Basic Toxicology

Contents:
i. Introduction to Toxicology
ii. Toxicity Tests
iii. Dose-Response Relationship
iv. Types of Toxic Hazards
i. Introduction to Toxicology

Toxicology is defined as the study of chemical or physical agents which interact with biologic systems
to produce a response in the organisms. Toxicity is the relative ability of a substance to cause injury to
biologic tissue. Given the broad range of toxicities any substance might eventually invoke in an
organism, it is easy to understand the wisdom of Paracelsus (1493-1541) when he said, All substances
are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.

The dose determines if the effects of any substance are toxic, non-toxic, or beneficial. Dose is the
quantity of a substance to which an organism is exposed. In toxicological studies, the dose given to test
animals is expressed in terms of quantity administered:

• Per unit weight, usually expressed as milligrams of substance per kilogram of body weight (mg/kg).

• Per area of skin surface, also expressed as mg/kg.

• Per unit volume of air inhaled, usually expressed as parts of vapor or gas per million parts (ppm) of
air by volume. Solids would be expressed as milligrams of material per cubic meter of air (mg/m3).
Inhaled doses can also be expressed by time.

ii. Toxicity Tests

The design of any toxicity test incorporates selection of:

• A test organism, which can range from cellular material and selected strains of bacteria through higher
order plants and animals.

• The response or biological endpoint, which can range from subtle changes in physiology and behavior
to death.

• An exposure or test period.

• Dose or series of doses.

The objective is to select a test species that is a good model of humans, a response that is not subjective
and can be consistently determined, and a test period that is relatively short. Often tests must be
selected that yield indirect measurements or responses that supposedly correlate well with the response
of interest — for example, determining carcinogenic potential by measuring mutagenic potential.
iii. Dose-Response Relationship

A particular toxicity test exhibits a dose-response relationship when there is a consistent mathematical
relationship between the proportion of individuals responding and a given dose for a given exposure
period. For example, the number of mortalities increases as the dose of chemical given to a group of
organisms increases.

Measurement of Response
Different species of test organisms differ in how they respond to a specific chemical. In addition, there
are variations in response to a given dose within a group of test organisms of the same species.
Typically, this intraspecies variation follows a normal (Gaussian) distribution when the number of
organisms responding is plotted against the degree of response for a given dose.

Several basic relationships can be readily identified from the plots. A dose is often described as either a
lethal dose (LD) in a test where the response is mortality, or effective dose (ED) in a test where the
response is some other observable effect.

Constructing an ultimate dose-response curve enables the identification of doses which affect a given
percent of the exposed population, e.g., the LD50 is that dose which is lethal to 50 percent of the test
organisms.

Dose-Response Terms
The National Institute for Occupational Safety and Health (NIOSH) defines a number of dose-response
terms:

• Lethal dose fifty (LD50) calculated dose of a substance which is expected to cause the death of 50
percent of an entire defined experimental animal population.

• Lethal dose low (LDLo) The lowest dose of substance introduced by any route other than inhalation
which has been reported to have caused death in humans or animals.

• Toxic dose low (TDLo): The lowest dose of a substance introduced by any route other than inhalation,
over any given period of time, and reported to produce any toxic effect in humans or carcinogenic,
neoplastigenic, or teratogenic effects in animals or humans.

• Toxic concentration low (TCLo) The lowest concentration of a substance in air to which humans or
animals have been exposed for any given period of time that has produced any toxic effect in humans
or carcinogenic, neoplastigenic, or teratogenic effects in animals or humans.

• Lethal concentration low (LCLo): The lowest concentration of a substance in air which has been
reported to have caused death in humans or animals.

Use of Dose-Response Relationship

Comparing the LD50 of chemicals in animals gives a relative ranking of acute toxicity of each. For
example, DDT (LD50 for rats = 113 mg/kg) would be considered more toxic than ethyl alcohol (LD50
for rats = 1400 mg/kg). Using this LD50 (mg/kg) and multiplying by 70 kg (average mass of human)
gives a rough extrapolation to humans, assuming they are as sensitive as the species tested to the
substance tested. However, LD50 serves only as a rough estimate of one aspect of the toxic potential
of a substance.
TOXICITY RATING CHART (oral)
Toxicity Rating Oral Acute LD50 for Rats
Extremely 1 mg/kg or less (e.g., dioxin,
toxic butulin toxin)
1 to 50 mg/kg (e.g.,
Highly toxic
strychnine)
Moderately toxic 50 to 500 mg/kg (e.g., DDT)
0.5 to 5 gm/kg (e.g.,
Slightly toxic
morphine)
Practically 5 to 15 gm/kg (e.g., ethyl
nontoxic alcohol)

Shortcomings of Dose-Response Data

Several shortcomings must be recognized in utilizing LD50 dose-response data for assessing the
overall toxicity of a compound. One is that an LD50 is a single value and does not indicate the shape of
the curve — that is, what the dose-response interval is, which is as important as how high or low the
LD50 is. Thus, comparing these values can give the wrong impression.

Second, the LD50 measures only acute toxicity. The full range of toxicity testing includes subacute,
chronic, carcinogenic and reproductive toxicity, amongst others. Therefore, while useful, the LD50
must be used with considerable discretion and caution.

Routes of Exposure
There are three main pathways for substances to enter the body:

· Absorption (through contact with skin, and eyes)

· Inhalation
· Ingestion

The primary function of the skin is to act as a barrier against entry of foreign materials into the body. If
this protective barrier is overcome, toxic chemicals enter. The barrier is greatly diminished by
lacerations and abrasions. Also, many organic solvents greatly increase the permeability of the skin to
materials that would otherwise not pass through it. Another factor is that the skin provides a large
surface area for contact with toxic agents.

Inhalation is the most rapid route, immediately introducing toxic chemicals to respiratory tissues and
the bloodstream. Once admitted to the blood through the lungs, these chemicals are quickly transported
throughout the body.

Health hazards to personnel from ingestion of materials are a lesser concern than skin and respiratory
hazards. The number of substances that can be ingested are limited — that is, it is difficult to swallow
vapors and gases.

iv. Types of Toxic Hazards

Systemic Poisons - chemical agents which act on specific target organs or organ systems.

Asphyxiants — agents which deprive the tissues of oxygen, a condition called anoxia. This group is
divided into simple and chemical asphyxiants. The simple asphyxiants act by diluting or displacing
atmospheric oxygen, which lowers the concentration of oxygen in air.

Chemical asphyxiants act in one of two ways. Some prevent the uptake of oxygen in the blood. Carbon
monoxide, forexample, interferes with the transport of oxygen to the tissues by strongly binding with
hemoglobin to form carboxyhemoglobin, which leaves inadequate hemoglobin available for oxygen
transport.

A second type of chemical asphyxiant does not permit the normal oxygen transfer either from the blood
to the tissues or within the cell itself. Hydrogen cyanide is an example of this type.

Irritants — materials that cause inflammation of membranes. The mechanism of irritation is either by
corrosive or drying action, and may affect the eyes, skin, respiratory membranes, or gastrointestinal
tract. The irritant must come in direct contact with the tissue to cause an inflammation reaction.

Allergic Sensitizers — sensitization to a chemical involves immune mechanisms. When a foreign

substance called an antigen enters body tissue, it triggers production of antibodies, which react with the
antigen to make it innocuous. Upon first exposure to a specific chemical, there are no antibodies in the
body. After subsequent exposures, the concentration of antibodies increases until a threshold is reached.
At this point, the antibody level is high enough that upon exposure to the chemical the antigen-
antibody reaction, also called an allergic reaction, is severe enough to manifest itself as one or more
symptoms. The body has become “sensitized” to that chemical.

Carcinogens — a substance that is known or suspected to cause cancer in an organism . The

following characteristics apply to carcinogens:

• Chemical carcinogens have distinct mechanisms compared to other toxic agents. The biologic effect is
persistent, cumulative, and delayed, and repeated doses can be more effective than large doses.

• They are defined by their ability to induce neoplasms. An organism can respond to a carcinogen by:
1) an increase in the incidence of one or more types of tumors compared to controls; 2) development of
tumors not seen in controls; 3) the occurrence of tumors earlier than controls; and 4) an increase in the
number of tumors in individual animals compared to controls.

• Carcinogens are diverse chemical (and physical, e.g., ionizing radiation) agents such as organic
( benzene) and inorganic (arsenic compounds) chemicals, solid-state materials, and hormones. The
widely divergent properties of these chemicals appear to produce neoplasms by different mechanisms.

• Some react directly with DNA and as a result are mutagenic, others do not bind covalently to DNA,
but produce neoplasms after the reaction with DNA.

Reproductive Toxins (Mutagens, Teratogens) — chemicals which affect reproductive capabilities,

including chromosomal damage (mutations) and effects on fetuses teratogenesis). A mutagen changes a
gene in a sperm or egg cell of the parent. The parent is not affected, but the offspring suffer the
consequences. Teratogenesis is also manifested in offspring but differs from mutagenesis in that it
results from exposure of the embryo or fetus to the agent itself.

Most of the information we have about reproductive hazards comes from testing animals. Most known
human reproductive toxins have similar effects in laboratory animals. Therefore, we usually assume
that most agents which adversely affect reproduction in animals also have the potential to harm human
reproduction.

Summary
The field of toxicology is evolving at a rapid rate. Considerable strides both in terms of elucidating the
mechanism of toxicity, as well as the specific effects of individual chemicals are being made. However,
the vast majority of chemicals have had little, incomplete or inadequate testing done on them. Newer
tests are often of greater sensitivity, thereby indicating effects at levels previously thought safe.

The result of our increasing knowledge is increasing caution - we see that the more we know the more
we realize how little we know. The message for us is this— minimize all exposure by reducing time,
frequency and concentration of exposures, and substituting less toxic materials whenever possible.

The Basics of Back Pain and Spinal Anatomy

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Spinal anatomy is a remarkably intricate structure of strong bones, flexible ligaments and tendons,
extensive muscles and highly sensitive nerves and nerve roots. Without question, the composition and
function of the spine is a marvel of nature, providing us with a unique combination of:
• Structure to allow us to stand upright and move with precision
• Protection for the spinal cord and nerve roots to safely relay messages to and from the brain and
the rest of the body
• Shock absorption accept jolts and stress as we move about
• Flexibility, especially in the lower and upper spine, allowing us to bend and twist in a full
variety of movements
• Strength provided by the bones, discs, joints and supportive muscles and connective tissue
Once back pain starts, however, the many benefits of this intricate anatomical construct can quickly be
lost. Here are the basics of anatomical causes of spine pain:

Neck Pain
The cervical spine (neck) supports the weight of your head and protects the nerves that come from your
brain to the rest of the body. This section of the spine has seven vertebral bodies (bones) that get
smaller – and provide more rotation - as they get closer to the base of the skull.
Most episodes of acute neck pain are due to a muscle, ligament or tendon strain, which is usually
caused by a sudden force (e.g. whiplash) or from straining the neck (e.g. sleeping in the wrong
position). If you have neck pain that lasts longer than two weeks to three months, or with
predominantly arm pain, numbness or tingling, there is often a specific anatomic abnormality causing
the symptoms, such as a herniated disc, spinal stenosis, etc.
Upper Back Pain
The 12 vertebral bodies in the upper back that are attached to the rib cage make up the thoracic spine
(middle or upper back) are firmly attached to the rib cage at each level, providing a great deal of
stability and structural support, protecting the heart, lungs and other important organs within the chest.
Because there is little motion in the upper spine, it is rare to have pain caused by a herniated or
degenerated thoracic disc. More common causes of upper back pain include irritation of the large back
and shoulder muscles or joint dysfunction...
Lower Back Pain Because the lower back carries the most load with the least
structural support, it is the most likely to wear down or suffer injury.
Most episodes of lower back pain are caused by muscle strain. Even though this
doesn't sound like a serious injury, the pain can be severe. Strong abdominal
muscles and back muscles are important to provide support for this area of the
spine and avoid injury.
Motion in the lower back is divided between the five motion segments, with a
disproportionate amount of the motion in the lower segments (L4-L5 and L5-S1)
- the two segments most likely to be a source of pain from conditions such as
degenerative disc disease or a herniated disc. Frequently, a lower back problem
can cause sciatica, or pain that radiates down the sciatic nerve into the leg.
Pain at the bottom of the spine The iliac bones are part of the pelvis, and the sacrum is connected to
this part of the pelvis by the sacroiliac joints. Pain can occur in the sacroiliac joints (where the sacrum
connects to the pelvis), called sacroiliac joint dysfunction, and in the coccyx (tailbone), called
coccydynia. Both of these conditions are more common in women than men.

SYCHOLOGY QUICK FACTS

What is a Psychologist?

A psychologist studies how we think, feel and behave from a scientific viewpoint and applies this
knowledge to help people understand, explain and change their behaviour.

Where Do Psychologists Work?

Some psychologists work primarily as researchers and faculty at universities and at governmental and
non-governmental organizations. Others work primarily as practitioners in hospitals, schools, clinics,
correctional facilities, employee assistance programs and private offices. Many psychologists are active
in both research and practice.
What Do Psychologists Do?

Psychologists engage in research, practice and teaching across a wide range of topics having to do with
how people think, feel and behave. Their work can involve individuals, groups, families and as well as
larger organizations in government and industry. Some psychologists focus their research on animals
rather than people. Here are some of the kinds of topics towards which psychologists focus their
research and practice:
• mental health problems such as depression, anxiety, phobias, etc.;
• neurological, genetic, psychological and social determinants of behaviour;
• brain injury, degenerative brain diseases;
• the perception and management of pain;
• psychological factors and problems associated with physical conditions and disease (e.g.
diabetes, heart disease, stroke);
• psychological factors and management of terminal illnesses such as cancer;
• cognitive functions such as learning, memory, problem solving, intellectual ability and
performance;
• developmental and behavioural abilities and problems across the lifespan;
• criminal behaviour, crime prevention, services for victims and perpetrators of criminal activity;
• addictions and substance use and abuse (e.g. smoking, alcohol, drugs);
• stress, anger and other aspects of lifestyle management;
• court consultations addressing the impact and role of psychological and cognitive factors in
accidents and injury, parental capacity, and competence to manage one’s personal affairs;
• the application of psychological factors and issues to work such as motivation, leadership,
productivity, marketing, healthy workplaces, ergonomics;
• marital and family relationships and problems;
• psychological factors necessary to maintaining wellness and preventing disease;
• social and cultural behaviour and attitudes, the relationship between the individual and the many
groups of which he or she is part (e.g. work, family, society); and
• the role and impact of psychological factors on performance at work, recreation and sport.
For more information on psychology and specific diseases and conditions see Your Health: 'Psychology
Works' Fact Sheets; for more information on how to choose a psychologist and psychological treatment
see Deciding to See a Psychologist: How to Choose One and What to Expect.

The Study of Psychology

Psychology courses and majors are among the most popular undergraduate courses and are available at
all Canadian universities. If you want some career direction or advice about what in psychology to
study at the graduate or undergraduate level, you should contact the psychology department at the
university where you are currently studying or where you are considering studying. Not all university
psychology departments offer the same courses or engage in the same kinds of research – both are
factors that might influence your choices of where to study. Psychology departments usually have a
faculty member or other staff person who acts as a counsellor or advisor to help students with course
and programme selection.

At the graduate level, there are several specialities and subspecialities of psychology. Common ones are
Industrial-Organizational Psychology, Experimental Psychology, Clinical Psychology, Counselling
Psychology, Neuropsychology, Forensic or Correctional Psychology, Developmental or Child
Psychology.

The CPA maintains a Graduate Guide which lists and describes graduate programmes in psychology in
Canada.

It typically takes 4 years to complete an honours bachelor’s degree in psychology, 2 years to complete a
master’s degree and up to another 4 years to complete a doctoral degree. Doctoral degrees in any of the
professional areas of psychology (e.g. clinical psychology, counselling psychology clinical
neuropsychology) have practicum and internship requirements in addition to coursework and research
requirements.

Competition for admission to graduate programmes in psychology can be stiff. Doctoral programmes in
professional areas of psychology (e.g. clinical psychology, counselling psychology, school psychology)
accept approximately 10% of applicants.

What are the Training and Credentials Psychologists Need to Practice Psychology?

To practice psychology in Canada, one must be licensed. Alternate terms for licensure are registered
and chartered. When considering the services of any professional, it is always wise to seek the services
of someone who is licensed. Licensure helps to protect the public by ensuring that the professional has
met, and is accountable to, rigorous standards of practice.

In Canada, psychologists, like other health care professionals, are licensed to practice by regulatory
bodies in each Canadian jurisdiction. A listing of all the Canadian regulatory bodies of psychology can
be accessed from the CPA Web site.

The requirements for licensure vary from jurisdiction to jurisdiction. In some jurisdictions, the
doctorate degree is required for registration and in others it is the master’s degree. Psychologists with a
doctoral degree can use the title ‘Dr. ’. A listing of all the provincial and territorial regulatory
requirements can be found on the CPA Web site.

For psychologists already registered in one Canadian jurisdiction wanting to practice in another
jurisdiction, their mobility might be facilitated by the Mutual Recognition Agreement.

For those trained in psychology outside of Canada, and who want to move to a Canadian jurisdiction to
practice psychology, they should contact the regulatory body in the jurisdiction in which they want to
practice to determine if they have the necessary qualifications for registration.

For those wanting to study psychology outside of Canada, and then return to work as a psychologist in
Canada, they should also contact the regulatory body in the jurisdiction to which they are likely to
return, to ensure that the foreign studies they are planning to undertake would give them the necessary
credentials for registration to practice psychology in Canada.

Accreditation

Whereas individual practitioners of psychology are licensed, programmes in psychology can be

accredited.
It is the doctoral or internship programme (not its students) that must voluntarily apply for and undergo
accreditation. A student can claim to have graduated from an accredited programme, if the programme
was accredited at the time of the student’s graduation.

Accreditation is a voluntary process but allows doctoral and internship programmes to demonstrate that
they have met a community standard of training.

Although, graduation from an accredited doctoral programme is not a requirement for registration as a
psychologist and not always a requirement of employers, it can be an advantage. Applicants for
registration or licensure who have graduated from accredited programmes often receive ‘fast-track’
credential reviews by regulatory bodies. Further, accredited programmes are encouraged to hire faculty
and staff who themselves have graduated from accredited programmes.

The CPA accredits doctoral programmes and internships in professional areas of psychology. A listing
of all CPA-accredited programmes can be found on our Web site.

The CPA’s Accreditation Standards and Procedures for Doctoral and Internship Programmes in
Psychology is available in pdf format from the CPA Web site.

Bound copies of the Standards and Procedures are also available from the Accreditation Office.

Organizations and Associations of Psychology - Who's Who and What's What?

The Canadian Psychological Association is a national professional association whose mandate is to

meet the needs of Canadian psychologists and to advocate for the science and practice of psychology in
Canada.

Each province and territory also has a psychological association with similar mandates within their own
jurisdictions. In addition, the provincial and territorial associations often maintain referral services and
can help members of the public access psychological services.

The Canadian Register of Health Service Providers in Psychology maintains a listing of psychologists
who have voluntarily submitted their credentials for evaluation as a health service provider.