Escolar Documentos
Profissional Documentos
Cultura Documentos
epidemiology
6T
Table Of Contents
6T
Page 2 of 79
6T
6T
Page 3 of 79
Describe the main effects and route of attack of hazardous substances on the
human body
Explain the relevance of toxicological data to the identification of work related ill
- health
Relevant Standards
International Labour Office, Safety in the Use of Chemicals at Work, an ILO Code
of Practice, ILO, 1993. ISBN: 9221080064
In this section we will give definitions of the physical forms - solids, liquids, dusts,
fibres, mists, gases, fumes and vapours.
We will then give an explanation of the following:
-toxic -definition of toxicity; examples of toxic effects of commonly occurring toxic
substances -trichloroethylene, asbestos, carbon monoxide, isocyanates, siliceous dusts,
lead
-corrosive -definition of corrosive; effects on the human body of contact with
corrosive substances; examples of commonly occurring corrosive substances -acids,
ammonia, sodium hydroxide
-irritant -definition of irritant; examples of irritant effects of commonly occurring
substances e.g. cleaning agents, silicates
-harmful -definition of harmful; examples of harmful effects and common substances
causing such effects
-dermatitic -definition of dermatitis; primary/contact and secondary/allergic or
sensitised forms of dermatitis; circumstances likely to lead to dermatitis; typical
workplace examples
-sensitisation -definition of sensitisation; skin, respiratory system; health effects and
typical workplace examples of sensitising agents
-carcinogenic -definition of carcinogen; examples of types of cancer relative to
specific substances (e.g. asbestos, coal tar, chromium, wood dust)
-mutagenic- definition of mutagen; examples of substances found in the workplace.
-asphyxiant - definition of asphyxiant; examples of substances found in the workplace
Page 5 of 79
Mist : Finer liquid droplets produced during condensation, (i.e. cooling of hot
vapours). Size 0.01 m 10 m
Smoke : Very small solid or liquid particles of complex shape arising from
incomplete combustion, (i.e. hot processes involving combustion). Size 0.01 m
1 m
Page 6 of 79
physical form of the airborne contaminant will affect its ability to penetrate the
respiratory tract and consequently cause harm.
Page 7 of 79
All substances or preparations which are dangerous for supply must be classified
under CHIP:
o The Approved Supply List provides classifications for around 2,000 chemicals.
o Substances dangerous for supply which are not given in the Approved Supply List
must be classified under specific categories of danger and assigned risk phrases.
Symbol
Hazard
Description of hazard
explosive
oxidising
(Physicochemical)
chemicals.
F
highly
flammable
F+
extremely
flammable
(Health)
Page 8 of 79
T+
very toxic
toxic
category 1
carcinogens
category 2
carcinogens
Xn
category 3
carcinogens
category 1
mutagens
category 2
mutagens
Xn
category 3
mutagens
category 1
category 2
reproductive
toxins
Xn
category 3
reproductive
toxins
Xn
harmful
corrosive
Xi
irritant
(Environmental)
N
Page 9 of 79
Risk Phrases
Risk phrases are an important part of the classification and are assigned according to particular
criteria. The risk phrase gives more information than the category of danger and is more
specific to the particular chemical. The Approved Supply List contains a section which lists 64
individual risk phrases and also gives a further 57 combined risk phrases. The complete list of
risk phrases is given in Table 1.2.
Identification of hazards
Fire-fighting measures
Toxicological information
Ecological information
Disposal considerations
Transport information
Regulatory information
Suppliers must ensure that safety data sheets are kept up to date and revised
accordingly.
Page 10 of 79
Severity
Score
Risk Phrase
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
Flammable
R11
Highly flammable
Page 11 of 79
Risk
Severity
Number
Score
Risk Phrase
R12
Extremely flammable
R14
R14/15
R15
R15/29
R16
R17
R18
R19
R20
Harmful by inhalation
R20/21
R20/21/22
R20/22
R21
R21/22
R22
Harmful if swallowed
R23
Toxic by inhalation
R23/24
R23/24/25
R23/25
R24
R24/25
R25
Toxic if swallowed
R26
R26/27
R26/27/28
R26/28
R27
R27/28
R28
R30
R31
R32
Page 12 of 79
Risk
Severity
Number
Score
Risk Phrase
R33
R34
Causes burns
R35
R36
Irritating to eyes
R36/37
R36/37/38
R36/38
R37
R37/38
R38
Irritating to skin
R39
R39/23
R39/23/24
R39/23/24/25
R39/23/25
R39/24
R39/24/25
1.5.1 Notes:
Extremely Flammable F+ and Highly Flammable F
For the purposes of CHIP, a Flammable Liquid is one with a flash point of less
than 37.8 C.
A Highly Flammable Liquid (F) is one with a flash point of less than 21 C
An Extremely Flammable Liquid (F+) is one with a flash point less than 0 C and
a boiling point of 35 C or less
Page 13 of 79
Carcinogens
Category 1 - substances known to be carcinogenic to humans
Category 2 - substances that should be regarded as if they are carcinogenic to
humans, for which there is sufficient evidence, based on long-term animal studies and
other relevant information, to provide a strong presumption that human exposure may
result in the development of cancer.
Category 3 - substances that cause concern owing to possible carcinogenic effects but
for which available information is not adequate to make satisfactory assessments.
Categories 1 and 2 carry the "toxic" (T) symbol and the Risk Phrase R45 (may cause
cancer) or R49 (may cause cancer by inhalation).
Category 3 carries the "harmful" (Xn) symbol and the Risk Phrase R40 (possible risk
of irreversible effects).
Very Toxic (T+) and Toxic (T)
Evident Toxicity- this concept is used to designate toxic effects after exposure to
a substance tested, which are so severe that exposure to the next highest fixed
dose would probably lead to death.
R28 "Very Toxic if swallowed" : LD 50 oral, rat < or = 25mg/kg : less than
100% survival at 5mg/kg oral, rat.
R27 "Very Toxic in contact with skin" : LD 50 dermal, rat or rabbit: < or =
50mg/kg.
Page 14 of 79
Toxic (T)
Acute lethal effects:
R24 "Toxic in contact with skin" : LD 50 dermal, rat or rabbit: 50 < LD 50 < or
= 400mg/kg.
Many countries already have regulatory systems in place for these types of
requirements. These systems may be similar in content and approach, but their
differences are significant enough to require multiple classifications, labels and safety
data sheets for the same product when marketed in different countries or even in the
same country when parts of the life cycle are covered by different regulatory
authorities. This leads to inconsistent protection for those potentially exposed to the
chemicals, as well as creating extensive regulatory burdens on companies producing
chemicals. For example, in the United States (U.S.) there are requirements for
classification and labelling of chemicals for the Consumer Product Safety Commission,
the Department of Transportation, the Environmental Protection Agency, and the
Occupational Safety and Health Administration.
Page 16 of 79
The GHS itself is not a regulation or a standard. The GHS Document (referred to as
"The Purple Book") establishes agreed hazard classification and communication
provisions with explanatory information on how to apply the system. The elements in
the GHS supply a mechanism to meet the basic requirement of any hazard
communication system, which is to decide if the chemical product produced and/or
supplied is hazardous and to prepare a label and/or Safety Data Sheet as appropriate.
Regulatory authorities in countries adopting the GHS will thus take the agreed criteria
and provisions, and implement them through their own regulatory process and
procedures rather than simply incorporating the text of the GHS into their national
requirements. The GHS Document thus provides countries with the regulatory building
blocks to develop or modify existing national programs that address classification of
hazards and transmittal of information about those hazards and associated protective
measures. This helps to ensure the safe use of chemicals as they move through the
product life cycle from "cradle to grave."
1.6 Labelling
Substances dangerous for supply must carry a label on their receptacle and on any
other packaging to ensure clear visibility of the following information:
For preparations the name of the constituents that make it dangerous for supply
Page 17 of 79
Note that the safety phrase, although not part of the classification, is an essential
element of compliance with CHIP. The safety phrase indicates the principal
precaution(s) that need to be taken with the substance and will normally be selected
when the substance is classified. The Approved Supply List contains a section which
lists 52 individual safety phrases and also gives a further 17 combined safety phrases.
The complete list of safety phrases is given in Table 1.3.
The physical characteristics of the label must include:
Secure fixing
Page 18 of 79
Safety
Number
Safety Phrase
S1
Keep locked up
S(1/2)
S2
S3
S3/7
S3/7/9
S3/9/14
S3/9/14/49
S3/9/49
S3/14
S4
S5
S6
S7
S7/8
S7/9
S7/47
Keep container tightly closed and at temperature not exceeding ... OC (to
be specified by the manufacturer)
S8
S9
S12
S13
S14
S15
S16
S17
S18
S20
S20/21
S21
Page 19 of 79
Safety
Number
Safety Phrase
S22
S23
S24
S24/25
S25
S26
In case of contact with eyes, rinse immediately with plenty of water and
seek medical advice
S27
S27/28
After contact with skin, take off immediately all contaminated clothing,
and wash immediately with plenty of ... (to be specified by the
manufacturer)
S28
After contact with skin, wash immediately with plenty of ... (to be
specified by the manufacturer)
S29
S29/35
Do not empty into drains; dispose of this material and its container in a
safe way
S29/56
Do not empty into drains, dispose of this material and its container at
hazardous or special waste collection point
S30
S33
S35
S36
S36/37
S36/37/39
S36/39
S37
S37/39
S38
S39
S40
To clean the floor and all objects contaminated by this material use ... (to
be specified by the manufacturer)
S41
S42
Page 20 of 79
Safety
Number
S43
Safety Phrase
In case of fire use ... (indicate in the space the precise type of firefighting equipment. If water increases the risk add - Never use water)
S45
S46
S47
S47/49
S48
S49
S50
S51
S52
S53
S56
S57
S59
S60
S61
S62
S63
S64
Table 1.3: (Note that certain Safety Phrases, e.g. 10, 11, 19, etc. are no longer
in use.)
Page 21 of 79
We have just examined the CHIP Regulations and established three broad categories of
harm under which we categorise dangerous health effects:
Toxic hazards (i.e. very toxic, toxic, harmful, carcinogenic, mutagenic, toxic for
reproduction)
Corrosive/irritant hazards
We shall now explore these categories of chemical agent in more detail, examining
particular examples and their specific harmful effects.
However, before we look at specific examples of the principal types of chemical agent
you will find it helpful to consider some of the factors that can affect the overall risk to
health of an individual following exposure.
Concentration
The concentration of a particular chemical agent is an important parameter in
determining the likelihood of harm occurring and also how much damage may be done.
Chemical reactions usually proceed faster if the concentration is higher and therefore a
toxic substance is likely to poison faster, or a corrosive one to burn quicker if the
concentration is higher. Also the higher the concentration, the more per unit volume of
substance we have to deliver a toxic dose or inflict a chemical burn. It is therefore a
fair generalisation (although there may be rare exceptions) that the higher the
concentration of a chemical agent we are handling, the greater the risk of harm.
The health and safety practitioner is likely to encounter chemical concentrations
expressed in two ways:
By volume:
By weight:
A gass concentration may be expressed as 500 mg/m3 i.e. 500 milligrams of dust in
1 cubic metre of atmosphere
Often the classification of the chemical agent itself depends on the concentration of the
substance, so in the Approved Supply List (and consequently under CHIP) an acid may
be classified as corrosive if supplied at 20% concentration, but only irritant if supplied
at 5%. This is because the corrosive properties of the acid depend on concentration
and are significantly reduced with dilution, until at very low concentrations (high
dilutions) the acid shows no corrosive properties at all.
It also follows from our knowledge of dose/response relationships that a very dilute
solution of a toxic agent is unlikely to contain enough of the substance to exceed the
threshold dose for a harmful effect. Thus knowledge of the concentrations at which
chemical agents are handled and used will enable us to estimate the likely effects of
exposure.
Similarly the effects of airborne contaminants are concentration dependent and this
information is published in EH40 in the form of Workplace Exposure Limits which are
used as control standards for airborne contaminants. We will be studying this in more
detail in the next unit Unit B3.
CAS Number
Substance Name
Project supervisors
Molecular formula
Do
EC Number
not
forget
to
consult
those
Page 24 of 79
Page 25 of 79
Previousley we have already looked at the main routes of entry of harmful substances
into the human body i.e. inhalation, ingestion, skin pervasion and injection. We also
identified target organs and target systems.
We will now add a little further to this by discussing the distinctions between inhalable
and respirable dust as this information will be needed in unit B5 (monitoring). In
addition we will further look at the body's defensive responses.
Page 26 of 79
Inspirable Particulate: Only part of the total quantity of dust that is present in the
worker's breathing zone is inhaled. This part is designated as the `inspirable
fraction' of dust and is governed by the flow rates in the nose and mouth areas, as
well as the airflow around the head.
Respirable Particulates: Dust particles having a 50% cut point of 4 m m (ACGIH) or
5 m m (BMRC). These particles may be hazardous when deposited in the gas
exchange region of the lungs.
Figure 2.2. British Medical Research Council penetration curve for respirable
particles showing 50% cut point at 5mm.
Page 28 of 79
Page 29 of 79
damaging dusts and fibres, air of excessive temperature or dryness, and biological
agents such as bacteria or viruses. Some of the defence processes are readily
identified:
Goblet cells in the conducting airways secrete mucus which, forming sputum, is
expectorated or swallowed; and the nose itself filters out the largest particles.
Initial filtration of particles larger than 10 m takes place in the hairs in the
nasal cavity.
Smaller particles and aerosols between 7 and 10 m are trapped in the mucus
secreted by goblet cells lining the conducting airways and then transported
upwards by the ciliary escalator to the pharynx where they can be either
swallowed or expectorated (see Figure 2.4).
Figure 2.4
Smaller particles and aerosols between 0.5 and 7 m pass into the respiratory
units where deposition takes place in the respiratory bronchioles and alveoli.
Here they may be ingested as foreign bodies by macrophages, large cells
normally found in tissues which produce blood cells. Macrophages may migrate
back along the respiratory pathways to the ciliary escalators, ultimately to be
swallowed or expectorated. It is also thought that some transport occurs through
the alveolar membrane and into the circulatory system.
Page 30 of 79
Deposition Site
Particle Size
Above 10 m
Nasal cavity
7-10 m
Ciliary escalator
0.5-7 m
Below 0.5 m
airway
or alveolar membrane
Table 1.2:Deposition of Aerosols and Particles in the Respiratory System
Once in the bloodstream, the toxic substance (e.g. benzene) may act upon the blood itself or be
carried around until it affects another organ, such as the liver, kidneys or bladder. Materials
swallowed may be excreted unchanged in the faeces.Others may be acted upon by enzymes,
acids, and other processes in the gut, or be absorbed and pass via the portal vein to the
liver.Here they may be further acted upon and metabolised or conjugated into a variety of
soluble by products to be excreted in the urine.
Some toxic materials, such as lead, are initially stored in the bones of the skeleton so the toxic
effects can be minimised by slowly allowing it to leach back into the bloodstream.
The various pathways which may be taken by toxic materials deposited in the conducting airways
and respiratory units are shown in Figure 2.5.
Substances which pass through the alveolar membrane enter directly into the pulmonary
capillaries or find their way into the tissue spaces of the lungs from which they are drained by the
lymphatic system.Substances reaching the interstitial spaces are sometimes stored harmlessly
prior to draining into the lymphatic system (e.g. tin and iron compounds), or may result in
damage or set up disease processes (e.g. fibrosis or pneumoconiosis).Because the lymph glands
act as filters for substances or micro-predators (such as phagocytes) which are being carried away
by the lymphatic system, they are often involved in lung disease.Many cancers of the lung, for
example, start in the lungs lymph glands.
Figure 2.5
Table 2.1 shows nine examples of input substances, their sites of contact in the respiratory
pathways, together with their principal effects.
Input Substance
Site of Contact
Page 31 of 79
Effect
Upper conducting
airways
Lower conducting
Inflammation
4 Di-isocyanates (TDI)
Inflammation
Conducting airways
Immuno-pathological
reaction
Immuno-pathological
reaction (e.g. asthma)
5 Cotton dust
Conducting airways
Immuno-pathological
reaction (e.g. byssinosis)
6 Fibrogenic dusts:
Silica
Asbestos
7 Radio-isotopes
Collagenous
respiratory units
pneumoconiosis (silicosis)
Lower conducting
Collagenous
pneumoconiosis
units
(asbestosis)
Neoplasia (cancers)
respiratory units
8 Hardwood dusts
Upper conducting
Neoplasia (cancers)
Metaplasia of bronchial
respiratory units
(b) Blood-borne defensive cells, which give rise to the immune response and the
inflammatory response.
Phagocytosis
Page 33 of 79
Page 34 of 79
Figure 2.6
Stage 1 : Chemotaxis - proximity of foreign body stimulates movement of phagocyte
towards intruder.
Stage 2 : Adhesion of foreign body to phagocyte. It is thought the immune response
(qv) is the basis for adhesion.
Stage 3 : Ingestion of foreign body into the phagocytic cell, and
Stage 4 : inclusion of the foreign body attracts a lysosome which discharges enzymes
into the phagosome, i.e. the mixture of enzymes and the foreign body.
Stage 5 : Nitric oxide synthesising enzymes chemically digest the foreign body which
may remain in the phagocyte's cytoplasm; or the phagosome may be deposited in the
surrounding tissue or fluids and thence into the lymphatic system. Alternatively, the
foreign body may remain as an indigestible inclusion while the phagocyte migrates to
other tissue.
Harmful particles, micropredators and other foreign bodies engulfed by phagocytes
may thus be rendered harmless.
Inflammatory Response
Inflammation is the reaction of tissue to a harmful agent which is insufficient to kill the
tissue. It can follow when a foreign body enters the body by way of inhalation,
ingestion, absorption, pervasion, implantation, surface penetration, trauma, or energy
transformation. Although inflammation is a defensive process of great importance, if
called upon to act for too long it can sometimes result in disease.
Acute Inflammation
Acute inflammation is the immediate defensive reaction of tissue to any injury and is
typified by the following sequence of events:
Page 35 of 79
(i) Initially the capillary vessels in the area of tissue affected briefly constrict.
(ii) Then the same blood vessels dilate and the capillary walls become more permeable.
(iii) Protein-rich fluid (plasma) exudes from the capillaries into the surrounding tissue,
causing swelling (oedema).
(iv) Phagocytes migrate through the capillary walls towards the harmful input, where
they ingest it together with any damaged tissue.
(v) Tissue-dwelling macrophages join with the phagocytes and scavenge the affected
area, which is sometimes additionally bonded by fibrinogen (a protein associated with
blood clotting).
Healing Process
Towards the end of the inflammatory phase, cells called fibroblasts appear and secrete
collagen. This is a fibrous protein which cross-links with polysaccharides (sugars) to
form a meshwork of scar tissue which steadily builds up to repair the affected area.
While this is going on, if the affected area is close to the skin, epidermal cells remove
any final debris in the area and begin to dismantle the scar tissue.
Chronic Inflammation
Sometimes excessive amounts of collagen are formed and in certain chronic
inflammatory responses, macrophages die and other macrophages phagocytose their
dead. The combination of living and dead macrophages forms structures known as
giant cells. Scarring is a repair process by which gaps in tissue are made good. In
some types of chronic inflammation, however, this repair process becomes disordered.
The overgrowth of scar tissue, brought about by over-production of collagen, shrinks
and contracts, tearing and distorting the surrounding tissues. In the lungs, this results
in the condition known as emphysema and some types of pneumoconiosis result in
extensive scarring and fibrosis.
Immune Response
This term describes the mechanisms concerned with defence and preservation of
normal body integrity. In its classical form a wide range of chemicals and
micropredators provoke an immune response which involves the production of
antibodies within the space of a few days. Whenever next the antigen enters the body,
Page 36 of 79
it reacts with the residual antibody and the combination of antigen and antibody can be
phagocytosed as detailed above.
In addition to the classical disposal of antigens, two other types of immune response
are recognised:
(i) Surveillance
Sometimes dividing cells give rise to mutant forms and any excess could result in the
growth of abnormal tissue (benign or malignant). Surveillance by immune response
results in these mutants being recognised as alien and destroyed.
(ii) Self-disposal
Redundant blood and tissue cells need to be phagocytosed from the body and the
immune response ensures that redundant cells are recognised as distinct from
functioning cells.
Respiratory Inflammation
The respiratory pathway is vulnerable to attack by many irritants and corrosives or any
other substances which attack the skin. The terminology of the inflammatory processes
follows the pathway of air into the lungs, via:
Rhinitis
Laryngitis
Page 37 of 79
Tracheitis
Bronchitis
Pneumonia In extreme cases the effects of inflammation lead to swelling and exudation
of fluids resulting in narrowing or even total blocking of the small conducting airways.
Exudation in the alveoli leads to interference with respiratory gas exchange, even to a
fatal degree. Gases of low solubility will penetrate the respiratory pathway deep into
the alveoli. Such gases include sulphur dioxide, ozone, phosgene and oxides of
nitrogen. The inflammation caused results in fluid accumulating in the respiratory units
(oedema). Other irritants include metal fumes (metal fume fever) and polymer fumes
(polymer fume fever).
Inflammation of the skin is much the same as for any other body organ; there are
blood capillary changes, there is increased permeability and there is migration of cells.
Inflamed skin is painful, sometimes itchy, often red and fissured, sometimes
accompanied by exudate and shedding of scales.
Chemicals attack the skin by pervasion or implantation, resulting in contact dermatitis,
which may take a number of forms:
Irritant Dermatitis
This is caused by corrosive irritants such as acids, alkalis, detergents, oils, metallic
particles, solvents, oxidising and reducing agents and some biological agents (e.g.
giant hogweed). If the irritant is particularly aggressive, it can result in destruction of
the skin.
Acute Irritant Dermatitis
This is brought about by contact with acids and alkalis, for example, which result in
acute inflammation.
Cumulative Insult Dermatitis
This typically develops after repeated exposure to weak irritants over a long period of
time.
Allergic Contact Dermatitis
Page 38 of 79
2.3 CARCINOGENESIS
Background
A cancer is a growing mass of non-productive tissue that is relentlessly progressive,
ending in the death of the individual. This tissue growth is termed a malignant tumour
and can spread within the body via the bloodstream or the lymphatic system. This
process, termed metastasis, leads to the formation of other small tumours scattered
widely throughout the body. These new tumours can grow into nearby tissues and
destroy them as a consequence by a process termed invasion. Metastasis and invasion
are the two characteristics that distinguish malignant tumours from those classified as
benign.
Descriptions of the important terms associated with carcinogenesis are as follows:
Tumour : a swelling related to the growth of diseased cells, which grows at the
expense of other healthy cells in its vicinity. There are basically two kinds:
benign and malignant.
Benign tumours usually grow very slowly, remain localised and their cell structure
is often similar to the cells of origin.
Malignant tumours grow rapidly without restraint, spread into surrounding tissue
and have their own cell structure, unlike the cells of origin. The term cancer is used to
describe the formation of malignant tumours.
Page 39 of 79
Carcinogen : an agent (either physical, chemical or viral) which has the ability
to produce malignant tumours. In terms of occupational cancer, the carcinogenic
agent will be physical and chemical.
They upset the fundamental cell reactions within the cell structure, whereas
ordinary toxic substances mainly upset the general metabolic processes which
prevent cells from functioning normally.
They evoke irreversible effects which continue after exposure to the carcinogen
has ceased. The action of ordinary toxic agents usually stops when the exposure
ceases and recovery generally follows.
The effects of a carcinogenic agent will not appear for many years after
exposure. The period of time is its latency period. Periods between 5 and 50
years are given for different agents. During this time, there is little or no
warning of the eventual tragic outcome. 'Ordinary' toxic agents can evoke an
acute response and also a chronic response.
The particular point made above highlights the importance of strict control in the use of
carcinogenic substances. Once the symptoms have been diagnosed, the problem will
often have reached the point of no return.
Page 40 of 79
instances these new properties may be passed on to daughter cells during cell division.
This hereditary transmission of new characteristics is an indication that the cell has
been mutated and the event that brings about this change is termed a 'mutation'. The
process of mutagenesis, therefore, is considered the first step in the process of
carcinogenesis and many short-term tests for carcinogenicity are based on the ability
of a chemical to induce mutations.
Generally, carcinogens and mutagens are categorised as such on the basis of human
or, more likely, animal data. The International Agency for Research on Cancer (IARC)
classifies substances as:
No-threshold Concepts
Later in this unit we will consider dose-response relationships which are based on the
concept of a minimum level of toxin exposure below which no harmful effect can be
detected. The assumption is that below this specific level, the degree of harm inflicted
by the toxin is insignificant and will cause lasting damage. This threshold level for
acute toxic effects can therefore be used to define occupational exposure limits.
In the case of carcinogenic toxins the situation is much more complex. Theoretically, a
single 'hit' or reaction of a compound or its metabolite on the crucial part of one DNA
molecule might be sufficient to initiate a cancerous change. Hence there is no threshold
of harm and any level of exposure to a carcinogen has the potential to cause cancer. In
practice, however, the chances of one molecule reaching the target site are probably
small for most compounds and depend on a number of factors including potency,
absorption, distribution, and metabolism. The capacity of the particular cell to repair
such damage will also be important. You should therefore appreciate how the concept
of a no-threshold level of harm for carcinogenic substances differs significantly from
the approach to exposure limits applied to other toxins and thus affects the assessment
of risk and the setting of appropriate control standards.
Page 41 of 79
Page 42 of 79
2.4 SUMMARY
Page 43 of 79
Class of Toxin
Target
Some Symptoms
Example
Jaundice, liver
Carbon tetrachloride
Organ/System
damaged
Hepatotoxins
Liver
enlargement
Nephrotoxins
Kidney
Neurotoxins
Nervous system
Narcosis,
Mercury and
behavioural changes compounds,
Chloroform, ether
Hematopoietic
Blood or hemato-
Cyanosis, loss of
Carbon monoxide,
agents
poietic system
consciousness
cyanides
Lung toxins
Lungs
Cough, difficulty
breathing
Asbestos, siliceous
dust
Lead and
developing foetus
defects,
compounds
Skin
Defatting, rashes,
Ketones, chlorinated
irritation
organic solvents
Conjunctivitis,
Acids, organic
corneal damage
solvents
Eye
Page 44 of 79
To determine if the substance has the ability to cause genetic damage and the
potential to induce cancer
Carcinogenicity:
-If mutagenicity tests prove positive the animal is subjected to lifetime exposure to the
substance and at post-mortem an examination is carried out to detect tumours
Teratogenicity:
To examine the effect of the substance on the development of the embryo and foetus
to identify gross anatomical abnormalities
In addition to these tests it may be necessary to repeat the studies using other species
of animals and/or alternative routes of exposure.
Dose/Response Relationships
Toxic substances have very different effects on organisms, including the minimum level
at which an effect is detectable; the sensitivity of the organism to small increases in
dose; and the level at which the harmful effect (most significantly, death!) occurs.
Such factors are indicated in the dose-response relationship, which is a key concept in
toxicology:
Dose is the amount per unit body mass of toxic substance to which the
organism is exposed.
At low doses no organisms will show a response, i.e. they all live.
Page 45 of 79
At higher doses all organisms show a response, i.e. they all die.
In between there is a range of doses over which some organisms respond and
others do not. This is shown in Figure 3.1.
The dose-response curve is S-shaped and the mid-point represents the dose which
would cause an effect (in this case death) in 50% of the organisms. It is designated as
the LD50.
You should appreciate that LD50 is not an exact value and in recent years there has
been much discussion as to its usefulness and necessity in toxicology. The LD50 values
may vary for the same compound between different groups of the same species of
animal.
However, the value is of use in comparing how toxic a substance is in relation to other
substances. Table 3.1 gives examples of LD50 values for a variety of chemical
substances.
Compound
LD50 (mg/kg)
Ethanol
10,000
DDT
100
Nicotine
Tetrodotoxin
0.1
Dioxin
0.001
Page 46 of 79
Botulinus toxin
0.00001
Table 3.1
ED50 (effective dose for 50%) and TD50 (toxic dose for 50%) are related parameters
which indicate the dose at which a biological response is likely. Comparison of ED50
with LD50 gives an indication of the margin of safety between the dose which causes
the first identifiable effect and that which is fatal.
Testing for carcinogenic potential is more complex since there is no simple doseresponse relationship. The toxicology of carcinogens is approached in a different way
but still involves exposing laboratory animals (usually rats and mice) to the chemical
by oral, inhalation or skin contact techniques.
There are also short-term predictive tests available which are considered to simulate
potential carcinogenicity in man. They are called short term, in contrast to the usual
lifetime studies in rodents which can take three to four years before a result is
available.
Short term tests include:
We will consider some of these tests in more detail later in this study unit.
Once a dose-response relationship has been demonstrated there are a number of
parameters that can be derived from it.
If exposure is oral and lethality is used as the end point, LD50 can be determined as
we have seen previously. LD50 is defined as 'a statistically derived expression of a
single dose of a material that can be expected to kill 50% of the animals'.
However, the S-shaped dose-response curve can be further analysed mathematically to
determine doses that have a higher or lower probability of fatality. The determination
of LD90 from the dose response curve, for example (see Figure 3.1) enables estimation
of the dose that will kill the majority (i.e. 90%) of a sample of animals.
Page 47 of 79
When the route of exposure is inhalation and lethality is used as the end point it is the
concentration of the airborne toxin that is of concern. Since the amount of toxin
inhaled depends on the duration of exposure there are two ways to express this data:
With all these parameters it is important to remember that they simply represent
statistically determined doses, concentrations or times, derived experimentally in the
manner described above. Their use in comparing the 'toxicity' of different substances
and consequently their potential to cause occupational ill-health must be qualified by a
clear understanding of the limitations of the method by which this statistical data is
derived.
We made reference earlier to the concept of a dose below which no effect or response
is measurable. This is termed the threshold dose and can be clearly demonstrated with
responses such as lethality. This concept of a threshold dose for the toxic effect is an
important one and implies that there will be a dose at which the response does not
occur in any member of the population.
This is shown in Figure 3.1 where the dose response curve shows no deviation from the
x-axis (% effect = 0) until log dose reaches a value of 5 units. The term for this is the
'no observed adverse effect level' or NOAEL. We have already discussed the converse
of this with carcinogens where a threshold dose cannot be established and therefore it
must be assumed that any exposure to carcinogenic substances has the possibility of
an adverse effect.
The NOAEL is important for setting exposure limits such as occupational exposure
standards which are designed to represent a level of exposure at which there is no
Page 48 of 79
evidence of harm. We will discuss the application of this type of toxicity data in
establishing criteria for occupational exposure limits in Unit B3.
Test Dosage
5 mg/kg
Result
Action/Classification
Page 49 of 79
at 50 mg/kg
50 mg/kg
500 mg/kg
mg/kg
Harmful, retest at 50
mg/kg Unclassified
Page 50 of 79
For all three types of toxicity test the following parameters should also be considered:
Type of chemical under study (novel compound or in use for some time)
Page 51 of 79
Gene Mutation
Page 52 of 79
the observation of appreciable growth indicates that reverse mutation has taken place
and the substance in question does have mutagenic properties.
Since this test only involves the exposure of bacteria to the mutagen it is termed an 'in
vitro' test. However, gene mutation tests can also be carried out 'in vivo' (in a host
animal, usually a mouse) by injecting the host with the mutagen and directly
examining either microorganisms or host cells for evidence of genetic damage.
Chromosomal Effects
Heritable Effects
Generally two or more species should be used that metabolise the chemical in a way
similar to humans (often rats and dogs are used due to size, availability and the
amount of toxicological data already available on these animals).
Equal numbers of male and female animals should be used, with from 10 to 50
animals in each dose group.
Route of administration:
Page 53 of 79
Decreased body weight gain is a simple but sensitive indicator of toxic effects.
Food consumption is also a useful indicator.
Laboratory tests: These include blood and urine sampling and testing.
Post-mortem examination:
Evaluation:
Page 54 of 79
Page 55 of 79
3.4 SUMMARY
In this study unit we have seen that there are legal requirements as to the toxicological
testing of new substances - the level of testing depends on the quantity of substance
to be produced.
A key concept in toxicology is the dose-response relationship, 'dose' being the amount
per unit body mass of toxic substance to which the organ is exposed, and 'response'
being the resultant effect. The mid-point of the S-shaped dose-response curve
represents the dose which would cause death in 50% of the organisms - LD50. LD90
enables estimation of the dose that will kill the majority (i.e. 90% of a sample of
animals). Lethal concentration (LC) can be determined for a specified duration of
exposure.
Page 56 of 79
There are three types of toxicity test - acute (to determine the effects which occur
within a short period after dosing); subacute (to provide information on the target
organs affected by the substance and the major toxic effects); and chronic (lifetime
exposure of animals to the substance under study).
Mutagenicity occurs as a result of interaction between mutagenic agents and the
genetic materials of organisms. The Ames test is the most common test for gene
mutation. Long-term animal toxicity studies, often with rats and dogs, are carried out
to assess the effects of human exposure to chemicals over long periods.
Chemical analogy studies assume that chemically related substances will show
similarities in toxic properties.
A collection of resources and online video lectures to supplement this element
can be found at http://www.agls.uidaho.edu/etoxweb/lectures/lectures.htm
4.0 Epidemiology
In this final section of study unit B5 we are going to look at epidemiology (determining
the cause having first observed the effects) by examining the main methodologies of
epidemiology, the sources of information available, their application and limitations and
also the use of epidemiological techniques in the workplace.
HISTORICAL PERSPECTIVE
You will remember that occupational health and hygiene are concerned with
recognition, measurement, evaluation and control. Epidemiology is the science which
forms the basis of the four stages. At its crudest, epidemiology may be said to be the
elucidation of the cause having first observed the effects. For example, if a number of
workers on a particular process are suddenly affected by dermatitis, i.e. the effect, it is
likely that the cause is of occupational origin, possibly a new raw material. However,
the cause can often only be established in the light of current knowledge and
understanding. John Snow (1813-1858) flew in the face of conventional wisdom when
he suggested that cholera was due to contaminated water rather than airborne
miasmas.
Page 57 of 79
On ventilation: 'If a shaft is very deep and no tunnel reaches to it, or no drift
from another shaft connects to it, or when a tunnel is of great length and no
shaft reaches to it, then the air does not replenish itself. In such a case it (the
air) weighs heavily upon them (the miners), causing them to breathe with
difficulty and extinguishing lamps. It is therefore necessary to install machines
to enable the air to be renewed and for the miners to carry on their work.' (See
Figure 4.1.)
Page 58 of 79
Figure 4.1.
Page 59 of 79
On diseases of the lung: 'If the dust has corrosive qualities, it eats away the
lungs and implants consumption in the body. In the mines of the Carpathian
mountains, women are found who have married seven husbands, all of whom
this terrible consumption has carried off to a premature death.'
To protect miners against the effects of the dust, Agricola advised purification of the air
by ventilation and the use of loose veils over their faces.
Paracelsus (1493-1541) published the first monograph devoted entirely to the
occupational diseases of mine and smelter workers (Von der Bergsucht und Anderen
Bergkrankheiten, 1567). Although he makes correct clinical observations, he then turns
to alchemical theories to explain them:
'The lung sickness comes through the power of the stars, in that their peculiar
characteristics are boiled out, which settle on the lungs in three different ways: in a
mercurial manner like a sublimated smoke that coagulates, like a salt spirit, which
passes from resolution to coagulation, and thirdly, like a sulphur, which is precipitated
on the walls by roasting.'
If Hippocrates is the father of medicine, then Bernardino Ramazzini (1633-1714) is the
father of occupational medicine. His De Morbis Artificum Diatriba (1700) contains
accounts of the occupational diseases suffered by miners of metals, healers by
inunction, chemists, potters, tinsmiths, glass-workers, painters, sulphur-workers,
blacksmiths, workers with gypsum and lime, apothecaries, cleaners of privies and
cesspits, fullers, oil pressers, tanners, cheese-makers, tobacco-workers, corpsecarriers, midwives, wetnurses, vintners and brewers, bakers and millers, starchmakers, sifters and measurers of grain, stone-cutters, launderers, workers handling
flax, jute and silk, bathmen, salt-makers, workers who stand for long periods,
sedentary workers, grooms, porters, athletes, runners, singers, preachers, farmers,
fishermen, soldiers, learner men, priests and nuns, printers, scribes and notaries,
confectioners, weavers, coppersmiths, carpenters, grinders of metals, brick-makers,
well-diggers, sailors and rowers, hunters, and soap-makers.
In short, most of the important occupations of the day. As a result of his investigations
he added an important question to the Hippocratic art, urging physicians to ask of their
patients, 'What is your occupation?' He also 'urged physicians to leave their
Page 60 of 79
apothecaries shop, which is redolent with cinnamon, and to visit the latrines where
they may see the cause of ill health.'
Cholera
Endemic in India for centuries, cholera became pandemic in Asia between 1816-1830 and reached
England in 1831. In the summer of 1854 cholera broke out in London, being particularly severe in
the poorly drained slums around St. Giles and Soho, giving the opportunity for John Snow to carry
out the first truly epidemiological investigation into the relationship between cause and effect of
a disease. The effect was obvious. After an incubation lasting about three days, victims suffer
from severe diarrhoea and vomiting, accompanied by cramps in the legs and abdomen. The skin
loses its elasticity due to dehydration, becoming cold and clammy, the heartbeat becomes
weakened and the pulse and voice very feeble. Before treatment with modern antibiotics,
patients would die after a few days and mortality rates were very high.
During the course of the epidemic Snow plotted the household of every death in the area and his
On the Mode of Communication of Cholera, 1855, includes the figures of his most famous field
study around the Broad Street pump. By plotting the incidence of deaths onto a map (Figure 4.2)
he was able to demonstrate that the nodal point was the Broad Street pump. This led to his initial
conclusion that it was the water from this pump which had been responsible for the outbreak.
Page 61 of 79
Further investigation revealed that shortly before the epidemic the Lambeth Water Company had
removed their waterworks to Thames Ditton, well above the tidal reaches of the Thames, and
hence the water was uncontaminated by London sewage. The Southwark and Vauxhall Water
Company, however, continued to supply water from the Thames at London Bridge. He found there
were 14 times more fatalities from cholera in people drinking the Southwark supply than in those
drinking the Thames Ditton supply. He became absolutely convinced when he learned of the
death of a Hampstead woman who sent a carrier daily to collect water from the Broad Street
pump and died of cholera as a result. Her niece, who had visited her for a day, also became the
only victim of the disease in her district. As Snow was proclaiming that dirty water was
responsible for the epidemic, so a Parliamentary enquiry was establishing the cause as stale air
from the closely packed tenements in the area, thus proving that Miasmatic Theory was still
prevalent amongst most eminent medical men of the day.
b2image036.jpg
Figure 4.2: Cholera Deaths Between 19 Aug and 30 Sept, 1854, as Plotted by John Snow
Page 62 of 79
Environmental Health Officers investigating two outbreaks of Legionnaires Disease around the
BBCs Bush House in 1987 and Leicester Square in 1988 used Snows method of plotting the
incidence onto maps in an effort to identify the source of the infection.
The technique has also been used in the investigation of complaints arising from the use of
pesticides and other agricultural chemicals. Some studies may take several years of intensive
investigation to complete, consuming thousands of man-hours of work.
Death Certificates
These provide a reasonably accurate and quantifiable measure of serious illness. However,
problems occur with:
The accuracy of the cause of death (this relies on the physicians decision as to the ultimate
The occupation of the deceased (this may be the occupation at the time of death but not
necessarily the one that caused the death).
Birth Certificates
These can be used in conjunction with data on congenital malformations and pregnancy
complications to study the effect of parents occupations on these conditions.
Morbidity
The Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995 (RIDDOR)
requires the reporting and central recording of industrial accidents and diseases, whilst industrial
injury benefit claims and prescribed diseases are reported to the Department of Social Security.
However, problems with these sources of data include:
Page 63 of 79
Local Records
Depending on the study in question, hospital records, data from family doctors, information
collected by professional associations (e.g. the Royal Society of Chemists morbidity and mortality
study) or trade union records may provide useful data for epidemiological studies.
In addition some large employers maintain continued surveillance on high risk workers as they
move within the company and also when they leave or retire.
If a specific study is being undertaken this type of local data may provide valuable information to
enable a fuller picture to be built up of particular employees health and employment history.
Biologically plausible: the relationship should not conflict with known facts of the
natural history and aetiology of the disease.
Analogy: similar chemicals, biological agents and physical inputs being likely to
have similar effects.
Preventive action: if the preventive action works, i.e. there is a reduction in the
effect, then it is likely the cause was correctly identified, e.g. a reduction in an
atmospheric contaminant affecting the frequency or severity of the disease or
other associated event. It is perhaps this final criterion which may be said to be
the proof of the pudding.
Page 64 of 79
In the case of the original 1976 American Legionella outbreak, health investigators
identified the following causal factors:
Strength: early on it had been established that the victims were mainly
convention delegates.
Consistency: a similar outbreak had occurred in Pontiac in 1968 and shortly after
other outbreaks were identified in Vermont (1977), Indiana (1978) and Oxford,
England (1979).
Analogy: all the evidence pointed to a biological cause (bacterium, virus, etc.)
Preventive action: cleaning and sterilising possible water sources eliminated the
bacterium from water tanks and other water supplies.
The success of preventative action is proof that the epidemiologists had correctly
identified the cause of the disease, together with the events and circumstances
necessary to link cause with effect.
Page 65 of 79
poisoning became notifiable in all factories in 1899 and the cases of poisoning fell from
more than a thousand in 1900 to 55 in 1960; but again the death rate did not follow a
similar pattern. Indeed, it increased in some years (see Figures 4.3 and 4.4). In the
electric accumulator industry the incidence of lead poisoning rose from 1900 until the
passing of the Lead Accumulator Regulations in 1924, after which there was a decline
in the incidence of poisonings (see Figure 4.5). Once again the death rate remained
relatively constant. It would have been comparatively easy in this period to suggest
that it was not lead which was responsible for the disease; but we now know that the
time lag is largely due to the long-term effects of lead poisoning and because the
bones store large amounts of lead, releasing it slowly over a number of years.
Figure 4.3: Lead Poisoning in the Potteries
Page 66 of 79
Example 2: Mesothelioma
Page 67 of 79
Page 68 of 79
Page 69 of 79
From the data contained in these weekly reports we can calculate the relative incidence
of each cause of death and, from successive weeks, it was possible to tell whether the
plague was increasing or decreasing. We also have a record in this instance of two
industrial accidents - a drowning and a fall! You may be surprised by some of the data;
for example, the number who died from 'teeth'. In fact this was a combination of blood
poisoning and infection as a consequence of poor dental care. A number died from food
poisoning or other digestive disorders (collick, griping in the guts, rising of the lights,
scowring, surfeit and winde) as a result of poor hygiene. One died 'suddenly'!
Modern epidemiological investigations are far more sophisticated than this, as you will
see below.
Page 70 of 79
For this reason cross-sectional studies are also known as prevalence studies. The
design of a cross-sectional study involves the following main stages:
(a) Establishing precise aims
(b) Defining the study population
(c) Determining the sample size - important for statistical purposes
(d) Recruitment of all relevant cases in the sample
(e) Analysis - prevalence rates in relation to sample groups
Longitudinal Studies
The longitudinal study involves investigation of the workforce over a significant period
of time. This type of investigation takes longer to carry out and is more expensive, but,
because it takes place over a period of time rather than at a specific point in time, it
provides the opportunity to study exposure and its outcome as a time-related chain of
events. Two types of longitudinal studies are commonly employed:
The Case-control Study
This type of study is retrospective, beginning with a definition of a group of cases and
relating these (along with non-cases or controls) to the past exposure history. The
main drawback of this type of study is obtaining accurate exposure history which may
need to go back as far as 40 years.
With the case-control study the investigation compares a group of individuals who have
the disease or condition with another group who do not. The comparison is made with
respect to past characteristics of both groups and, unlike the follow-up study (see
below) the outcome is known.
The case-control method may be used, for example, to investigate the frequency of
asbestos workers who have respiratory problems or lung disease against a control
group drawn from the general population. It is quicker and less expensive than a
cohort study (see below) and is often used as the first step to see if there may be an
association between a suspected cause and a known effect. It is also useful in
Page 71 of 79
Page 72 of 79
Cohort studies are concerned with the relationship between the cause, as evidenced by
the history and nature of the exposure, and the effect, i.e. the presence of the disease.
The advantages of cohort studies are that they provide:
A more accurate account of exposure related to deaths or disease and a direct
estimate of the risk associated with the causal factors;
Information on secular trends which reveal changes in the degree of risk.
Against this must be set the following disadvantages:
It may be necessary to wait many years for the development of the disease
(mesothelioma might take as long as 40 years to manifest itself);
Some of the cohort may be lost over the period of study.
Community studies reveal how many people are affected and how seriously.
Priorities can then be established enabling preventive action to be taken when
and where it is needed.
Evaluating health services to find out how they are used, their success in
reaching certain standards and the value attached to them by the population
they serve.
Page 73 of 79
Establish the objectives of the study and what hypotheses need to be tested. (Is
disease A caused by agent B?)
Define the study population bearing in mind statistical limitations of study and
control group size.
The exact detail of the study will depend on the type of epidemiological investigation
that is being performed.
Limitations of Epidemiology
The main problems of epidemiological studies, which have been touched on in the
previous sections, include:
Page 74 of 79
The 'healthy worker' effect, whereby the control group has a different health
status compared with the cases (pre-employment health screening has the effect
of excluding less healthy individuals and consequently raising the general health
of employed persons in comparison to those not in work).
A poor response rate which reduces the sample size and its statistical
significance.
The latency period between exposure and effect is longer than the study period.
In this way the cause-association hypothesis that aims to relate occupational exposure
to incidences of ill-health should be able to be validated, either positively or negatively.
Page 75 of 79
New substance is anything which does not appear on the European Inventory of
Existing Commercial Chemical Substances (EINECS) an inventory which was
closed to new entries in 1981. Note, some chemicals which are not specifically listed
are deemed to be included (e.g. hydrates like copper sulphate pentahydrate is not
listed but is deemed to be included in the entry for the anhydrous). Even if something
is technically a new substance, it may be exempt from notification and testing e.g.
certain polymers and also chemicals below certain thresholds. The regulations place
duties on each manufacturer or importer (not downstream users/suppliers) who
manufactures in the EU or who imports into the EU. Notified chemicals will eventually
appear in the European LIst of Notified Commercial Chemical Substances (ELINCS).
Such an entry may then also make it to the Approved Supply List (UK implementation
of Annex I to the Dangerous Substances Directive 67/548/EEC) once the European
Chemicals Bureau have assessed the data and decided on a satisfactory EU-wide
classification.
This whole regime will be replaced with the Registration, Evaluation and Authorisation
of Chemicals (REACh) regulations (a directly enforceable European regulation) which
will remove the distinction between new and existing and require all chemicals
above certain thresholds to be registered and, if insufficient data available, tested too.
Some more hazardous chemicals will be subject to authorisation by the competent
authority to allow continued use. This will effectively extend the current system for new
substances to existing substances too (with some changes).
4.8 SUMMARY
Epidemiology is the determination of the cause having first observed the effects.
Sources of epidemiological data include national records, such as birth and death
certificates and morbidity records, and local medical and trade union records and
surveillance of high risk workers.
Important criteria that must be satisfied in order to establish a definite relationship
between a diseases cause and effect include: strength; consistency; specificity;
biological gradient; biologically plausible; analogy; and preventive action.
There are two main types of epidemiological study.
Cross-sectional studies (prevalence studies) are outcome-selective (examines the
prevalence of a particular occupational condition within the population) or exposureselective (examines a particular population that has been exposed to a specified
occupational condition). The design of a cross-sectional study involves establishing
Page 76 of 79
precise aims; defining the study population; determining the sample size; recruitment
of all the relevant cases in the sample; and analysis.
Longitudinal studies investigate the workforce over a significant period of time. The
case-control study (retrospective) begins with a definition of a group of causes and
relates these (along with controls) to the past exposure history.
The follow-up study (prospective) takes a group of exposed persons (and possibly nonexposed controls) and follows them up over an appropriate time period to assess the
eventual outcome of the exposure. Cohort studies are a specific type of follow-up
study.
There are, of course, limitations to epidemiology including the healthy worker effect; a
poor response rate; a high turnover of the study population; latency period between
exposure and effect longer than the study period; poor quality of data; and no effect of
exposure noted, perhaps due to a poor or small study population.
For an epidemiological study to be effective there should be: a clear hypothesis and
study objective; appropriate study design; collection of good quality data; valid
population choice; high response rate and good sampling strategy; large enough
population; and a no effect study result investigated for validity.
Weblink http://pmep.cce.cornell.edu/profiles/extoxnet/TIB/epidemiology.html
discusses the link between cigarette smoking and lung cancer.
Types of toxic effects caused by industrial chemicals
Toxic
Part of body
property
affected
Time scale
of
Effect
Example
appearence
Ammonia,
Irritant or
A few
Inflammation,
corrosive
minutes to
acid, nitrogen
Page 77 of 79
caustic soda
Fibrogenic
Generally lungs
Years
Gradual
Bauxite dust,
bagasse
leading to
disability and
death if there is
chronic exposure.
Allergic
Days to
years
(TDI), amine
permanent
hardeners for
disability. In skin
epoxy resins.
may produce
industrial
dermatitis.
Dermatitic
Skin
Days to
Inflamed, peeling
Strong acids,
years
alkalis,
carbon
ene.
Any organs, bu
10 to 40
Cancer in affected 2-
frequently skin,
years
organ or tissue.
Naphthylamin
Ultimately this
e, certain tars
may cause
and oils,
premature death.
benzidine,
lungs, bladder
asbestos
Poisonous
A few
Death of cells in
Carbon
frequently liver,
minutes to
tetrachloride,
brain, kidney
carbon
biological
monoxide,
functions.
hydrogen
Ultimately can
cyanide.
cause death.
Page 78 of 79
Asphyxiants
Lungs
Minutes
Page 79 of 79
Gases replace
Acetylene,
normal oxygen
carbon
content of air
dioxide