ASTM E2045-22
(Practice)Standard Practice for Detailed Clinical Observations of Test Animals
Standard Practice for Detailed Clinical Observations of Test Animals
SIGNIFICANCE AND USE
3.1 This practice pertains to all forms of toxicological testing (acute, subchronic, or chronic) performed by any route of administration (inhalation, oral, dermal, ocular, or other).
3.2 The U.S. Environmental Protection Agency, Good Laboratory Practices for Nonclinical Laboratory Studies, as listed in 40 CFR, requires that a testing facility maintain specific standard operating procedures (SOPs) including an SOP covering clinical observations in test animals.
3.3 This practice serves as a basis for consistency in clinical observations and is not meant to serve as a comprehensive list of observations that may be observed. Actual procedures and forms to be used in recording observations must be described in individual study protocols.
SCOPE
1.1 This practice describes the terms used in observing and recording cutaneous, gastrointestinal, respiratory, reproductive, neuromuscular, ocular, and general clinical signs of animals undergoing toxicological testing. This practice also assists in properly observing and assessing laboratory animals for signs of disease or adverse effects of compound administration.
1.2 This practice includes codes and descriptions for a wide variety of clinical signs, anatomical locations, and other descriptive qualifiers, and a technique for scoring the extent or severity of clinical signs.
1.3 This practice assumes that the reader is knowledgeable in animal toxicology and related pertinent areas and is trained in making clinical observations.
1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.
1.5 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
General Information
- Status
- Published
- Publication Date
- 31-Jul-2022
- Technical Committee
- E50 - Environmental Assessment, Risk Management and Corrective Action
- Drafting Committee
- E50.47 - Biological Effects and Environmental Fate
Overview
ASTM E2045-22: Standard Practice for Detailed Clinical Observations of Test Animals provides a systematic approach for observing, recording, and assessing clinical signs in animals undergoing toxicological testing. This standard is issued by ASTM International and is applicable to acute, subchronic, or chronic toxicological studies conducted by various routes of administration, including inhalation, oral, dermal, and ocular exposure. ASTM E2045-22 supports consistency and reliability in test animal health assessments, aligning with regulatory requirements such as those mandated by the U.S. Environmental Protection Agency (EPA) and Good Laboratory Practices (GLP) outlined in 40 CFR.
Key Topics
Clinical Observation Methodology
- Outlines procedures for systematic clinical observation of laboratory animals, capturing both general and specific clinical signs across cutaneous, gastrointestinal, respiratory, neuromuscular, reproductive, and ocular systems.
- Emphasizes the importance of both distant and close-up observations, evaluating animal behavior, environment, physical condition, and physiological processes.
Data Standardization and Scoring
- Provides a comprehensive terminology, clinical signs codes, descriptive qualifiers, and a technique for severity scoring of observed clinical signs.
- Includes tables for coding clinical signs (e.g., alopecia, edema, hemorrhage), extent and severity scales, and anatomical location codes to ensure standardized data entry and reporting.
Regulatory and Protocol Alignment
- Facilitates compliance with EPA Good Laboratory Practices for Nonclinical Laboratory Studies (40 CFR 160, 792, 798), which require standard operating procedures for clinical observations.
- Reinforces that while the standard guides consistent practices, specific study protocols must detail actual procedures and recording forms to be used.
Quality Assurance
- Specifies adherence to GLP principles and quality assurance processes to ensure the reliability of data from toxicological studies.
Applications
ASTM E2045-22 is essential for organizations conducting toxicological testing on laboratory animals in the pharmaceutical, chemical, agrochemical, and biotechnological sectors. Its adoption provides several practical benefits:
- Facilitates regulatory compliance with national and international requirements for nonclinical study conduct.
- Ensures objective and consistent data collection, improving inter-study comparability and interpretation of toxicological findings.
- Supports early identification of adverse reactions, allowing for timely intervention in animal care and improved welfare.
- Enables accurate reporting and documentation for submission to regulatory agencies, audits, and scientific publications.
- Serves as a training tool for personnel in the proper recognition and description of clinical signs in test animals.
Related Standards
- EPA Good Laboratory Practice Standards (40 CFR Part 160, 792, 798) - Federal requirements for laboratory studies in the United States.
- OECD Principles of Good Laboratory Practice - International guidelines for conducting nonclinical safety testing.
- ASTM E2626 - Practice for the Evaluation of the Effect of Chemical Substances on Reproduction and Fertility in Test Animals.
- OECD Test Guidelines for Toxicity Studies - Widely recognized methodologies for chemical safety assessment.
Conclusion
Adopting ASTM E2045-22 enhances the quality, reliability, and regulatory acceptability of toxicological testing in animals. By promoting standardized clinical observation and reporting practices, this standard underpins both animal welfare and the integrity of scientific data in laboratory research settings. For professionals in toxicology and laboratory animal science, compliance with ASTM E2045-22 is vital for meeting both ethical and legal obligations in nonclinical safety assessment.
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Frequently Asked Questions
ASTM E2045-22 is a standard published by ASTM International. Its full title is "Standard Practice for Detailed Clinical Observations of Test Animals". This standard covers: SIGNIFICANCE AND USE 3.1 This practice pertains to all forms of toxicological testing (acute, subchronic, or chronic) performed by any route of administration (inhalation, oral, dermal, ocular, or other). 3.2 The U.S. Environmental Protection Agency, Good Laboratory Practices for Nonclinical Laboratory Studies, as listed in 40 CFR, requires that a testing facility maintain specific standard operating procedures (SOPs) including an SOP covering clinical observations in test animals. 3.3 This practice serves as a basis for consistency in clinical observations and is not meant to serve as a comprehensive list of observations that may be observed. Actual procedures and forms to be used in recording observations must be described in individual study protocols. SCOPE 1.1 This practice describes the terms used in observing and recording cutaneous, gastrointestinal, respiratory, reproductive, neuromuscular, ocular, and general clinical signs of animals undergoing toxicological testing. This practice also assists in properly observing and assessing laboratory animals for signs of disease or adverse effects of compound administration. 1.2 This practice includes codes and descriptions for a wide variety of clinical signs, anatomical locations, and other descriptive qualifiers, and a technique for scoring the extent or severity of clinical signs. 1.3 This practice assumes that the reader is knowledgeable in animal toxicology and related pertinent areas and is trained in making clinical observations. 1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.5 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
SIGNIFICANCE AND USE 3.1 This practice pertains to all forms of toxicological testing (acute, subchronic, or chronic) performed by any route of administration (inhalation, oral, dermal, ocular, or other). 3.2 The U.S. Environmental Protection Agency, Good Laboratory Practices for Nonclinical Laboratory Studies, as listed in 40 CFR, requires that a testing facility maintain specific standard operating procedures (SOPs) including an SOP covering clinical observations in test animals. 3.3 This practice serves as a basis for consistency in clinical observations and is not meant to serve as a comprehensive list of observations that may be observed. Actual procedures and forms to be used in recording observations must be described in individual study protocols. SCOPE 1.1 This practice describes the terms used in observing and recording cutaneous, gastrointestinal, respiratory, reproductive, neuromuscular, ocular, and general clinical signs of animals undergoing toxicological testing. This practice also assists in properly observing and assessing laboratory animals for signs of disease or adverse effects of compound administration. 1.2 This practice includes codes and descriptions for a wide variety of clinical signs, anatomical locations, and other descriptive qualifiers, and a technique for scoring the extent or severity of clinical signs. 1.3 This practice assumes that the reader is knowledgeable in animal toxicology and related pertinent areas and is trained in making clinical observations. 1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.5 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
ASTM E2045-22 is classified under the following ICS (International Classification for Standards) categories: 11.220 - Veterinary medicine. The ICS classification helps identify the subject area and facilitates finding related standards.
ASTM E2045-22 is available in PDF format for immediate download after purchase. The document can be added to your cart and obtained through the secure checkout process. Digital delivery ensures instant access to the complete standard document.
Standards Content (Sample)
This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: E2045 − 22
Standard Practice for
Detailed Clinical Observations of Test Animals
This standard is issued under the fixed designation E2045; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope Title 40, Code of Federal Regulations (CFR), Environmental
Protection Agency, Part 798, Health Effects Testing
1.1 This practice describes the terms used in observing and
Guidelines
recordingcutaneous,gastrointestinal,respiratory,reproductive,
neuromuscular, ocular, and general clinical signs of animals
3. Significance and Use
undergoing toxicological testing. This practice also assists in
properly observing and assessing laboratory animals for signs
3.1 This practice pertains to all forms of toxicological
of disease or adverse effects of compound administration.
testing (acute, subchronic, or chronic) performed by any route
of administration (inhalation, oral, dermal, ocular, or other).
1.2 This practice includes codes and descriptions for a wide
variety of clinical signs, anatomical locations, and other
3.2 The U.S. Environmental Protection Agency, Good
descriptive qualifiers, and a technique for scoring the extent or
Laboratory Practices for Nonclinical Laboratory Studies, as
severity of clinical signs.
listed in 40 CFR, requires that a testing facility maintain
specific standard operating procedures (SOPs) including an
1.3 This practice assumes that the reader is knowledgeable
SOP covering clinical observations in test animals.
in animal toxicology and related pertinent areas and is trained
in making clinical observations.
3.3 This practice serves as a basis for consistency in clinical
1.4 This standard does not purport to address all of the
observations and is not meant to serve as a comprehensive list
safety concerns, if any, associated with its use. It is the
of observations that may be observed. Actual procedures and
responsibility of the user of this standard to establish appro-
forms to be used in recording observations must be described
priate safety, health, and environmental practices and deter-
in individual study protocols.
mine the applicability of regulatory limitations prior to use.
1.5 This international standard was developed in accor-
4. Procedure
dance with internationally recognized principles on standard-
4.1 Observe the health of an animal at a distance and of its
ization established in the Decision on Principles for the
housing environment to gain a general impression of its health.
Development of International Standards, Guides and Recom-
Alsonoteenvironmentalfactorssuchastemperature,humidity,
mendations issued by the World Trade Organization Technical
ventilation, air quality and hygienic conditions.
Barriers to Trade (TBT) Committee.
4.2 Observe each animal and note any subtle changes in
2. Referenced Documents
animal behavior, physical appearance, posture, gait,
vocalization, food and water consumption, and waste produc-
2.1 Federal Standards:
tion. See Section 5 for details.
Title 40, Code of Federal Regulations (CFR), Environmental
Protection Agency, Subchapter E, Pesticide Programs,
4.3 Observe animals blinded to treatment group, or at least
Part 160, Good Laboratory Practice Standards
in random order, to minimize unintentional bias.
Title 40, Code of Federal Regulations (CFR), Toxic Sub-
4.4 Note any dead animals and collect necessary tissues and
stances Control Act, Part 792, Good Laboratory Practice
data to minimize the extent of tissue decomposition.
Standards
4.5 Report animals that show signs of sickness so that
appropriate diagnosis, treatment, or euthanasia, if appropriate,
This practice is under the jurisdiction of ASTM Committee E50 on Environ- can be performed.
mental Assessment, Risk Management and Corrective Action and is the direct
responsibility of E50.47 on Biological Effects and Environmental Fate.
5. General Clinical Signs
Current edition approved Aug. 1, 2022. Published September 2022. Originally
approved in 1999. Last previous edition approved in 2009 as E2045 – 99(2014).
5.1 Note the overall activity, behavior, and condition of the
DOI: 10.1520/E2045-22.
animal. Determine the hydration status by examining skin
Available from U.S. Government Printing Office, Superintendent of
Documents, Washington, DC 20402. turgor, position of the eyes such as normal or sunken, mucous
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
E2045 − 22
membrane color, and capillary refill time. Look for asymmetry 6.1.2 Haircoat condition (HC) may be described as: oily
or the presence of abnormal swellings, hemorrhage or signs of (HCO); rough (HCR); wet (HCW); soiled (HCS); dry (D);
pain. bloody (HEH); or piloerection (HCP), that is, distinctly raised
fur, excluding the vibrissae, giving a bristled or porcupine-like
5.2 The following are some general conditions along with
appearance.
suggested codes for record keeping that do not fall into any
6.1.3 Swelling (SW) is an increase in tissue size or in-
specific organ system. Refer to Annex A1 – Annex A3 for a
creased abnormal shape of the skin or other organs from
detailed listing of the codes and their descriptions. Other
3,4,5
abnormal presence of: air, that is, emphysema (SWA); fluid or
general reference material will also be helpful.
water, that is, edema (SWE); solid tissue or tumor (SWT);
5.2.1 Activity may be described as: decreased (ACD);
blood, that is, hematoma (SWH); pus, that is, abscess (SWB).
increased (ACI); hyperexcitable (HX); hyperactive (HYP);
6.1.4 Skin condition (SK) may be described as: thickened
lethargic (LE); irritable (IRR); moribund (MB), that is near
(SKT); thinned (SKH); scaly (SKS); dry (SKD); or red (SKY)
death; prostate (PRO), that is, exhibiting inability or unwill-
(see 6.1.5).
ingness to maintain upright posture.
6.1.5 Erythema (ERY) is an increased pink or red color on
5.2.2 Body condition may be described as: obese (OBS);
smooth skin.
thin (THN); decreased rectal temperature (BTD); increased
6.1.6 Rash (RAS) is small red, pink or white dots or
rectal temperature (BTI); hypothermia that is cold to touch
pustules on the skin; petechiae (PET) are red dots formed from
(HPO); hyperthermia that is warm to touch (HPR).
blood.
5.2.3 Death may be described as: accidental death (AD);
6.1.7 Blisters (BLS) are fluid-filled vesicles. The fluid is
euthanized (ETH); found dead (FD).
usually clear, but can be pink (blood-tinged) or red/brown
5.2.4 Examineskinfordehydration(DHY).Theskinshould
(filled with blood). White-filled vesicles are either pustules
fallbackintoplaceimmediatelyafteritispulledoutofposition
(RAS) (< 5 mm) or abscesses (SW) (> 5 mm).
or tented; if the skin is pulled out of position and tends to stick
6.1.8 Color change (CC) may be other than pink or red, for
together or slowly fall back into place, the animal may be
example, bluish-black as in brushing, green as in bruising or
dehydrated. Other signs of dehydration include sunken eyeball
severe infection, brown as in increased pigmentation, or white
(SUN), pale or dry mucous membranes (MM), and a capillary
as in blanching.
refill time of >3 s (CR4). Distinguish between dehydration and
6.1.9 Abrasions (ABR) are denuded skin or mucous mem-
various types of shock.
5.2.5 Generalized edema (EDE) may appear as swelling of brane.
the limbs, lower abdomen, head or under the mandible. When 6.1.10 Lacerations(LCN)arecutsintheskinfrommechani-
the apparently fluid-filled tissue is pressed, an indentation may cal injury, that is, bite, scratch, foreign object, and so forth.
persist for a short time. 6.1.11 Ulceration (ULC) is an open sore accompanied by
5.2.6 Evidence of hemorrhage (HE) may appear on the
the disintegration of tissue, usually with necrosis, that is, death
haircoat (HEH) or underlying skin or nails (HES), in urine of tissue.
(HEU) or feces (HEF), from the mouth (HEM), nose or
6.1.12 Scab (SCB) is an eschar formed from sloughed skin.
epistaxis (EPI), eyes (HEO), ears (HEE), genitalia (HEG), or
6.1.13 Pruritis (PRU) is itching evidenced by scratching,
anus (HEA).
with or without a rash or abrasion.
5.2.7 Jaundice (JAU) is an overall slight yellow to pale
6.1.14 Urticaria (URT) is a transient appearance of smooth,
orange tinge to the skin and mucous membranes.
slightly elevated bumps which are redder or paler than the
5.2.8 Mucous membrane condition (MM) is noted by the
surrounding skin and often accompanied by severe itching.
color and condition of the mucous membranes of the eye, nose,
Uricaria often appears as localized, discrete or confluent areas
mouth, or external genitalia.
of edema.
5.2.9 Swelling (SW) is noted by the size, location and
6.1.15 Purpura (PUR) is confluent petechiae, that is, pin-
probable cause, such as edema (SWE) from: a solid tissue or
point hemorrhages, which form ecchymoses, that is, blotchy
tumor (SWT); blood (SWH); air (SWA); or pus (SWB).
hemorrhages over any part of the body.
6.1.16 Common manifestations of dermal sensitivity reac-
6. Specific Clinical Signs
tions are:
6.1 Inspect the entire haircoat and underlying skin for 6.1.16.1 Contact dermatitis (COD) is pruritis, erythema and
vesiculation that may be followed by pustulation and necrosis
integumentary signs. Some common clinical signs and their
suggested codes are as follows: and that has a pattern consistent with the touch of a foreign
6.1.1 Alopecia, that is, hair loss (ALO), includes hair object or substance.
thinning, patchy/focal hair loss or balding. 6.1.16.2 Exanthema (EXA) is macular or papular redness in
discrete areas.
6.1.16.3 Exfoliation (EXF) is loss of superficial skin layers
with redness, swelling, and presence of free blood.
Taylor, E.J., ed., Dorland’s Illustrated Medical Dictionary, W.B. Saunders,
Philadelphia, PA, 27th edition, 1988.
6.1.16.4 Bullous eruption (BUL) is the presence of discrete
Stedman’s Medical Dictionary, Williams and Wilkins, Baltimore, MD, 25th
serous or seropustular areas.
edition, 1990 .
6.1.16.5 Erythema multiform (EMF) is the presence of
Thomas, C.L., ed., Tabor’s Cyclopedic Medical Dictionary, F. A. Davis Co.,
Philadelphia, PA, 17th edition, 1993. multiple types of macules, papules and nodules.
E2045 − 22
6.2 Gastrointestinal signs are observed during external 6.4.1.1 For external genitalia, look for the presence (TSB),
evaluations of the gastrointestinal system conducted from the absence (TSA or TSC), and condition of the testicles (TSE,
oral cavity to the anal area. Visually inspect the teeth and TED, or TSN); paraphimosis (PM), that is, inability to retract
mucousmembranesoftheoralcavity,palpatetheabdomenand penis into foreskin, or abnormal discharge from the penis.
inspect the perianal area. An inspection of the animal’s cage 6.4.1.2 Penile discharge is either none (PDA), normal
will allow evaluation of the volume, color, and consistency of (PDN), increased (PDI), bloody (PDB), serous (PDS), or
the stool. mucous (PDM).
6.2.1 Oral cavity signs and codes are: 6.4.2 Female examinations include:
6.2.1.1 Salivation may be described as: increased salivation 6.4.2.1 In external genitalia look for mucous membrane
(SAL); or lack of salvia, that is, xerostomia (XER). abnormalities (MM) or swellings (SW) of the vagina (VA) or
6.2.1.2 Dentition (TE) includes: missing teeth (TEM); loose vulva (VA).
teeth (TEL); discolored teeth (TEC); damaged teeth (TED); or 6.4.2.2 In vaginal discharge types or consistency of dis-
malocculation (TEO). charge are: none (VDN), normal (VDN), increased (VDI),
6.2.1.3 For mucous membranes, note capillary refill time decreased (VDD), bloody (VDB), serus (VDS), or mucous
(CR), color, and condition, such as erosions or vesicles. (VDM).
6.2.1.4 Gums may be described as: healthy, intact (GUH); 6.4.3 For urine or urination note the following conditions:
or gingivitis (GUI), that is, inflamed or bleeding gums. 6.4.3.1 Hematuria (HEU) is bloody urine. Use caution with
6.2.2 For the abdomen, look at the overall symmetry and rabbitsastheirurinemayrangefromambertolightredwithout
size. The abdomen may be described as: smaller or more the presence of blood.
“tucked-in” (STA) if the animal is dehydrated; larger as 6.4.3.2 Anuria (ANU) is the absence of urine for a pro-
distended or pendulous abdomen (OPA); or asymmetrical as if longed period.
an enlargement or swelling in a focal area (SW). 6.4.3.3 Dysuria (DYU) is difficulty urinating; be sure to
6.2.3 In the perianal area, look for: abnormal anal sphincter differentiate with tenesmus.
(OEA);fecal(FEF)orurinestaining(PEU);matterhair(PEH); 6.4.3.4 Polyuria (PLY) is excessive volume of urine.
mucous (PEM); or rectal prolapse (RPR), that is, a red to dark
6.4.4 Fertility signs include the following:
red tubular protrusion from the anus. 6.4.4.1 Breeding efficiency may be failure to breed (FTB),
6.2.4 For feces, note: consistency, s
...
This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: E2045 − 99 (Reapproved 2014) E2045 − 22
Standard Practice for
Detailed Clinical Observations of Test Animals
This standard is issued under the fixed designation E2045; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope
1.1 This practice describes the terms used in observing and recording cutaneous, gastrointestinal, respiratory, reproductive,
neuromuscular, ocular, and general clinical signs of animals undergoing toxicological testing. This practice also assists in properly
observing and assessing laboratory animals for signs of disease or adverse effects of compound administration.
1.2 This practice includes codes and descriptions for a wide variety of clinical signs, anatomical locations, and other descriptive
qualifiers, and a technique for scoring the extent or severity of clinical signs.
1.3 This practice assumes that the reader is knowledgeable in animal toxicology and related pertinent areas and is trained in
making clinical observations.
1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility
of the user of this standard to establish appropriate safety safety, health, and healthenvironmental practices and determine the
applicability of regulatory limitations prior to use.
1.5 This international standard was developed in accordance with internationally recognized principles on standardization
established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued
by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
2. Referenced Documents
2.1 Federal Standards:
Title 40, Code of Federal Regulations (CFR), Environmental Protection Agency, Subchapter E, Pesticide Programs, Part 160,
Good Laboratory Practice Standards
Title 40, Code of Federal Regulations (CFR), Toxic Substances Control Act, Part 792, Good Laboratory Practice Standards
Title 40, Code of Federal Regulations (CFR), Environmental Protection Agency, Part 798, Health Effects Testing Guidelines
3. Significance and Use
3.1 This practice pertains to all forms of toxicological testing (acute, subchronic, or chronic) performed by any route of
administration (inhalation, oral, dermal, ocular, or other).
3.2 The U.S. Environmental Protection Agency, Good Laboratory Practices for Nonclinical Laboratory Studies, as listed in 40
CFR, requires that a testing facility maintain specific standard operating procedures (SOPs) including an SOP covering clinical
observations in test animals.
This practice is under the jurisdiction of ASTM Committee E50 on Environmental Assessment, Risk Management and Corrective Action and is the direct responsibility
of E50.47 on Biological Effects and Environmental Fate.
Current edition approved Oct. 1, 2014Aug. 1, 2022. Published December 2014September 2022. Originally approved in 1999. Last previous edition approved in 2009 as
E2045 – 99(2009).(2014). DOI: 10.1520/E2045-99R14.10.1520/E2045-22.
Available from U.S. Government Printing Office, Superintendent of Documents, Washington, DC 20402.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
E2045 − 22
3.3 This practice serves as a basis for consistency in clinical observations. observations and is not meant to serve as a
comprehensive list of observations that may be observed. Actual procedures and forms to be used in recording observations must
be described in individual study protocols.
4. Procedure
4.1 Observe the health of an animal at a distance and of its housing environment to gain a general impression of its health. Also
note environmental factors such as temperature, humidity, ventilation, air quality and hygienic conditions.
4.2 Observe each animal and note any subtle changes in animal behavior, physical appearance, posture, gait, vocalization, food
and water consumption, and waste production. See Section 5 for details.
4.3 Observe control animals first, followed by test groups in order of increasing level of treatment. Observe positive control group,
if any, last.animals blinded to treatment group, or at least in random order, to minimize unintentional bias.
4.4 Note any dead animals and collect necessary tissues and data before decomposition occurs.to minimize the extent of tissue
decomposition.
4.5 Report animals that show signs of sickness so that appropriate diagnosis, treatment, or euthanasia, if appropriate, can be
performed.
5. General Clinical Signs
5.1 Note the overall activity, behavior, and condition of the animal. Determine the hydration status by examining skin turgor,
position of the eyes such as normal or sunken, mucous membrane color, and capillary refill time. Look for asymmetry or the
presence of abnormal swellings, hemorrhage or signs of pain.
5.2 The following are some general conditions along with suggested codes for record keeping that do not fall into any specific
organ system. Refer to Annex A1 – Annex A3 for a detailed listing of the codes and their descriptions. Other general reference
3,4,5
material will also be helpful.
5.2.1 Activity may be described as: decreased (ACD); increased (ACI); hyperexcitable (HX); hyperactive (HYP); lethargic (LE);
irritable (IRR); moribund (MB), that is near death; prostate (PRO), that is, exhibiting inability or unwillingness to maintain upright
posture.
5.2.2 Body condition may be described as: obese (OBS); thin (THN); decreased rectal temperature (BTD); increased rectal
temperature (BTI); hypothermia that is cold to touch (HPO); hyperthermia that is warm to touch (HPR).
5.2.3 Death may be described as: accidental death (AD); euthanized (ETH); found dead (FD).
5.2.4 Examine skin for dehydration (DHY). The skin should fall back into place immediately after it is pulled out of position;
position or tented; if the skin is pulled out of position and tends to stick together or slowly fall back into place, the animal may
be dehydrated. Other signs of dehydration include sunken eyeball (SUN), pale or dry mucous membranes (MM), and a capillary
refill time of >3 s (CR4). Distinguish between dehydration and various types of shock.
5.2.5 Generalized edema (EDE) may appear as swelling of the limbs, lower abdomen, head or under the mandible. When the
apparently fluid-filled tissue is pressed, an indentation may persist for a short time.
5.2.6 Evidence of hemorrhage (HE) may appear on the haircoat (HEH) or underlying skin or nails (HES), in urine (HEU) or feces
(HEF), from the mouth (HEM), nose or epistaxis (EPI), eyes (HEO), ears (HEE), genitalia (HEG), or anus (HEA).
5.2.7 Jaundice (JAU) is an overall slight yellow to pale orange tinge to the skin and mucous membranes.
Taylor, E.J., ed., Dorland’s Illustrated Medical Dictionary, W.B. Saunders, Philadelphia, PA, 27th edition, 1988.
Stedman’s Medical Dictionary, Williams and Wilkins, Baltimore, MD, 25th edition, 1990 .
Thomas, C.L., ed., Tabor’s Cyclopedic Medical Dictionary, F. A. Davis Co., Philadelphia, PA, 17th edition, 1993.
E2045 − 22
5.2.8 Mucous membrane condition (MM) is noted by the color and condition of the mucous membranes of the eye, nose, mouth,
or external genitalia.
5.2.9 Swelling (SW) is noted by the size, location and probable cause, such as edema (SWE) from: a solid tissue or tumor (SWT);
blood (SWH); air (SWA); or pus (SWB).
6. Specific Clinical Signs
6.1 Inspect the entire haircoat and underlying skin for integumentary signs. Some common clinical signs and their suggested codes
are as follows:
6.1.1 Alopecia, that is, hair loss (ALO), includes hair thinning, patchy/focal hair loss or balding.
6.1.2 Haircoat condition (HC) may be described as: oily (HCO); rough (HCR); wet (HCW); soiled (HCS); dry (D); bloody (HEH);
or piloerection (HCP), that is, distinctly raised fur, excluding the vibrissae, giving a bristled or porcupine-like appearance.
6.1.3 Swelling (SW) is an increase in tissue size or increased abnormal shape of the skin or other organs from abnormal presence
of: air, that is, emphysema (SWA); fluid or water, that is, edema (SWE); solid tissue or tumor (SWT); blood, that is, hematoma
(SWH); pus, that is, abscess (SWB).
6.1.4 Skin condition (SK) may be described as: thickened (SKT); thinned (SKH); scaly (SKS); dry (SKD); or red (SKY) (see
6.1.5).
6.1.5 Erythema (ERY) is an increased pink or red color on smooth skin.
6.1.6 Rash (RAS) is small red, pink or white dots or pustules on the skin; petechiae (PET) are red dots formed from blood.
6.1.7 Blisters (BLS) are fluid-filled vesicles. The fluid is usually clear, but can be pink (blood-tinged) or red/brown (filled with
blood). White-filled vesicles are either pustules (RAS) (< 5 mm) or abscesses (SW) (> 5 mm).
6.1.8 Color change (CC) may be other than pink or red, for example, bluish-black as in brushing, green as in bruising or severe
infection, brown as in increased pigmentation, or white as in blanching.
6.1.9 Abrasions (ABR) are denuded skin or mucous membrane.
6.1.10 Lacerations (LCN) are cuts in the skin from mechanical injury, that is, bite, scratch, foreign object, and so forth.
6.1.11 Ulceration (ULC) is an open sore accompanied by the disintegration of tissue, usually with necrosis, that is, death of tissue.
6.1.12 Scab (SCB) is an eschar formed from sloughed skin.
6.1.13 Pruritis (PRU) is itching evidenced by scratching, with or without a rash or abrasion.
6.1.14 Urticaria (URT) is a transient appearance of smooth, slightly elevated bumps which are redder or paler than the surrounding
skin and often accompanied by severe itching. Uricaria often appears as localized, discrete or confluent areas of edema.
6.1.15 Purpura (PUR) is confluent petechiae, that is, pinpoint hemorrhages, which form ecchymoses, that is, blotchy hemorrhages
over any part of the body.
6.1.16 Common manifestations of dermal sensitivity reactions are:
6.1.16.1 Contact dermatitis (COD) is pruritis, erythema and vesiculation that may be followed by pustulation and necrosis and that
has a pattern consistent with the touch of a foreign object or substance.
6.1.16.2 Exanthema (EXA) is macular or papular redness in discrete areas.
6.1.16.3 Exfoliation (EXF) is loss of superficial skin layers with redness, swelling, and presence of free blood.
E2045 − 22
6.1.16.4 Bullous eruption (BUL) is the presence of discrete serous or seropustular areas.
6.1.16.5 Erythema multiform (EMF) is the presence of multiple types of macules, papules and nodules.
6.2 Gastrointestinal signs are observed during external evaluations of the gastrointestinal system conducted from the oral cavity
to the anal area. Visually inspect the teeth and mucous membranes of the oral cavity, palpate the abdomen and inspect the perianal
area. An inspection of the animal’s cage will allow evaluation of the volume, color, and consistency of the stool.
6.2.1 Oral cavity signs and codes are:
6.2.1.1 Salivation may be described as: increased salivation (SAL); or lack of salvia, that is, xerostomia (XER).
6.2.1.2 Dentition (TE) includes: missing teeth (TEM); loose teeth (TEL); discolored teeth (TEC); damaged teeth (TED); or
malocculation (TEO).
6.2.1.3 For mucous membranes, note capillary refill time (CR), color, and condition, such as erosions or vesicles.
6.2.1.4 Gums may be described as: healthy, intact (GUH); or gingivitis (GUI), that is, inflamed or bleeding gums.
6.2.2 For the abdomen, look at the overall symmetry and size. The abdomen may be described as: smaller or more “tucked-in”
(STA) if the animal is dehydrated; larger as distended or pendulous abdomen (OPA); or asymmetrical as if an enlargement or
swelling in a focal area (SW).
6.2.3 In the perianal area, look for: abnormal anal sphincter (OEA); fecal (FEF) or urine staining (PEU); matter hair (PEH);
mucous (PEM); or rectal prolapse (RPR), that is, a red to dark red tubular protrusion from the anus.
6.2.4 For feces, note: consistency, such as normal (FEN), hard or dry (FEH), soft or watery (FED), oily (FEO); amount, such as
none (FEA), small (FES), normal (FEN) or large (FEL); content, such as normal (FEN), blood (FEB), mucous (FEM) or foreign
material (FEF); or evidence of straining to defecate, that is, tenesmus (TEN). Hard feces may indicate constipation. Soft or watery
feces may indicate diarrhea.
6.2.5 Function may be anorexia or loss of appetite (ANO), emesis or vomiting (EM).
6.3 Respiratory signs are found by evaluating the following:
6.3.1 Rate of breathing (RR) may be slow (RRS), normal (RRN), or fast (RRF).
6.3.2 Depth of breathing (RD) may be shallow (RDS), normal (RDN), or deep (RDD).
6.3.3 Difficulty in breathing is dyspnea (DYS).
6.3.4 Periodic cessation of breathing is apnea (APN).
6.3.5 Nasal discharge (ND) is either none (NDN), clear (NDC), red (NDR), yellow (NDY), green (NDG), or white (NDW).
6.3.6 Respiratory sounds include rales (RAL), coughing (COU), gasping for air (G), and sneezing (SNE).
6.3.7 Epistaxis (EPI) is the free flow of blood or hemorrhage from the nose. This is so
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