Chapter 2: Toxicology

Considers worker exposures

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 Learning Objectives:
Chapter 2: Toxicology

1. Learn how toxicants enter and are eliminated from

the body.
2. Understand effects of toxicants, including
response vs. dose
3. Use probit equations to determine response to
dose.
4. Understand exposure limits such as Threshold
Limit Value (TLV) and Permissible Exposure Limit
(PEL).

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 Definitions
Toxicology: - entry of toxicants into organism
- elimination from organism Quantitative
- effects on organism
Industrial hygiene: prevention or reduction of entry
- chemical agents
- physical agents: particulates < 5 µm,
noise, radiation
Toxicity: The quality, state, or degree to which a substance is
poisonous and/or may chemically produce an injurious or deadly
effect upon introduction into a living organism.
Problem: organisms respond via a distribution of effects

Toxic hazard: A measure of the danger posed to living

organisms by a toxic agent, determined not only by the toxicity
of the agent itself, but also by the means by which it may be
introduced into the subject organisms under prevailing
conditions. 3
Entry Routes for Toxicants

ROUTE ENTRY CONTROL

Ingestion Mouth, stomach Enforcement of rules on
eating, drinking, smoking
Inhalation Mouth, nose Ventilation, respirators,
hoods, personal protective
equipment

Injection Cuts in skin Protective clothing

Dermal Absorption Skin Protective clothing

* industrially most significant

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Entry Routes for Toxicants

Skin absorption for males:

Foot: 1
Palm/Ankle: 5x
Back/Forearm: 10x
Forehead/Scalp: 34x

http://www.cdc.gov/niosh/topics/skin/

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 Various Responses to Toxicants

Effects that are irreversible:

Carcinogen—causes cancer
Mutagen—causes chromosome damage
Reproductive hazard—causes damage to reproductive
system
Teratogen—causes birth defects

Effects that 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 6
 Routes and elimination

DIGESTIVE TRACK BLOOD TARGET ORGAN

LIVER KIDNEYS / LUNGS

EXCRETION: Kidneys (urine), liver (bile), lungs

(breath), skin (perspiration), …
DETOXIFICATION: Liver
STORAGE: Fat tissue, bones, hair, brain, …

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Figure 2-1 Toxic blood levels
WIDE VARIATIONS EXPECTED

Injection
BLOOD LEVEL

Inhalation

Ingestion
Dermal

TIME
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Toxicology Experiment with Rabbits!

Start with 50 rabbits.

Expose each to a fixed concentration.
Wait for a period of time.
Get a variety of responses. 9
 Determine Response Curve

Response Number Fraction

Least 1 2 0.04
2 14 0.28
3 18 0.36
4 15 0.30
Worst 5 1 0.02
50 1.00

Average = (1x2+2x14+3x18+4x15+5x1)/50 =
= 149/50 = 2.98
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 Plot Bar Chart

Average = 2.98

20

15
Number

10

0
1 2 3 4 5
Response

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Repeat experiment at different doses.

Dose Average Response

D1 R1 = 2.98
D2 R2
D3 R3

D4 R4

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 Plot Response vs. Dose

Average X
Response X
X

R1 X

D1
Dose
This form not very useful, particularly at low doses.
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 Take the log of the dose.

X
Average X

Response

Log ( Dose )
Get S-shaped curve - better at low dose
values 14
 Transform into Probit
Change S-shape into straight line using a
mathematical transformation called a probit.

X
Probit
X
X

Log ( Dose)
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Probit Transform

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 Probit Transform
% 0 1 2 3 4 5 6 7 8 9

0 — 2.67 2.95 3.12 3.25 3.36 3.45 3.52 3.59 3.66

10 3.72 3.77 3.82 3.87 3.92 3.96 4.01 4.05 4.08 4.12
20 4.16 4.19 4.23 4.26 4.29 4.33 4.36 4.39 4.42 4.45
30 4.48 4.50 4.53 4.56 4.59 4.61 4.64 4.67 4.69 4.72
40 4.75 4.77 4.80 4.82 4.85 4.87 4.90 4.92 4.95 4.97
50 5.00 5.03 5.05 5.08 5.10 5.13 5.15 5.18 5.20 5.23
60 5.25 5.28 5.31 5.33 5.36 5.39 5.41 5.44 5.47 5.50
70 5.52 5.55 5.58 5.61 5.64 5.67 5.71 5.74 5.77 5.81
80 5.84 5.88 5.92 5.95 5.99 6.04 6.08 6.13 6.18 6.23
90 6.28 6.34 6.41 6.48 6.55 6.64 6.75 6.88 7.05 7.33
% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
99 7.33 7.37 7.41 7.46 7.51 7.58 7.65 7.75 7.88 8.09

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 Probit Equations
Using probits, most response vs. dose
curves can be represented in the form:
Y=k1+k2ln V
where Y = Probit variable
k1, k2 are constants
V = causitive variable
See Table 2-5 for a list of probit equations
for toxic exposures, fires and explosions.
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 Type of injury or damage Causative Probit parameters
variable
k1 k2
Firea
Burn deaths from flash fire teIe4/3/104 -14.9 2.56 te effective time duration (s)
4/3 4
Burn deaths from pool burning tI /10 -14.9 2.56
Ie effective radiation intensity
Explosiona (W/m2)
Deaths from lung hemorrhage po -77.1 6.91
t time duration of pool burning
Eardrum ruptures po -15.6 1.93 (s)
Deaths from impact J -46.1 4.82
I radiation intensity from pool
Injuries from impact J -39.1 4.45 burning (W/m2)
Injuries from flying fragments J -27.1 4.26
po peak overpressure (N/m2)
Structural damage po -23.8 2.92
Glass breakage po -18.1 2.79 J impulse (N s/m2)
Toxic releaseb
Ammonia deaths ∑ C2.0T -35.9 1.85 C concentration (ppm)
Carbon monoxide deaths ∑ C1.0T -37.98 3.7 T time interval (min)
Chlorine deaths ∑ C2.0T -8.29 0.92
c 1.0
Ethylene oxide deaths ∑C T -6.19 1.0
Hydrogen chloride deaths ∑ C1.0T -16.85 2.0
Nitrogen dioxide deaths ∑ C2.0T -13.79 1.4
Phosgene deaths ∑ C1.0T -19.27 3.69
Propylene oxide deaths ∑ C2.0T -7.42 0.51
Sulfur dioxide deaths ∑ C1.0T -15.67 1.0
Toluene deaths ∑ C2.5T -6.79 0.41
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 Conversion from Probit to %

 Y 5  Y  5 
P  50 1  erf   (2-6)
 Y  5  2  
P = Percentage
Y = Probit
erf = error function (available on spreadsheet)

This is very useful for spreadsheet calculations!

On Excel:
Y = 5 + NORM.S.INV(P)
Reverse calc is given by
P = 100*NORM.S.Dist(Y-5, TRUE) 20
 Example

Eisenberg reported the following data on the effect of

explosion peak overpressures on eardrum rupture in
humans:

Percentage affected Peak overpressure (N/m2)

1 16,500
10 19,300
50 43,500
90 84,300

Confirm the probit correlation for this type of exposure, as

shown in the table.
22
Solution
The percentage is converted to a probit variable. The
results are:

Percentage Probit
1 2.67
10 3.72
50 5.00
90 6.28

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24
 TLV and PEL
The Threshold Limit Value (TLV) is the maximum
exposure limit to humans for 8 hours a day, 40 hours
per week, that does not cause any noticeable effect.

The TWA is the time weighted average.

The TLVs are promulgated by the American

Conference of Governmental Industrial Hygienists
(ACGIH), a professional society, and does not have
legal authority.

The Permissible Exposure Limit is the same thing,

but is promulgated by OSHA, a government
organization, and the PEL’s do have legal authority.
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 Threshold Limit Values
THRESHOLD DOSE: NO DETECTABLE EFFECT
Threshold Limit Value TLV: worker’s lifetime
This is for 8 hours per day, 40 hours per week.

NOT FOR CONTINUOUS EXPOSURES!

TLV - TWA * Time weighed average

TLV - STEL Short term exposure limit

TLV - C Ceiling limit

More values are available for TWAs than for

STEL or C.

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TLV type Definition
TLV-TWA Threshold limit value—time-weighted average
  The concentration for a conventional 8-hour workday and a 40-
hour workweek, to which it is believed that nearly all workers
may be repeatedly exposed, day after day, for a working lifetime
without adverse effect.
TLV-STEL Threshold limit value—short-term exposure limit
  A 15-minute TWA exposure that should not be exceeded at any
time during a workday, even if the 8-hour TWA is within the TLV-
TWA. The TLV-STEL is the concentration to which it is believed
that workers can be exposed continuously for a short period of
time without suffering (1) irritation, (2) chronic or irreversible
tissue damage, (3) dose-rate-dependent toxic effects, or (4)
narcosis of sufficient degree to increase the likelihood of
accidental injury, impaired self-rescue, or materially reduced
work efficiency. Exposures above the TLV-TWA up to the TLV-
STEL should be less than 15 minutes, should occur no more
than four times per day, and there should be at least 60 minutes
between successive exposures in this range.
TLV-C Threshold limit value - ceiling
  The concentration that should not be exceeded during any part
of the working exposure.
 Threshold Limit Values
Published by ACGIH: American Conference of
Governmental Industrial Hygienists, a
professional organization without legal
authority.
Cannot be used as indication of relative toxicity.
Cannot be used for air pollution exposures.

Some toxicants have zero thresholds

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TLV – Example Values
Acetone 500 ppm
Ammonia 25 ppm
ppm = parts per
CO 25 ppm
million by volume
Chlorine 0.5 ppm
Gasoline 300 ppm
Hexane 50 ppm
Phosgene 0.1 ppm
For flammables, TLV is ¼ of lower flammable limit.
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TLV – Example Values

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Conversion from mg/m3 to ppm
100% = 1 million ppm; 10% = 100,000 ppm; 1% = 10,000 ppm

For liquid mixtures ppm = mg/m3, but this is

not true for vapors!
Vv 6
 mv / v 
C ppm  10    106
Vb  V 
 b 
 
 RgT   mv   mv  kg/m3  (mg/m3) 106

     106  
 PM   Vb




Vb

 

 RgT   T 
C ppm 
PM
3
 
 mg/m  0.08205 
 PM 

mg/m 3
 
 

Equation (2-7)
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 Dose–response curve
Toxicants are compared for relative toxicity based on
the LD, ED, or TD curve

10%

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 Problem with Relative Toxicity
Incorrect statement: “Chemical A is more toxic than
B since its TLV is lower.”
Correct statement: “Chemical A has a lower TLV, so
we need to work harder to prevent exposures.”

Chemical A
Average
Response Chemical B

Log ( Dose ) 33
PEL - Permissible Exposure Level
Published by OSHA, and have legal authority.
Defined the same as TLV.
Most PELs are same as TLVs.
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 unique, but most require EXPLICIT data
that workers are not exposed.
See OSHA.gov web site for regulations. 34
End of Chapter 2: Toxicology

Questions?

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