Industrial Safety Series

Toxicology in the
workplace
Dr. Ir. Yulianto S Nugroho, MSc.
Department of Mechanical Engineering University of Indonesia
 Outline of talk
• Introduction
• Route of Body Entry
• Dose-response relationship
• Acute and chronic effect
• Air-contaminate exposure
• Neoplasms
• Permissible exposure limits
• Problems

Reference :
Charles A. Wentz, Safety, Health and Environmental Protection, MGH, 1998.
2 ©Dr. Ir. Yulianto S Nugroho, MSc
 Introduction
Toxicology is the study of the adverse
effects of chemicals on living organisms.
The science of toxicology is concerned
mainly with the toxic or poisonous
properties of chemical substances.
At sufficiently high concentrations and
levels of exposure, all chemicals have
the potential of being a hazard. But, at
sufficiently low concentration and level
of exposure, all chemicals are safe and
do not have the potential of being a
hazard.
Medication, vaccines, and chemical
exposure can result in side effects that
Vaccine ampoules are life-threatening. The benefit of
medicines must be weighted against
their adverse effects.
3 ©Dr. Ir. Yulianto S Nugroho, MSc
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 Introduction (cont)
The main objectives of toxicology is to
define how much is unacceptable and to
recommend precautionary measures and
constraints to assure that under normal
workplace conditions employees are not
exposed to those unacceptable levels.
Main factors contribute to toxicity:
 Route of entry
 Dosage level
 Physiological state of the receiver
 Environmental conditions
 Physical properties of the chemical
 Chemical properties of the chemical
Pharmaceutical samples

4 ©Dr. Ir. Yulianto S Nugroho, MSc

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 Route of body entry
The route of entry into the body plays an
important role in chemical toxicity. The
toxic effects of a substance are
dependent upon how it gains entrance
into the body and, further, into the
bloodstream.
The most common routes of entry into the
body are inhalation, absorption through
the skin, ingestion, and injection.
A substance can enter via more than one
route at a time, depending upon the
chemical properties and surrounding
conditions (i.e. by both inhalation and
skin absorption).
Once the chemical has entered the
bloodstream, the toxic effect may be
Intravenous feeding bag
general or specific to certain organs or
5 tissue. ©Dr. Ir. Yulianto S Nugroho, MSc
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 Route of body entry (cont)

When air and its contaminates

are inhaled, they first pass
through the upper respiratory
tract: the nose, throat, trachea,
and bronchial tubes.

The major parts of the human

respiratory system.
6 ©Dr. Ir. Yulianto S Nugroho, MSc
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 Route of body entry (cont)

The air is transported to the

alveoli, where the gases are
diffused across thin membrane
cells walls.

The gas exchange of air in an

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alveolus.
©Dr. Ir. Yulianto S Nugroho, MSc
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 Route of body entry (cont)

This gas diffusion model is

based mainly upon the
differential partial pressures of
oxygen and carbon dioxide in
the respiratory system.

Gas diffusion model for the respiratory

system and the bloodstream.
8 ©Dr. Ir. Yulianto S Nugroho, MSc
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 Route of body entry (cont)
The oxygen concentration in the bloodstream
is greater than in the tissue cells, causing
oxygen to permeate the capillary walls to
increase the level of oxygen in the tissue cells.
Oxygen deficiency for normal adults:
 21% to 15% : no immediate effects
 15% to 10% : dizziness and breathless
 7% to 5% : life-threatening conditions
 < 5% : death in minutes.
Possible outcomes when a chemical in contact
with skin:
 The skin may block entry into the body
 The chemical may cause skin irritation
 It may produce skin sensitization
 It may penetrate the skin and enter
Gas diffusion model for the
bloodstream and tissue cells. the bloodstream.

9 ©Dr. Ir. Yulianto S Nugroho, MSc

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 Dose-response relationship

Test Tubes

Test Tubes

The dose-response relationship is the basis for toxicological

considerations. A dose of a chemical is administered to a test animal
species and the outcome is observed. This methodology is continued
by trial and error until a range is identified where all or most of the
test animals die at one end and all or most of the test animals survive
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at the other end of the range. ©Dr. Ir. Yulianto S Nugroho, MSc
 Dose-response relationship (cont)
Typical dose-response relationship.
The data from the specific test conditions
are plotted to form a typical relation as
shown on the left.
Dosage levels are reported as:
 Quantity per unit of body weight
 Quantity per unit of air volume
respired
 Quantity per unit of exposed skin
surface
The length of time of exposure is also
critical to the dose-response relationship.
When the chemical concentration and the
exposure time are considered together, their
product becomes an important criterion,
since high concentrations for short time
periods produce similar effects a s low
concentrations over longer time frames.

11 ©Dr. Ir. Yulianto S Nugroho, MSc

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 Dose-response relationship (cont)
Chemical LD 50
Ethyl alcohol 10,000.00000
Sodium cloride 4,000.00000
Ferrous sulfate 1,500.00000
Strychnine sulfate 2.00000
Nicotine 1.00000
2,3,7,8 tetrachlorodibenzo-p-dioxin 0.00100
Botilinus toxin 0.00001

The dose-response curve can be used to study the lethal dose (LD) in the test
animal population.

LD50 is the dose of a substance that will be fatal to 50% of a defined animal
population.

LD0 and LD100 refer to 0 or 100% fatalities, respectively. The LD units are
expresses in mg per kg weight.
12 ©Dr. Ir. Yulianto S Nugroho, MSc
13 ©Dr. Ir. Yulianto S Nugroho, MSc
 Relative Toxicity Classifications

14 ©Dr. Ir. Yulianto S Nugroho, MSc

 Threshold effect of chemical exposure

Since low-level exposures to most chemicals are not harmful, it follows that
there is a threshold level below which there is no effect or a potentially beneficial
effect.
As shown above, as dose is increased, there is a point that begins to produce a
measurable adverse effect. This initial toxicity observation and the rate of
increasingly adverse effect are used to define the degree of toxicity of a
15 substance. ©Dr. Ir. Yulianto S Nugroho, MSc
 Acute and Chronic effects
ACUTE :
Acute exposures and effects are short-term at
high concentrations with almost immediate
results.
Acute exposures usually last less than 24
hours and are often related to an accident.

CHRONIC :
Chronic effects have symptoms of illness of
long duration or frequent recurrence. The
chronic effects develop slowly over a long
period of time.
The symptoms of chronic poisoning occur at
low levels of contaminant and are not apparent
for a long time period-years or even decades of
exposure.

Green Laser

16 ©Dr. Ir. Yulianto S Nugroho, MSc

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 Air-contaminate exposure
Air pollution caused by forest fires
Inhalation of air contaminates is the
most common exposure route for
toxic chemicals in the workplace. It
can be classified into : irritants,
asphyxiants and narcotics.
Irritant causes aggravation upon
contact with tissue,
Asphyxiants block or otherwise
interfere with the transfer of oxygen
to body tissue and will result in
suffocation.
Narcotics interfere with the central
nervous system by causing
anesthesia, the loss of sensation.

17 ©Dr. Ir. Yulianto S Nugroho, MSc

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 Neoplasms

Chemical barrels

A neoplasms is a new growth of tissue that serves no physiological function. This

abnormal tissue growth is often used to describe cancerous or potentially
cancerous tissue.

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A carcinogen is an agent that produces or causes cancer.
©Dr. Ir. Yulianto S Nugroho, MSc
 Permissible exposure limits

The permissible exposure limits for industrial chemical

exposure are usually based upon the threshold limit values
(TLVs). If the TLV for a substance is exceeded, a person
could be harmed.
The TLVs are determined for :
 Gas in ppm and mg/m3
 Particulate in mg/m3
Conversion : mg/m3 = ppm (mol wt)/24.5 …… at 25oC

19 ©Dr. Ir. Yulianto S Nugroho, MSc

 Permissible exposure limits (cont)
n

1. TLV, time weighted average: t C i i

TLV  TWA  i 1
n

t
i 1
i

n
2. TLV, short-term-exposure limit:
t C i i
TLV  STEL  i 1

0.25

3. TLV, ceiling: n
Ci
TLV mix 
i 1 TLV i
20 ©Dr. Ir. Yulianto S Nugroho, MSc
 TLV-TWA

21 ©Dr. Ir. Yulianto S Nugroho, MSc

 Problems (homework)
1. Define LD50 for a chemical substance ?
2. Which is more important in industrial toxicology – the toxicity of
the substance or the risk and hazard associated with its use ?
3. What are the major routes by which toxic chemicals gain access
to the body ?
4. What is the difference between acute and chronic exposure to
toxic chemicals ?
5. Name some lifestyle factors that cause cancer ?
6. Workplace air contains 120 ppm isoproplyl alcohol (TLV, 400
ppm), 0.3 ppm chlorine (TLV, 0.5 ppm) and 45 ppm nitroethane
(TLV, 100 ppm). Are combined effects of this mixture in
compliance ?

22 ©Dr. Ir. Yulianto S Nugroho, MSc

 Problems (homework)

7. In the sixteenth century. Paracelsus, a Swiss alchemist and physician

who introduced lead, sulfur, iron, and arsenic into pharmaceutical
chemistry said, "All substances are poisons, there is none which is not
a poison, the right dose differentiates a poison and remedy." How does
his statement relate to the present-day science of toxicology`?
8. Which is more important in industrial toxicology-the toxicity of the
substance or the risk or hazard associated with its use.
9. What constitutes an acceptable risk for exposure to a toxic chemical?
10. Name some factors that could be considered in determining an
acceptable toxicology risk.
11. What constitutes safe and highly toxic oral chemical-dose levels for
humans?
12. What are the major routes by which toxic chemicals gain access to the
body?

23 ©Dr. Ir. Yulianto S Nugroho, MSc

 Problems (homework)
13. What route to the body would produce the greatest toxic effect and the
most rapid response for a dose of a toxic chemical?
14. A toxic chemical is known to be detoxified in the liver. Would it be more
or less toxic if ingested rather than inhaled?
15. Which of the major routes to the body relate more frequently to
industrial exposure?
16. What is the difference between acute and chronic exposure to toxic
chemicals?
17. Describe the effects of a single benzene exposure as compared to
repeated benzene exposures at the same dosage level.
18. In attempting to characterize the toxicity for a specific chemical, would
you need acute or chronic exposure information?
19. How does fractionation of the chemical dose relate to the effect of the
chemical exposure? 15 Name some known human carcinogens and
their adverse effects on humans.
20. What lifestyle factors are known to cause cancer?

24 ©Dr. Ir. Yulianto S Nugroho, MSc

 Problems (homework)
21. Why is the term chemical looked upon unfavorably by society?
22. How does the public perception of risk to chemical exposure differ
from that of scientists and engineers?
23. What are carcinogens?
24. Define TLV-TWA, TLV-STEL, and TLV-C for hazardous chemicals.
25. Based on the acute LDSo values in Table 3-2, would you expect
nicotine or strychnine sulfate to be more toxic?
26. Name some lifestyle factors that cause cancer.
27. Where can the list of known carcinogens be found? 24 Where can the
list of suspected carcinogens be found? 25 Where can the TLV for
chemicals be found?
28. What is the concentration in mg/m; of 5 ppm of carbon tetrachloride?
27 What is the concentration in mg/m3 of 25 ppm of ammonia?
29. The 8-hour TWA of airborne acetic acid concentration in the workplace
measures 15 ppm. The TLV-TWA measures 10 ppm. Is this location in
compliance?

25 ©Dr. Ir. Yulianto S Nugroho, MSc

 Problems (homework)
30. The 8-hour TWA of airborne methyl ethyl ketone (MEK) concentration
in the workplace measures 40 ppm. The TLV-TWA measures 200 ppm.
Is this location in compliance? 30 Workplace air contains 100 ppm
butane (TLV 800 ppm), 50 ppm pentane (TLV 600 ppm) and 10 ppm
hexane (TLV 50 ppm). Are the combined effects of this mixture in
compliance?
31. Workplace air contains 120 ppm isopropyl alcohol (TLV 400 ppm), 0.3
ppm chlorine (TLV 0.5 ppm), and 45 ppm nitroethane (TLV 100 ppm).
Are the combined effects of this mixture in compliance?
32. A liquid contains 40 wt % heptane (TLV 400 ppm), 35 wt % methyl
chloroform (TLV 350 ppm) and 25 wt % perchloroethylene (TLV, 25
ppm). Assume the atmospheric composition to be the same as the
liquid. What is the TLV of this mixture in mg/m'?
33. What are the main chemical exposure routes in the workplace?
34. What is the key gas or vapor property that determines the rate of
uptake from the alveoli into the bloodstream?

26 ©Dr. Ir. Yulianto S Nugroho, MSc

 Problems (homework)
35. What is the target organ for the toxic effects of a narcotic substance?
36. What is the target organ for the toxic effects of chronic mercury
exposure?
37. During an 8-hour workday the ammonia levels at a work location were
10 ppm (5 h), 20 ppm (1 h), and 30 ppm (2 h). Is the air level in
compliance if the NH3 PEL is 25 ppm? 38 The isopropyl alcohol vapor
levels at a workstation during an 8-h workday were 450 ppm (2 h), 375
ppm (3 h), and 385 ppm (3 h). Is this exposure level in compliance if
the isopropyl alcohol PEL is 400 ppm?
38. What is the partial pressure of oxygen POZ in air at standard
conditions?
39. What adverse skin conditions could be caused by exposure to coal tar
chemicals?
40. In lower molecular weight chlorinated aliphatic compounds, what is the
TLV effect of increasing the chlorine content?
41. What is the chemical classification of benzene, toluene, and xylene?

27 ©Dr. Ir. Yulianto S Nugroho, MSc