TOX2000 NotesRegulatory ToxicologyLec 1-Can potentially toxic substances be used “safely”?Risk Assessment Paradigm -Hazard assessment oToxicological description of what substance is capable of doing-Dose response evaluationoEffects you would see at various levels of exposure, adverse effects-Exposure assessmentoModify exposureo35% of cancer due to tobaccooreduce exposure-Risk characterizationoWhat you’ve done, how you’ve done it, limitationsDetermination of Safety:-Risk = Hazard (toxicity) x exposure-To minimize risk, must minimize exposure-When exposure increases, risk increases as well-Hazard is a natural property of toxicological agent-Exposure: any route it is taken up – occupational, food, air, waterPotential exposure pathways in assessing exposure of the general public:1.Researcha.Lab and field observationsb.Information on extrapolation methodsc.Field measurements, characterization of populationsd.Research needs identified from risk assessment processes2.Risk assessmenta.Taking data and putting into a risk characterizationb.Toxicity assessment hazard identification and dose response assessmentc.Exposure assessment emissions characterization3.Risk managementa.Minister of health needs to determine if its an acceptable riskb.Development of regulatory options
c.Evaluation of public health, economic, social, political consequences of regulatory optionsHazard assessment and dose response evaluation:-Hazard assessment: involves identification and description of the toxicological features of the substance being considered; it is not an expression of riskoDoes not tell you assessment of riskToxicological studies-Acute-Eye and skin irritancy-Sub-chronic-Chronic-Carcinogenicity-Reproductive-Teratology (developmental)Acute-Primarily labelling information carried out in rats and mice-Can be traditional median lethal dose or more contemporary “limit” studyEye and skin irritants-Carried out in rabbits-Eye studies don’t have to be done if chemical physical properties predict irritancy-Considerable debate on rabbit as an appropriate model for eye irritancySub-chronic-Conducted in rats-Periods of up to 90 days-Typically oral route-Most useful for planning of long term feeding studiesChronic-Must include at least 90% of anticipated life span-Often include mice and rats-Study parameters include body weight, hematology (blood), biochemistry and gross pathologySept 24 Lec 2Chronic dog-Studied from 6 months to a year-Used since 1975/1980
-Little practical value because group sizes are small (2 dogs)-Not statistically useful-Used to identify whether results with rat or mice are consistent -To make studies more relevant is to increase dose (exposure) level, however this is not realistic as we are not exposed to such high levels in real life-MTD (maximum tolerated dose) – highest practical dose to inject without affecting an animalCarcinogenicity -Doses selected in part on the basis of 90 day studies-Often approach a maximum tolerated dose for a high dose-
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