ERT 312Lecture 3

Toxicology

What is toxicology?• Qualitative and quantitative study of adverse

effects of toxicants on biological organisms• Toxicant - A chemical or physical agent,

including dusts, fibers, noise and radiation• Toxicity – property of the toxicants describing

its effect on biological organisms• Toxic hazard – a likelihood of damage to

biological organisms based on exposure resulting from transport and other physical factors of usage

Trivia

Which one can be reduced? ToxicityToxic Hazard

Things that should be clarified

Getting the toxic into your body

Ways to eliminateHarmful effects of toxicants

4 entry modes

Ingestion - mouthInhalation – Respiratory system

Injection – skin cutDermal absorption - skin

3 exit modes

Excretion – kidneys, liver, lungs, skin

Detoxification – downgrade the toxicants into something less harmful

Storage – fatty tissue

Table 1: Various Responses to Toxicants

(Crowl & Louvar, 2002)

Irreversible Effects

Reversible/Irreversible Effects

Carcinogen Dermatoxic

Mutagen Hemotoxic

Reproductive hazard Hepatoxic

Teratogen Nephrotoxic

Neurotoxic

Pulmonotoxic

Dose vs. Response

Average response High responseLow response

Indi

vidu

als

affec

ted

Gaussian/Normal Distribution Curve (Equa.1)

2)(2

1

2

1)(

x

exf

f(x) the probability (or fraction) of individuals experiencing a specific response

x the responseσ the standard deviation µ the mean

n

ii

n

iii

xf

xfx

1

1

)(

)(

n

ii

n

iii

xf

xfx

1

1

2

2

)(

)()(

MEAN,

VARIANCE,

Equa.2

Equa.3

Example 1A safety engineer of one leading fertilizer brand is very concern on the irritancy effect of ammonia, a main raw material used to produce the fertilizer. A toxicology study has been conducted on 75 employees. The responses are recorded on scale from 0 to 10, with 0 indicating no response and 10 indicating a high response. Details of the findings are presented in the table 2

Table 2Response Number 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

a. Plot a histogram of the number of individuals affected vs. the response

b. Determine the mean and the standard deviation

c. Plot the normal distribution on the histogram of the original data

Answers

2)51.4(100.03.13)( xexf

Mean, µ = 338/75 = 4.51 Variance, σ2 = 374.75/75 = 5 SD, σ = 2.24

Therefore; the normal distribution is,

2)51.4(100.0178.0)( xexf

To plot a normal distribution curve, you need to convert a distribution equation to a function representing the number of individuals affected.

In this case, total individuals affected = 75

Refer to table 2.3 (Crowl & Louvar, 2002)

x f(x) 75f(x)

0 0.0232 1.74

1 0.0519 3.89

2 0.0948 7.11

3 10.6

4 13.0

4.51 13.3

5 13.0

6 10.7

7 7.18

8 3.95

9 1.78

10 0.655

Response – Log Dose Curve For convenience, the response is plotted

versus the logarithm of the dose If the response of the interest is death

or lethality = lethal dose curve, LD LC = lethal concentration (gas) If the response to the chemical or agent

is minor or irreversible = effective dose, ED

If the response to the agent is toxic (not lethal but irreversible) = toxic dose, TD

Models for Dose and Response Curves

The probit (probability unit) method is very common for single exposure computational.

The probit variable Y is related to the probability P by (Equa.4)

5 2

2

1 )2

exp()2(

1 Y

duu

P

Fig X: The probit transformation converts the sigmoidal response vs. log dose curve into a straight line when plotted on a linear probit scale

Question 2.2 (Crowl & Louvar, 2002)

The effect of rotenone on macrosiphoniella sanborni sp. was investigated. Rotenone was applied in a medium of 0.5% saponin, containing 5% alcohol. The insects were examined and classified one day after spraying. The obtained date were:

From the given data, plot the percentage of insects affected versus the natural logarithm of dose

Convert the data to a probit variable, and plot the probit versus the natural logarithm of the dose. If the results is linear, determine a straight line that fits the data. Compare the probit and number of insects affected predicted by the straight line fit to the actual data

Dose (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

Probit Variable Y Equa.5

k1, k2Probit parameters

V Causative factor represents the dose

VkkY ln21

OTOH, conversion from probits to percentage is given by (Equa.6)

erf the error function of Y

2

5

5

5150

Yerf

Y

YP