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

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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

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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

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