Contract No. DAMD17-79-C-9161 I ITRI Project No. L6121 Study … · 2018. 8. 22. · contract no. damd17-79-c-9161 i itri project no. l6121 study no. 6 determination of the chronic

Contract No. DAMD17-79-C-9161 I ITRI Project No. L6121 Study No. 6

DETERMINATION OF THE CHRONIC MAMMALIAN TOXICOLOGICAL EFFECTS OF ROX

TWENTY-FOUR MONTH CHRONIC TOXICITY/CARCINOGENICITY STUDY OF HEXAHYDR0-1,3,5-TRINITR0-1,3,5-TRIAZINE CRDXJ IN THE

FISCHER 344 RAT

PHASE V FINAL REPORT Volume 2

Prepared by:

Barry S. Levine E. Marianna Furedt Donovan E. Gordon John M. Burns Paul M. Lish

I IT Research Institute 10 West 35th Street Chicago, IL 60616

Supported by:

U.S. Army Medtcal Research and Development Command

Fort Detrick, Fredertck, MD 21701

Project Officer: Jesse J. Barkley, Jr.

November 1983

Approved for pub I le release: Distribution Uni lmlted

The findings In thls report are not to be construed as an official Department of the Army position unless so designated by other authorized documents.

IIT RESEARCH INSTITUTE

I

Disclaimer: The findings in this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents.

'

APPENDIX X

OPHTHALMOLOGY REPORT

IIT RESEARCH INSTITUTE

339

340

S?UDY Iit:i,''.3~R: ~EST Arl.TICLE: SPECIES, RAT

L6121-6 R!JX

KEY NO'?E: ·rhe figure "X" ·;;2.s used to denote an ar.imal exa:-:1.i:1ed without any abnormal cli::!ical finjings ai: the desisnated test week.

su;:;.-:ARY OF OFHTHALr1iIC FINDINGS

Ocula!' conjunctivitis and discharge were observeC. in all test groups throughout the study and probably v,'ere a result of chronic external irritation. Throughout the study, there appeared to be a correlation between orbi~al bleeding and cataracts, phthisis, enophthalmia, iritis, and retinal and choroidal vascular attenuation. Since it ·::as not recorded which eye was bled, it is difficult to sa~e a definitive assessment, but ocular trauma or penetra~ion could cause the aforementioned abnormalities. Prominent lens nuclei and suture lines and vitreal strands are ~ormal aging changes that were observed in all groups, espec.:ally at Test ~eek lOJ.

Two animals (602, 603) were examined on 2-26-81 in addition to che scheduled examination weeks because of morbidity observed by IITRI Staff. Data Sheets are so labelled.

The high dose (40 mg/kg/day) female group, at Test ~foek 103, showed a definite increased incidence in c2.--:;aracts 1 luxated lenses, phthisis, buphthalmia, iritis, hyphe~a, and retinal degenerative changes which may be related to test article toxicity. Scleral icterus was also observed, and was probably related to disorders or tumors else·,·;here in the body (liver). The high nortality rate of the high dose (L:-o rng;/kg/day) mflles, at Test ':Jeek 103, makes useful interpr0tation of that data difficult.

C, Sue West, D.V.~. Diplornate, American College of Veteri~ary Ophthalmologists

w ~

Study Number L6121-6 Test Artich: '"

LESION

Lid Laceration Ocular Discharge Con June ti vi tis Buphthalmia l'ieratitis Corneal Scar Iritl~/Anterior Uveitis Anterior Synechia Posterior Sgnechia Iris Bombe Cataract Retinal Folds Vascular Attenuation: Retinal

Choroidal Retinal Hgperreflectlvity

Males

Q.,_Q Q...2 .L..1!. B.O

0/7'J 0/75 0/7'J 0/75 0/7'J 2/73 0/75 1/7'J 0/75 2/7:;I 0/7'J 1/7'J 0/75 0/7'J 0/7'J 0/75 0175 0/7'J 0175 0/7::1 0175 0175 0175 017S 0/7::1 0/75 0175 0/75 117'J 0175 017S 0175 1/75 0/75 0175 0/75 0/75 0/75 0l7S 0/7'J 2175 0175 0/75 1/75 0/75 0/75 0/7'J 0/75 l/75 0/75 0/75 0/75 0/75 0/7'J 1175 0/75 1/7'J 0/7'J 1/7S 0175

OPHTHALMIC INCIDENCE TADLE SUMMARY - TEST WEEK 25

Dose Smq/kq/dau)

Erma1e1

40. 0 Q.,_Q o..;, w, !LQ ~ 1/72 0/75 0/75 0/75 0/7'J 0/7'J 1/72 717'J l/7'J 5/7'J 2/T'J 2/7'J J/72 7/7'J 1/7'J 6/7'J 2/7'J 2/75 l/72 0/75 0/75 0/75 0/75 0175 2172 017'J 0175 017'J 0/75 0175 0172 0/75 0/75 0175 1175 0/75 0/72 0/75 0175 0/75 0175 0175 2172 0/75 0/75 0/75 1175 0175 2/72 0/75 0/75 0/75 0/75 0/75 1172 0/75 0/75 0/75 0/75 0/75 2172 0175 0/75 0/75 0/75 0/75 0/72 0175 0/75 0/75 0/75 1/75 0/72 0/75 0/75 0/75 0/75 0175 0/72 0/75 0/75 0/75 0/75 0175 0/72 0/75 0/7:l l/7'J 0/75 1/75

w J --

~ ~

w

Studq Number L6121-6 Test Article: "'

....,_,,,. Lid Scarring Ocular Discharga Ccn J unc ti vi tis Buphthalmia Phthisis Enophthalmia Keratiti1, Corneal Edema Cot-neat Scat-Hyphema Iritis/Anteriol' Uveitis Antet-iot- Synechia Posterior Svnechia Cataract Retinal Folds V•scular Attenuation: Retinal

Choroldal Retinal Hyparreflactivity Papllledema Orbit;,! Man Nystagmus

t:!lill

0. 0 .... w,_ 0/54 0/52 0/47 4/54 1/52 1/47 1/54 0/52 0/47 0/54 0/52 1/47 1/54 0/52 0/47 0/54 0/52 0/47 0/54 0/52 0/47 0/54 1/52 0/47 1/54 1/52 0/47 0/54 0/52 1/47 2/54 0/52 1/47 2/54 1/52 0/47 2/::!4 1/52 0/47 5/::!4 11:,2 0/47 0/54 0/52 0/47 0/54 0/:12 0/47 0/54 0/52 1/47 0/54 0/52 1/47 0/54 0/52 0/47 0/54 0/52 0/47 0/54 0/52 0/47

OPHTHALMIC INCIDENCE TABLE SUMMARY - TEST ~EEK 76

R.2il (mg/kg/day)

Etm•le!i

~ ...._. Q,_Q_ .... W! B. 0 ..... 0/53 l/ 19 0/:12 0/54 0/53 2/04 0/47 1153 1/19 5/02 7/54 14/53 0/:14 3/47 0/53 0/1'? 0/52 0/54 0/53 0/54 0/49 0/53 0/19 0/52 0/54 0/53 o,~ 0/47 0/53 2/19 1152 0/54 1/53 3/54 2/47 0/53 0/19 0/52 0/54 0/53 0/54 0/47 0/53 0/19 0/52 0/54 0/53 1/54 0/47 1/::;3 0/19 01:,2 0/54 1/53 0/54 1/47 0/53 0/19 0/52 0/54 0/53 0/54 0147 1/53 0/19 0/52 0/54 0/53 0/54 l/49 2/53 1/19 1/52 0/54 2/53 0/54 4/47 0/53 1/ 19 0/52 0/54 0/53 1/54 0/47 0/53 1/19 0/52 0/54 0/53 l/54 1/47 8/53 1/19 31:,2 0/54 3/53 l/54 11147 0/:13 0/19 0/52 01:,4 0/53 0/54 1/47 0/53 0/29 1/52 01:,4 1/:13 1/54 0/47 0/53 0/19 0/52 0/04 0/53 0/54 0/47 0/5:J 0/19 3/52 0/04 1/53 l/54 0/47 0/:J:] Oil'>' 0/52 0/54 1/53 0/54 0/47 0/53 0/19 0/52 0/54 0/53 0/54 t/47 01:,3 0/19 1/52 0/54 0/53 0/54 0/47

~I

344

-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0-0 ,,,,,,,,,,,,,,,,,,,,,,,,,,, OOOOOOOOOOOOOONOOONNOOOO-oo

nnnnnnnnnnnnnnnnnnnnnnnnnnn nnnnnnnnnnnnnnnnnnnnnnnnnnn ,,,,,,,,,,,,,,,,,,,,,,,,,,, 0-0000000-000-mo-onnooooru-o

---------------------------nnnnnnnnnnnnnnnnnnnnnnnnnnn ,,,,,,,,,,,,,,,,,,,,,,,,,,, 0~0000000-00-0-0000-noo-oruoo

• • • " • J

" • • • • " ' • • •• > • • 0

• :, ..... ::> ::>

.,. .c Ill Z

• " ' • • ... ...... ... '° • "" . • 0 .. ,:: ::,, .. 0:: u .....

• 0 •• •• • •

"" ,, "" •• 0. ., .

a 1-.CU \/1.C::> • •••

OH 1- "' o u o, "' \II -., ~ ................... +'ll+>..C+> .. -"'" u .... P:lll;o..,.,Ca;

STUDY IWI-IBER L6121-6

TEST ARTICLE ROX - --- ---

DOSE mg/kg/day 0.0

SEX Male -' "' "' ~ ,: "' ,._,:::: z~ - N "' z M .,,. m

W'ithin normal limits X X X X X

Lid Laceration

Lid scarring

Ocular discharge

Co,njunctivitis

"Chernosis

cluphthalmia ~-

Ptithis is

Er.ophthalmia

Keratitis Corneal Edema

Corneal scar

Hv~hema

Iritis/Anterior Uveitis

Anterior Svnechia Posterior Svnechia

Iris Bombe Prominent Lens Suture Lines

Prominent Lens Nucleus KEY.

L = 1 eft ~

~ R = right ~ U = both

Sl= suture line A "' anterior

ltlCIDENCE OF OPHTHALMIC LESIONS

TEST I/EEK 25

0 - N M .,,. m w ~ OJ w ~ OJ "' - - - - - - - - -X X X X X X X X X X X - -

f--

-

~ - ~

---

-

L

L

-

C = capsular I = immature S = sector N = nucleus

"' C - N - N N N X X X X

-

Co= cortical *=previously died or B = brunescent sacrificed V = vacuoles .. - -~

w ~

"' STUDY IIUMBER L6121-6

TEST ARTICLE ROX

DOSE mq/kg/day O.O

--' "' SEX Male ~~

INCIDENCE OF OPHTIIALMIC LESIONS

TEST !!EEK 125

--:z::S -· Or-1NMtj-l.()

STUDY IIUI-IBER L6121-6

TEST ARTICLE ROX

DOSE mq/kg/day ....Q.:.Q

SEX Ma] e

Within normal limits

Lid Laceration

Lid scarring Ocular discharge

Conjunctivitis

Chemosis

I ..., "' "" w

'"" I .._.. Z lO Z => N «z X

" 00 "' 0 N N N M

X X X X

IIICIDENCE or OPHTIIALMIC LESIONS TEST I/EEK 25

- N M .,. "' ~ " 00 0-, 0 M M M M M M M M M .,. -.,. X X X X X X X X X X X

-

N M .,. "' ~ " 00 ~ 01 .,. " .,. .,.

" .,. .,. .,. "',

X X X X X X X X X

I Buphthalmia I I I I \-l--l--Phth1s1s

-t--1 I I I I I I I I I I I ! 1-1-1-Enophthalmia

Keratitis

Corneal Edema

Corneal scar

Hyphema

iri tis/ An_t_~rior Uvei_t_i s

Anterior S_ynechia Posterior Synechia

Prominent Lens Suture Lines I I I I I I \ I I I f--f--~1-1---J-1 I I I l--I Iris Born be 1 1 1

~· ~--,

Prominent Lens Nucleus I I I I I I I I I I I I I I '--1---'----'--'---'-_J'--'-J_...L_j__l KEY:

L = R = u = Sl= A =

left right both suture line anterior ___ .. __ : __

C = capsular I = immature S = sector N = nucleus Co= cortical *~previously died or B = brunescent sacrificed V = vacuoles ,.1 = m::1t1,rP

~ .,,. 00

STUDY IIUIIBER L6121-6

TEST ARTICLE ROX -

HICIDENCE OF OPHTIIAU\l C LES IONS

TEST i,EEK 25 --- --·-- ------- - . -~-- ---·- ---,-

DOSE mq/kg/day 0.0

SEX Male ~ °'

STUDY NUMBER L6121-6

TEST ARTICLE ROX -DOSE mg/kg/day 0.0

SEX Male --"" ""' w :;: "' ,.....z

~ E M st ~ z => ""'z

~ ~ ~ ~

Within normal limits X X X X X

lid Laceration

Lid scarring

' Ocular discharge

Conjunctivitis

Chemosis Buphthalmia

•Phthisis

Enophtha lmi a

Kera ti tis .

Corneal Edema

Corneal scar

H··-hema

Iritis'Anterior Uveitis Anterior Svnechia Posterior Svnechia


Prominent Lens Nucleus KEY,

L = left w R = right ~ U = both ~ Sl= suture line

A = anterior P = posterior

INCIDENCE OF OPHTHALMIC LESIONS

TEST WEEK 25

N n ~

!UDY IIUl·\BER L6 I 21-6

TEST ARTICLE ROX -OOSE mg/kg/day O.O

SEX Male

1 "0:: 1.-. ....

r;it,. .. ,.,..+

luxated Lens Vitreal Strands

Vitreal Hemorrhage Retinal Folds

Vascular Attenuation: .

Retina 1

Choroidal

Retinal Hyperreflectivity Sparse Choroidal Vascular Pattern

Retinal Hemorrhaqe

1 Retinal Degeneration

Papil ledema

Icterus

Orbital Mass

Mystagmus

'Bled - orbital sinus

_, _____________ .. KEY.

L = R = u = Sl= A = p =

~"' "" w ::: o:J ...... == - N M " z =, « z m m m m

left right both suture line anterior P.• s teri or

m m


TEST HEEK 25

"' ~ 00 ~ 0 - N M " m m m m m "' "' "' "' "' "'

- -B Bl 1

G ~ "' 00 "' "' "'

~ -

- -

·- -· -

-

~

C = capsular I = immature N = nucleus

0 - N ~ ~ ~

R

R

Bl

S = sector Co= cortical *=previously died or

sacrificed

M ~

B = brunescent V = vacuoles Bl= specific eye used not M = mature recorded

" m ~ ~

-

B - -

-

"' u C

" u ·-u C -2

1

1

10

'

,, •[

., ,,, I

I ·1l

'

STUDY IIUMBER L6121-6

TEST ARTICLE ROX DOSE mg/kg/day -9.:.Q

SEX Female ~"' "" w :,: ro ...... ::::::: z~ "" z

INCIDENCE OF OPHTIIALl1IC LESIONS

TEST I/EEK 25 --.-~-

'°I " ~ " 001 ml 0 1 -1 NIMl•l~l'°I~ ~ ~ ro 00 OC1 00 00 00 00 00 001 ml 0 1 -1 NIMl"'"I~ 00 OCI O'\ cr-, O> c.n O'I en C

'°I ~1 "'I crl c c.nc.ncnc.n,-1

Within normal limits ~1-!'.--\_:

~

n 0


TEST ARTICLE ROX ----


TEST 14EEK 25

DOSE mq/kg/day O.O --·- - ·-- -· -~-~ ------

SEX Female ~~

~

~ ~

STUDY NUMBER L6!21-6

TEST ARTICLE ROX -DOSE mg/kg/day 0.0

SEX Female


Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis


Phthisis

Enophthalmia

Kera titi s

Corneal Edema

Corneal scar

Hvnhema

Iritis!Anterior Uveitis

Anterior Svnechia

Posterior Svnechia

Iris 13ombe Prominent Lens Suture Lines

Prominent Lens Nucleus KEY:

---,·- - .

..., "' ""' w :c "' ~ N M tj" m ...... == 0 0 0 0 0 z~ ""' z

~ ~ ~ ~ ~

X X X X

u u

-

- -

L = left R = right U = both 51= suture line A= anterior P .. posterior

INClDENCE OF OPHTHALMIC LESIONS

TEST 14EEK 25

"' ~ "' cr, 0 ~ N M tj" m 0 0 C" 0 ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ - - - ~ X X X X X X X X X X

"' ~ co cr,

~ ~ ~ ~

~ - - -X X X X

-- -

·-

·-

-

C = capsul a·r I = immature S = sector N = nucleus

0 ~ N N N N - - ~ X X X

Co= cortical * = previous1y died or B = brunescent sacrificed V = vacuoles t-1 = mature

M tj" m N N N - ~ ~ X X X

-

" n ~


TEST ARTICLE ROX

DOSE mg/kg/day __!l.Jl

SEX Female

1 Pdnn

r.r1tr1rnr.t

IrlCIOENCE OF OPHTIIAUIIC LESIONS

TEST HEEK 25 -·----·.-·· r- ----, r ---.-----,

__J "'

!~1~1NIMl"lml' -:3 O CG O C' C ~z:-r-1.-1....-1.-lr

~1 "'I °'I O 1 ~ 1 NIM Is, Im I , 0 C C' ,-, ,..... ,--1 ..-, .-1 ,....... , .-l ...--I ,-1 ,-1 ...... ...... r-1 r-1 ,--1 ...

~1 00 l°'l 0 1~1N1 Ml s,I m ,....;r-1.-lNNN NNN ....... ...... ...... ...... ...... ...... ,....; ,-1 .-,

~~::::~ ~~~:nds ~I I I I ttttttl I I I 1-t1=1=1-1jjjj---1 Vitreal Hemorrhage

Retinal Folds

Vascular A_ttenuation: Retinal

Choroidal

\ Retinal Hyperreflectivity \ 1--~ I I I I I I I I--I-S£arse Choro1dal Vascular Pattern

Retinal Hemorrhage

Retinal De~eneration

\ Papil 1 edema \ \ \ \ 1-1--1--f-l- I I i----1-1----l---1-+-t--+-+-Icterus

Orbital Mass

Nystagmus

\ Bled - orbital sinus J I f1 I +l-+-H-~f--~1-1 IB1 H I I -1--f \ f \ \ l-!1--+-+-l-l-l--l---1-I I I I 1-1-1--

KEY: L = left R = right U = both Sl= suture line A = anterior P =~ n.r,

STUDY llUI-IBER L6121-6

TEST ARTICLE ROX ~--!NC!OENCE OF OPHTIIALM!C LESIONS

TEST I/EEK 25

DOSE mg/kg/day O.O ~ ~~ C

SEX Female ,::c I..LJ ~ ~~

I

STUDY llUMBER L6121-6 TEST ARTICLE ROX ---DOSE mq/kg/day O.O

SEX Female

1--~'"ln

.C:".. .

Lux a ted lens Vitreal Strands

Vitreal Hemorrhage

Retinal Folds

Vascular Attenuation: .

~"' "" w :,-: ro - ,c z~ ""z

Retinal Choro1dal

Retinal Hvoerreflect1vitv Sparse Choroidal Vascular Pattern

Retinal Hemorrhage

Retinal Degeneration

Papilledema lcterus

Orbital Mass

Nys tagmus

Bled - orbital sinus

- -~----- ---KEY:

L = left R = right U = both

- -· -

"' ~ N N - -

-

Sl= suture line A= anterior P = poc: tP,ri qr

--- -

00 "' 0 N N M - - --

-

Bl


TEST I/EEK 25

- N f ~ ~ "' ~ 00 "' 0 - N M M M M M M M M ST ST ST ST - - - - - - - - - - -- - -

-- -~ -

_,_

- - - - -

I- j__ I- - j__

,-,-

,_ - - I- -.

C = capsular I = immature S = sector H = nucleus

ST ~ "' ST ST ST - - -

---

-

- - I-

Co= cortical *=previously died or 8 = brunescent sacrificed

~ cc ST ST - -

~l

- -

V = vacuoles Bl= specific eye used not M = mature recorded

ru u C ru u --

"' 0 u ST ~ C - - -

-··-

C----1

,__

- I- 10

- I-'

STUDY llUMBER

TEST ARTICLE

L612!-6

RDX

DDSE mg/kg/day

SEX Male

0.3 -

Within normal limits Lid Laceration

Lid scarring

' .J "" -0: w ,: ro I ~ s: z C, -0: z

INCIDENCE OF DPHTHALMIC LESIONS

TEST l!EEK 25

' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' '

~~ ~ ~ ~ ~ 00 0 £ ~

., n p

STUDY 11urmrn L6121-6 TEST ARTICLE ROX

DOSE mq/kg/day ~ SEX Male

_J_c_s.1 nn

_cataract


TEST lffEK 25 ,-- - ... -----,----------.-----i- --,- --r-

~"' ~~1-1N1M1S,1~1 ~ ~I ~I ~I§\ ~l~\§\;\~l~I ~I §\§l~ISl~I Ml "'I ~ ,_. •- LO LC> LD LO LD ~ ~ ~ ~~ ..... -- ..... - - - -

-t-t-r--+-t-1-l-1-l-l-1-1-1-f-l-l--+--1--+----J-l_j

I Luxated Lens I l I I I 1-1-1-1-~ ! I I I 1-1-1-1-1-1-H I 1-1-1 Y.i tr_e__Qj Strands Vi trea l_ Hemorrhage

Ret1na1 Folds_

'lascular Atte11uation: Rttinal

Chor_oidal

I Retinal Hyperreflect1vity \ I I ! f \ I \ I I H I I f---1-1-l I I I I I I ~ I Sparse Choroidal Vascular Pattern I I I I I t-t-\-1--

Retinal Hemorrhage

I Retinal Degeneration r1

I I I I f-f-1-1--1-1-Papil ledema

1 lcterus Orbital Mass _,_ I

1

.

1

Nys tagmus Bled - orbital sinus Rl Bl Bl . - I-

KEY:

L = 1 e ft C = capsular I = inuna ture

R = right S = sector N = nucleus

U = both Co= cort i ca 1 S1= suture line B = brunescent

*=previously died or

A= anterior V = vacuoles sacrificed

Bl= specific eye used not P ,- -·1str- ... i"-r 1-1 = mature "'€.CQ:"'rl.P,:\

STUDY IWMBER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day 0.3

SEX Male

Within normnl limit.s

Lid Laceration

lid scarring

Ocular discharge

Conjunctivitis


-Phthisis

~"' «w ,: "' I ,_.. :::C::: lD z co ~ « z -

X

~ 00 '" 0 ~ ~ ~ 00 - - - _, X X X X


TEST \!EEK 25

~ C - N ;;' ~ "' ~ 00 '" 00 00 00 00 00 co 00 '" - - - - - - - --

X X X X X X X X X X

- N M "" ~ "' ~ 00 '" < '" ~- '" ~ '" '" '" ~- '" < - - - - - - - - - < X X X X X X X X X X

--· --

LI_ I I I I I I --

Enophthalmia I ! I I I -J,-l-+-+--+-+-+--t--t--1-1-1 I I I I I I I Kera ti tis

Corneal Edema

I Hvnhema Corneal scar - - _J~

Iritis/Anterior Uveitis .

Anterior Synech i a -1 - • :

Posterior Synechia ----1--1-! _ i 1 1 1 1 J 1 , 1 : t 1 1 1......., Iris Bombe

I :~:;~:~~:~~:~::.Lines I I I I I ljj-!j-1 I I tt-t/j-1-1 I I \j I l w V,

"'

KEY: L a 1 eft Ra right U a both 51 = suture 1 ine A= anterior p a posterior

C = capsular 5 = sector Co= cortical 8 = brunescent V = vacuoles M = mature

I = immature N = nucleus *=previously died or

sacrificed

w

"' 0

STUDY IIUIIBER Lfil21-6

TEST ARTICLE ROX

DOSE mq/kg/day ~

SEX Male

1 oc inn

r ... ..... ~..,,. ..

INCIDENCE OF OPHTIIALll!C LESIONS

TEST I/EEK 25 -·1·-1--·r--.----1--r- 1 ·r----,·---,------,-~,- . .., -- ,--

~ °'

STUDY IHJMBER L6121-6

TEST ARTICLE ROX

DOSE mq/kg/day .2..:1 SEX Male -""

I NC !DENCE OF OPHTHALMIC LES JONS

TEST I/EEK 25

: ~ I~ IN IM I sc I ~ "'I "I "'I "'\ 0 \ ~,NIM I sc Im I"' z::JOCOO OOCQ,-

~

~

N

STUDY IWl·\BER L6!21-6

TEST ARTICLE ROX


TEST HEEK 25

DOSE mg/kg/day 0.3 ~ ~~ w SEX Male

STUDY NUMBER L6121-6 TEST ARTICLE ROX DOSE mg/kg/day o. 3 SEX Female_

Within Normnl I imitc;

Lid Laceration


Conjunctivitis

Chemosis

Buphthalmia -Phthisis

Enophtha lmi a

Keratitis Cornea 1 Edema

Corneal scar H11nhema


Anterior Svnechia Posterior Synechia

Iris Bombe

Prominent Lens Suture Lines Prominent Lens Nucleus

KEY:

~

~

~

..J °' "" w :c"' ill

~ 00 O', 0 ...... :::::

z C, N N N M "' z

N N N N

X X X X X

L = left R = right U = both Sl= suture line A = anterior P = pas teri or


TEST HEEK 25

N M " ~ ill ~ lS ~ 0 N M - -M M M M M M M M "" " " " N N N N N N N N N N N N

-

X X X X X X X X X X X X X

-

->-

--

C = capsular I = founa ture S = sector N = nucleus

" ~ ill " .,,.

"" N N N

X X X

-

-

Co= cortical *=previously died or B = brunescent sacrificed V = vacuoles M = mature

~ cc O' C, .,,. .,,. "" ~ N N N N

X X X X

'

,_

w ~ .,,.


TEST ARTICLE ROX

DOSE mg/kg/day .Q.,l

SEX Female

1 es ion

HICIOENCE OF OPHTHALMIC LESIONS

TEST HEEK 25

I --' "' ,'~I'° I ~1 00 I~ IO 1- IN I 61 ~I ~I ~ I fl I~ I 15 I~ I~ I ,_.~ N N N N M M M Z:=J N N N N N N N ""z ~ ~I ~I ml '°!~I'" I ~I

0

STUDY IIUl·IOER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day 0.3

SEX Female


Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis

Chemosis l3uphthalmia

Phthisis

£naphtha lmia

Kera ti tis

Corneal Edema

Corneal scar

H·"--hema

lritis/Anterior Uveitis


Iris Bombe

Prominent Lens Suture Lines

Prominent Lens Nucleus ·---~--KEY:

w

"' ~

--· ------

.J"'

w

"' "' STUDY IIUIIBER L6121-6

TE5T ARTICLE ROX

ItlCIDEMCE OF OPHTIIALIHC LESIDNS

TEST I/EEK 25 DOSE mg/kg/da-;D.3- - - - -- - - -- ·-- -•• - - -- --· 1 SEX Female ~ ~

:,::!;f' ,-, NM

STUDY IIUl·IOER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day o. 3

~ °' SEX Female "" w ,: ro ~ f ~ g_ a, - :c z co ,._ « z N N N

\,,1ithin normal limits X X X X x -Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis

Chemosis Guphthalmia -

.Phthisis

Enophthalmia

Keratitis

Corneal Edema

Corneal scar

H•,..,hema

Iritis/Anterior Uve1tis

Anterior Svnechia

Posterior Svnechia Iris Bombe


-Prominent_~en~_Nucleus KEY:

~ L • left m R a right ~

U a both Sl= suture line A = anterior p = posterior


TEST lsEEK 25

- N M .., ~ ~ ,._ 1 1 D ro a) ro co ro ro ro m N N N N N N N N ,_ X X X X X X X X X -

·-u

- ,_ - - -u

-

- N M .., ~ ~ m m m m m cr N N N N N N X X X X X X I- - - I- -- I- - - 1--

- - - --

- I-

,_ ,_ - - ,_ - 1--

1--

I- -

1-- - - - ,_ - ,_ - I- -

..

C = capsular I = inuua ture S = sector N = nucleus

,._ ro m m N N

X X - 1--

- -

- ,_

- ,_ ,_

Co= cart i cal *=previously died or 8 = brunescent sacrificed V = vacuoles M = mature

" _, C

" To ·-cr C m 0 u N M C -X X 74 - -

,_ -.

1

1

~-- -

-

-

--

- -- I-

~

"' 00 STUDY NUHOER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day Q.,J.

SEX Female

1 PS inn

-"''


TEST I/EEK 25

~~I '°I ,-.j "'I ~1 cl-lNIMl"'l~l'°l~l o;J zl 0 1-1 NI Ml"'l~l'°I ~1 "'I a,I 0 ~~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ N N ~ gJ R: gJ g:; R; R; ~ Ri gJ ~ \,--1..Jl."'1.L"'-"'--------------+---t----f-\ H-1--11-1-----1-----+--+--+--f-l-f-f-l I I I I I ·+-

I Luxa ted Lens 11 I I I I I I \-J--1__J--1----+--+--+----l-l-l-l-l-l-l I Vi trea_l Strands --l-l-+--1-+-+--l-·

I Vitreal Hemorrhage \ \ \ \ \ \ \ \ -1--\ I I I I I 11

f-f-1-1-H-I I I I

I I

Retinal f'

STUDY I/UMBER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day 2:§. SEX Male


..J "' « w ~ cc - ,: z "' « z

l--1T-

- N M "' m 0 0 0 0 0 M M M M M X X X X x·

INCIDENCE OF OPHTHALl1JC LESIONS

TEST HEEK 25

"' ~ co "' 0 - N M "'~

0 0 0 C - - - - - - -M M M M M M M M MM M X X X X X X X X X X X

~ co ~ 0 - N M "' m - - - N N N N N N M M M M M M M M M X X X X X X X X X

lid Laceration

I ~:~I :~a:~::~~rge ~U=1=ttttt=w=1=ttt1=tl=l=ljjjjjj ConJunct1v1t1s

Chemosis lluphthalrnia

Phthisis

Enophthalmia , 1-1-1 I I I I I --j,--,.-J-\--\-\-1 I I I I I I -l Kera ti tis

Corneal Edema

Corneal scar

IHyph~a --Iritis/Anterior Uveitis

1

~

"' co

Anterior Svnechia j Posterior Synechia ___ ----------------·---·---· ·--------. .----. ___________ .

Iris Bombe I I I 1--1-1 I I I I l-I I I ~1--1-1-1 I I I I I L-1 Prominent Lens Suture Lines

Prom in e1J_Llen1 __ N_!]c 1 eus i_L_L_J_.L.J_L..L-1_1-_1.-1_ 1-..L-1--'-....L-'---'-...J._.1........L-1_1 KEY:

L = R = u = SI= A = p =

left right both suture line anterior pas teri or

C = carsular I = immature S = sector N = nucleus Co= cortical *=previously died or B = brunescent sacrificed V = vacuoles M = mature

~

~

~

STUDY 11u1,mrn L6121-6 TEST ARTICLE ROX


TEST HEEK 25

DOSE rnq/kc1/day SEX Male

1.5 •T --••,--•r• --,.............- r--•,-----~ -r-'f"-r-"T 1-------r--,------.----,--,-'

~ °'

1no:;1--Iii~~~~~ ~1~1 001 ml 0 1-1N1M1q1~ C O O O r-< r-< r-< r-< r-< r-< M M M M M M M M M M ~1 ~1 ""l°'l 0 l-1N r-


TEST ARTICLE ROX

DOSE mg/kg/day 1. 5

SEX Male


Lid scarring

Ocular discharge

Conjunctivitis

Chemosis

Buphthalmia

Phthisis

Enophthalmia

Kera ti tis

Corneal Edema

Corneal scar H1mhema


Anterior Svnechia

Posterior Svnechia

Iris Bombe



w ~

- - ----·

-"'' ---,__ -

-


q ~ co q q q M M M

X X X

-

-,_ -


~ co C' ~ q q " M M M

X X X X

~ - -

,, ~ ~


TEST ARTICLE ROX

DOSE mq/kg/day D SEX Male

lesinn

_Cataract

~~

~"' I ......... _ z~

STUDY llUMBER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day Ll SEX Male ~""

'

~

~

~


TEST ARTICLE ROX ~ -

DOSE mg/kg/day l .5

SEX Male

, __ , __

,.._._ ____ ~+-

Luxated I e--

Vi trea l Strands Vitreal Hemor~ha--

Retinal Folds

Vascular Attenuation:

__, ~ "" w :c ro - ,-: z~ «z

Retinal .. Choroidal '

Retinal Hvoerreflectivitv

Sparse Choroidal Vascular Pattern 1

Retinal Hemorrhaae


Papilledema

Icterus

Orbital Mass

. Nystagmus

I Bled - orbital sinus

I_ ~,~- ---~--KEY:


·-· --

~ N m m M M

Sl= suture line A= anterior P __ = rtos.t_eri o.r

M s,- m m m m M M M

II-ICIDEI-ICE OF OPHTHALMIC LESIONS

TEST \!EEK 25


TEST ARTICLE ROX

DOSE mg/kg/day .1.,2

SEX Female


TEST IJEEK 25 --·-,-r -~~~~,-

~"' ~~I '°I "I "'I ml 0 \ ~IN IM I" ,...... ~ r--.. r--- r--- r--- 00 CO OCI OCI OJ ~~ MM MM MM MM M ~1 "'\ "\ "'\ ~1c1~1N1M co co ro co co a, a, ~ a, M M M M M M M M M "\~\'°\"\'°\ml c a, a, O'> a, o-, a, C M M M M M M "

Within normal limits 1----------:f-+-Vl-~~l--~l--\-x Ix Ix Ix ~~l~~f:_\ x I x Ix \ x I ~~~ Lid Laceration

Lid scarring

~~:l~:::::::::ge ~ B=B=~tll I FI_I_EEl--1--1-!--l--ljj Buphthalmia

I :~~:::::,mia I I I i tttttt I I I I I ttjjj I I I I ~-1 Keratitis

Corneal Edema

Corneal scar

w ~

~

Hyphema

Iritis/Ant_er_i_o_r Uveitis

Anterior S.vnechia

Posterior Synechia

Iris Bombe Prominent Lens Suture Lines I I I I I I I f-j-j I I I I H 1--'--f--l-j I I I 1-f--Prominent Len~_Nucleus I I I I I I I I I I I I I I I

KEY: L = left R = right U = both Sl= suture line A= anterior P = posterior

C = capsular S = sector Co= cortical B = brunescent V = vacuoles M = mature

I = inm1a ture N = nucleus *=previously died or

sacrificed

'" ~ m

STUDY 11u1mrn L6121-6

TEST ARTICLE ROX

DOSE mq/kg/day J...5. SEX Female

lPe:inn

~~

INCIDENCE OF OPHTHAUIIC LESIONS

TEST HEEK 25 · - -, · .-- --1-- r·--,-- ,---,-

f \91 9 9 ~ 9 ~ 9 NI Ml sci m I ~ I " I 00 I m I O 1- I NI MI sc I m ~ " ao m c ,_. ·- co CD co ro co O'.l ro co cn O'I a, a-, o-, O'I cr, a, en cn o ~~ M M M M M M M M M M (V) M M M M M M M ~ - --

l_l.il='----------1-l-l-l-l-l-l-l-l-l-l,-+--+-I-I-I-I-I-I I I I I 1-l-t l-H-1-~ I I 1-1--H I I 1-1-1-1-1-+--+-_,_-1-1-

Luxa ted Lene;

I Vitreal Strands I I I I l-l-l-1-1-1-I I I I I l-l-l-l-+--1-\----j--l--~i treal Hemorrhage

Retina] Foldi

Vascular Attenuation: Retinal rt-t-t-ttl 11 \ H-[-j I i 1113 Retinal Hvoerreflectlvit~horoldal , t=l=l=-l=+--+-1--=1--~:~:_-_+-l---'r=l==-:~+--:_-:-::_-:=~·___;--l S~arse Choroidal Vascular Pattern

Retinal Hemorrhage

Retinal De1eneration

Papilledema j---1-1--1-1-•-'

Icterus I \jjj-Orbi tal Mass _ ___ . 1--1--1--1--->-+--l Nystagmus _\jjjjj L' Bled - orbital sinus Bl B Bl! Bl -1--

1 1-------------t I I I 1-1 I I I I 1-1-1-1-l-1-I-I I I I 1-1--

KEY:

L = left C = capsular I = immature

R = right S = sector N = nucleus

U = both Co= cortical *=previously died or Sl= suture line B = brunescent sacrificed A= anterior V = vacuoles Bl= specific eye used not p ~- oos ter_ior M = mature recorded '

STUDY IIUl·IBER L6121-6

TEST ARTICLE ROX -DOSE mq/kg/day 1.S

--- -

SEX Female --"" "" w "'00 - N M .,,. ~ ...... ::.:: 0 0 C' 0 0 z~ .,,. .,,. .,,. .,,. .,,. "" z

Within normal limits X X X X X

Lid Laceration

Lid scarring Ocular discharge Conjunctivitis

Chemosis Buphthalmia -Phthisis

Enophtha lmi a

Keratitis

Corneal Edema

Corneal scar H"nhema




Promi nenJ_~_en~yuc 1 eus KEY:

~

"' L = left "' R = right U = both Sl = suture line A = anterior P • pos ter1or


TEST HEEK 25

~ ~ 00 ~ 0 - N M .,,. ~ ~ ~ 00 0 0 0 0 - - - - - - - - -.,,. .,,. .,,. .,,. .,,. .,,. .,,. .,,. .,,. .,,. .,,. .,,. .,,. X X X X X X X X X X X X X

- - - -

~ ,_

--

,_ - - -


~ C -- N N " " " X X X

-


N M .,,. ~ N N N N

" .,,. .,,. .,,.

X X X

-

j I

--

' ~


TEST ARTICLE ROX

DOSE mq/kg/day 1. 5 --- -- -- . -- -- .

SEX Female ..J ~


TEST ARTICLE ROX ---

INCIDENCE DF OPHTl~LMIC LESIONS

TEST WEEK 25

DOSE mg/kg/day LS [ ~ SEX Female i E5 -~ ,:'.:; ~ l : C cr, C ,..... N M q Lfl lD r--. CO cr, 0 ,- N M tj- Lfl \.0 r--. OJ cr-, c .;.... :z:5 C N f" MM MM MM MM M

~

00 G

STUDY NUMBER L6121-6 TEST ARTICLE ROX DOSE rnq/kg/day l. 5

SEX Female

1 - - , -. ""

__c;:,'-•··-~f-

Luxated Lens Vitreal Strands

Vitreal HemorrhaN~

Retinal Folds Vascular Attenuation:

.

--' "' "" w :Coo ,._. == z co "" z

Retinal

Choroidal Retinal Hvnerreflectivitv Sparse Choroida1 Vascular Pattern

Retinal Hemorrhane


Papil ledema

Icterus

Orbital Mass Nystagmus

ed - orbital sinus

··-------- --~- .. E KEY:


. -

"' ~ N N tj tj

81

Sl= suture line A = anterior P = p_si~t_eri~r

·--· -- --

00 ~- 0 N N M tj tj tj

-

INCIDENCE OF OPHTHALMIC LESIDNS

TEST liEEK 25 ..

; N M tj "' "' ~ 00 "' 0 - N M M M M M M M M M tj tj tj tj tj tj tj tj tj " tj tj tj tj tj tj tj - . ~ - - -

- - - - - - -

- - - -,_ -

I- - -

-Bl ,1 1 Bl ,_ - - - - -

C = capsular I = irrnua ture S = sector N = nucleus

tj "' ~ tj tj tj tj tj tj

- - --

-

-

Co= cortical *=previously died or 8 = brunescent sacrificed

~ 00 tj tj tj tj

,_

V = vacuoles Bl= specific eye used not M = mature recorded

" u C

" u ·-"' 0 u tj "' C tj· tj -

.

1

'

,_

I- 10 -

STUDY NUMBER

TEST ARTICLE

DOSE mg/kg/day

SEX Male

L6121-6 ROX

8.0


Lid scarring

Ocular discharge

Conjunctivitis

Chemosis

.J °'

'~ QO

'" INCIDENCE OF OPHTHALMIC LESIONS

TEST I/EEK 25 STUDY 11u1mrn L6121-6

TEST ARTICLE _..BQ._X_

DOSE mq/kg/day JL..Q. SEX Male

-- -, ··.,. --,--r--.-------.-,-- i- ·T----i-,---1-,-,--r--r~

1 "

STUDY NUl·\BER L6121-6

TEST ARTICLE RDX

DOSE mg/kg/day 8.0 --- -.

SEX Male _,~

~

°" ~

I

STUDY rrurmrn L6121-6 TEST ARTICLE ROX

UUJL Ill{!/ r.~!f u,,.y - . .,

SEX Male

ln

STUDY IIUl·IBER L6!21-6

TEST ARTICLE ROX

DOSE mq/kg/day !:,9_ SEX Male ~"' «w z: ro ,_..z

z~ « z ~ ~ M " m 0 0 C m m m

INCIDENCE OF DPHTIIALMIC LESIONS

TEST HEEK 25

~ ~

w a,

"' STUDY HUMBER L6!21-6

TEST ARTICLE ROX

DOSE mg/kg/day .§.:.Q SEX Male

l~r~~-

r-~+-"'""'"t

-~yxated Lens.

~ °'


TEST ARTICLE ROX --

DOSE mg/kg/day 8.0

SEX Fema 1 e ~ °" "" w :c "' w ~ co m 0 ...... :::: N N N N M z co m m m m m "" z

Within normal limits X X X X X -Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis


-Phthisis Enophthalmia

Keratitis

Corneal Edema

Corneal scar

Hvrhema


Anterior Svnechia

Posterior Svnechia

Iris Bombe


Prominent Lens Nucleus --·--KEY:

~

w L = left ..., R = right U = both Sl = suture line A= anterior P = posterior


TEST I/EEK 25

- N M st m w ~ co m 0 M M M M M M M M M st m m m m m m m m m m X X X X X X X X X X

+-- - -

I-

--

- - I-

I-

,_

- -

- N M st st "' m m m X X

I- -

,_ L

- +-- --L

-- -

-

- - --

-,_ -

- +---

.

st m w st st st m m m

X X X

- - --

- - +--

1-

-

- ,_

+--

- - ,_

C = capsular I = irnma ture S = sector N = nucleus

~ co m C st st st m m m m m

X X X X - f-- - ,_

-

I

-

- ,- -- +--- +--

- - - -


~

00 00

STUDY llUM8ER L6121-6 TEST ARTICLE ROX DOSE mq/kg/day .!h.Q SEX Female

l p_s_jnn


TEST I/EEK 25 --.----,- ·-1-r r- r---i · -

___, °' ~te 1~1~1ao1m I ~ ~I ~I al ~l~l~l~\~\~I~\ ~ ~l ~l~l~l~l~I ,_..:... N N N N Z: ::, lJ") U") LO Ln "" z

O'I ~I 0 ~- w w ~ \1__l.---+--+-+-l-t--,

Luxated I""' \--H ttttt1-1--H-1---J-H-Vitreal Strands -~~i- - -- -H-----4-+--l~-i Vitreal Hemorrhane t--Retinal Folds f--f-1-- I I 1-1-1-1-1-I I I I 1-+-I Vascular Attenuatio_~ R .!'_ti _!l__._j

_(;_hor_o!dal

\ Retinal Hyperreflectivity \ \ \ \ \-1-1-1-1-\ I I I I 1-1--1-1-1-H I I 1-1--1 I Sparse Choroidal Vascular Pattern f-1-- \ I \ I I l-l--1-\-\-1~f-l-H-l-l--1--

STUDY NUMBER L612J-6 TEST ARTICLE ROX

ay 8.0

--··


lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis


-Phthisis

Enophthalmia

Kera ti tis

Corneal Edema

Corneal scar

H11 nhema


Anterior Svnechia




w

"" "'

-"" "" w t ,: "' - M ..- m ~:c m m m m z~ m m m m

"" z

X X X X X

L = left R = right U = both Sl = suture line A= anterior P = posterior


TEST HEEK 25

"' ~ ro °' 0 - N M ..- m "' ~ "' m m m m "' "' "' "' "' "' "' "' "' m m m m m m m m m m m m m X X X X X X X X X X X X

-

-

- - -L

L

-


~ cr, 0 -"' ~ ~ m m m X X X X

-

Co= cortical B = brunescent

*=previously died or

V = vacuoles sacrificed

M = mature

M ..- m ~ ~ ~ m m m

X X X

- I-

,_ --

- -

·--

~

"" 0


TEST ARTICLE RDX - -

DOSE mq/kg/day 8 0

SEX Female _, °' "" w :,, t ,: 00 ._. == w z =, 1 odnn

STUDY I/UMBER L612!-6

TEST ARTICLE RDX

DOSE mg/kg/day 8.0

SEX Female


Lid scarring

Ocular discharge

Conjunctivitis

Chemos is

[3uphthalmia

-Phthisis

Enophtha lmi a

Kera ti tis

Corneal Edema

Corneal scar

Hvohema


Anterior Svnechia Paster ior Synechi a


Prominent Lens Nucleus ·-·--·- . KEY:

~

~

__, ~

STUDY NUMBER L612!-6

TEST ARTICLE RDX

DOSE mg/kg/day 4o.O

SEX Male


Lid scarring

Ocular discharge

Conjunctivitis

Chemosis lluphthalmia

.Phthisis

Enophthalmia

Kera tit is

Corneal Edema

Corneal scar

Hvohema

lritis/Anterior Uveitis Anterior Svnechia


__ ,,,,

~

w ~

' '

STUDY 11u1mrn L6121-6 TEST ~RTICLE ROX

- -

DOSE 111q/hJ/di1y 10.0

SEX Male _J rr:: ,n:: tJJ - 1 ;::: cc ...... ::::::: cl z~

l nc>L-.n


TEST ARTICLE RDX

DOSE mg/kg/day 4o.o SEX Male


lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis


-Phthi sis

Enophthalmia

Keratitis

Corneal Edema

Corneal scar

H""hema

Jrit1s/Anterior Uveitis

Anterior Svnechia Posterior Svnechia Iris Bombe


Prominent Len1_~ucleus KEY:

w

"' ~

-' "'

~

co m

; I

STUDY IWl·IOER L6121-6

TEST ARTICLE ROX -

DOSE mq/kq/day 4o.O

SEX Male

1~.-_inn

r:it-.--.--1-

luxated 11'1~'"

Vitreal Strands Vitreal Hemorrhane

Retinal Fo 1 ds


--

~"' "' w w :,:: o:! ...... ::: N z~ w ""' z

Retinal

Choroldal

Retinal Hvnerreflectlvitv

Sparse Choroidal Vascular Pattern

Retinal Hemorrhaqe


Papil ledema

Icterus

Orbital Mass

Nys tagmus


-·-----KEY:

L = left R = right U = both S1= suture line A= anterior

---Pr- n,:iste-.... ""'"

f a) "' N N w w

- -

-


TEST l,EEK 25 -- -- --,-

0 ~ N M "' m w ~ a) "' 0 ~ N M "' m w ~ a) "' 0 M M M M M M M M M M "' "' "' "' "' "' "' "' "' "' m w w w w w "' "' "' "' "' "' "' w "' w "' "' "' "' w co

- - - - - -·- - -

- -

- - - - - -- - I- - "- - - j

I - - C- -- - - - - - --

-- - --

' - - - - - -- - - - --

- - -- -- I

- - - - - - - - - - - _I 1 Bl Bl ll -

- - - - - - - -

C = capsular I = irrn11a ture S = sector N = nucleus Co= cortical *=previously died or B = brunescent sacrificed V = vacuoles Bl= specific eye used not t-1 =_.r!l.a turP recorded


TEST ARTICLE ROX 40.0 -


TEST I/EEK 25

DOSE mg/kg/day

SEX Male ~ °' "" w :::::: ro -z z co "" z

~~~~~~ ~1 00! ml 0 1~1N1M1~1m1~ ~ ~ ~ lD lD

~

"' 00


TEST ARTICLE ROX

DOSE mq/kq/day

SEX Male

1 p,;; inn

10.0

~ °' "" w ::::: CC! -,: z~ "" z

INC!OENCE OF OPHTHALMIC LESIONS

TEST HEEK25 -----,-------,-.--r-1···~------.~~--~~~-.~~--~~-.---.-,

st ~1~ I~ I tii[ §[ [§ I ~I ~I :;[ t; I~ I - N M m -1NIMl"lml"'l~1oo " m m m m m I.O t.O lO \0


TEST ARTICLE ROX

DOSE mg/kg/day !£.:..9. SEX Female


Lid Laceration

Lid scarring

~ °' « w ,: 00 ..... ;.:::: z~ « z


TEST HEEK 25

wl ~ "'I "'I • 1-1 NI Ml •1 mlw 1~ I' r--. ...... t-- r--.. co co co OJ OJ co OJ OJ ( lO lO lO lO lO \D lO lO lO lO

c-o 0

ItlCIDENCE OF OPHTIIALIIIC LESIONS

TEST I/EEK 25 STUDY IIUIIBER L6121-6

TEST ARTICLE ROX

DOSE mq/kg/day 4o.O

SEX Female

--- -,-- -,-- ·-,-,- ,--1 -----,-T-a-,-r- ,--T-

... HX

i~ \ r;;I ~ t;I r:;t ~l ii ~lililffil~lil ~I ii ~I -1 N1M1sr1=1~ I ~I "'lmlo o-, cr, °' en m "' m m o


TEST ARTICLE ROX DOSE mg/kg/day 4o.O

SEX Female


Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis

Chemosis

Buphtha lmi a

-Phthisis

-

--"'' ""' w ,: co ....... ::::: z~ ""' z

" g: - M D ~ 0 0 ~ 0 ~ ~ ~

X X X X X


TEST I/EEK 25

~ I ~ ~ ~I ~I ~I 21 ~I;: I~ I ~ ~I ~I ~I ~ '° ~ co ~ 0 0 0 0 0 -~ ~ ~ ~ ~ X X X X X xix lxlx !xi xlxl xix I I xix\ x Ix ]x

u u

I ~:~~~:~::mia I I I I jtt1jj=!-jffl==l=ttl=1J I ljJ Corneal Edema

Corneal scat

H hema Jritis/8nterior l!veitis I I I I I I I I --1--1 I I I I I I l-1-1-- I I I I ! I I An t_eri or Synech i a

I Posterior Synechia I I l---l--\-1--1--1--1-1-l--+-1---'I-I-I-I I 1-1-1--l--l--l-'-Iris Bombe Prominent Lens Suture Lines

Prominent Lens_Nucleus I I I I I I I I I I I I I L I I I I I I I I I I I I - . ~

a

KEY:

L = R = u = Sl= A = p =

left right both suture line anterior posterior

C = capsular I = inuua ture S = sector N = nucleus Co= cart ica l * - previously died or B = brunescent sacrificed V = vacuoles M = mature

= 0 N

STUDY NUl·IBER L6121-6

TEST ARTICLE ROX DOSE mg/f,g/day 4o.O

SEX Female

lesinn

r;i f",)r;tc..t_

Luxa ted I Pnc:

__, "' « w ~ cc ...... :::: z~ « z

IMCIDENCE OF OPHTHALMIC LESIONS

TEST I/EEK 25 ------,-...-··--1-1 --,- I -;

-1 NI Ml q1~1~1~1 00 1~1c1-o O O D O O O O O r-< ,...., r-- r-- r-- r-- r-- r-- r-- r-- r-- r-- r-- NI Ml qi ml ~1~1 00 ,~, .............................. r-1 ............ r-- r-- r-- r-- r-- r-- r-- r-- 0 I -1 NI Mlqlm NNNNNN r-- r- r-- r-- r-- r--

~: :~::~ ~::~~~age I tt1-ttttttttttttt t_)j=n-jj=t Retinal Folds

Vascular_litt~nuation: Retinal

C_horoi d_e_l

I Retinal Hyperreflectivity I , l-f--.1---1-f---+- I I 1 1----1---f-l I I I I 1-'-.

I ~::~~:lc~:::~~~:g~ascular Pattern I I I \_ltttH-1 I I I tt-ttHjj I I I j Retinal Oe1eneration

I Pa pi 77 edema I I ,, I 1-1----1----1----l-l---->-+---+---+--t--t--l----l----l--f---1-11->-+--+--·-I c terus

Orbital Mass

Nystagmus ! Bled - orbital sinus Bl IBl Bll

)----------------1-+-+--t---t-f--f--\ ) ) ) f-l-f---1-1-1---+---l-\-l,---+---l

KEY: L = left C = capsular I = immature R = right S = sector N = nucleus U = both , Co= cortical * = pre~iously died or Sl= suture line B = brunescent sacrificed A = anterior V = vacuoles Bl = specific eye used not p • posterior" M = mature recorded - . . . '

INCIDENCE OF OPHTIIALl1JC LESIONS STUDY IIUIIBER L6121-6

TEST ARTICLE ROX TEST Ii EEK 25

-----DOSE mq/kg/day .MW!

0, u C

SEX Ferna 1 e __, "'

~ 0,

.i:··

0 ~

STUDY IIIJIIBER L6121-6

TEST ARTICLE ROX DOSE mg/kg/day 40.0

SEX Female

1--•,o

,.~ .. ~-~- ..

Lux a ted 1 ....... ,.

Vitreal Strands

Vitreal Hemorrhage Retinal Folds

I Vascular Attenuation: ' i -

..J ~

"" w :c OJ -::::: z co '"' z

Retina 1

Choroidal 1 Retinal Hvnerreflectivitv

Sparse Choroidal Vascular Pattern

Retinal Hemorrhaoe


Papil l edema

Icterus Orbital Mass

Nys tagmus , Bled - orbital sinus

---~ ---~---- -- - --KEY:

L = 1 eft R = right U = both

~ ~ N N ~ ~

1

Sl= suture line A = anterior P "' r,.ns t_eri or

00 "' 0 N N M ~ ~ ~

-


TEST l,EEK 25

~ N M st ~ ~ ~ OJ "' 0 M M M M M M M M M st ~ ~ ~ ~ ~ ~ ~ ~ ~ ~

-~ -

- - -

,-

,_ - - - •-1 Bl

~ N M st st st st st ~ ~ ~ ~

1-- -

·-

-

-

_,__ -

,_

- ~ -

~ Bl

-

C = capsular I = inuna ture S = sector N = nucleus

~ ~ st st ~ ~

-

Co= cortical B = brunescent *=previously died or sacrificed

~

"' ~

V = vacuoles M = mature Bl= specific eye used not l"Pr-nrde~

.,.

"' u C 0,

V 00 "' 0 ·-

,, "' "' ~

u ~ ~ ~ C .. -

• " • ,,

'

1

1

Bl 1--

ID -

I

,,

STUOY 11111-llJEII

TEST ART! CLE

~-- .. ' , .... ' --

Within normal

Lid Laceration

lid scarring

L.6121-fi --·- --·--- --- ---ROX

ay 0.0

1 imi ts

Ocular discharge

Conjunctivitis


Phthisis

Enophthalmia

l

~

0

"' STUDY IIIJl,IBER L6121-6

TEST AllTICLE ROX

DOS[ mq/kq/day --11..:.Q

SEX Male_

lP


TEST ARTICLE ROX -0.0 ·-- ·-·

.. -DOSE mq/kg/day SEX Male ~ °" "" w :;:: co

....... ::'.': "' ~ 0:, °' 0 z =, N N N N M

"" z

Within normal limits X X X X x Lid Laceration

lid scarring

Ocular discharge

Conjunctivitis


Phthisis

Enophthalmia

Kera ti tis

Corneal Edema

Corneal scar

Hvnhema


Anterior Svnechia

Posterior Svnechia


Promine~_U~~-N~cleus KEY:

~

0 L = 1 eft ~ R = right

U = both Sl= suture line A= anterior P = pas teri or

IIICIDENCE OF OPHTHALI\IC LESIONS

TEST 1'EEK 51

- N M st ~ "' ~ 0:, °' 0 - N M M M M M M M M M M st st st st X X X X * X X X X X X X

~ -- '--

~ -

~

R

I = immature C = capsular S = sector N = nucleus

·--st ~ "' ~ .,. .,. .,. .,.

X X X X


0:, O' 0 .,. .,. ~ '

X X *

-

•·-

~


TEST ARTICLE ROX

DOSE mq/kq/day ..Q.,.Q

SEX Male

les1nn

_,"' "" w

- --, ---,- --, --


TEST 1,EEK 51 -..----i-r- ____.., .. -r---.- - , - ~ ---··, ·- -,--

; ~ I ~1 N "'I "'I 0 1 -1 NI MI "'I~ I~ ~z" N N N N M M M M M M M ~1 °'I "''I cl -1 ~ I MI"' I ~1 ~1 ~1 cc I rn I 0 M M C',


TEST ARTICLE ROX

DOSE mg/kg/day -2..:.Q SEX Male ..J "' ""~ :;: co - "' z C, ""z ~1 0 m "


TEST I/EEK 51

Ml ~1 ml "'I ~100\m\o[~I~ ~ ~ ~ ~ w ~ ~ w w_~ Ml ~1 ml "'I ~1oo\mlo1~ w ~ w w w w w r-- r-- NI M\~lm r-- r-- r-- r--

~Jithin normal limit.c; X X X X X X X X X X -ir X X X * X -ir X X X X X X X Lid Laceration Lid scarring - ---

Ocul_ar d~s~h~rge ·-- I ~==-,-ConJunct1v1t1s ,__ ~ ~ Chemosis - ' ,-

Buphthalmia H-+-l,-i--l-,-l-f-l-1-1-1-1 , 1-1-•-•Phthisis

I Enophthalmia I I I \ I I I I j \ I I I I I I j-j-j I I I I I I --1 Keratitis Cornea 1 Edema

Corneal scar:_

H hema Iritis/Anterior Uveitis 1-1 I I I 1'-'--H I I 1-\-\-1-1 I I I I Anter:jor Syn_echia

Posterior Synechia

I ~~~;~:~\ens Suture Lines I I I I I I ij-jj=ttttltLJ_j_j I l=t:=: Prom ine11 t LenL._~uc l eus

~

0

"'

KEY:

L = left R = right U = both 51= suture line A = anterior P = posterior

C = capsular S = sector Co= cortical B = brunescent V = vacuoles M = mature


sacrificed

ru u C ru u u C -6!)

1

1

1

f-2-·-1 1 '

f--' 1 .I -·1

8

~ ~

0


TEST ARTICLE ROX

DOS[

SEX

mq/k9/d,1y

Male

1 o


TEST ARTICLE ROX -DOSE mq/kg/day 0.0

·--

SEX Female _, °' -,: w ::r.: c:c -~ ~ ~ 00 "' 0 z co ~ ~ ~ 00 -,: z ~/ithin normal limits X X " X ;~ . -lid Laceration


Conjunctivitis


Phthisis

Enophthalmia

Kera ti tis

Corneal Edema

Corneal scar

H"nhema

Iritis/Anterior Uveitis Anterior Svnechia Posterior Svnechia Iris Bombe Prominent Lens Suture Lines Prom i ne_n_t Len~_N~c 1 eus

KEY: _.,. L = left

R = right U = both Sl= suture line A = anterior P = posterior

JtlCIOENCE OF OPHTIIALl1IC LESIONS

TEST HEEK 51

- N M .,. = ~ ,_ 00 "' 0 - N M 00 00 00 co 00 00 00 co 00 "' "' "' 0, * X X X X X X X X X X - - -

u L - -

~-~

-

C = capsular I= immature S = sector N = nucleus

.,. = ~ "' "' "' X X X


C ~ 00 " C "' "' "' -

X

L u

L ~ j -


TEST ARTICLE ROX

DOSE mq/kg/da_y ..Q.:.Q SEX Female

l i:,.c: inn

""'"""'""t

---~--

~"'


TEST I/EEK 51 -,--r-r- 1 --,--~

~ i I co\ ~I oo\ ml O 1-1 NI"'\.,-\ ~I col ~I ool "'I O 1-1 NIM \.,- I~ lco I~ I 00 I c I ~ ~ z r-- r-- r-- r--. co co ro co ro co co co ro co m m m m m m m a, m m ... L

R

M --t-t-1 I t-H-1 I I 1-1-f-/-i-H--\ I I I 4

I Luxated Lens \ \ \ I I \-1-\-f- I ! I I I I I I l-1-l-l-/-1--\-l-_Vilrea 1 Strands

Vi_trea_l Hemorrhage

Retinal Fo_l_cl_,_

; Vascular Attenuation: Retinal I ! I I l-f--+-I-H-f--l I I I I I 1-1-1 I ! I I \_I i Choroi da_l_ 1 Retinal Hyperreflectivity -'-'--\ I I I I 1-1--

Searse Choro1dal Vascular Pattern -e--l-1 I I I I I I I I I 1 I I 1---l-

Retina 1 Hemorrh_?_ge

Retinal De~enerat1on

Papilledema

Icterus

Orbital Mass

Nystagmus


------ KEY: I I I I I I '

L = left R = right U = both Sl= suture line A = anterior P =: pqste_riqr

STUDY IWl·IBER L612!-6

TEST ARTICLE ROX -DOSE mq/kg/day 0.0

.~ - --

SEX Female .J ~ ...-c I.JJ -~-- :: rn _, ~, M tj ,n .... : ~ 0 c• 0 0 0 :;--:;:;:, - - - - --Posterior Svnechia

1--

Iris Bombe


Prominent Len1_N_uc1eus KEY:

~ L = left -w R = right

U = both S1 = suture line A = anterior P ,. posterior


TEST HEEK 51

-STUDY IIUIIBER L6121-6

TEST ARTICLE ROX ---/d;iy. Q,0

~·-" , '·""". C

loo.Joo

f':ii-e.----'-

Luxated Lens Vitreal Strands

Vitreal Hemorrhane

Retinal Folds


___, ~ r( lJJ :,_ Cf:! ...... :.:..: z=:i


TEST ARTICLE ROX

DOSE mg/kg/day

SEX Male

0.3 --' ~

~

00


TEST ARTICLE ROX

OOSE mq/kq/day _()__]_

SEX Male

1es1nn

~~


TEST HEEK 51 ------.--·, ----·r·--,--,-,-,--- ·i----i 1

~ ~ I~ IN IM Is,- Im I ~ ~1 "'I ml cl ~1 NI MI"' Im I'° I ~1 °"I

STUDY IWI-IBER L6!21-6

TEST ARTICLE ROX -DOSE mg/kg/day O.O

__, ~ SEX Female

"

STUDY tiUMBER L6121-6

TEST ARTICLE ROX ay 0.0

-' °'

STUDY NUI-IBER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day JW. SEX Male

Within nornrnl limit_~

Lid Laceration

Lid scarring

Ocular discharge

J"' d'. w :;: 00

~

N 0

STUDY NUHBER L6121-6

TEST ARTICLE ROX

DOSE mq/kg/day .Q.,l

SEX Male

lP

J"' 1-


TEST IIEEK 51 STUDY Nlll-lBER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day .Q..1.

SEX Male

2S$1-1N1M1~1 ~3 ~ !-S~ -NM~[§_~~ 001 ~1 °1-1N1 Ml 71 ~ ~~ ~ ~ ~ ~ . ~ ~ ~ ~;::;;::;;::;;::; ;:/;::;;::; N;::;;::; ~ ~ ~ ~ ~ ~ \lithin normal limits Xx Xx xi xlx:1-2'._J Xl Ix I X[tj_:_L_:_j:_j_?'_~!_I XI* IX Lid Laceration -~-Lid scarring --- -- _,_,_ Ocular discharge ___ ·1 r-1-l--l-l-l-l-.;-,-•-•-Conjunctivitis ,_ 1-- -\-1-1-1-1-1 1 I I I Chemosis - -- _,_ -~·

Buphthalmia ---'- ul-1-l-t--•Phthisis _,_,_,_ _,_ - ,-1--t-•-

1~-•-

-•-•-•·-•-•-•-!--!-! I I-

Enophthalmia ·-· - - 1._

Keratitis 1- - 1--- - _j7 Corneal Edema - - - - - - -]-J

'--------------t-t-l-l-l-l-l-l-1--1.-H--1.-

~

N N


TEST ARTICLE ROX

DOSE mg/kg/day .lll SEX Male

, ,...,. ~ ""

---

I ~"' d'. w ;;§@1~1NIMl""l"'I z:=iOOCOO o::t:zNNNNN

I NC !DENCE OF OPHTHALMIC LES IONS

TEST HEEK 51

~ ~1~1~1~1~1z121~1~1 ~ ~I ;:1/ ~! ~1 ~I~! ~( ~! "' N N \ cataract I l-l-i-H-1--1 I I I I i-\-1--1----1---__,_-1_,_

luxated Len,

I ~::~::~ :::~~~age 1-t=1-t=1~=1=j-r I I ! l=l=w=l=1 I I I-I-I Retinal_ Fol~_,_

i Vascular _ _btt~nuat_ion; Rg_tina1 I I • rhor_o1dal

' · Retinal Hyperreflect1vitv Srarse Choro1dal Vascular Pattern

Retinal Hemorrhage

Retinal Oe_generation -1--1-1--!-t--l--t--;---,

I Papilledema I I ~1-1 I 1-1--1-1-H f I I l-l-l-1--1-1-1 , 1-. Icterus H-1- -1--!-+---l I I I-H-1--1--1--1--I-H--!-1-1-

0rbital Mass

Nys tagmus

I Bled - orbital sinus I I I I I 1 · I I -i--t-l-+-\1-+-l-+-t-l-l-t--l--! -•-in: B I I I I I --1-1 1-1---1 I I I-I-H-1-1---f-J

w u ~) ';

~ ·-u C -=:!J

-I I I

I I

10

\---

-- ---·-- ------ ... KEY:

--,,:,:------'-.L....J..--l_L...L-1._I_.L..J......J._L._..l_.L- --~--

L = left C = capsular R = right S = sector U = both Co= cortical Sl= suture line B = brunescent A = anterior V = vacuoles P = _posterior /.1 = mature

I = immature N = nucleus

*=previously died or sacrificed

Bl= specific eye used not recorded


TEST ARTICLE ROX

DOSE mg/kg/day .£.:2 SEX Female_

Within Norm~l I imit~ lid Laceration

--"" -0: w :c "' ~,: z C, -0: z

"' ~ °' 0

N N M N N N

* xix X X


TEST WEEK 51

~ N M rj" m "' ~ t ~ 0 M M M M M M M M tj N N N N N N N N N -

X X X X X X X * X X ----

~ N M rj" m "' ~ cc ~- 0 rj" rj" rj" rj" rj" rj" rj" rj" tj m N N N N N N N N N N

X X * X X X X X X X

I Lid scarring \ \ \ \ \ \ \ \ -1-1 . \-\- I \ I I l-l-1-1----1-1 I Ocular discharge

\ ~~:~~:~~ivitis 111 l~j I IJj-1-1 I tttttl=td=tljj Buphthalm,a

-Phthisis

I ~:~::~:~:mia I I I I I I I j_\j_\_\ I I I-1-lj=IJ_\j I 1-1 1 Corneal Edema

Corneal sea,:

I Hyphema lritis/Anterior Uveitis I I I \---I I I 1-\--\ I I f----1--1 I I I I I I I ! I _ Anterior Synechia Posterior Synechia I f--1 I I I I I I I 1--Iris Bombe

I :~::~:~~ ~:~: ~~~~::s Lines I I I I I I I Hj I I I ttt I I I I I I I I I -~

N ~

KEY:

L = R = u = Sl= A = p a


C = capsular I = immature S = sector N = nucleus Co= cortical *=previously died or B = brunescent sacrificed V = vacuoles M = mature

~

N ~

I


TEST ARTICLE ROX

IJU)t ll!!j/ t::lj/ u,1,y - • -

SEX Female

1--'on

C, • .

Luxated 1 ,..,.,,.

Vitreal Strands

Vitreal Hemorrhaae

Retinal Fo 1 ds


~~ .-.i:: t,J ;:~ ~ ,_. ::::::: z cc,


TEST ARTICLE ROX -OOSE mg/kg/day 0.3

-- --,-.--

SEX Female ..J ~ « w :7- i:c ~ N M ST ~>= m m m m z => N N « z N N

Within normal limits X X X X

Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis

Chemosis Cuphthalmia

Phthisis

Enophthalmia

Kera tit is

Corneal Edema

Corneal scar

H1mhema


Anterior Svnechia Posterior Synechia

Iris Bombe


Prominent Lens Nucleus KEY.

~ L = left N ~ R = right

U = both 51= suture line A = anterior P = posterior


TEST l!EEK 51

I

m '° ,-.. ro "' C ~ N M ST m m m m m m '° '° '° '° '° '° N N N,N N N N N N N N I I

' X X * " X X * X X

R L

- '---

- --

-

- - -

-

'° ,-.. ~ ~ '° '° N N

X X X X

- -

-

~ - --

-

- - -

-

-


0 ~ N ,-.. ,-.. ,-.. N N N

X X

R


M ST m ,-.. ,-.. ,-.. N N N

X X .,

-

-

--

.,-N

"'

i

STUDY 11u1mrn L6121-6 TEST ARTICLE ROX DOSE mg/kg/day 0.3

SEX Female

1,., .. ~.,n

,..~ .. ~-~- ..

Luxa ted 1 """

Vitreal Strands Vitreal Hemorrhage Retinal Folds


---"'' '"' w :,: a, - ::: z co '"' z

Retinal

Choro1dal

Retinal Hvoerreflectivitv

Sparse Choro1dal Vascular Pattern

Retinal Hemorrhaqe


Papilledema

lcterus Orbital Mass

Nystagmus Bled - orbital sinus

-------· KEY:


--- ··- -

- N m m N N

Bl

S1= suture line A= anterior

-P "·"aster.inr

M m N

ST m m m N N

- -


TEST HEEK 51

"' ~ 00 "' 0 - N M ST m m m m m "' "' "' "' "' "' N N N N N N N N N N -

- - - ,__

"' ~ 00 "' 0 - N "' "' "' "' ~ ~ ~ N N N N N N N - ,__

- ,__ -

-

-- -- ,__ -

- -- - - - ~ -

- -- ~ - -

- - - - -Bl B Bl Bl B ,__ Bl - ,__ - - ,__ - - - - ,_ -

C =·capsular I = irrnna ture S = sector N = nucleus Co= cortical * = previous1y died or B = brunescent sacrificed V = vacuoles Bl= specific eye used not M = mature recorded

M ""' ; ~ ~ N N

-

=I j

' ,__ -l - ~

,__ - =I -- - ,__

STUDY fllJl,\BER L6121-6

TEST ARTlCLE ROX - -

DOSE mg/kg/day o. 3 . ' - . ----

Female ~ °" SEX

~ ~

'" STUDY IWl·\BER L6121-6 TEST ARTICLE ROX DOSE mg/kg/day 0.3

SEX Female

loo l no

r::11t----t

Luxated 1 ---,c:

Vi trea 1 Strands

Vitreal Hemorrhaae

Retinal Folds Vascular Attenuation:

I •

~"' ""w :,: ro - :c z =, «z

Retinal Choroidal

Retinal Hvoerreflectivitv Sparse Choroidal Vascular Pattern Retinal Hemorrhaoe Retinal Degeneration

Papilledema Icterus


: Bled - orbital sinus

- -.-----. ~ - ----KEY:


"' f ~ N

-

S1= suture line A= anterior P_ = p.ost.erio.r .

ro "' G ~ ~ ro N N N


TEST WEEK 51

~ N M "' m "' ~ I i 0 ro ro ro ro ro 00 00 O'-N N N N N N N N I

•-

Bl

~ N M "' "' "' "' "' N N N N

-

--

STUDY IIUI\BER L6121-6

TEST ARTICLE ROX -DOSE mq/kg/day 1. 5

---,------ -

SEX Male -"'' « w :c: "' - N M "' = ~ :c: 0 0 0 0 0 z~ M M M M M d;Z

Within normal limits * X X X * Lid Laceration -Lid scarring

Ocular discharge -

Conjunctivitis

Chemosis Ouphthalmia

Phthisis

Enoph tha l mi a

Kera titi s

Corneal Edema

Corneal scar H" .... hema

Iritis/Anterior Uveitis Anterior Svnechia Posterior Svnechia


Prominen_Llen~_~Jcleus KEY:

L = left "'" R = right w '"'

U = both 51= suture line A = anterior P = posterior


TEST HEEK 51

~ ~ "' °' 0 - N M "' ~ ~ ~ 00 "' 0 0 0 C - - - - - - - - - -M M M M M M M M M M M M M M X * X X X X X X X X X X X X

·-1--1-- - - 1-- - -

-

-


0 - N N N N M M M X X X

-


M "' ~ N N N M M M

X X X

1--

.r:-,, 0

STUDY 11u1mrn L6121-6 TEST ARTICLE ROX

--·- --·· -~ DOSE mq/kg/day 1.5

SEX Male ~"' "" w :::: cc ~ I ;; ,_,:::::: z cc,

1 odnn -0: z

,._ .. ____ ..

Lux a ted 1 ,:,.,c;

Vitreal Strands Vitreal Hernorrhan


TEST ARTICLE RDX

DOSE mg/kg/day l,:i SEX Male

INCIDENCE OF OPIITIIAU11 C LES IONS

TEST HEEK 51 ----.~-.----.-r,---- -

~*I w I ~1 00 1 m IO 1-1N IM I "'I ml wl ~1 00 1 m I c 1-1 ~ Ml s,·1 ml w I~ I 00 1° I c .....,~ N N C"J N M M M M M MM M M M tj- rj-

~

~

N


TEST ARTICLE RDX

DOSE mq/kg/day Ll SEX Male

l oc, -T nn

J"' "" w :::: cc ,_.;;::: z C, .::CZ


TEST !- =I Bled - orbital sinus 31 Rl Bl B Bl .

I I I I I I I 1-1- I I I 1-1 I I 1--1-1--------·--··

KEY:

L = left C = capsular I = immature R = right S = sector N = nucleus U = both Co= cortical *: previously died or Sl= suture line 8 = brunescent sacrificed A = anterior V = vacuoles Bl= specific eye used not P ."'- n.os teri or . - M = mature recorded ·- -- "

STUDY HUMBER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day Ll SEX Male ~"' d'. w

:c"' - 0c z =, d'. z ~ ~ ~ "'I ~ ~ ~1 M M


TEST I/EEK 51

~I ~I ~I ~l ~\~l~l~l~\ ~ ~ ~ 1-

"'l°'lcl~INIM lO lO r-. r-. r-- r-. M M M r,; M M

"'I~ ~ ~ MM W. h' l l' 't " X X X ,X I ,t ,n norma 1m1 s -H !._J~l!._l~l~~~(_:\~Lll_l~l!._~j_~_J~~~l~ Lid Laceration 1 1-t--

Lid scarring L__ --•- ,-- ,--,--,--1--+--+--•--Ocul_ar discharge ___ L f---·jjj I I I ConJunct1v1t1s _ _ f- _ _ ,-l---1-1--Chemosis

Buphtha lmi a j I I R j 1-1-----1-l----1----1 I I I l--l--l-1--\-1-1--1 ! l-+-----1-, .Phth is is

i Enophthalmia I 11 i 1-ljjjj-1 I I ttt-1=1=\jjjjj_;--l Kerat1t1s 1 Cornea 1 Edema

Corneal scar I \ 1---1-J j I --l-\--1-l-+-+--l--+---1--1-1--I--J---+--+--+--I~. ---< ):ly_R._hema

lritis/Anterior_~_y~itis

Anterior Synechia R

Po~terior Synechia "' --- --~jj I I ~l Iris Bombe +-

'" u C

"' u u C

61

1

1

1

Prominent Lens Suture Lines --H·--1--1--1 1 Promine!lL~en~.N~cleus . I I J ,,,. w w

KEY:

L = left R = right U = both 51= suture line A = anterior P = pas teri or

C = capsular S = sector Co= cortical B = brunescent V = vacuoles t-1 = mature


sacrificed

~ ~

~

STUDY NUMBER L6!21-6

TEST ARTICLE ROX

DOSE mg/kg/day ..1.,.5.

SEX Male

lesion

~ °' "" w ,: co -,c ~ z =, = "" z

M

N M tj" = m m m m M M M M


TEST HEEK 51

'° ~ co m 0 ~ N M .,,. = m m m m '° '° '° co co co M M M M M M M M M M J '° ~ co m 0 ~ N M tj" co co co co ~ ~ ~ ~ ~ M M M M M M M M M I f-\-L-H-1-1-1-1-1 I f-f-f-f-l-l-l-----1-1-1--1-•--~-----------------1---1---1----1-J I I I l I I I I I I 1-1-1-1-1-1-t-t-'--

I ~~:~::~ ;:~:nds ~I I I I I 1~=1=1=~\=!t=t=t=t=t=l=l=l--11 I I I Yitreal HemorrhaoP Retinal Folds_

Vascular Attenuation: Retina}

Choroidal

I Retinal Hyperreflectivity I \ \ I \ \ \ \ \ -1 I I I I I I -1-l-l Sparse Choroidal Vascular Pattern

Retinal Hemorrhage Retinal Degeneration R

Papilledema

Icterus Orbital Mass

'" u C

'" u --u C -

1

1

1 I

f.-..J •

. Nys tagmus , ,

i Bled - orbital sinus rt I I I I I111-~r=-~I IB1I I I I I1~-tl ~-·-·- -·-- --- ..

KEY:

L = left C = capsular I = immature R = right S = sector N = nucleus U = both Co= cortical *=previously died or S1= suture line B = brunescent sacrificed A = anterior V = vacuoles Bl= specific eye used not o = o.0c:teri.nr_ M = J.Da ture recorded


TEST ARTICLE RDX --- ·-- - -OOSE mq/kg/day 1.S

SEX Female -' ~ < w :::: en ~ ~ 00 m 0 ...... ::-.:: ~ ~ ~ ~ ro z~ M M M M M < z

Within normal 1 imits X X X X - -lid Laceration Lid scarring

Ocular discharge L

Conjunctivitis

Chemosis

Buphthalmia

Phthisis Enophthalmia

Keratitis

Corneal Edema

Corneal scar

H" .... hema

Iritis/Anterior Uveitis Anterior Svnechia Posterior Stnechia

Iris Bombe



~ L = left w V, R = right

U = both Sl = suture 1 ine A= anterior P = pas teri or


TEST l!EEK 51

~ N M tj· m ~ ~ ro m C ~ N M 00 ro 00 00 00 00 00 00 00 m m m m M M M M M M M M M M M M M

X X X * X X X X * X X '---

f--

u R - f-- -

- -

-- -


tj m ~ m m m M M M

X X X

-

-


~ 00 m 1 m m m M M M X X X X

---

-- j

-'

- f---

~

w

"' STUDY IIUIIBER L612!-6

TEST ARTICLE ROX -

DOSE mq/kq/day 1.5

SEX Female --' °' « w ~ cc

~ ~-1--J--

z =, CZ

- . -· Lux a ted Lens

Vitreal Strands Vitreal Hemorrhage Retinal Folds Vascular Attenuation: Retinal -

Choroidal Retinal Hvoerreflectivitv Sparse Choroidal Vascular Pattern

Retinal Hernorrhaae Retinal Degeneration

Papilledema lcterus


Bled orbital sinus 1

KEY:

L = left R = right U = both Sl= suture line A = anterior

~-P =.,r10


TEST ARTICLE ROX -DOSE mq/kg/day 1.S

--~~~

SEX Female __J "' «w ::-..: o:! - N M " ~ ,.....z 0 0 C 0 0 z~ " " " " " « z

Within normal limits X X

Lid Laceration

lid scarring

Ocular discharge L R R

Conjunct i vi tis


Phthisis

Enophthalmia

Keratitis

Corneal Edema

Corneal scar

Hvnhema


Anterior Svnechia Posterior Svnechia Iris Bombe Prominent Lens Suture Lines

Promi nen1-.1_en~_~uc l eus KEY:

.,,. L = left w ~ R = right

U = both Sl= suture line A= anterior P" posterior


TEST HEEK 51

"' "- a) "' 0 -N M " ~ "' "- a) 0 0 0 0 --- - - - - - -" .,. " " " " " " " " " " " X X * * X X * * X X * - - -

L L - -

-

-


"' C - N - N N N " " "' " X X X

-


M " ~ N N N " " " X X X

r

-

~

w co

I


TEST ARTICLE ROX ----- ·-·- - -

/kg/day 1.5

.emale _, 0-C

- - " " lnc:i~~ CZ C,h .

Luxated Lens Vitreal Strands Vitreal Hemorrhane

Retinal Folds Vascular Attenuation: Retinal

Choroidal

Retinal Hyperreflectivitv

Sparse Choroidal Vascular Pattern Retinal Hemorrhaoe Retinal Degeneration Papilledema Icterus



KEY:

L = left R = right U = both S1= suture line A= anterior

· P -::- -,..·-s te~ ~ ,.., ...

M 0

"

-·

" m D D " "


TEST HEEK 51

~ ~ co "' D -D D C, D - -" " " " " " -

- - -

-

C = capsular S = sector Co= cortical

-Bl -

8 = brunescent V = vacuoles M ;:_ m_.:1 ture

-

N M " - - -" " " ---

m ~ ~ co "' C - N M - - - - N N N N " rj " " " " " " " - - _,

-- -

- ,_ -f--

R ~,. - -

u -- -

-- - - - -,_

- - --

- - - - - ,_ - - -·

I = im111a ture N = nucleus


Bl= specific eye used not recorded ' .

" m N N " rj

I

-

'

,_

-j

- f--

STUDY IIUHOER L6121-6

TEST ARTICLE ROX

OOSE mg/kg/day .L§. SEX Female

INC!OENCE OF OPIITIIALMIC LESIONS

TEST HEEK 51

-"" "' w ,: 00 ,_..z z C, "' z

~ ~ t1 ~1 ~1 ;:;;I ~'1 ;:::I ;,;

~

~

0

STUDY NUMBER L6121-6 TEST ARTICLE ROX 005[ mg/kg/day !c.:i SEX Female

1 ac, ~ nn


TEST HEEK 51 -~r· ----.-.--,--,---,-~-,---,-,--,--,--,--~-,---,-,--,---,---,---,-,-,

~ °' ~ $ I ~ I ~ I 00 Io; IO [ ;;j NI Ml "'[ ~ I ~ I ~ I 00 I o; IO [ ~ ~~ ~ ~ ~ ~ ~' tj-1 ~ ~ !;? ~ !;;? ~ ~ ~:; :; NI Ml "'I ~1 "'l~l"' I"' IC tj"tj",::j"


TEST ARTICLE ROX 8.0 --- -. ···-DOSE mq/kg/day

SEX Male ..J "' '"'w "00 ~ N M s, m - :c m m m m m z~ s, s, .,,. .,,. .,,. '"'z

Within normal limits X X X X

Lid Laceration Lid scarring

Ocular discharge

Conjunctivitis

Chemosis

Buphthalm1a

Phthisis

Enophthalmia

Keratitis

Corneal Edema

Corneal scar

Hvnhema

Iritis/Anterior Uveitis Anterior Svnechia Posterior Svnechia Iris Bombe Prominent Lens Suture Lines

Prominent Lens Nucleus ·------KEY:

~ L = left ~ R = right

U = both Sl= suture line A = anterior P = posterior

IIICIDENCE OF OPHTIIALMIC LESIONS

TEST HEEK 51

"' ~ 00 "' 0 ~ N M s, m "' ~ 00 m m m m "' "' "' "' "' "' "' "' "' .,,. s, .,,. .,,. .,,. .,,. .,,. .,,. .,,. .,,. s, ST ST

X X X X X X * X X X X X X - f-- - -

-

f-- -

,_

-

f-- ..

-f--

·-


"' C ~ "' ~ ~ .,,. ST ST

X X X


N M .,,. l ~ ~ ~ ST ST ST X * X X

~ - ~

~ p N

STUDY IIUIIBER · L6121-6

TEST ARTICLE ROX

DOSE mq/kg/day b.Q. SEX Male

,~sinn

--' ~

lrlCIDENCE OF OPHTHALMIC LESIONS

TEST !!EEK 51 . ·-,--r .-.--r-.- ---,-~--,-,-,--,-·

~ :5 LO LO LO LO LO LO LO LO LO lD lD lD lD lD


TEST ARTICLE ROX --- ---· --

OOSE mg/kg/day 8.0 SEX Male _, "'

~

-~ ~

STUDY IIUll8ER L612!--6

TEST ARTICLE ROX ------DOSE rnq/kq/day .Q.,Q

SEX Male

lcinn

-' "'

STUDY NUl•mER L612!-6

TEST ARTICLE ROX

DOSE mq/kg/day ~ SEX Male .J °'

"-~

O'

STUDY NUl1BER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day llJi. SEX Male

,~~~~~

~~ d'. w

;':; "' I z C, d'. z §I ~ ~1 ~1


TEST WEEK 51

~l~l§\5ll~l~l~\81 ~ ~ ~I ~[~]~\~!~\ 511 ~I Ml"I~ N N N ~ ~ ~ M

I Cataract L I l--l----1----H----1--1--1----1 I I I /----R

----1---- ----l----+---r-t--l-1--1--

Luxa ted Lens \ 11 11 I \ I \ \-t----1----\ I I H----1--- -Vi trea 1 Strands ri---t--\----\-j-----j-j----\----1-1-1-----J----V i t real Hemorrhage !--l---J-j----J--J----J----J-----1---- ---- ----f-----l--l-l-1-/----1-/----1----1---+--l----,----,--j

I I I 1-1----/--j--j---,----,,--1-1

Retinal Folds

Vascular Attenuation: R~tinal l;_horo1 de_! ----' I

Retinal H erreflectivit I , /----H-!--1--1----f--l I I f--1----Sparse Choroidal Vascular Pattern I I I I 1---1-1-1- ----1-+--+---H----I-Retinal Hemorrhage

\ Retinal Degeneration I I I I \-\-\-1-\ j \ I /----f----H-i----i I I I I I ! Papilledema

I c terus 1---1--1 J-----i-l-----l----l-l-l-1-----'--l---l--+-l-+--+--+---t--+---t---1 Orbital Mass

Nys tagmus

j Bled - orbital sinus H--IBl I I I I ~-H I I I + I I I /-~1 j j I I __,_,___ I I I I I I /----f--1-t-t I I I /-'-- -l--+-1-1-1---

'" u C

'" u ·-u C -

1

10

.1

I ---.\

I ., I '

I I

·---·-- ----- '-'---'---'---'----'--'---'---'--'--'-'----'--'--k--'-+--~-L.__.L~-+---~1-----KEY:

L = left R = right U = both 51= suture line A = anterior

_p =_pas. teri or

C = capsular S = sector Co= cortical 8 = brunescent V = vacuoles M = mature

I = immature N = nucleus


Bl= specific eye used not recorded

STUDY IIUMBER L6!21-6

TEST ARTICLE ROX

DOSE mq/kg/day 8.0 ---- - -

SEX Female ~ °' -0: w Zoo "'

.

"

STUDY IWI-IBER L6121-6 TEST ~RTICLE ROX DOSE mq/kg/day §_,.Q SEX Female

lac-I--

INCIDENCE OF OPHTl~LMIC LESIONS

TEST lffEK 51 - , - ,·"- .----r--T--r-~~--.--.-,-,-----,-.,. ---.---,----r --, -- 1 ---,--· --,--·

--l


TEST ARTICLE ROX

DOSE mg/kg/day !:.Q. SEX Female


lid Laceration

lid scarring

--""

~

~

0

STUDY IIUl·IBER L612!-6

TEST ARTICLE ROX

DOSE mg/kg/day .JL..Q

SEX Female

7 oc,~rw

_, °'


TEST ARTICLE RDX ---DOSE mq/kg/day 8.0

SEX Female


Lid scarring

Ocular discharge

Conjunctivitis


-Phthisis

Enophthalmia

Keratitis

1

1 Corneal Edema

Corneal scar

H··-hema

Iritis'Anterior Uveitis

Anterior Svnechia Posterior S11nechia

Iris Bombe


Prominent Lens Nucleus . ----- -KEY:

~

~

~"'

C

" J


TEST ARTICLE ROX

DOSE mg/kg/day S.O

SEX Female

, ~~ ~

_( •- - . - ,

Luxated 1 e--

Vitreal Strands

Vitreal Hemorrha~~

I Retinal Folds ' 1 Vascular Attenuation: I . '

--' "'

STUDY NUIJBER L6121-6

TEST ARTICLE ROX

DOSE mg/kg/day 4o.O

SEX Male ~ °' "'w l 1 ,: "' ~ r r -:::: z =,

"'z

Within normal limits * ,,

* Lid Laceration

lid scarring

Ocular discharge

Conjunctivitis


-Phthisis l,

Enophthalmia Kera ti tis

Cornea 1 Edema

Corneal scar

H•mhema


Anterior Svnechia L

Posterior S_ynechia Iris Bombe

Prominent Lens Suture Lines Prominent Lens Nucleus ··-~-

KEY: ~

~ L = left w R = right

U = both S1 = suture line A= anterior P = posterior


TEST \!EEK 51

5 ~ 0) m 0 ~ N M " ~ '° ~ 0) 0 0 0 ~ ~ ~ ~ ~ ~ ~ ~ ~ '° '° '° '° '° '° '° '° '° '° '° '° * X * X X * * X * X X X

-~ -

L

C = carsular I = im111a ture S = sector N = nucleus

m C ~ ~ N N

'° '° '°

X X *


N M " ~ N N N ~ '° '° '° * *

R

R

e n ~

I '

S TUOY IIUI IC ER L6 l 21-6

TEST ARTICLE ROX --- -40.0 -DOSE mg/kg/day

SEX Male _, "' "" w ;; 1 :;:: o:J ~~


TEST ARTICLE ROX

DOSE mg/kg/day 4o.O

SEX Male


Lid Laceration

Lid scarring

Ocular discharge

Conjunct i vi tis

Chemosis

Buphthalmia

-Phthisis

Enoph tha l mi a

Keratitis

Corneal Edema

Corneal scar

Hvohema




Prominent Len~ . .N~cleus KEY:

~

V; V;

.., "'

C

n ~


TEST ARTICLE RDX

DOSE

SEX

111q/k9/d,1y j.2..:..Q

Male

1 r>sj nn

_J °' I ~I .,,.,. w

~ ~I ;;~ cc Z§


TEST ARTICLE ROX

DOSE mg/kg/day 40.0

SEX Male ..J °' "" w ~ [ t ;;' :c co - :c z C, " ""z

Within norma 1 limits X * X Lid Laceration

Lid scarring u

Ocular discharge

Conjunctivitis


-Phthisis LJ Enophtha lmi a

Keratitis

Cornea 1 Edema

Corneal scar

Hvnhema

Tritis/Anterior Uveitis

Anterior Svnechia Posterior Synechia Iris Bombe


Prominent lens Nucleus ·-----·-· KEY:

~ L = left V, R = right ~

U = both S1= suture line A = anterior P = posterior

t

X

INCIDENCE OF DPHTHALMI C LES IONS

TEST I/EEK 51

~ ~ co "' M 0 ~ N st ~ ~ ~ ~ '° '° '° '° '° '° '° '° '° '° '° '° '° '° '° ,_

X * X * X X * * X

'° ~ '° '° '° '°

* X - - - - -

- - -· - - - -

- - - - - - - - -

1- - -L

- ,_ - - - - ,- - -- -- - -

-,_ - - - -1- - - -

L -·

co "' 0 ~ N M st ~ '° '° ~ ~ ~ ~ ~ ~ '° '° '° '° '° '° '° '°

* * X X X X * - - 1-- - - - - -- - - - - -- - - - - - - --- - - - - ·- - -

- -

j= - - - -- -

- -

-

1-L

f-- -

-

-L - - - - - ---

- - - - -- - f-- - - - - - - - -

..

C = capsular I = immature S = sector N = nucleus Co= cortical *=previously died or B = brunescent sacrificed V = vacuoles M = mature

ru u C ~

" ·-u C -

34

1

4

1

4

2

-·--

~

n ,,

STUDY IIUMBER L6!21-6

TEST ARTICLE ROX

DOSE mg/kg/day

SEX Male

1 os i ""

40.0 -


TEST HEEK 51

_, "' ~~1~1N1M1cy1~l"'l~l°'I §I IBI ~1N1M1cy1~1"'1~1ro1m ;'.:; """ Ln Ln Ln LO LO LC> ln Ln lO I.O I.O lO lO lO I.O lO lO :z:: :=j lO I.O

STUDY HUMBER L6121-6

TEST ARTICLE ROX -DOSE mg/kg/day 4o.o SEX Female


Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis


-Phthisis

Enophthalmia

Kera tit is

Corneal Edema

Corneal scar

Hvnhema




Prominent L'l!J_~_Nucl eus

~

~

co

KEY:

L = R = u = Sl= A = p =

..J °' "" w "' 5 ,:: co - ,: " z~ "' ""z

X X


00 "" 0 " " 00 "' "' "'

X ;, * f--


TEST I/EEK 51 ; '

~ N M 7 ~ "' " 1 cr 0 00 co co co co 00 co ~ "' "' "' "' "' "' "' "' "' X X X X X X X * * ·>

- -

~ N M 7 ~

"' "' "' "' "' "' "' "' "' "'

X X X X

- -

-


"' " "' "' "' "'

X

-


00 "' 0 "' "' 0 "' "' "

X X X

--l-

--

! ,I

-

.-"' 0

IIIC!DENCE OF OPHTIIALl11C LESIONS

TEST HEEK 51 STUDY IIUI\BER L6121-6

TEST ARTICLE ROX DOSE mq/kq/da_y 4o.O SEX Female

--, -~~-,-- r-· ,--, r .,....-;·--,--·1·--,----.--..,. --1--1 -· ! - , -

~"' "'~ I ~I ~ !;[ ~I ~\ i:l[ ~lilffi\IB!f2!ffil ~I ffi\ ~I -1 N1M1~1=1


TEST ARTICLE RDX --DOSE mg/kg/day 40.0

SEX Female


Lid Laceration

lid scarring

Ocular discharge

Conjunctivitis


-Phthisis

Enophthalrnia

Keratiti s

Corneal Edema

Corneal scar

H""hema




Prominent Lens_~ucleus KEY:

~

~

J"'

L-

O' N

STUDY NUIIBER L6121-6 TEST ARTICLE ROX -DOSE mq/eg/day 4o.o SEX Female

1~-::i~~

C,h_,e,

Luxa ted 1 ~~ ..

Vitreal Strands Vitreal Hemorrhaae Retina 1 Folds Vascular Attenuation:

_, O' = 00 ...... ::::: z C,


TEST ARTICLE RDX

DOSE mg/kg/day 4o.O

SEX Female

Within normal 1 imits

Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis

Chemos is

Buphthalmia

-Phthisis

Enophtha lmia

Keratitis

Cornea 1 Edema

Corneal scar

Hvnhema


!interior Svnechia

Posterior Synechia


Promin~rit_L_en§: _Nucleus KEY:

.,,.. ,,., ~

_, "' ~ ~ ~ ~

"" z

X X X X

C-- -

INCIDENCE OF OPHTIIAL11IC LESIOIIS

TEST I/EEK 51

0 - N M "' = ~ ~ co m 0 M M M ~ M M M M M M "' ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ * X X X * X X * - - -- - ,-

i _)_ - - - - - - ~

- - - - - - - --R

- -

- - - ·- - - -- ·- -

- - - -L

L R - -

- - - - - -R

- N M "' = ~ co ~- ~ ~ "' "' "' "' "' "' "' "' .,,. ~ ~ ~ ~ ~ ~ ~ ~ ~ ~

* * ~} X X X X X X X - - - - - C-- - -- ·- - - - ,_ - - - ~-

- - - - -- - - - -·- ·- ·- -- - - - - - -- - - - - ,_ - - - -

-

-- - - -- - - - - - -- - - - ,_ - - - - -

- - - - -- - - -

- - - - - - -·--

- - - - - - - - -- ·- - - - - - - - - - -- -· - - - - - - - - -

- - - - - - - - - - - - - - - -- - -

L = left C = capsular I = immature R = right S = sector N = nucleus U = both Co= cortical *: previously died or Sl= suture line 13 = brunescent A = anterior V = vacuoles

sacrificed

P = posterior M = mature

" u C

" u ·-u C -

50

3 ----1

1-1 -·--1

' I-·-'

1-1~

-i I

' '.!

1

3

1

' j __ ., _I

,,

~

~

~

STUDY IIIIIIBER L6121-6

TEST ARTICLE ROX

1)05[ mg/kg/day 40 ·0 --- . ·-

~~

SEX Female « w

STUDY IWI-IBER L6!2!-6

TEST ART! CLE ROX -DOSE mq/kg/day 0.0

SEX Male


lid Laceration

Lid scarring

Ocular discharge

Conjuncti vi tis


Phthisis

Enophthalmia

Keratitis

Corneal Edema

Corneal scar

H"nhema

Iritis/Anterior Uveitis Anterior Svnechia Posterior Svnechia



~ 0--~

--- -- -- -

-"'' "" w :c "' -:::: z co CZ

~ N M s,- m

X -r~ * X

I,

I,

L = 1 eft R = right U = both Sl= suture line A = anterior P = posterior

ltlCIDENCE OF OPHTHALl1IC LESIONS

TEST I/EEK ','6

0 ~ N M s,- ~ ~ ~ "' ""

~ ~ ~ ~ ~ ~

X X * * X X X ~

u u

~

u

-

I

I,

~ ~ "' O' ~ ~ ~ ~

X X * 1~

-

-'--

-


C ~ N N N N

X * X


M s,- ~ N N N

* * X

j - ~

'

STUDY IIUt,tBER L6121-6

TEST AIHICLE ROX

DOSE mg/kg/day _Q,,_Q

SEX Male

1,:,cinn

--' ~ COO ...... z:


TEST HEEK 76

~~l.--1\N\ '"'1


TEST ARTICLE ROX -DOSE mg/kg/day D.D

--- ·--- - -· --·

SEX Male .J °' "" w :z ~ ...... ::::: ~ ~ co "' 0 z C, ""z N N N N M

Within normal limits X X X X * -Lid Laceration

Lid scarring

Ocular discharge

Conjunctivitis

Chernosis

Buphthalmia

Phthisis

Enophthalmia

Kera titi s

Cornea 1 Edema

Corneal scar

H•mhema




Prominen.:L1_en~_N_!:lcl eus KEY:

~ L = left "' ~ R = right

U = both 51= suture line A = anterior P = pas teri or

IIICIDEHCE or DPIITIIALI\IC LESIONS TEST HEEK 76

- N M "' ~ ~ ~ co "' 0 M M M M M M M M M "' -

X X * X * X X * X X

- N M "' "' "' "' "' X

f-- -

f-- - --

Documents

Contract No. DAMD17-79-C-9161 I ITRI Project No. L6121 Study … · 2018. 8. 22. · contract no. damd17-79-c-9161 i itri project no. l6121 study no. 6 determination of the chronic