External considerations. &s Certain chemicals, for example chlorinated pesticides and other chlorinated hydrocarbons, will be stored in the tissues(23y) of a wide range of living organisms and may accumulate to toxic level(致纛水1 s This phenomenon is exacerbated (k) by the fact that the lower forms of life or the organism at lower trophic(营养的 stages are subsequently consumed as food by fish, mammals and birds %s These species in turn may be consumed by human
❖ Certain chemicals, for example chlorinated pesticides and other chlorinated hydrocarbons, will be stored in the tissues (组织) of a wide range of living organisms and may accumulate to toxic level (致毒水平). ❖ This phenomenon is exacerbated (恶化) by the fact that the lower forms of life or the organism at lower trophic (营养的) stages are subsequently consumed as food by fish, mammals and birds. ❖ These species in turn may be consumed by human. External considerations:
External considerations: Reduction of exposures or accessibility Bio-magnification Food chain s Hence, the substances of concerns may both bio-accumulate in lower life forms and bio magnify or increase their concentration in higher life forms by orders of magnitude as they accumulate and migrate up the food chain 毒物可在低级生命形式中聚集,并会随着食物链 在更高一级的生命形式中被生物放大到更动数 量级,如此出低级生命形式传递到更高级的生 形式
❖ Bio-magnification → Food chain ❖ Hence, the substances of concerns may both bio-accumulate in lower life forms and biomagnify or increase their concentration in higher life forms by orders of magnitude as they accumulate and migrate up the food chain. 毒物可在低级生命形式中聚集，并会随着食物链 在更高一级的生命形式中被生物放大到更大的数 量级，如此由低级生命形式传递到更高级的生命 形式。 External considerations: Reduction of exposure or accessibility
External considerations. Reduction of exposure or accessibility i o D Reduction/elimination of impurities 1. Generation of impurities of different chemica/ classes(不同化学类别的不纯物) 2. Presence of toxic homologs(同系物) 3. Presence of geometric, conformational or stereoisomers(何、构象及光学异构角)
❖ D. Reduction/elimination of impurities 1. Generation of impurities of different chemical classes （不同化学类别的不纯物） 2. Presence of toxic homologs（同系物） 3. Presence of geometric, conformational or stereoisomers (几何、构象及光学异构体) External considerations: Reduction of exposure or accessibility
Internal considerations: prevention of toxic efes预防毒性 They generally include approaches using molecular manipulations to Facilitate bio- detoxication(生物解毒性) 冷 Avoid direct toxicity Avoid indirect bio-toxicity or bio-activation
❖ They generally include approaches using molecular manipulations to : ❖ Facilitate bio-detoxication (生物解毒性) ❖ Avoid direct toxicity ❖ Avoid indirect bio-toxicity or bio-activation Internal considerations: Prevention of toxic effects (预防毒性)
nternal considerations- Prevention of toxic eifects ☆A. Facilitation of de-toxication(促进生物解毒性) 1. Facilitation of excretion(排泄) a.se/ ection of hydrophilic(亲水的) compounds b. facilitation of conjugation/acetylation(乙酷化) conjugated with: glucuronic acid(葡萄糖醛酸 sulfate(碗酸盐, amino acid to accelerate urinary(泌尿器的)orAB biliary(胆汁的 excretion C. other considerations 2. Facilitation of biodegradation(可生物降解 a oXidation; b reduction; C hydrolysis
Internal considerations-Prevention of toxic effects ❖ A.Facilitation of de-toxication （促进生物解毒性） ❖ 1. Facilitation of excretion（排泄） a. selection of hydrophilic(亲水的) compounds b. facilitation of conjugation/acetylation(乙酰化) conjugated with: glucuronic acid(葡萄糖醛酸) sulfate(硫酸盐), amino acid to accelerate urinary（泌尿器的） or biliary (胆汁的) excretion c. other considerations ❖ 2. Facilitation of biodegradation (可生物降解性) a. oxidation； b. reduction； c. hydrolysis