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