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.