Irwin Screen
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In the fields of
toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating ex ...
and
pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...
, the Irwin screen is utilised to determine whether the subject(s) show adverse effects from a course of
pharmaceutical Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
treatment or
environmental pollution ''Environmental Pollution'' is a peer-reviewed academic journal covering the biological, health, and ecological effects of environmental pollution. It was established in 1980 as two parts: ''Environmental Pollution Series A: Ecological and Biologi ...
. It is an observational
methodology In its most common sense, methodology is the study of research methods. However, the term can also refer to the methods themselves or to the philosophical discussion of associated background assumptions. A method is a structured procedure for bri ...
.


History

Mice were first used systematically to determine a
drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
's
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
side effects In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...
by S. Irwin in 1962 and then again in 1968. Its use in the
pharmaceutical industry The pharmaceutical industry is a medical industry that discovers, develops, produces, and markets pharmaceutical goods such as medications and medical devices. Medications are then administered to (or self-administered by) patients for curing ...
has become ingrained since then, as below. The
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
issued in 1975 a position paper on the "Principles for Evaluating Chemicals in the Environment." This paper influenced government and academic circles, and was adopted by e.g. Brimblecombe for his study of
atmospheric An atmosphere () is a layer of gases that envelop an astronomical object, held in place by the gravity of the object. A planet retains an atmosphere when the gravity is great and the temperature of the atmosphere is low. A stellar atmosphere ...
arsenic Arsenic is a chemical element; it has Symbol (chemistry), symbol As and atomic number 33. It is a metalloid and one of the pnictogens, and therefore shares many properties with its group 15 neighbors phosphorus and antimony. Arsenic is not ...
levels. The critical review in 1982 by Mitchell and Tilson, caused the US EPA to develop guidelines for several behavioural tests including a test series based on the Irwin Screen, named the Functional Observational Battery (FOB) by Sette in 1989. In 1998, the FOB was published in the late 1990s as EPA Human Health 870 Series Test Guidelines, and in praxis the Irwin screen and the FOB "overlap and to some extent are interchangeable." The American batteries were harmonised with the
OECD The Organisation for Economic Co-operation and Development (OECD; , OCDE) is an international organization, intergovernmental organization with 38 member countries, founded in 1961 to stimulate economic progress and international trade, wor ...
's from the same era. Similar tests on food chemicals were recommended by the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
in their Red Book. Behavioural test batteries are now required for new drugs by the S7A group of the
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an initiative that brings together regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of p ...
(ICH).


Interchangeability with FOB

The Irwin screen was as of 2010 in the pharmaceutical industry almost exclusively used with
lab mice The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory animal sources for these mice are usually of the species ''Mus musculus''. They a ...
, whereas the FOB, or some modification thereof, was used with lab rats and other nonrodent species, such as
rabbits Rabbits are small mammals in the family Leporidae (which also includes the hares), which is in the order Lagomorpha (which also includes pikas). They are familiar throughout the world as a small herbivore, a prey animal, a domesticated form ...
,
dogs The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the gray wolf. Also called the domestic dog, it was selectively bred from a population of wolves during the Late Pleistocene by hunter-gatherers ...
,
guinea pigs The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy ( ), is a species of rodent belonging to the genus ''Cavia'', family Caviidae. Breeders tend to use the name "cavy" for the animal, but "gui ...
and nonhuman primates.


Sample checklist

A sample Irwin screen includes overt behavior observations and autonomic observations: Overt Behavior * increased activity * decreased activity *
sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...
*
tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...
*
convulsions A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...
** myoclonic ** tonic/clonic * straub tail *
stereotypy A stereotypy (, ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are foun ...
* increased exploration * decreased exploration *
ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
*
weakness Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...
*
catalepsy Catalepsy (from Ancient Greek , , "seizing, grasping") is a neurological condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and symptoms Sympt ...
* pain threshold (tail pinch) * loss of
righting reflex The righting reflex, also known as the labyrinthine righting reflex, or the Cervico-collic reflex; is a reflex that corrects the orientation of the body when it is taken out of its normal upright position. It is initiated by the vestibular system, ...
* writhing (i.p. administration) Autonomic Observations *
piloerection Goose bumps, goosebumps or goose pimples are the bumps on a person's skin at the base of body hairs which may involuntarily develop when a person is tickled, cold or experiencing strong emotions such as fear, euphoria or sexual arousal. The f ...
*
diarrhoea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
*
exophthalmos Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
*
salivation Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DN ...
*
vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...
*
vasodilatation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel ...
*
cyanosis Cyanosis is the change of Tissue (biology), tissue color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Cyanosis is apparent usually in the Tissue (bi ...
* lacrymation * ptosis *
miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...
*
mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...
*
hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...


References

{{reflist Toxicology Environmental toxicology Pathology Pharmacology Neurology Laboratory mice Clinical research Pharmaceuticals policy Drug safety Life sciences industry