Carcinogens

August 2010
Carcinogens

0. Introduction
1. Definitions
2. Mechanism
3. Toxicology
4. Carcinogens
5. Preventive measures
6. What needs to be documented
0. Introduction

1. Examples of cancers?
2. Examples of products causing cancer?
3. Only cancer at workplace?
4. What do e.g. asbest and cigarette smoke
have in common?
0. Introduction

1. Examples of cancers?
Breast cancer, lung cancer, colon cancer, skin cancer, ...

2. Examples of products causing cancer?

Benzene, asbest, cigarette smoke, food, ethylene oxide, chromium VI,
toluene, …

3. Only cancer at workplace? No!

4. What do e.g. asbest and cigarette smoke
have in common?
In beginning, these were ‘promoted’ to use

It took years before link between exposure to asbest or cigarette

smoke and cancer was known

Exposure limits are very often lowered in progress of time

1. Definitions

• Carcinogen:
Substance that can cause cancer by
inhalation, ingestion or skin contact

• Mutagen:
Substance that can damage the hereditary
material (DNA)

Mutagen may cause cancer, but not always

1. Definitions
• Repro-toxic substance:
Substance that can be toxic to the
development of the unborn child (= teratogen)
or can cause impairment of fertility in male
and/or and female subjects

Can be a chemical substance, a virus,

ionizing radiation

Most countries: same requirements

applicable for carcinogens, mutagens and
repro-toxic substances = CMR legislation
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2. Mechanism

Cancer
= unrestrained cellular proliferation

For this different steps are necessary:

1. Initiation
2. Promotion
3. Progression
2. Mechanism

!Important!

Cancer development is a multistep process:

- For the growth of a cancer several factors must

work together

- Several influencing factors play an additional

large role if a cancer will develop: food, age,
hormones, …
2. Mechanism

• The begin of cancer generally needs many years

• Different carcinogens have different working

mechanism
3. Toxicology
Basic Toxicological Terms

Cancer =

• Chronic effect
– Occur some time after exposure
– Usually from repeated lower doses over many months / years
– Usually irreversible

• Stochastic - describes likelihood of an event taking place

– synonymous with random
– e.g. malignant disease such as cancer for which the probability of
an effect occurring is a function of dose without threshold
– Paracelsus: not 100 % applicable here (see next slide)
– Once it occurs consequence is independent of initiating dose
– Stochastic effects do not have a threshold dose
3. Toxicology
Paracelsus?

‘All substances are poisons, there is none which is not a poison. The right dose differentiates a poison and a

remedy.’

Paracelsus (1493-1541)

Response

Dose

Any chemical may be toxic if the dose is high enough

3. Toxicology
Problems linking cause and effect

• The effect may not occur at time of exposure

– By the time it occurs the person may not be working
with the substance (latency time)

• People vary in susceptibility (react differently)

– Variations may be due to age, gender, health status, ...

• Complications of combined effects

– Exposure to different substances
– Exposure to alcohol, tobacco or prescribed drugs (e.g.
synergistic effects asbestos and tobacco)

• Impact of life style

• Detailed toxicological information is

often not available for many substances
3. Toxicology
Problems linking cause and effect

Conclusion:

Association between certain cancers and a

profession difficult

Important that we can demonstrate that we

fulfilled our duty to prevent exposure to
carcinogens at work!
3. Toxicology
Exposure routes - end points

• Different exposure routes:

inhalation
ingestion
skin contact
• Different end points:
respiratory system
digestive system
skin
bones
blood
… 14
3. Toxicology
Causes of cancer

Estimation of % of cancer deaths due to several

factors (Doll en Peto, 1981)
Tabacco: 30% (range 25-40)
Food : 35% (range 10-70)
Infections:10% (range 1-7)
Alcohol: 3% (range 2-4)
Sexual behaviour: 7% (range1-13)
Profession: 4% (range 2-8)
Geographical factors: 3% (range 2-4)
Out door air pollution: 2% (range 1-5)
Medicine: 1% (range 0,5 -3)

Learns us that most of the cancers are avoidable when people have a healthy lifestyle
3. Toxicology
Work related cancers

• Lung membrane cancer (mesothelioom)

– Asbestos
• Cancer nose
– Tropical hardwood
• Leukaemia
– Benzene, ionizing radiation
• Bladder cancer
– Aniline industry – dyes

Mostly avoidable causes

4. Carcinogens - where to find information
• Legislation China takes IARC (see further) as a
basis

• Other sources to look at:

- J&J guidance list:
carcinogens following agencies like IARC, ACGIH, EU

Guidance list J&J

- MSDS:
Risk (R)-sentences (GHS: H-sentences)
see heading 15 of the MSDS
Reach-legislation (MSDS needs to be more extended on how exactly to
handle compounds in a safe way in different applications)
4. Carcinogens
Important R-sentences (between brackets: H-sentence GHS):
R 40 : Carcinogenetic impact have not been excluded (insufficient
proof or insufficiently examined) (H351)
R 45: Can cause cancer (H 350)
R 46: Can cause hereditary genetic damage (H340)
R 49: Can cause cancer due to inhalation (H350i)
R 60: May impair fertility (H360F)
R 61: May cause harm to the unborn child (H360D)
R 62: Possible risk of impaired fertility (H361f)
R 63: Possible risk of harm to the unborn child (H361d)
R 64: May cause harm to breastfed babies (H362)

GHS: pictogram will be used for e.g. carcinogens -

mutagens – repro-toxic substances

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4. Carcinogens
IARC - International Agency for Research on Cancer

IARC

• Since 1971
• 900 substances examined
• Extensive work: complete range of studies necessary e.g.:
- bacterial mutagenese e.g. Ames test
- study at molecular level (DNA)
- animal tests
etc..
4. Carcinogens
IARC - International Agency for Research on Cancer - http://www.iarc.fr/

1 Carcinogenic to humans Sufficient evidence

2A Probably carcinogenic tot humans Limited indication
2B Possibly carcinogenic to humans Insufficient indication in
lab situations
3 Not classifiable as to carcinogenicity to Limited indication in
humans animal surveys
4 Probably not carcinogenic to humans Indication for absence of
carcinogenicity

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4. Carcinogens
J&J products - see monograph

• Own toxicological department

• Estimation is reflected in monograph
(notation ‘carc’)
• Difficulty: not all compounds are tested
even extensively (e.g. intermediates)
4. Carcinogens

• Show list of carcinogens in use on your

site
5. Preventive measures

Objective:

Protect workers against risks specifically arising or likely to arise from

exposure to carcinogens at work

Basic principles:
1. Risk evaluation
2. Measures in certain hierarchical order
3. Medical surveillance
5. Preventive measures
• SUBSTITUTION by less hazardous compound

• Risk assessment of activities with carcinogens

= general RA with RBEAP-approach
= for class 1 carcinogens: additional detailed RA
(with e.g. what-if technique) - see example attached:

Example risk
assessment

• Limit quantity of carcinogens handled

• Limit # of persons to zone where carcinogens

are handled 24
5. Preventive measures
• Good design of work processes and engineering controls
to avoid or minimize the release of carcinogens
(work as closed as possible - avoid open handling)

• Removal of the carcinogens at the source - appropriate local

and general ventilation as needed

• Collective protection measures and/or, where exposure cannot

be avoided by other means, individual protection measures

• Good hygiene practices!

(in particular regular cleaning of floors, walls and other surfaces)

• All people need to be well informed and trained specifically to

work with carcinogens 25
5. Preventive measures
• Clearly trace / indicate zone where carcinogens are handled

• Make up emergency plan how to deal with emergencies likely

to result in abnormally high exposure of carcinogens

• Means for safe storage (e.g. keep carcinogens separated from flammables),
handling and transportation, using sealed and clearly and
visibly labeled containers

• Means for safe collection, storage and disposal of waste,

including use of sealed, clearly and visibly labeled containers

• People who work with carcinogens need to receive appropriate

medical checks (goal: early detection)
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6. What needs to be documented

• What persons handled what quantity of what carcinogen on

what day during what kind of activity (logbook)
• Activities and/or industrial processes carried out, including the
motivation why carcinogens are used
• Quantities of substances or preparations manufactured or used
which contain carcinogens
• Number of workers exposed
• Preventive measures taken
• Type of protective equipment used
• Nature and degree of exposure
• Cases of substitution

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