External considerations Reduction of exposure or accessibility A Properties related to environmental distribution/dispersion 1. Volatility/density/melting point 2. Water solubility 3. Persistence/biodegradation a oxidation, b hydrolysis, C. microbial degradation 4. Conversion to biologically active substances 5. Conversion to biologically inactive substances 四大学化学学院 2002年7月26日
四川大学化学学院 2002年7月26日 6 External considerations------ Reduction of exposure or accessibility ◼ A. Properties related to environmental distribution/dispersion ◼ 1. Volatility/density/melting point ◼ 2. Water solubility ◼ 3. Persistence/biodegradation ◼ a. oxidation, b. hydrolysis, ◼ c. microbial degradation ◼ 4. Conversion to biologically active substances ◼ 5. Conversion to biologically inactive substances
External considerations Reduction of exposure or accessibility B Properties related to uptake by organisms 1. Volatility 2. Lipophilicity(亲油性) 3. Molecular size 4. Degradation a hydrolysis(水解),b. Effect of p C susceptibility to digestive enzymes (消化酶) 四大学化学学院 2002年7月26日
四川大学化学学院 2002年7月26日 7 External considerations------ Reduction of exposure or accessibility ◼ B. Properties related to uptake by organisms ◼ 1. Volatility ◼ 2. Lipophilicity（亲油性） ◼ 3. Molecular size ◼ 4. Degradation ◼ a. hydrolysis（水解）, b. Effect of pH, ◼ c. susceptibility to digestive enzymes （消化酶）
External considerations Reduction of exposure or accessibility C Consideration of routes of absorption by man animals or aquatic life 1.Skin/eves 2. Lungs 3. Gastrointestinal tract(消化系统) 4.Gills(#B)or other specific routes 四大学化学学院 2002年7月26日
四川大学化学学院 2002年7月26日 8 External considerations------ Reduction of exposure or accessibility ◼ C. Consideration of routes of absorption by man, animals or aquatic life ◼ 1. Skin/eyes ◼ 2. Lungs ◼ 3. Gastrointestinal tract（消化系统） ◼ 4. Gills(鳃) or other specific routes
External considerations Reduction of exposure or accessibility D. Reduction/elimination of impurities 1. Generation of impurities of different chemical classes 2. Presence of toxic homologs(同系物) 3. Presence of geometric, conformational or stereoisomers 四大学化学学院 2002年7月26日
四川大学化学学院 2002年7月26日 9 External considerations------ Reduction of exposure or accessibility ◼ D. Reduction/elimination of impurities ◼ 1. Generation of impurities of different chemical classes ◼ 2. Presence of toxic homologs（同系物） ◼ 3. Presence of geometric, conformational or stereoisomers
External considerations The routes of absorption include the following the skin, eyes, lungs, gastrointestinal tract ilIs or other routes depending on the organism 四大学化学学院 2002年7月26日 10
四川大学化学学院 2002年7月26日 10 External considerations ◼ The routes of absorption include the following: ◼ the skin, ◼ eyes, ◼ lungs, ◼ gastrointestinal tract, ◼ gills or ◼ other routes depending on the organism