Toxicology

An introduction for chemical engineers

Toxicology

Definitions Toxicological studies Dose-response correlations Threshold limit values Examples

Environmental Health Paradigm

Exposure AssessmentExposure Assessment

Emission Sources Environmental

Concentrations

Effects AssessmentEffects Assessment

Internal Dose Human Exposure

Health Effects

Hazardous

Denotes the probability of injury or illness from contact or use

Industrial Hazards– Toxicity– Explosivity– Ignitability– Reactivity

Toxic Substance

Capacity of a substance to produce injury or illness

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

Three Types of Toxic Hazardous Materials

Chemical Agents (poisons)

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

Biological Agents (pathogens)

Definitions

Toxicology is the quantitative and qualitative study of the adverse effects of toxicants on biological organisms

Toxicant is a chemical or physical agent that produces adverse effects on biological organisms.

So Toxicology is the study of:

How toxicants enter the organism

How toxicants effect the organism

How toxicants are eliminated from (leave) the organism

All substances are toxic if taken in the wrong quantities

How toxicants enter organism

Inhalation (mouth or nose to lungs) then into blood(+*)

Ingestion (mouth to stomach) then into blood(+)

Injection (cuts, punctures in skin) into blood Dermal absorption (through skin) into blood(+*)

+ Involve membrane transport

* Greatest threats in industry

Effects of Toxicants

Irreversible Effects Carcinogen - causes cancer Mutagen - causes chromosome damage Reproductive hazard - damage to reproductive

system Teratogen - causes birth defects

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

Definitions

Pharmacokinetics – the absorption, distribution, metabolism and excretion of chemicals through the (human) system.

Bioaccumulation – things such as lead, mercury, PCBs, carbon tetrachloride that build up in organs and have low excretion rate. Low exposure over a long time leads to response

Elimination of toxins

Excretion through kidneys, liver and lungs

Detoxification is the biotransformation of chemicals into something less harmful

Storage in fatty tissue

Toxicological Studies

Baseline study with no toxicant

Toxicology study to quantify response to toxicants in specified physical state

Difficulties in Toxicological studies

Baseline study required (control group) Response not necessarily numerical Specificity of individual response

– Allergy or immunity– Statistical study required– Organism specific response, not applicable to humans– Dosage response– Response time, latency, acute versus chronic– Difficulty in measuring intended variable (lead in liver

measured by lead in blood)

Difficulties in Toxicological Studies

Major Problem– No ethical way to get human volunteers, hence

need to use “model” systems of rats, cats, dogs, rabbits, etc.

Hinders production of a new chemical, almost as stringent as a new drug– Currently averages 17 years and 1 million pages

Dose versus Response

Run test on “large” population

Given same dose (usually in dose/body mass)

Determine the numberor fraction of individuals that have a response

Dose versus Response (cont)

Repeat tests using different doses

Find average response to each dose

Plot Response versus logarithm of dose

Forms Sigmoid shaped curve

Dose Limit Values

EDf – Effective dose for f percent of population. Reversible response

TDf – Toxic dose for f percent of population. Undesirable response that is irreversible

LDf – Lethal dose for f percent of population.

Definitions

Therapeutic Margin– TM = LD50% - ED50%

Margin of Safety– MOS = LD5% - ED95%

Safety Index– SI = LD5%/ED95%

Therapeutic Index– TI = LD50%/ED50%

Relative Toxicity Classification

Classification Human Oral LD50

Extremely Toxic Taste (1 grain)

Highly Toxic 1 tsp

Moderately Toxic 1 oz

Slightly Toxic 1 pt

Practically nontoxic 1 qt

Relatively harmless > 1 qt

Dose/Response Models

Use Probits to Linearize Dose-Response Curve– P(Y) = ½[erf(Y-5/2) + 1]

Use Table 2.4 Some calculators calculate the erfc

(complimentary error function) erfc = 1 – erf(x)

Probit Correlations

Table 2-5 gives values of a linear interpolation of Dose/Response data that has been linearized using Probits.

Y = k1 + k2*Ln(V)

Y – Probit

V – Causative variable

Chemical Vapors

When dealing with exposures of a chemical vapor (toxic cloud) then the probit constants are correlated by:– 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

Chemical Vapors

When the exposed subjects receive different doses as a function of time

Received handout with constants, ought to place in your book

2

1

tn n n

i iit

C t C dt C t

Threshold Limit Values

Lowest value on the response versus dose curve is called the threshold dose.

American Conference of Governmental Industrial Hygienists (ACGIH) has established “Threshold Limit Values” (TLV)

United States Occupational Safety and Health Administration (OSHA) has established “Permissible Exposure Limits” (PEL)

Table 2-8 gives the TLVs and PELs for many substances

Threshold Limit Values

TLVTWA Time weighted average for a normal 8 hour workday or 40 hour workweek

TLVSTEL Short-term exposure limit. The maximum concentration can be exposed to for up to 15 minutes. Four excursions per day with at least 60 minutes between

TLVC Ceiling limit. This concentration should not be exceeded

Converting from mg/m3 to ppm

M is molecular weight T is temperature in Kelvin P is pressure in atm

322.4 1( / )

273ppm

TC mg m

M P