have been improved over recent years) to obtain reliable information in shorter time and
|
From page 147... ...
Despite the value of proxy information, there is no substitute for human data (Erdreich and Burnett, 1985~. Therefore, epidem~olo~cal research continues to be a central component of heal elf s en action Epidemiologica1 research must be supported and nourished as a complement to to~ncolo~cal research Coordinated Oration of unusually highly exposed human populations for study to complement particular toncol~cal research win be essential.
|
From page 148... ...
CI~.ccification according to chemical structure, mutagenicity to SalmoneLla and level of caranogenicity of a furler 42 chemicals tested for carcinogenic by the U.S.National Toxicology Program. Mutat.
|
From page 149... ...
1989. Biological Markers in Pulmonary Toxicology.
|
From page 151... ...
Errol Geiger, NIEHS, Research Triangle Park Whole-Animal Tests Dr. Michael GaBo, Hair, UMDNJ, R.W.
|
From page 152... ...
Jack Moore, Institute for Evaluating Health Risks, Ike, Califom~a Dr. Andrew Sivak, Health Effects Institute, Cambridge Dr.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.