TOXICOLOGY

WhatisToxicology?

WhatareHarmfulorAdverseeffects?
Those effects which are damaging to either the survival of normal function of the individual

WhatisTOXICITY?

WhatisTOXIC?

WhatisTOXICANT?

WhatisTOXIN?

WhatisaToxicsymptom?

WhatisaToxicEffect?

WhatisSelectiveToxicity?

WhatisaDOSE?

WhatisaDOSERESPONSE?

WhatisaThresholdDose?

SubdisciplinesofTOXICOLOGY
EnvironmentalToxicology OccupationalToxicology RegulatoryToxicology FoodToxicology ClinicalToxicology DescriptiveToxicology ForensicToxicology AnalyticalToxicology MechanisticToxicology

EnvironmentalToxicology

OccupationalToxicology

RegulatoryToxicology

FoodToxicology

ClinicalToxicology

DescriptiveToxicology

ForensicToxicology

AnalyticalToxicology

MechanisticToxicology

ClassificationofToxicAgents
HeavyMetals SolventsandVapors RadiationandRadioactiveMaterials Pesticides PlantToxins AnimalToxins

SubcategoriesforClassifications
Theireffectontargetorgans(liver,kidney, hematopoieticsystem,etc.) Theiruse(pesticide,solvent,foodadditive, etc.) Thesourceoftheagent(animalandplant toxins) Theireffects(cancermutation,liverinjury, etc.)

SubcategoriesforClassifications
Physicalstate(gas,dust,liquid) Labellingrequirements(explosive,flammable, oxidizer)

AsChemicalEngineers
Thewaytoxicantsenterbiologicalorganisms Thewaytoxicantsareeliminatedfrom biologicalorganisms Theeffectsoftoxicantsonbiological organisms,and Methodstopreventorreducetheentryof toxicantsintobiologicalorganisms

HowToxicantsEnterBiological Organisms?
Ingestion:throughthemouthintothe stomach Inhalation:throughthemouthornoseinto thelungs Injection:throughcutsintotheskin Dermalabsorption:throughskinmembrane

EntryRoutesforToxicantsand MethodsforControl
Entryroute Ingestion Mouth Entry organ Method forcontrol Enforcement ofruleson eating,drinking,and smoking Ventilation,respirators, hoods,andotherpersonal protectionequipment Properprotectiveclothing Properprotectiveclothing

Inhalation

Mouth ornose

Injection Dermal absorption

Cutsinskin Skin

HowToxicantsAreEliminatedfrom BiologicalOrganisms?
Excretion:throughthekidneys,liver,lungs,or otherorgans; Detoxification:bychangingthechemicalinto somethinglessharmfulbybiotransformation; Storage:inthefattyacid

VariousResponsestoToxicants
Effects thatareirreversible Carcinogen causescancer Mutagencauses chromosomedamage Reproductivehazardcausesdamageto reproductivesystem Teratogen causesbirthdefects Effects thatmayormaynotbereversible Dermatotoxic affectsskin Hematoxic affects blood Hepatotoxic affectsliver Nephrotoxic affectskidneys Neurotoxic affectsnervoussystem Pulmonotoxic affectslungs

DoseversusResponse

f(x)istheprobability(orfraction)of individualsexperiencingaspecificresponse, xistheresponse, isthestandarddeviation,and isthemean.

Mean

Variance

GAUSSIANDISTRIBUTION

Problem1
Seventyfive people are tested for skin irritation because of a specific dose of a substance. The responses are recorded on a scale from 0 to 10, with 0 indicating no response and 10 indicating a high response. The number of individuals exhibiting a specific response is given in the following table:

RESPONSE 0 1 2 3 4 5 6 7 8 9 10 SUM

#OFINDIVIDUALSAFFECTED 0 5 10 13 13 11 9 6 3 3 2 75

a. Plotahistogramofthenumberofindividualsaffectedversustheresponse b. Determinethemeanandthestandarddeviation. c. Plotthenormaldistributiononthehistogramoftheoriginaldata

x 0 1 2 3 4 5 6 7 8 9 10

f(x)

75f(x)

PROBITANALYSIS

ModelforDoseandResponseCurve
PROBITMETHOD
Conversionfromprobitstopercentage WhereerfIstheerrorfunction

ProbabilityCorrelationsforaVarietyofExposures
Probit Parameters TypeofInjury/damage Fire Burndeathsfromflashfire Burndeathsfrompoolburning Explosion Deathsfromlunghemorrhage Eardrumruptures Deathsfromimpact Injuriesfromimpact Injuriesfromflyingfragments Structuraldamage Glassbreakage p0 p0 J J J p0 p0 77.1 15.6 46.1 39.1 27.1 23.8 18.1 6.91 1.93 4.82 4.45 4.26 2.92 2.79 teIe4/3/104 tI4/3/104 14.9 14.9 2.56 2.56 CausativeVariable k1 k2

ProbabilityCorrelationsforaVarietyofExposures
Probit Parameters TypeofInjury/damage Toxicrelease Ammoniadeaths Carbonmonoxidedeaths Chlorinedeaths Ethyleneoxidedeaths Hydrogenchloridedeaths Nitrogenoxidedeaths Phosgenedeaths Propyleneoxidedeaths Sulfurdioxidedeaths Toluene C2.0T C1.0T C2.0T C1.0T C1.0T C2.0T C1.0T C2.0T C1.0T C2.5T 35.9 37.98 8.29 6.19 16.85 13.79 19.27 7.42 15.67 6.79 1.85 3.7 0.92 1.0 2.0 1.4 3.69 0.51 1.0 0.41 CausativeVariable k1 k2

te =effectivetimeduration(s) Ie =effectiveradiationintensity(W/m2) t=timedurationofpoolburning(s) I=radiationintensityfrompoolburning(W/m2) p0 =peakoverpressure(N/m2) J=impulse(Ns/m2) C=concentration(ppm) T=timeinterval(min)

Problem
Eisenbergreportedthefollowingdataonthe effectofexplosionpeakoverpressureoneardrum ruptureinhumans:
Percentageaffected 1 10 50 90 Peakoverpressure (N/m2) 16,500 19,300 43,500 84,300

Confirmtheprobitcorrelationforthistypeof exposure.

Problem
A group of 100 people is exposed to phosgene in two consecutive periods as follows (a) 10 ppm for 30 min and (b) 1 ppm for 300 min. Determine the expected number of fatalities.

Problem
Dose ofrotenone (mg/L) 10.2 7.7 5.1 3.8 2.6 0 Numberofinsects 50 49 46 48 50 49 Numberaffected 44 42 24 16 6 0

From the given data, plot the percentage of insects affected versus the natural logarithm of the dose. Convert the data to a probit variable, and plot the probit versus the natural logarithm of the dose. If the result is linear, determine a straight line that fits the data.