1. An introduction for chemical engineers
Toxicology
An introduction for chemical engineers

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

3. Environmental Health Paradigm
Exposure Assessment
Emission Sources  Environmental
Concentrations
Effects Assessment 
Internal Dose  Human Exposure 
Health Effects

4. Hazardous
Denotes the probability of injury or illness from contact or use
Industrial Hazards
Toxicity
Explosivity
Ignitability
Reactivity

5. 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

6. Three Types of Toxic Hazardous Materials
Chemical Agents (poisons)
Physical Agents (dusts, fibers, heat, noise, corrosive)
Biological Agents (pathogens)

7. 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.

8. 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

9. 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

10. Effects of Toxicants Irreversible Effects Carcinogen - causes cancer
Mutagen - causes chromosome damage
Reproductive hazard - damage to reproductive system
Teratogen - causes birth defects

11. 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

12. 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

13. Elimination of toxins Excretion through kidneys, liver and lungs
Detoxification is the biotransformation of chemicals into something less harmful
Storage in fatty tissue

14. Toxicological Studies
Baseline study with no toxicant
Toxicology study to quantify response to toxicants in specified physical state

15. 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)

16. 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

17. 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

18. 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

19. 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.

20. 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%

21. 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

22. 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)

23. 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

24. 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

25. Chemical Vapors
When the exposed subjects receive different doses as a function of time
Received handout with constants, ought to place in your book

26. 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

27. 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

28. Converting from mg/m3 to ppm
M is molecular weight
T is temperature in Kelvin
P is pressure in atm