Document 4JmBZvbQ4djE3JeoRmBzpZ4O1
Acute ocular Irritation Test with T-2997CoC
in Albino Rabbits
Experiment No-: Conducted At: Dates Conducted: Conducted By:
0682EB0009
Safety Evaluation Laboratory Riker Laboratories, Inc. St. Paul, Minnesota November 19, 1981 to December 10, 1981
D. M. Markoe, Jr., BS ToxiColog4St
Study Director
Date
Reviewed By:
dc: M. T. Case K. L. Ebbens F. D. Griffith W. C. McCormick
K. L. Ebbens, BS
Date
Supervisor, Acute Toxicology
Summary The results of the acute ocular irritation test conducted from
November 19, 1981 to December 10, 1981 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-2997CoC is severely irritating (60.3/110.0) when allowed a five second contact and severely irritating (59.0/110.0) when allowed a thirty second contact.
Mild corneal opacity, iritis and severe conjunctivitis were produced during the five and thirty second contact procedures by the one hour evaluation. The corneal opacity increased to moderate by the one day evaluation.
The irritation persisted and epithelial sloughing and vascularization were noted at the three and seven day evaluations. The fourteen day evaluation revealed diminished irritation and by the twenty-one day evaluation the irritation had generally subsided with the exception of one animal of the five second contact aroup.
Introduction The objective of this study was to assess the ocular irritation
potential of T-2997CoC to the washed eye of female albino rabbits. This study was conducted in accordance with the Food and Drug Administration's Good Laboratory Practice Regulation of 1976. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives.
2.
Method and Results a
young albino rabbits of the New Zealand breed were used to evaluate the ocular irritating properties of the test article. The test method was modeled after that of Draize et alb .
The test article was instilled into the conjunctival sac of the right eye of each rabbit according to the treatment procedure presented in Table 1 with the left eye of each animal serving as a control. At each scoring inter-val, the cornea, iris and palpebral conjunctiva were examined and graded
b. for irritation and injury according to a standard scoring systenr- The maximum possible score at any one examination and scoring period is 110 points, which indicates maximal irritation and damage to all three ocular tissues (cornea, iris, conjunctiva) while a score of zero indicates no irritation (Table 2). In this scoring system, special emphasis is placed upon irritation or damage to the cornea, while less emphasis is placed upon damage to the iris and conjunctiva.
After completion of the test, the scores were analyzed, and a descriptive eye irritation rating was assigned to the test article. The criteria used for assignment of the descriptive rating were the frequency, the extent, and the persistence of irritation or damage which occurred to the three ocular tissues (Table 3). The individual results are presented in Table 4.
Dutchland, Inc., Denver, Pennsylvania Draize: Appraisal of the Safety of Chemicals (1965)
in Foods, Drugs and Cosmetics
3.
The rating is arrived at by selectina the maximum mean irritation score at one hour, one, two, or three days after instillation. if the rate of dissipation of injury does not meet the requirements defined for the descriptive rating appropriate for a particular numerical score, the descriptive rating is raised by one or more levels. The rating system is presented in Table 3. The protocol, principal personnel involved in the study, composition characteristics, and Quality Assurance statement are contained in Appendices I - IV.
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TABLE 2
EYE IRRITATION TEST - ALBINO RABBITS
Scale of Weighted Scores for Grading the Severity of ocular Lesions
Description
opacity (A) opacity - Degree of density (area which is most dense is taken for reading). Scattered or diffuse area, details of iris
clearly visible. Easily discernible translucent areas, details
of iris slightly obscured. r-)nalescentareas. no details of iris visible, size of pupil barely discernible. opaque, iris invisible.
Area of Cornea Involved (B) One quarter (or less) but not zero Greater than one-quarter, but less than onehalf. Greater than one-half, but less than three-
quarters. Greater than three-quarters, up to whole
area.
Score equals A x B x 5 Total maximum = 80
Values (A) Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is
positive). No reaction to light, hemorrhage, gross des-
struction (any or all of these).
Score equals A x 5
Total maximum = 10
Draize Grade
1 2 3 4 1 2 3 4
1
2
ocular Tissues
Conjunctiva
TABLE 2 (concluded) EYE IRRITATION TEST - ALBINO RABBITS
Scale of Weighted Scores for Grading the Severity of ocular lesions
Description
Draize Grade
Redness (A)
Redness (refers to palpebral conjunctiva only).
1
Vessels definitely injected above normal.
More diffuse, deeper crimson red, individual
2
vessels not easily discernible.
Diffuse beefy red.
3
Chemosis (B)
Any swelling above normal (includes nictitating
1
membrane). obvious swelling with partial eversion of the lids. 2
Swelling with lids about half-closed.
3
Swelling with lids about half-closed to completely
4
closed.
Discharge (C)
Any amount different from normal (does not include
1
small amount observed in inner canthus of normal
animals).
Discharge with moistening of the lids and hairs
2
just adjacent to the lids.
Discharge with moistening of the lids and hairs
3
and considerable area around eye.
Score (A + B + C) x 2
Total maximum = 20
Note:
The maximum total score is the sum of all scores obtained for the cornea, iris, and conjunctiva.
Rating Non-Irritating
Practically Non-Irritating Minimally Irritating Mildly Irritating
Moderately Irritating
Severely Irritating
Extremely Irritating
7.
TABLE 3 EYE IRRITATION TEST - ALBINO RABBITS
Classification of Test Materials Based on Eye Irritation Properties
Range 0.0 - 0.5 > 0.5 - 2.5 > 2.5 - 15.0 > 15.0 - 25.0 > 25.0 - 50.0
> 50.0 80.0
> ec.0 - iie.0
Definition
To maintain this rating, all scores by the one day reading must be zero; otherwise, increase rating one level.
To maintain this rating, all scores by the one day reading must be zero; co'@herwise,
To maintain this rating, all scores by the three day reading must be zero; otherwise, increase rating one level.
To maintain this rating, all scores by the 7-day reading must be zero; otherwise, increase rating one level.
To maintain this rating, scores by 7 days must be < 10 for 60% or more of the animals. Also, mean 7-day score must be < 20. If 7-day mean score is < 20 but < 60% of animals show scores < 10, then no animal among those showing scores > 10 can exceed a score of 30 if rating is to be maintained; otherwise, ra.se rating cne le-,;-cl.
To maintain this rating, scores by 7 days must be < 30 for 60% or more of the animals. Also, mean 7-day score must be < 40. If 7-day mean score is < 40 but < 60% of the animals show scores < 30, then no animal among those showing scores > 30 can exceed a score of 60 if rating is to be maintained; otherwise, raise rating one level.
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RikerExperiment No.:
12. APPENDIX I
PROTOCOL
TEST: Acute ocular IrritatiToenst
SPONSOR: CONDUCTED
3M BY: SafetyEvaluationLaboratory,RikerLaboratoriesI,nc.,St.Paul,Minnesota
I -@
I %"
TEST ARTICLE:
CONTROL ARTICLE: PROPOSED START ING/COM PLET ION DATE OF TEST:
TEST SYSTEM: Female New Zealand White AlbinoRabbits
SOURCE:
Division
OBJECTIVE: METHOD:
The objectiveofthistestwillbe todeterminethe irritatipoontentiaolfthe testarticlteo the oculartissues
(cornea,irisand conjunctivao)f
albinorabbitsR.abbitswere selectedas the testsystem
fortheirsensitivittoyirritanthsi,storicaulse,ease of handlingand generalavailability.
The animals willbe housed in standardwire-mesh cages in temperatureand humiditycontrolled
rooms with toodg and water offeredad libitum.Each animalwillbe assigned a numbered ear tag
which willcorrespondto a card affixedto the outsideofthe cage. The testarticlweillbe instilliendto
the conjunctivaslac of the righteye at a dose of servingas a controlA.t
withthe contralateraelye of each animal
hours and
days
(additionaslcoringintervalmsay be added tofurthercharacteriztehe ocularreactions)t,he tissueswill
be examined and graded forirritatiaonnd injuryaccordingto a standardscoringsystem of Draize
et alt.Aftercompletionofthe test,the scoreswillbe analyzed,and a descriptiveeye irritatiroanting
assigned tothe testarticleE.ye examinationsmay be carriedout withthe aidof sodium fluorescein.
Ifdeemed necessary by the studydirectorw,ashed eye proceduresentailinag 5 and 30 second
contactperiodwitha I @r @,
wash over a -,,r.,I - periodwillbe conductedusing
3 animalsper procedure.Allraw data generated by the study directorand the finalreportwillbe
storedinthe RikerLaboratoriesA'rchive,St.Paul,Minnesota.
PurinaRabbitChow, Ralston-PurinaS,t.Louis,Missouri Draise:AppraisaloftheSafetyofChemicals inFoods, Drugs,and Cosmetics (1965) Publishedby the EditoriaClommittee ofThe Associationof Food and Drug Officials
ofthe United States.
Sponsor
Fom 19171-7-A-PWO
Date
Study Director
rlate
t":t
2. 3. 4.
Riker Lxperiment No.:
APPENDIX I (concluded) 13.
Deviations and/or Amendments to P rotocol
LA,
Study Director
Date
'Study Director
Date
Study Director
Date
Study Director
Date
Study Director
Date
6.
study Director
Date
7.
study Director
Date
Study Director
Date
14. APPENDIX 11 Principal Participating Personnel involved in the Study
Name D. M. Markoe, Jr., BS
K. L. Ebbens, BS G. C. Pecore
Function
Acute Toxicology Toxicologist Study Director
Supervisor Acute Toxicology
Supervisor Animal Laboratory
APPENDIX III
Test ano/or Control Article Characterization for
T-2997CoC
1. The idlntity strength, uniformity, compositiott,purity or other pertinent characterizations of the test and/or control substances have
buci@ determined and documented &5 of
.7-4/ /f",-.I.,--f@47
2. 'I'limethod of.synthesis or origin of the test and control substances,
ijiclucii.ti4tjheir ank>unt and the Int-Lixxlof biocasrd3y (it aloillical)JC) it;
documented.
yes
no
3. U'lisetability of the tedt and/or control substances have been deter-
mined or will be determined as of
14/,'// Ii/.Cc,
et 1L$Ot
ce7
The above information and documentation &re locat*d in the sponsor's re-
cords.
-7
Z-
Ap6nsbr
Date
foom 19793 PW(i
RECLIVED
NC.V ")-1980 ig.,Iflly
16.
APPENDIX IV
QUALITY ASSURANCE STATEMENT
Acute Toxicology Laboratory Studies
Study No.: .0882EB0009
Th.-@Lshort term study wab auCAiteL@,i.@y the final report examined against the raw data on January 25, 1982 The results of the audit were reported to the study director and to the management on January 25, 1982
In addition to the data audit, different significantphases for studies underway in the Acute Toxicology Laboratory are inspected weeklv on a recurring cycle, and the facilities are examined bv Compliance Audit on a three month schedule.
Colmpliance11,@uit@ January 25, 1982
Date