An introduction for chemical engineers Toxicology An introduction for chemical engineers

Toxicology Definitions Toxicological studies Dose-response correlations Threshold limit values Examples

Environmental Health Paradigm Exposure Assessment Emission Sources  Environmental Concentrations Effects 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 number or 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 Margin of Safety Safety Index 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

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