影响毒物在生物体内所表现的毒性作用之因素.ppt

* 影響毒物在生物體內所表現的毒性作用之因素： 主要-劑量(dose) 暴露時間長短 (duration of exposure) Dose-Response Relationship: As the dose of a toxicant increases,  so does the response.  2 3 4 0 1 DOSE RESPONSE 0-1 NOAEL 2-3 Linear Range 4 Maximum Response DOSE DETERMINES THE BIOLOGICAL RESPONSE Exposure: Duration Acute 24hr usually 1 exposure Subacute 1 month repeated doses Subchronic 1-3mo repeated doses Chronic 3mo repeated doses Over time, the amount of chemical in the body can build up, it can redistribute, or it can overwhelm repair and removal mechanisms Acute Toxicity: (short-term exposure) Chronic Toxicity: (repeated exposures) Routes of Entry: Oral = Ingestion by mouth Dermal = Skin exposure Inhalation = Absorbed by lungs Ocular = Eye exposure 暴露途徑 a. 呼吸道: 氣體、分子小、脂溶性物質可由肺泡吸收，經由擴散(CO、 HCN) 或吞噬作用(石綿、鉛) b. 消化道:毒物隨食物飲水進入腸胃，重金屬需和必需金屬(鈣、鐵) 競爭載體，不易吸收。 c. 皮膚的表皮不易穿透，角質層阻擋水溶性物質之吸收，脂溶性物質則易穿透，角質層依身體之部位不同有差異，影響吸收速率。 Dermal Exposure Variables Area Rate* forehead 4.2 forearm 1.0 abdomen 2.1 palm 1.3 scrotum 11.8 ball of foot 1.8 mjweaver,1997 *Absorption rate compared to forearm, which is 1.0 毒物的化學性質和活性 The toxicity of mercury vapor differs greatly from methyl mercury.? 2. Another example is chromium.? Cr3+ is relatively nontoxic whereas Cr6+ causes skin or nasal corrosion and lung cancer. 3. The innate chemical activity of substances also varies greatly. Some can quickly damage cells causing immediate cell death. Others slowly interfere only with a cells function Ex. hydrogen cyanide binds to cytochrome oxidase resulting in cellular hypoxia and rapid death, nicotine binds to cholinergic receptors in the CNS altering nerve conduction and inducing gradual onset of paralysis Data from article in Scientific American, February 1986. Organism LD50(micrograms/kg) Guinea pig (male) 0.6 Guinea pig (female) 2.1 Rabbit 115 Monkey (female) 70 Rat (male) 22 Rat (female) 45-500 Mouse (male) 150 Dog (male) 30-300 Dog (female) 100 Frog 1,000 Hamster