ASTM E2045-1999(2003) Standard Practice for Detailed Clinical Observations of Test Animals《试验动物详细临床观察的标准实施规范》.pdf

1、Designation: E 2045 99 (Reapproved 2003)Standard Practice forDetailed Clinical Observations of Test Animals1This standard is issued under the fixed designation E 2045; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year of las

2、t revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.1. Scope1.1 This practice describes the terms used in observing andrecording cutaneous, gastrointestinal, respiratory, reproductive,

3、neuromuscular, ocular, and general clinical signs of animalsundergoing toxicological testing. This practice also assists inproperly observing and assessing laboratory animals for signsof disease or adverse effects of compound administration.1.2 This practice includes codes and descriptions for a wid

4、evariety of clinical signs, anatomical locations, and otherdescriptive qualifiers, and a technique for scoring the extent orseverity of clinical signs.1.3 This practice assumes that the reader is knowledgeablein animal toxicology and related pertinent areas and is trainedin making clinical observati

5、ons.2. Referenced Documents2.1 Federal Standards:Title 40, Code of Federal Regulations (CFR), Environmen-tal Protection Agency, Subchapter E, Pesticide Programs,Part 160, Good Laboratory Practice Standards2Title 40, Code of Federal Regulations (CFR), Toxic Sub-stances Control Act, Part 792, Good Lab

6、oratory PracticeStandards2Title 40, Code of Federal Regulations (CFR), Environmen-tal Protection Agency, Part 798, Health Effects TestingGuidelines23. Significance and Use3.1 This practice pertains to all forms of toxicologicaltesting (acute, subchronic, or chronic) performed by any routeof administ

7、ration (inhalation, oral, dermal, ocular, or other).3.2 The U.S. Environmental Protection Agency, GoodLaboratory Practices for Nonclinical Laboratory Studies, aslisted in 40 CFR, requires that a testing facility maintainspecific standard operating procedures (SOPs) including anSOP covering clinical

8、observations in test animals.3.3 This practice serves as a basis for consistency in clinicalobservations. Actual procedures and forms to be used inrecording observations must be described in individual studyprotocols.4. Procedure4.1 Observe the health of an animal at a distance and of itshousing env

9、ironment 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 inanimal behavior, physical appearance, posture, gait, vocaliza-tion, food and water

10、consumption, and waste production. SeeSection 5 for details.4.3 Observe control animals first, followed by test groups inorder of increasing level of treatment. Observe positive controlgroup, if any, last.4.4 Note any dead animals and collect necessary tissues anddata before decomposition occurs.4.5

11、 Report animals that show signs of sickness so thatappropriate diagnosis, treatment, or euthanasia, if appropriate,can be performed.5. General Clinical Signs5.1 Note the overall activity, behavior, and condition of theanimal. Determine the hydration status by examining skinturgor, position of the ey

12、es such as normal or sunken, mucousmembrane color, and capillary refill time. Look for asymmetryor the presence of abnormal swellings, hemorrhage or signs ofpain.5.2 The following are some general conditions along withsuggested codes for record keeping that do not fall into anyspecific organ system.

13、 Refer to Annex A1-Annex A3 for adetailed listing of the codes and their descriptions. Othergeneral reference material will also be helpful.3,4,55.2.1 Activity may be described as: decreased (ACD);increased (ACI); hyperexcitable (HX); hyperactive (HYP);1This practice is under the jurisdiction of AST

14、M Committee E35 on Pesticidesand Alternative Control Agents and is the direct responsibility of E35.26 on Safetyto Man.Current edition approved Oct. 1, 2003. Published October 2003. Originallyapproved in 1999. Last previous edition approved in 1999 as E 2045 99.2Available from U.S. Government Printi

15、ng Office, Superintendent of Docu-ments, Washington, DC 20402.3Taylor, E.J., ed., Dorlands Illustrated Medical Dictionary, W.B. Saunders,Philadelphia, PA, 27th edition, 1988.4Stedmans Medical Dictionary, Williams and Wilkins, Baltimore, MD, 25thedition, 1990.5Thomas, C.L., ed., Tabors Cyclopedic Med

16、ical Dictionary, F. A. Davis Co.,Philadelphia, PA, 17th edition, 1993.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.lethargic (LE); irritable (IRR); moribund (MB), that is neardeath; prostate (PRO), that is, exhibiting inability or

17、 unwill-ingness to maintain upright posture.5.2.2 Body condition may be described as: obese (OBS);thin (THN); decreased rectal temperature (BTD); increasedrectal temperature (BTI); hypothermia that is cold to touch(HPO); hyperthermia that is warm to touch (HPR).5.2.3 Death may be described as: accid

18、ental death (AD);euthanized (ETH); found dead (FD).5.2.4 Examine skin for dehydration (DHY). The skin shouldfall back into place immediately after it is pulled out ofposition; if the skin is pulled out of position and tends to sticktogether or slowly fall back into place, the animal may bedehydrated

19、. Other signs of dehydration include sunken eyeball(SUN), pale or dry mucous membranes (MM), and a capillaryrefill time of 3 s (CR4). Distinguish between dehydration andvarious types of shock.5.2.5 Generalized edema (EDE) may appear as swelling ofthe limbs, lower abdomen, head or under the mandible.

20、 Whenthe apparently fluid-filled tissue is pressed, an indentation maypersist for a short time.5.2.6 Evidence of hemorrhage (HE) may appear on thehaircoat (HEH) or underlying skin or nails (HES), in urine(HEU) or feces (HEF), from the mouth (HEM), nose orepistaxis (EPI), eyes (HEO), ears (HEE), geni

21、talia (HEG), oranus (HEA).5.2.7 Jaundice (JAU) is an overall slight yellow to paleorange tinge to the skin and mucous membranes.5.2.8 Mucous membrane condition (MM) is noted by thecolor and condition of the mucous membranes of the eye, nose,mouth, or external genitalia.5.2.9 Swelling (SW) is noted b

22、y the size, location andprobable cause, such as edema (SWE) from: a solid tissue ortumor (SWT); blood (SWH); air (SWA); or pus (SWB).6. Specific Clinical Signs6.1 Inspect the entire haircoat and underlying skin forintegumentary signs. Some common clinical signs and theirsuggested codes are as follow

23、s:6.1.1 Alopecia, that is, hair loss (ALO), includes hairthinning, 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 raisedfur, excluding the vibrissae

24、, giving a bristled or porcupine-likeappearance.6.1.3 Swelling (SW) is an increase in tissue size or in-creased abnormal shape of the skin or other organs fromabnormal presence of: air, that is, emphysema (SWA); fluid orwater, that is, edema (SWE); solid tissue or tumor (SWT);blood, that is, hematom

25、a (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 onsmooth skin.6.1.6 Rash (RAS) is small red, pink or white dots orpustules on the

26、skin; petechiae (PET) are red dots formed fromblood.6.1.7 Blisters (BLS) are fluid-filled vesicles. The fluid isusually clear, but can be pink (blood-tinged) or red/brown(filled with blood). White-filled vesicles are either pustules(RAS) ( 5 mm).6.1.8 Color change (CC) may be other than pink or red,

27、 forexample, bluish-black as in brushing, green as in bruising orsevere infection, brown as in increased pigmentation, or whiteas in blanching.6.1.9 Abrasions (ABR) are denuded skin or mucous mem-brane.6.1.10 Lacerations (LCN) are cuts in the skin from mechani-cal injury, that is, bite, scratch, for

28、eign object, and so forth.6.1.11 Ulceration (ULC) is an open sore accompanied bythe disintegration of tissue, usually with necrosis, that is, deathof 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 abr

29、asion.6.1.14 Urticaria (URT) is a transient appearance of smooth,slightly elevated bumps which are redder or paler than thesurrounding skin and often accompanied by severe itching.Uricaria often appears as localized, discrete or confluent areasof edema.6.1.15 Purpura (PUR) is confluent petechiae, th

30、at is, pin-point hemorrhages, which form ecchymoses, that is, blotchyhemorrhages over any part of the body.6.1.16 Common manifestations of dermal sensitivity reac-tions are:6.1.16.1 Contact dermatitis (COD) is pruritis, erythema andvesiculation that may be followed by pustulation and necrosisand tha

31、t has a pattern consistent with the touch of a foreignobject or substance.6.1.16.2 Exanthema (EXA) is macular or papular redness indiscrete areas.6.1.16.3 Exfoliation (EXF) is loss of superficial skin layerswith redness, swelling, and presence of free blood.6.1.16.4 Bullous eruption (BUL) is the pre

32、sence of discreteserous or seropustular areas.6.1.16.5 Erythema multiform (EMF) is the presence ofmultiple types of macules, papules and nodules.6.2 Gastrointestinal signs are observed during externalevaluations of the gastrointestinal system conducted from theoral cavity to the anal area. Visually

33、inspect the teeth andmucous membranes of the oral cavity, palpate the abdomen andinspect the perianal area. An inspection of the animals cagewill allow evaluation of the volume, color, and consistency ofthe stool.6.2.1 Oral cavity signs and codes are:6.2.1.1 Salivation may be described as: increased

34、 salivation(SAL); or lack of salvia, that is, xerostomia (XER).6.2.1.2 Dentition (TE) includes: missing teeth (TEM); looseteeth (TEL); discolored teeth (TEC); damaged teeth (TED); ormalocculation (TEO).6.2.1.3 For mucous membranes, note capillary refill time(CR), color, and condition, such as erosio

35、ns or vesicles.6.2.1.4 Gums may be described as: healthy, intact (GUH);or gingivitis (GUI), that is, inflamed or bleeding gums.E 2045 99 (2003)26.2.2 For the abdomen, look at the overall symmetry andsize. The abdomen may be described as: smaller or more“tucked-in” (STA) if the animal is dehydrated;

36、larger asdistended or pendulous abdomen (OPA); or asymmetrical as ifan 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 dar

37、kred 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); o

38、r evidence of straining todefecate, that is, tenesmus (TEN). Hard feces may indicateconstipation. 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 brea

39、thing (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), yel

40、low (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 hemorrhagefrom the nose. This is sometimes indicated by the presence ofdry blood or dark material around the

41、nose.6.4 For reproductive or urogenital signs, carefully examinethe external genitalia and look for evidence of normal orabnormal reproductive discharge. Examine the amount andcolor of urine and whether or not the animal is expressing signsof incontinence or difficulty in urination (difficult to dis

42、tinguishfrom tenesmus). When applicable, note breeding behavior,pregnancy, abortion, and quality of mothering.6.4.1 Male examination is as follows:6.4.1.1 For external genitalia, look for the presence (TSB),absence (TSA or TSC), and condition of the testicles (TSE,TED, or TSN); paraphimosis (PM), th

43、at is, inability to retractpenis into foreskin, or abnormal discharge from the penis.6.4.1.2 Penile discharge is either none (PDA), normal(PDN), increased (PDI), bloody (PDB), serous (PDS), ormucous (PDM).6.4.2 Female examinations include:6.4.2.1 In external genitalia look for mucous membraneabnorma

44、lities (MM) or swellings (SW) of the vagina (VA) orvulva (VA).6.4.2.2 In vaginal discharge types or consistency of dis-charge are: none (VDN), normal (VDN), increased (VDI),decreased (VDD), bloody (VDB), serus (VDS), or mucous(VDM).6.4.3 For urine or urination note the following conditions:6.4.3.1 H

45、ematuria (HEU) is bloody urine. Use caution withrabbits as their urine may range from amber to light red withoutthe presence of blood.6.4.3.2 Anuria (ANU) is the absence of urine for a pro-longed period.6.4.3.3 Dysuria (DYU) is difficulty urinating; be sure todifferentiate with tenesmus.6.4.3.4 Poly

46、uria (PLY) is excessive volume of urine.6.4.4 Fertility signs include the following:6.4.4.1 Breeding efficiency may be failure to breed (FTB),conceive (FTC), or low litter size or weight (LLS).6.4.4.2 Abortion (ABO) is premature delivery of deadoffspring.6.4.4.3 For pregnancy status, animal appears

47、pregnant(APR).6.4.4.4 Mothering may be described as: poor care of young(PCY); evidence of cannibalism (CAN); or poor milk produc-tion (PMP).6.5 Neuromuscular signs include disease, trauma, and com-pounds which adversely affect the central or peripheral nervoussystem resulting in structural or functi

48、onal changes being seenin the neuromuscular system, or degree of alertness or activityin animals. Evaluation of locomotion and coordinated move-ments may reflect the status of the animals neuromuscularsystem.6.5.1 Musculoskeletal signs may be lameness or weightbearing (LMW) or non-weight bearing (LM

49、N), limb paralysis(LP), or enlarged appendage (ENA).6.5.2 Posture or head carriage may be normal (HDN), tilted(HDT), raised (HDR), lowered (HDL), or hunched posture(HP); gait may be normal (GAN), exaggerated (GAE), or slow(GAS).6.5.3 Central nervous systems signs include comatose(COM), tremors (TR), convulsions (CON), ataxia (ATX),circling (CIR), or paralysis (PAR).6.6 For ocular signs, carefully examine the orbit and eyeballincluding the eyelids, conjunctiva, cornea, sclera and pupil. Ifnecessary, use a penlight to determine the direct and consen-sual pupillary light reflexes. No