Post on 30-Oct-2014
TOXICOLOGY
What is Toxicology?
What are Harmful or Adverse effects?
• Those effects which are damaging to eitherthe survival of normal function of theindividual
What is TOXICITY?
What is TOXIC?
What is TOXICANT?
What is TOXIN?
What is a Toxic symptom?
What is a Toxic Effect?
What is Selective Toxicity?
What is a DOSE?
What is a DOSE‐RESPONSE?
What is a Threshold Dose?
Sub‐disciplines of TOXICOLOGY
• Environmental Toxicology• Occupational Toxicology• Regulatory Toxicology• Food Toxicology• Clinical Toxicology• Descriptive Toxicology• Forensic Toxicology• Analytical Toxicology• Mechanistic Toxicology
Environmental Toxicology
Occupational Toxicology
Regulatory Toxicology
Food Toxicology
Clinical Toxicology
Descriptive Toxicology
Forensic Toxicology
Analytical Toxicology
Mechanistic Toxicology
Classification of Toxic Agents
• Heavy Metals
• Solvents and Vapors
• Radiation and Radioactive Materials
• Pesticides
• Plant Toxins
• Animal Toxins
Subcategories for Classifications
• Their effect on target organs (liver, kidney, hematopoietic system, etc.)
• Their use (pesticide, solvent, food additive, etc.)
• The source of the agent (animal and plant toxins)
• Their effects (cancer mutation, liver injury, etc.)
Subcategories for Classifications
• Physical state (gas, dust, liquid)
• Labelling requirements (explosive, flammable, oxidizer)
As Chemical Engineers……
• The way toxicants enter biological organisms
• The way toxicants are eliminated from biological organisms
• The effects of toxicants on biological organisms, and
• Methods to prevent or reduce the entry of toxicants into biological organisms
How Toxicants Enter Biological Organisms?
• Ingestion: through the mouth into the stomach
• Inhalation: through the mouth or nose into the lungs
• Injection: through cuts into the skin
• Dermal absorption: through skin membrane
Entry Routes for Toxicants and Methods for Control
Entry route Entry organ Method for control
Ingestion Mouth Enforcement of rules on eating, drinking, and smoking
Inhalation Mouth or nose Ventilation, respirators,hoods, and other personal protection equipment
Injection Cuts in skin Proper protective clothing
Dermal absorption Skin Proper protective clothing
How Toxicants Are Eliminated from Biological Organisms?
• Excretion: through the kidneys, liver, lungs, or other organs;
• Detoxification: by changing the chemical into something less harmful by biotransformation;
• Storage: in the fatty acid
Various Responses to Toxicants
Effects that are irreversible Effects that may or may not be reversible
Carcinogen causes cancer Dermatotoxic affects skin
Mutagen causes chromosome damage Hematoxic affects blood
Reproductive hazard causes damage to reproductive system
Hepatotoxic affects liver
Teratogen causes birth defects Nephrotoxic affects kidneys
Neurotoxic affects nervous system
Pulmonotoxic affects lungs
Dose versus Response
• f(x) is the probability (or fraction) of individuals experiencing a specific response,
• x is the response,
• σ is the standard deviation, and
• μ is the mean.
Mean
Variance
GAUSSIAN DISTRIBUTION
Problem 1
• Seventy‐five people are tested for skinirritation because of a specific dose of asubstance. The responses are recorded on ascale from 0 to 10, with 0 indicating noresponse and 10 indicating a high response.The number of individuals exhibiting a specificresponse is given in the following table:
RESPONSE # OF INDIVIDUALS AFFECTED
0 0
1 5
2 10
3 13
4 13
5 11
6 9
7 6
8 3
9 3
10 2
SUM 75
a. Plot a histogram of the number of individuals affected versus the responseb. Determine the mean and the standard deviation.c. Plot the normal distribution on the histogram of the original data
x f(x) 75f(x)
0
1
2
3
4
5
6
7
8
9
10
PROBIT ANALYSIS
Model for Dose and Response Curve
• PROBIT METHOD– Conversion from probits to percentage
– Where erf Is the error function
Probability Correlations for a Variety of Exposures
Probit Parameters
Type of Injury/damage Causative Variable k1 k2Fire
Burn deaths from flash fire teIe4/3/104 ‐14.9 2.56
Burn deaths from pool burning tI4/3/104 ‐14.9 2.56
Explosion
Deaths from lung hemorrhage p0 ‐77.1 6.91
Eardrum ruptures p0 ‐15.6 1.93
Deaths from impact J ‐46.1 4.82
Injuries from impact J ‐39.1 4.45
Injuries from flying fragments J ‐27.1 4.26
Structural damage p0 ‐23.8 2.92
Glass breakage p0 ‐18.1 2.79
Probability Correlations for a Variety of Exposures
Probit Parameters
Type of Injury/damage Causative Variable k1 k2Toxic release
Ammonia deaths ΣC2.0T ‐35.9 1.85
Carbon monoxide deaths ΣC1.0T ‐37.98 3.7
Chlorine deaths ΣC2.0T ‐8.29 0.92
Ethylene oxide deaths ΣC1.0T ‐6.19 1.0
Hydrogen chloride deaths ΣC1.0T ‐16.85 2.0
Nitrogen oxide deaths ΣC2.0T ‐13.79 1.4
Phosgene deaths ΣC1.0T ‐19.27 3.69
Propylene oxide deaths ΣC2.0T ‐7.42 0.51
Sulfur dioxide deaths ΣC1.0T ‐15.67 1.0
Toluene ΣC2.5T ‐6.79 0.41
• te = effective time duration (s)
• Ie = effective radiation intensity (W/m2)
• t = time duration of pool burning (s)
• I = radiation intensity from pool burning (W/m2)
• p0 = peak overpressure (N/m2)
• J = impulse (N‐s/m2)
• C = concentration (ppm)
• T = time interval (min)
Problem
• Eisenberg reported the following data on the effect of explosion peak overpressure on eardrum rupture in humans:
Confirm the probit correlation for this type of exposure.
Percentage affected Peak overpressure(N/m2)
1 16,500
10 19,300
50 43,500
90 84,300
Problem
• A group of 100 people is exposed to phosgenein two consecutive periods as follows (a) 10ppm for 30 min and (b) 1 ppm for 300 min.Determine the expected number of fatalities.
ProblemDose of rotenone
(mg/L)Number of insects Number affected
10.2 50 44
7.7 49 42
5.1 46 24
3.8 48 16
2.6 50 6
0 49 0
• From the given data, plot the percentage of insects affected versus thenatural logarithm of the dose.• Convert the data to a probit variable, and plot the probit versus the naturallogarithm of the dose. If the result is linear, determine a straight line that fitsthe data.