CM4310: Chapter 2 September 8, 2006

Chapter 2: Toxicology Definitions

Considers worker exposures Toxicology: - entry of toxicants into organism
- elimination from organism Quantitative
- effects on organism

Industrial hygiene: prevention or reduction of entry

Toxicant - chemical agents

- physical agents: particulates < 5 µm,
noise, radiation

Toxicity: property related to effect on organism

Problem: organisms respond via a
distribution of effects
Toxic hazard: likelihood of damage based on exposure
reduction by appropriate techniques

Entry Routes for Toxicants Routes and elimination

ROUTE ENTRY CONTROL DIGESTIVE TRACK BLOOD TARGET ORGAN

Ingestion Mouth, stomach Rules on eating, drinking,

smoking
LIVER KIDNEYS / LUNGS
Inhalation Mouth, nose Ventilation, hoods,
* protection equipment
Injection Cuts in skin Protective clothing EXCRETION kidneys (urine), liver (bile), lungs, skin

* Dermal Absorption Skin Protective clothing DETOXIFICATION liver

* industrially most significant STORAGE fat tissue

INACTIVATION

Figure 2-1 Toxic blood levels Toxicology Experiment with Rabbits!

WIDE VARIATIONS EXPECTED

Injection
BLOOD LEVEL

Inhalation
Start with 50 rabbits.
Ingestion
Expose each to a fixed concentration.
Dermal
Get a variety of responses.
TIME

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CM4310: Chapter 2 September 8, 2006

Plot Bar Chart

Determine Response Curve
Average
Response Number Fraction
Least 1 2 0.04 20
2 14 0.28 15
3 18 0.36

Number
4 15 0.30 10

Worst 5 1 0.02 5
50 1.00
0
1 2 3 4 5
Response
Average = (1x2+2x14+3x18+4x15+5x1)/50 = 149/50
= 2.98

Repeat experiment at different doses. Plot Response vs. Dose

Dose Average Response Average X

Response X
D1 R = 2.98
1
X
D2 R
2
R X
D3 R3 1

D4 R
4
D1
Dose
This form not very useful, particularly at low doses.

Take the log of the dose. Transform into Probit

Change S-shape into straight line using a
X
mathematical transformation called a probit.
Average X
See Table 2-4 in text for numerical conversion.
Response
X
X Probit
X
X
X
Log ( Dose ) X

Get S-shaped curve - better at low dose values Log ( Dose)

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CM4310: Chapter 2 September 8, 2006

Probit Equations Conversion from Probit to %

Using probits, most response vs. dose curves can ⎡ Y −5 ⎛ Y −5 ⎞⎤
be represented in the form: P = 50 ⎢1 + erf ⎜ ⎟⎥
Y = k1 + k2 ln (V)
⎢⎣ Y − 5 ⎝ 2 ⎠ ⎥⎦
P = Percentage
where Y = Probit variable
Y = probit
k1, k2 are constants
erf = error function (available on spreadsheet)
V = causitive variable
This is very useful for spreadsheet calculations!
See Table 2-5 for a list of probit equations for
toxic exposures, fires and explosions.

Threshold Limit Values

Threshold Limit Values - 2
THRESHOLD DOSE: NO DETECTABLE EFFECT
Threshold Limit Value TLV: worker’s lifetime Published by ACGIH: American Conference of
This is for 8 hours per day, 40 hours per week. Governmental Industrial Hygienists, a professional
NOT CONTINUOUS EXPOSURE! organization without legal authority.
TLV - TWA * Time weighed average Cannot be used as indication of relative toxicity.
TLV - STEL Short term exposure limit Cannot be used for air pollution exposures.
TLV - C Ceiling limit

See Table 2-7 for detailed definitions of these.

Some toxicants have zero thresholds
See Table 2-8 for specific values for a number of
chemicals. More values are available for TWAs than
for STEL or C.

TLV – Example Values Table 2-8 Conversion from mg/m3 to ppm

Acetone 750 ppm
Ammonia 25 ppm
⎛ 22.4 ⎞ ⎛ T ⎞ ⎛ 1 ⎞ ⎛ T ⎞
ppm = ⎜ ⎟ ⎜ ⎟ ( mg/m ) = 0.08205 ⎜ ⎟ ( mg/m )
3 3
⎟⎜
CO 25 ppm ⎝ M ⎠ ⎝ 273 ⎠ ⎝ P ⎠ ⎝ PM ⎠
Chlorine 0.5 ppm
Gasoline 300 ppm Equation (2-7)
Hexane 50 ppm
For liquid mixtures ppm = mg/m3, but this is not
Phosgene 0.1 ppm true for vapors!
For flammables, TLV is ¼ of lower flammable limit.

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CM4310: Chapter 2 September 8, 2006

Problem with Relative Toxicity PEL - Permissible Exposure Level

Published by OSHA, and have legal authority.
Chemical A
Average Defined the same as TLV.

Response Most PELs are same as TLVs.

Chemical B
Not updated as regularly as TLVs.
Most companies use lowest of the two values.

For some chemicals, i.e. benzene, vinyl chloride, a specific

OSHA regulation has been published. Each regulation is
Log ( Dose ) unique, but most require EXPLICIT data that workers are
not exposed.
See OSHA.gov web site for regulations.