chapter 2 toxicology

7/25/2019 Chapter 2 Toxicology

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Toxicology

An introduction forchemical engineers


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Toxicology

Definitions

Toxicological studies

Dose-response correlations Threshold limit values

Examples


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Toxic Substance

Capacity of a substance to produce injury orillness

Acute Effects Short term, appear shortly after exposure. Can be

from single exposure

Chronic Effects There is a latency, long period of time before you

see effect


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Three Types of Toxic HazardousMaterials

Chemical Agents (poisons)

Physical Agents (dusts, fibers, heat, noise,corrosive)

Biological Agents (pathogens)


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Definitions

Toxicology is the quantitative and qualitativestudy of the adverse effects of toxicants on

Toxicant is a chemical or physical agent that

produces adverse effects on biologicalorganisms.


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So Toxicology is the study of:

How toxicants enter the organism

How toxicants are eliminated from (leave) the organism

All substances are toxic if taken in the wrong quantities


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How toxicants enter organism

Inhalation (mouth or nose to lungs) then intoblood(+*)

blood(+)

Injection (cuts, punctures in skin) into blood

Dermal absorption (through skin) into blood(+*)

+ Involve membrane transport

* Greatest threats in industry


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Entry Routes for Toxicants andMethods for control


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Blood level concentration vs Timeand Route of entry


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Effects of Toxicants

Irreversible Effects

Carcinogen - causes cancer

Mutagen - causes chromosome damage Reproductive hazard - damage to reproductive

system

Teratogen - causes birth defects


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Effects of Toxicants

May or may not be reversible

Dermatotoxic affects skin

Hemotoxic affects blood Hepatotoxic affects liver

Nephrotoxic affects kidneys

Neurotoxic affects nervous system

Pulmonotoxic affects lungs


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Elimination of toxins

Excretion through kidneys, liver and lungs

Detoxification is the biotransformation ofchemicals into something less harmful orharmless substances.

Storage in fatty tissue


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Toxicological Studies

Baseline study with no toxicant

Toxicology study to quantify response totoxicants in specified physical state


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Dose versus Response

Biological organismsrespond differently to thesame dose of a oxican

Given same dose(usually in dose/bodymass)

Determine the numberor fraction of individualsthat have a response

Age, sex, weight, diet,

health and other factors

A Gaussian or Normal distribution


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F(x) probability ofindividual experiencing aspecific response

X- responsestandard deviation

-mean

A Gaussian or Normal distribution

Mean determine the location of the curve with respect to x axisand standard deviation determines the shape


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Effect of the standard deviation on a

normal distribution with a mean of 0

The area under the curve

represents the % of individual

affected for a specifiedresponse interval


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Dose versus Response (cont)

Repeat tests usingdifferent doses

to each dose

Plot Response versuslogarithm of dose

Forms Sigmoid shapedcurve

Lethal Dose Curve


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Dose Limit Values

EDf Effective dose for fpercent of population.Reversible res onse

(eye irritation) TDf Toxic dose for f

percent of population.Undesirable responsethat is irreversible (liveror lung damage)

LDf Lethal dose for f

percent of population.


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Definitions

Therapeutic Margin TM = LD50% - ED50%

MOS = LD5% - ED95%

Safety Index SI = LD5%/ED95%

Therapeutic Index TI = LD50%/ED50%


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Relative Toxicity Classification

Classification Human Oral LD50

Extreme y Tox c Taste gra n

Highly Toxic 1 tsp

Moderately Toxic 1 ounce

Slightly Toxic 1 pint

Practically nontoxic 1 quart

Relatively harmless > 1 qt


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Threshold Limit Values

Toxicant A is more toxic at high

doses, whereas toxicant B is

more toxic at low doses


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Threshold Limit Values (TLV) or Maximum Allowable Concentration (MAC)Airborne concentration that corresponds to conditions under which NO adverse

effects are normally expected during a workers lifetime.

TLV type Definition

TLV-TWA Time wei hted avera e for a normal 8-hr workda to

which nearly all workers can be exposed, day after day,without adverse effects

TLV-STEL

Short-term exposure limit. The maximum concentration towhich workers can be exposed for a period of up to 15

minutes continuously without suffering intolerable irritation,chronic tissue change, materially reduce worker efficiency.

TLV-C Ceiling Limit. The concentration that should not beexceeded, even instantaneously


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Dose/Response Models

For Computational purposes the responseversus dose curve is not convenient; so

.

For single exposure the Probit(Y) Probabilityunit method is suited.

The probit variable is related to the probabilityP by


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Probit Correlations

Table 2-5 gives values of a linear interpolationof Dose/Response data that has been

.

Y = k1 + k2*Ln(V)

Y ProbitV Causative variable


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Chemical Vapors

When dealing with exposures of a chemicalvapor (toxic cloud) then the probit constants

Y = a + b ln Cnt

a, b and n are experimentally determined constants

C is concentration in ppm

t is the exposure time in minutes


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Converting from mg/m3 to ppm

322.4 1T

M is molecular weight

T is temperature in Kelvin

P is pressure in atm

273ppm M P


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chapter 2 toxicology

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