The document defines terminology used in OECD guidelines for non-clinical health and environmental safety studies. It discusses terms related to good laboratory practice, test facilities, studies, test items, toxicity studies including acute toxicity and repeated dose 28-day toxicity, prenatal developmental toxicity studies, toxicokinetics, and the mammalian erythrocyte micronucleus test. The terms are defined concisely with the context of OECD guidelines and standards for conducting non-clinical studies.

1. Terminologies In OECD
Guidelines
Anas Saifi
M.Pharm (Pharmacology) 2nd Sem.
School of Pharmaceutical Education And Research
Jamia Hamdard 1

2. Presentation Outline
• Good Laboratory Practice
• Terms Concerning the Organisation of a Test Facility
• Terms Concerning the Non-Clinical Health and Environmental Safety Study
• Terms Concerning the Test Item
• Terms Concerning the Acute Toxicity
• Terms Concerning Repeated Dose 28-Day Toxicity Study
• Terms Concerning Prenatal developmental toxicity study
• Terms Concerning Toxicokinetics
• Terms Concerning Mammalian Erythrocyte Micronucleus Test
• Reference
2

3. Good Laboratory Practice
Good Laboratory Practice (GLP) is a quality system concerned with the
organizational process and the conditions under which non-clinical health
and environmental safety studies are planned, performed, monitored,
recorded, archived and reported.
3

4. Terms Concerning the Organisation of a Test
Facility
• Test facility means the persons, premises and operational unit(s) that are
necessary for conducting the non-clinical health and environmental safety
study.
• Test site means the location at which a phase of a study is conducted.
• Sponsor means an entity which commissions, supports and/or submits a
non-clinical health and environmental safety study.
• Study Director means the individual responsible for the overall conduct of
the nonclinical health and environmental safety study.
4

5. Terms Concerning the Organisation of a Test
Facility
• Principal Investigator means an individual who acts on behalf of the Study
Director and has defined responsibility for delegated phases of the study.
• Quality Assurance Programme: means a defined system, including
personnel, independent of study conduct and is designed to assure test
facility management of compliance with these Principles of Good
Laboratory Practice.
• Standard Operating Procedures (SOPs) means documented procedures
which describe how to perform tests or activities normally not specified in
detail in study plans or test Guidelines.
• Master schedule means a compilation of information to assist in the
assessment of workload and for the tracking of studies at a test facility.
5

6. Terms Concerning the Non-Clinical Health and
Environmental Safety Study
• Short-term study means a study of short duration with widely used,
routine techniques.
• Study plan means a document which defines the objectives and
experimental design for the conduct of the study, and includes any
amendments.
• Study plan amendment means an intended change to the study plan after
the study initiation date.
• Test system means any biological, chemical or physical system or a
combination thereof used in a study.
• Specimen means any material derived from a test system for examination,
analysis, or retention.
6

7. Terms Concerning the Non-Clinical Health and
Environmental Safety Study
• Raw data means all original test facility records and documentation, or
verified copies, which are the result of the original observations and
activities in a study.
• For e.g.
• photographs,
• microfilm or microfiche copies,
• computer readable media,
• dictated observations,
• recorded data from automated instruments
7

8. Terms Concerning the Test Item
• Test item means an article that is the subject of a study.
• UVCBs: substance of unknown or variable composition, complex reaction
products or biological materials
• Reference item (“control item”) means any article used to provide a basis
for comparison with the test item.
8

9. Terms Concerning the Test Item
• Batch means a specific quantity or lot of a test item or reference item
produced during a defined cycle of manufacture in such a way that it could
be expected to be of a uniform character and should be designated as
such.
• Vehicle means any agent which serves as a carrier used to mix, disperse, or
solubilize the test item or reference item to facilitate the
administration/application to the test system.
9

10. Terms Concerning the Acute Toxicity
• Acute toxicity is the adverse effect caused by a test chemical following a
single uninterrupted exposure over a short period of time (24 h or less)
• Dose is the amount of test chemical administered. Dose is expressed as
weight of test chemical per unit weight of test animal (e.g., mg/kg bw).
• GHS: Globally Harmonised Classification System for Chemical Substances
and Mixtures
• Impending death is when moribund state or death is expected prior to the
next planned time of observation.
10

11. Terms Concerning the Acute Toxicity
• LD50 (median lethal dose) is a statistically derived single dose, that can be
expected to cause death in 50 percent of animals when administered by
the given route of exposure.
• Limit test refers to a dose at an upper limitation on testing.
• Moribund status is being in a state of dying or inability to survive, even if
treated.
• Predictable death: presence of clinical signs indicative of death at a known
time in the future before the planned end of the experiment.
11

12. Terms Concerning Repeated Dose 28-Day
Toxicity Study
• Dose is the amount of test substance administered. The dose is expressed
as weight of test substance per unit body weight of test animal per day.
• Dosage is a general term comprising of dose, its frequency and the
duration of dosing
• Evident toxicity is a general term describing clear signs of toxicity following
administration of test substance.
• NOAEL is the abbreviation for no-observed-adverse-effect level. This is the
highest dose level where no adverse treatment-related findings are
observed due to treatment.
12

13. Terms Concerning Repeated Dose 28-Day
Toxicity Study
• Satellite group scheduled for follow-up observations should be kept for at least
14 days without treatment to detect delayed occurrence, or persistence of, or
recovery from toxic effects.
• Oestrogenicity is the capability of a chemical to act like a natural oestrogenic
hormone (e.g. oestradiol 17ß) in a mammalian organism.
• Androgenicity is the capability of a chemical to act like a natural androgenic
hormone (e.g. testosterone) in a mammalian organism.
• Thyroid activity is the capability of a chemical to act like a natural thyroid
hormone (e.g. T3) in a mammalian organism.
• Antioestrogenicity is the capability of a chemical to suppress the action of a
natural oestrogenic hormone (e.g. oestradiol 17ß) in a mammalian organism.
13

14. Terms Concerning Repeated Dose 28-Day
Toxicity Study
• Antiandrogenicity is the capability of a chemical to suppress the action of a
natural androgenic hormone (e.g. testosterone) in a mammalian organism.
• Antithyroid activity is the capability of a chemical to suppress the action of
a natural thyroid hormone (e.g. T3) in a mammalian organism.
• Validation is a scientific process designed to characterise the operational
requirements and limitations of a test method and to demonstrate its
reliability and relevance for a particular purpose.
• Cumulative toxicity is the adverse effects of repeated doses occurring as a
result of prolonged action on, or increased concentration of the
administered substance or its metabolites in, susceptible tissues.
14

15. Terms Concerning Prenatal developmental
toxicity study
• Developmental toxicology: formerly often referred to as teratology,
• the study of adverse effects on the developing organism that may result from
exposure prior to conception, during prenatal development, or postnatally to
the time of sexual maturation.
• The major manifestations of developmental toxicity include
a) death of the organism,
b) structural abnormality,
c) altered growth,
d) functional deficiency.
• Teratogens: defined as any chemical, drug, infection or factor that interferes with
normal embryonic development.
15

16. Terms Concerning Prenatal developmental
toxicity study
• Adverse effect: any treatment-related alteration from baseline that
diminishes an organism’s ability to survive, reproduce or adapt to the
environment.
• Variation/Minor Abnormality: Structural change considered to have little
or no detrimental effect on the animal.
• Conceptus: the sum of derivatives of a fertilised ovum at any stage of
development from fertilization until birth including the extra-embryonic
membranes as well as the embryo or fetus.
• Implantation (nidation): attachment of the blastocyst to the epithelial
lining of the uterus, including its penetration through the uterine
epithelium, and its embedding in the endometrium.
16

17. Terms Concerning Prenatal developmental
toxicity study
• Embryo: the early or developing stage of any organism, especially the
developing product of fertilisation of an egg after the long axis appears and
until all major structures are present.
• Fetus: the unborn offspring in the post-embryonic period.
• Resorption: a conceptus which, having implanted in the uterus,
subsequently died and is being, or hasbeen resorbed:
• Early resorption: evidence of implantation without recognisable
embryo/fetus.
• Late resorption: dead embryo or fetus with external degenerative changes.
17

18. Terms Concerning Toxicokinetics
• Toxicokinetic: Study of the absorption, distribution, metabolism, and
excretion of substances over time.
• Absorption: Process(es) of uptake of substances into or across tissues.
Absorption refers to parent compound and all its metabolites.
• Biotransformation (metabolism): (Usually enzymatic) chemical conversion
of a substance of interest into a different chemical within the body.
• Distribution: Dispersal of a substance and its derivatives throughout an
organism.
• Excretion: Process(es) by which an administered substance and/or its
metabolites are removed from the body.
• Accumulation: Increase of the amount of a substance over time within
tissues.
18

19. Terms Concerning Toxicokinetics
• Extrapolation: Inference of one or more unknown values on the basis of
that which is known or has been observed.
• Target tissue: Tissue in which a principal adverse effect of a toxicant is
manifested.
• Tissue distribution: Reversible movement of a substance from one location
in the body to another.
• Validation of models: Process of assessing the adequacy of a model to
consistently describe the available toxicokinetic data.
19

20. Terms Concerning Mammalian Erythrocyte
Micronucleus Test
• The mammalian in vivo micronucleus test is used for the detection of
damage induced by the test substance to the chromosomes or the mitotic
apparatus of erythroblasts, by analysis of erythrocytes as sampled in bone
marrow and/or peripheral blood cells of animals, usually rodents.
• Micronuclei: Small nuclei, separate from and additional to the main nuclei
of cells, produced during telophase of mitosis (meiosis) by lagging
chromosome fragments or whole chromosomes.
• Reticulocyte: A newly formed erythrocyte stained with a vital stain that
causes residual cellular RNA to clump into a characteristic reticulum.
Reticulocytes and polychromatic erythrocytes have a similar cellular age
distribution
20

21. References
• OECD PRINCIPLES OF GOOD LABORATORY PRACTICE Part 1 Published In 1992
Revised In 1997.
• OECD (2017), Test No. 402: Acute Dermal Toxicity, OECD Guidelines for the Testing
of Chemicals, Section 4, OECD Publishing,
Paris, https://doi.org/10.1787/9789264070585-en.
• OECD (2008), Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents,
OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing,
Paris, https://doi.org/10.1787/9789264070684-en.
• OECD (1981), Test No. 410: Repeated Dose Dermal Toxicity: 21/28-day Study,
OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing,
Paris, https://doi.org/10.1787/9789264070745-en
21

22. References
• OECD (2018), Test No. 414: Prenatal Developmental Toxicity Study, OECD
Guidelines for the Testing of Chemicals, Section 4, OECD Publishing,
Paris, https://doi.org/10.1787/9789264070820-en.
• OECD (2010), Test No. 417: Toxicokinetics, OECD Guidelines for the Testing of
Chemicals, Section 4, OECD Publishing,
Paris, https://doi.org/10.1787/9789264070882-en
• OECD (2016), Test No. 474: Mammalian Erythrocyte Micronucleus Test, OECD
Guidelines for the Testing of Chemicals, Section 4, OECD Publishing,
Paris, https://doi.org/10.1787/9789264264762-en
22