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Industrial
Pharmaceutical
University
Clinical
Forensic
Eco-toxicologist
Regulatory
Occupational
Careers in Toxicology
www.thebts.org
For anup-to-dateguide to coursesand relatedsubjects in the UK,please visit theBritish ToxicologySociety web-siteat www.thebts.org
Careers in Toxicology
What is Toxicology?In today’s world, many thousands of chemicals that are used within our environment have been
developed for our benefit. Unfortunately, some may have harmful effects on living systems.
Toxicology is the study of how these harmful effects may occur - in humans, other animals,
plants and the environment - and how they can be avoided or minimised. It combines a wide
variety of scientific disciplines which include general subjects such as biology and chemistry, and
more specific areas such as pharmacology, physiology, molecular biology, immunology, pathology,
epidemiology - and, of course, statistics.
Toxicology plays a vital part in many aspects of our lives. It can help to ensure that the food we
eat and the water we drink are clean and free from contaminants, that the air we breathe is
pollutant-free, and that the drugs we take to treat disease are as safe as possible.
Toxicology also has a central role in protecting the environment from the harmful effects of
chemicals and other noxious agents - for example, the damage to vegetation caused by acid rain,
or the problems of increased exposure to ultra-violet radiation caused by changes in the earth’s
atmosphere.
Toxicology is a dynamic subject which is expanding and adapting as society changes and new
demands have to be met. It offers tremendous mental stimulation and is becoming increasingly
important in determining our quality of life and that of future generations.
As with most sciences, pure or applied, toxicology can be viewed as an attempt to solve a
detective puzzle set by nature. In addition to offering a satisfying intellectual challenge,
toxicology also has the advantage of making a very tangible social contribution in terms of
increased public safety by either identifying toxic chemicals, or enabling safer ones to be
developed.
Toxicology is
the study of how
harmful effects
may occur - in
humans, other
animals, plants and
the environment -
and how they can
be avoided or
minimised
Toxicologists monitor the impact of a toxic material
on human health and are concerned with the impact
of such materials on the health and status of
the environment
How do I become a toxicologist?Toxicology may be studied at both undergraduate and postgraduate level. For example, those
students who have passed A or A/S levels in science subjects, or have passed their BTEC or an
appropriate HNC, can enter directly into several degree courses in which toxicology is taught in
combination with other subjects such as biochemistry or pharmacology.
For those students with a
relevant degree, such as
chemistry, biochemistry,
pharmacology, pharmacy,
medicine, veterinary
medicine or environmental
sciences, there are a number of full or part-time postgraduate courses in which toxicology is
taught as a single subject, or combined with a second discipline such as forensic science or
analytical chemistry. This type of course often leads to the qualification of MSc. Toxicology also
forms a large component of degree courses in occupational hygiene, at both undergraduate and
postgraduate level, and in the postgraduate training of occupational health workers.
Once qualified, these graduates may study for a higher degree (PhD or MPhil) by performing
research in toxicology in a suitable university science department (e.g. pharmacology,
biochemistry or molecular toxicology).
Alternatively, they can gain experience in toxicology by working in a research laboratory, or
perhaps in regulatory services at industrial or government research establishments.
After several years’ relevant experience, they can gain an
advanced qualification in toxicology, such as the Diploma of
the Institute of Biology in Toxicology, Diploma of the American
Board of Toxicology or the Diploma in Toxicology from the
Royal College of Pathologists.
Those students seeking qualifications in environmental
toxicology or ecotoxicology will receive a general training in
subjects such as biology, ecology, environmental science or atmospheric science, which will
contain elements of toxicology, often disguised as pollution studies. However, for those who seek
specialist training in environmental or ecotoxicology, diplomas in subjects such as pollution
science, pesticide science or waste management are also now available.
But remember - whichever route you choose to follow, once you have qualified, then becoming a
Member of the British Toxicology Society is not only an excellent way of keeping ‘up-to-date’ in
toxicology, but also of obtaining important information on further training and qualification
requirements - and career opportunities.
For an up-to-date guide to courses and related subjectsin the UK, please visit the British Toxicology Societyweb-site at www.thebts.org
Industrial ToxicologistThe industrial toxicologist plays a vital role in developing effective, and
safe, products such as pharmaceuticals, petrochemicals, pesticides,
cosmetics, food and drink, household products - and even radioactive
materials for medical diagnosis.
With the current emphasis by manufacturers and government alike on
protecting production workers, consumers and the environment, all new
products and their constituents must be carefully checked for any toxic
potential. Of course, any production process can also be inadvertently
contaminated with toxic materials, so toxicologists must be employed to test
products during - and after - their manufacture. How extensively any product
is tested will depend on factors such as its intended use, how much is used,
and for how long. For example, a new drug will be tested much more
intensely than a component of a highly specialised alloy.
Career opportunities for industrial toxicologists occur in
a wide range of companies, although exactly how many -
and with which skills - are employed will depend largely
on the company’s size and their range of products. For
example, a large company might employ several
specialising in topics such as genetics and reproductive
toxicology, pathology, clinical biochemistry,
toxicokinetics, occupational hygiene, ecotoxicology or
clinical toxicology. Often, an industrial toxicologist will work closely with
regulatory authorities to ensure that a company’s products and production
processes conform to local, national and international regulations.
On the other hand, a small company might employ only one industrial
toxicologist, but he or she would probably be more of a ‘generalist’.
Toxicologists are also employed by contract research laboratories, which
perform toxicity studies for other companies, large and small. These
laboratories conduct studies in a wide range of specialities and consequently
offer numerous different careers in toxicology.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
Toxicologists and drug developmentAny newly-prepared material, whether an industrial chemical, a drug, or a household product,
must - for safety’s sake - be considered to have a toxic potential until proven otherwise. But
since ‘toxicity’ is a very broad-based concept and can appear in many guises, how does a
toxicologist investigate a ‘toxicological profile’?
An ideal example is that of a new drug, because before it can be used to
treat a disease, its safety must be proved in a series of in vivo and in vitro
laboratory tests. To some extent, the nature of these tests is governed by the
information required by regulatory authorities such as the Department of
Health in the United Kingdom, or the Food and Drug Administration (FDA) in
the USA. These authorities will then give the final permission for a new drug
to be used, after the preliminary results have been obtained and the risk to humans exposed to
the drug has been carefully assessed.
In order to assess such risk for a new drug accurately, the toxicologist must be able to understand
and evaluate data in several ways:
Knowing the toxicity of similar drugs may eliminate or at least reduce the need for tests on the
new drug; in vivo and in vitro tests may quickly indicate whether the new drug causes skin and/
or eye irritation, or is mutagenic.
It is important to take into account the drug’s pharmacological action, which in exaggerated
form may cause its toxicity. For this reason, it’s particularly important to understand sex- and
species-related differences in pharmacology.
Since toxicity may be due to the effects of either the parent drug or its metabolite(s), it is also
important to appreciate species differences in drug metabolism and disposition - and
particularly how these relate to man.
A new drug may adversely affect the body’s organs after either single or
multiple dosing; these may appear as changes in clinical condition, altered
blood drug levels and/or organ function. For example, liver damage may
cause raised serum enzyme levels, kidney damage may affect the urine’s
constituents, and cardiovascular disturbances may cause changes in blood
cell parameters. Such changes in function may, or may not, be
accompanied by structural changes that are visible by eye, or through the
microscope.
Any changes which are not immediately understood may represent a potential hazard to man,
and must be investigated more closely. Carefully selected biochemical, immunological,
molecular biological or specialised microscopic techniques may help to assess any immediate
hazard.
Where a drug is intended for long-term therapy, it is important to assess its carcinogenic
potential, initially by using short-term in vitro assays that detect direct DNA damage. True
carcinogenic potential, however, can only be reliably assessed by long-term exposure of animals.
When - and only when - this plethora of experimental data has been collected, the toxicologist
can make a full assessment of the new drug’s toxicity - and balance its potential benefits against
any inherent risk that may occur during treatment.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
University ToxicologistThe academic toxicologist’s work is characterised not only by its variety, but also by the
excitement and stimulation that it can provide. Much of his or her time is spent in lecturing
and practical instruction, where there’s a lively, friendly and satisfying working environment.
Each academic year a new challenge begins - with a year-end reward as the students qualify.
As well as the teaching the academic toxicologist spends a lot of time in the laboratory.
Increasingly, this research is conducted in collaboration with industry, although UK Research
Councils and independent charities fund much work. Many research programmes - such as
investigating the biochemical mechanisms by which a toxic agent exerts its damaging effect - are
fundamental in nature and utilise a number of increasingly complex techniques and disciplines
such as:
Computer-assisted systems can link the structure-activity
relationship of a toxic material with the pathological changes
seen in affected tissues.
Gene-array technologies that can provide vast amounts of
information on the expression of many thousands of genes in
response to a toxic chemical/drug.
Techniques in recombinant DNA and cell biology, and the use
of transgenic models have helped enormously in the
understanding of toxicology - and will continue to do so.
By publishing data, improved communications among
toxicologists allows rapid and effective progress in the design of
new materials, such as selective pesticides, or medicines for safe,
effective therapy against disease.
Of course, management ability is important too. Toxicology is a practical
subject that needs a well-developed, well-organised and well-equipped
laboratory - plus a capable research team. In fact, it’s possible to develop a
‘centre of excellence’ in toxicological research which will provide the
opportunity to interact with other scientists, perhaps at international
meetings. There are also increasing links between academia, industry and
government. Today, these institutions often work hand-in-hand, so that data
obtained within academia can complement the often more applied findings of
industry, helping to protect man and the environment. Many academic
toxicologists also serve on Government advisory committees where they
provide an independent, expert source of advice on the safety of chemicals.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
Clinical ToxicologistTypically, the clinical toxicologist is a medically-qualified graduate, who has specialist
knowledge of the adverse effects of drugs and other chemicals in humans - and especially
how to treat poisoning by such materials. Most clinical toxicologists work in hospitals, and
have close links with university clinical pharmacology departments.
At any one time, the clinical toxicologist may be responsible for solving a variety of problems:
Treating patients who have been poisoned with a drug or other material either accidentally or
intentionally.
Providing (via a poisons information service) advice to colleagues on the management of
poisoned patients.
Interpreting and applying the results of analyses performed in poisoned patients.
Collating and assessing data on the adverse effects of prescribed drugs.
Training in, and teaching of, toxicology at both undergraduate and postgraduate levels.
Nowadays, the clinical toxicologist is
also increasingly invited to advise on
the environmental issues and
occupational hazards associated
with new chemicals. To do this well
requires a comprehensive clinical
training, since there may often be an
alternative, clinically-based, rather
than toxicologically-based
explanation for an unusual symptom presented
or for some abnormal results obtained from a
clinical investigation. Because this can cause confusion,
the clinical toxicologist may often become involved in
the medico-legal aspects of toxicology.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
Forensic ToxicologistThe forensic toxicologist deals mainly with medico-legal aspects of drugs and poisons, his or
her main responsibilities being to establish and explain the circumstances of legal cases where
drugs or other chemicals are implicated. These can range from simple ‘drink driving’ cases
to fatal accident, suicide and murder investigations where deliberate or accidental
poisoning is suspected.
Since the forensic toxicologist may need to demonstrate evidence of drug
intake, he or she must be able to isolate, identify and quantify toxic
substances in biological materials. This involves using modern analytical
procedures, from immunoassays to identify groups of drugs to sophisticated
chromatographic and spectrometric assays to measure very small amounts of
drugs - often in very small biological samples.
Often, he or she may be called by the Courts as an ‘expert witness’ to identify
a drug, to say how much was found, when the drug entered the body, and by which route. They
may also be asked whether measured drug levels could account for a clinical condition, or
whether the drug was taken as a therapeutic dose, or as an accidental or intentional overdose.
In order to do this, the forensic toxicologist must be able
to assess the significance of analytical data, to identify
relationships between drug levels and clinical response,
and to recognise how the drug’s metabolism can affect
its concentrations and pharmacological effect. But
factors such as drug interactions, tolerance, age-related
effects and inter-individual differences, which might also
affect drug response, must also be taken into account.
Clearly, with so many different types of legal case,
forensic toxicology can provide an ideal scientific
challenge, with career opportunities in the Home Office
Forensic Science Service, private
forensic laboratories and in hospital
departments of forensic medicine.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
EcotoxicologistEcotoxicology - which studies the toxic effects of chemicals on the environment - is a science
that has emerged only recently. Although the ecotoxicologist studies the immediate effect on
individual organisms, his or her ultimate interest is the effect on populations, and on
ecosystems.
In this respect, sub-lethal effects, such as changes in behaviour or in reproductive efficiency,
may be much more important than any lethal effect. Typically, the ecotoxicologist will be
concerned with aspects such as:
Tracing the movement of pollutants through terrestrial and aquatic food chains.
Following the metabolism and bioaccumulation of these pollutants in food chains.
Identifying population changes after exposure to pollutants; particularly genetic changes, such
as the development of resistance to pesticides in insects.
Monitoring the physiological and biochemical responses of organisms to pollutant exposure,
which may reflect a toxic effect.
Undertaking detailed ecological and toxicological studies of invertebrates and fish in polluted
rivers and estuaries.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
Although the ecotoxicologist’s
main task is to develop models
which can be used to predict the
fate and effects of chemicals
within an ecosystem, it may take
many years to achieve results.
This is because ecosystems are
extremely complex - there are
very often major variations in the
way that the different species
respond to pollutants.
Often, to produce successful ecotoxicological research, there must be a very close co-
operation between those ecologists working ‘in the field’, often on behalf of organisations
whose aim is to protect the environment, and those in the laboratory who may have the latest
techniques of biochemical toxicology and chemistry at their disposal.
Regulatory ToxicologistEach day, the regulatory toxicologist - who generally will work for the government - may face
a battery of questions relating to hazards within the environment, to which the public and
politicians alike will expect clear, and certainly informative, answers
An example would be:
Do the toxicological data provided by a company on a new product satisfy the legal
requirements such that a product license or other marketing authority can be issued?
Are there as yet unrecognised behavioural effects in factory workers exposed to solvents -
and can they somehow be measured in order to set safe exposure limits?
What action can be taken when food is deliberately contaminated with mercury or cyanide -
especially without knowing when or where the next episode of ‘tampering’ will occur?
What standards of testing should be adopted for chemicals which have been used for many
years, but were first used before toxicology and toxicity testing were fully developed?
Unfortunately, in many cases, the regulatory toxicologist may not
initially be provided with sufficient information to assess such
hazards, and so to provide a solution for a problem must rely on his or
her knowledge of different toxicological mechanisms - and how these
can be applied to different species, including man.
Often, however, it may be insufficient to make a straightforward
assessment of a hazard, and the regulatory toxicologist will be
required to predict the degree of risk to the general public in a given
situation. So this is where a little diplomacy is useful
in order to communicate effectively with - and to
help educate - the public, because one individual’s
idea of risk may be very different from another’s!
Of course, applying toxicological science to such a
wide variety of problems is rather more than a matter
of careful judgement - it also forms the basis of a
fascinating and varied career.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
Occupational ToxicologistMost of the chemicals that we use routinely - such as drugs, veterinary products, cosmetics,
food and food additives, pesticides and household products - can be called ‘industrial
chemicals’ at some point in their manufacture, use and disposal.
The occupational toxicologist is concerned with both the
potential toxicity of such materials, and with the toxicity of
products which contain them and, ultimately, of any waste
formed from them. In fact, the occupational toxicologist spends
most of his or her time assessing the effects of such chemicals on
human health, on ensuring safe working conditions for the
people producing them, or advising people on how they can be
safely handled.
Occasionally, the occupational toxicologist might be asked to
advise on how to treat patients after they have been accidentally
exposed to a chemical, or what precautions should be taken if
the chemical has been accidentally released into the
environment. This advice would be based on previous experience in dealing with such a situation,
perhaps in combination with that from laboratory studies in which animals were exposed to the
chemical in question.
Often, government regulations concerning the use of a new chemical will require specific
information on how it may affect a person’s health. So the toxicologist will be asked to evaluate
existing toxicological data - and may also need to organise new studies to obtain the necessary
evidence.
Although the occupational
toxicologist may be involved with a
very wide range of industrial
chemicals, it is impossible for him or
her to be an expert on them all, so
they will often concentrate on the
regulatory and toxicity requirements
of just one type. However, it is very
important that they can recognise the
potential dangers of simultaneous
exposure to more than one
type of chemical.
Industrial
Pharmaceutical
University
Clinical
Forensic
Ecotoxicologist
Regulatory
Occupational
The British Toxicology SocietySpeciality Groups
The following sub-groups are just examples of some of the areas the British Toxicology
Society (BTS) members have organised into sub-speciality areas. The grouping of these fields
enables greater in-depth discussions between ‘like-minded’ toxicologists and facilitates the
arrangement of meetings focussed to that particular field of toxicology. Speciality Sections are
endorsed by the BTS Executive upon demonstration of adequate interest amongst the
membership.
NeurotoxicologyAmongst the several target organ-defined sub-disciplines within toxicology, neurotoxicology is
one of the most specialised. This is because the techniques needed both to detect and also to
understand neurotoxicology are very specific. Many neurotoxic chemicals disrupt function but are
not cytotoxic, so standard tests for cytotoxicity only tell half of the story. Nearly all neurotoxic
chemicals are very selective, and damage just one or two specific components of the nervous
system such as peripheral cholinergic synapses or brain myelin. This means that it is easy to miss
neurotoxicity unless one looks carefully. The reasons for this selectivity are mostly unknown, and a
better understanding of selectivity is a major goal for neurotoxicologists.
The nervous system is a very important target, since even minor damage can alter quality of life
and earning potential. Someone with a 90% functioning kidney or liver can live a perfectly normal
life, but a 90% functioning brain may limit its owner severely. The adult brain has very little
capacity for repair. A final complication is that subtle impairments of nervous system function
may be caused by poor upbringing or education, alcohol abuse, or many other social factors in
addition to neurotoxicity. This means that adverse effects in the human population can be very
difficult to investigate, and to attribute to particular causes. The other major challenge to
neurotoxicologists is to develop better and more specific diagnostic tools to recognise
neurotoxicity when it does happen, and to distinguish it from the normal background level of
human stupidity.
Most neurotoxicologists have a training in general neuroscience, with neurochemistry
predominating, but some understanding of all of neuroscience (neuro-anatomy, physiology and
psychology) is vital. Then comes basic toxicology, since the nervous system is still subject to the
fundamentals of dose-response, pharmacokinetics, exposure assessments, strain and species
variability, and all the other factors important for every kind of toxicology.
Employment is usually in relation to pharmaceuticals (many either target the nervous system or
produce neurotoxic side-effect) or pesticides (most of which are designed to attack the nervous
system), but most large organisations with toxicologists need someone who understands
neurotoxicology. The brain expresses a greater proportion of the genome than any other organ,
so if you are not daunted by a major challenge, neurotoxicology is the career for you.
ImmunotoxicologyImmunotoxicology describes the study of the adverse health effects that may
result from the interaction of chemicals with the immune system. Two broad
areas of interest can be identified: immunotoxicity and allergy. The former is
defined as xenobiotic-induced perturbations to one or more components to
the immune system such as to cause altered or suppressed immune function
associated with compromised host resistance to infectious and/or malignant
disease. In contrast, allergy is best defined as the adverse effects that may
result from the stimulation of a specific immune response.
The challenges for immunotoxicologists are to define at the cellular and
molecular levels the mechanisms through which chemicals may interact with the immune system
such as to impair normal immunological function, and to characterise the conditions under which
allergic sensitization is induced and allergic reactions provoked. A clearer understanding of the
interactions of xenobiotics with the immune system will provide the foundations for the
development and application of improved methods for the identification of immunotoxicants and
allergens and for defining their potential risk to human health.
Safety PharmacologyThere are three main types of pharmacology studies carried out in pharmaceutical research and
development. Primary pharmacodynamic studies are concerned with identifying the desired
properties of a substance, which will be responsible for its therapeutic action in the clinic.
Secondary pharmacodynamic studies (sometimes known as general pharmacology) are concerned
with the mode of action and/or effects of a substance, which are not directly related to its
therapeutic application. Safety pharmacology studies are carried out to identify the potential
undesirable pharmacodynamic effects of a substance on physiological functions. A key difference
between safety pharmacology and toxicology studies is that the former concentrate on the
effects of a substance on physiological function, whereas the latter tend to concentrate on
effects on structure. There are of course areas of overlap between safety pharmacology and
toxicology, and one does not replace the other – they are complementary disciplines in non-
clinical safety assessment.
Data from safety pharmacology studies are used for several purposes in the research and
development process. When the studies are carried out sufficiently early they can be a useful
candidate selection tool, allowing the identification of potential problems with a compound
before the formal development process begins. Since the studies give information on the effects
of a substance on physiological function, they provide useful information to the clinicians who
will conduct early studies in humans, indicating to them the sorts of effects they might see. As
well as providing important safety data that will help protect humans from the adverse effects of
a substance, safety pharmacology studies are required as part of a regulatory submission for a
product license. An indication of the increasing status of safety pharmacology in the drug
development process is its adoption as
an ICH topic (International Conference
on Harmonisation – an attempt to get
global approval on which tests to
undertake at what stage in the drug
development process).
Occupational ToxicologyThe Occupational Toxicology Speciality Section is a forum for toxicologists who are particularly
concerned with the hazards and risks to health of chemicals encountered in a working situation.
Toxicologists within several of the categories described earlier - “occupational”, “industrial”,
“university” and “regulatory” toxicologists - might or will be involved in the occupational arena.
The section also brings in those from other disciplines whose work interacts with toxicology in the
occupational context, such as occupational hygiene, epidemiology, occupational medicine and
biological monitoring. Both short-term (including accidents) and long-term exposure situations
are relevant and all aspects of toxicology are of potential interest. The inhalation and dermal
exposure routes are particular concerns and site-of-contact effects to the skin, eyes and
respiratory tract are as frequent an issue as the consequences of systemic absorption and
distribution. The occupational environment has distinctive features in terms of the characteristics
of those exposed, the nature and pattern of their exposure and the historical progression of the
surrounding culture and regulatory framework.
Toxicology of biotechnology productsThe development of recombinant DNA, large-scale cell culture technologies, and
advances in synthetic DNA and protein chemistry has introduced a wide range of
potential pharmaceutical products including cytokines, hormones, growth factors,
monoclonal antibodies and gene therapy products. Recombinant DNA technology is
also impacting on food and agriculture. Fifteen years after the initial creation of
transgenic plants, the first commercial products are now arriving at the market place.
The complex structural and biological characteristics of biotech products, dictate different
approaches to their non-clinical safety evaluation. Knowledge gained from non-clinical and
clinical evaluation of some of the early biotech products has demonstrated that toxicological
evaluation of these products requires a case-by-case and mechanistic-based approach.
The safety evaluation of genetically modified crops departs significantly from conventional
toxicology. For many reasons, conventional toxicology studies on the whole food are unlikely to
give rise to meaningful data. The evaluation of GM crops therefore starts from a position of
comparing that crop with its conventional counterpart which, on the basis of long term usage,
has traditionally been accepted as safe. Subsequent studies are then determined, on a case by
case basis, once both intended and unintended secondary effects of the genetic modification have
been identified and characterised. In practice, this often means that there needs to be an
evaluation of the potential health effects due to new protein(s) expressed in the crop. In addition
to this, the safety evaluation also demands a thorough characterisation of the molecular events
leading to the production of the GM crops.
For anup-to-date
guide to coursesand related
subjects in theUK, please visit
the BritishToxicology Society
web-site atwww.thebts.org
Designed by Visual Communications Glaxo Wellcome on behalf of the British Toxicology Society printed by Hensal Press Ltd