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SUBACUTE TOXCIT OFF"D

AD Submitted To:Office of Naval Research

S800 N. Quincy Street•.. Arlington, Virginia-. Contract No •Ad• l4- 73-C-162

•/ - -.1" iiIi

Submitted By: FE 17

I i L~~~~1itton Bionetics, Inc. .•, _,,•Il"5516 Nicholson LaneetKensington, Marylgand

SJuly 19, 1974 B

DISTRIBUTIOINS.., -I .IH3 BIONETICS Approved fox )1:,bK:: reeakse;

Utton Distributic/ Unhim,:ed . £-

SUBACUTE TOXICITY OF RDX AND TNT IN DOGS

Contract No. N00014-73-C-0162

TABLE OF CONTENTS

Page No.

I. SUMMARY ------------------------------------------------------ 1

II. OBJECTIVE ---------------------------------------------------- 2

III. MATERIALS ----------------------------------------------------- 2

IV. METHODOLOGY --------------------------------------------------- 2

A. Animals and Husbandry --------------------------------------- 2

B. Group Assignments ------------------------------------------- 3

C. Diet Preparatijn and Administration --------------------------- 3

D. Observations ----------------------------------------------- 4

E. Laboratory Diagnostic Procedures ------------------------------ 5

F. Termination ----------------------------------------------- 5

V. RESULTS ------------------------------------------------------ 6

A. Observations ----------------------------------------------- 6

B. Laboratory Diagnostic Procedures ------------------------------ 7

C. Pathology ------------------------------------------------- 7

"VI. CONCLUSIONS --------------------------------------------------- 8

VII. APPENDIX

Table 1: Body Weight ------------------------------------------ A-i

Table 2: Hematology - Cytology --------------------------------- A-6

Table 3: Hematology - Heinz Bodies ------------------------------ A-344 I

Table 4: Hematology - Red Cell Fragility ------------------------- A-37

Tab'e 5: Blood Biochemistry ------------------------------------ A-65

j m BIONCL;CSUtton

ii

TABLE OF CONTENTS (cont'd)

Page No.

VII. APPENDIX (cont'd)

Table 6: Sulfobromophthalein, U.S.P., Dye Clearance Test (BSP) --- A-93

Table 7: Methemoglobin --------------------------------------- A-96

Table 8: Urinalysis ------------------------------------------ A-99

Pathology Summary -------------------------------------------- A-169

Summary of Microscopic Lesions --------------------------------- A-170

Pathology Reports, Individual Animals --------------------------- A-171

I

-, I

•,•,I .. BIONETICS

Uto

SPONSOR: Office of Naval Research DATE: July 19, 1974

MATERIAL: Cyclonite (RDX)Trinitrotoluene (TNT)

SUBJECT: FINAL REPORTSubacute Toxicity of RDX and TNT in DogsLBI Project No. 1399Contract No. N00014-73-C-0162 Mod. #1

I. UMMARY

Dogs given daily dosages of RDX of 0.1, 1 or 10 mg/kg/day for 90 days

developed no signs of toxicity other than teimporary episodes of emesis to which

a tolerance apparently developed. One medium level animal died for reasons

unrelated to the study.

Dogs given daily dosages of TNT of 0.02, 0.1 or 1 mg/kg/day for 90 days

developed no signs of toxicity other than temporary episodes of emesis to which

tolerance apparently developed.

Laboratory diagnostic procedures and both gross and microscopic postmortem

examinations revealed no important differences from controls.

of I

Il

03 BIONETICS1utton

-2-

II. OBJECTIVE

The objective of this study was to evaluate and characterize the toxicity

of RDX and TNT when given to dogs by repeated oral administration over a 90-day

peri od.

III. MATERIALS

RDX is the common designation for an explosive also known as Cyclonite.

It bears the chemical name hexahydro-l,3,5-trinitro-s-triazine. It was supplied

to Litton Bionetics for this study in the form of a pre-mix with ground dog chow

containing 20 mg RDX/gm chow. The pre-mix was received at Litton Bionetics on

July 3, 1973, and assigned LBI No. 698A.

TNT is the common designation for an explosive which is known chemically as

trinitrotoluene. It was supplied to Litton Bionetics for this study in the form

of a pre-mix with ground dog chow containing 2 mg TNT/gm chow. The pre-mix was

received at Litton Bionetics on July 3, 1973, and assigned LBI No. 697A.

IV. METHODOLOGY

A. Animals and Husbandry

Forty-two (42) healthy, young, adult, purebred beagle dogs, 21 males

and 21 females, were obtained from Hazleton Research Animals. They were examined

by a staff veterinarian on receipt and housed in individual stainless steel cages,

provided with fresh water several times daily and fed Wayne Dog Food in the form

of ground meal. This same food is available in pelleted form, but the ground

form was utilized in this study to facilitate admixture of the test material.

The dogs were held in quarantine in order to assure their good health

and to allow incubation of any diseases which might have been present at the time

Si .. 3 BIONETICS•.• Uttonl

-3-

of receipt. Two sets of clinical laboratory studies were performed. These had

the deuole purpose of demonstrating good health and of providing baseline values

for comrir,;tive purposes.

B. Group Assignments

Near the end of the quarantine period, the dogs were assigned to the

various treatment groups with attention to accomplishing groups balanced with

respect to sex and body weight. Final assignments were as follows:

Group No. Treatment Level Dog No. and SexMale Female

1 Control 65 3766 4372 45

2 RDX-High 55 49(10 mg/kg/day) 73 50

74 76

3 RDX Medium 64 40(I mg/kg/day) 68 41

75 54

4 RDX-Low 59 35(0.1 mg/kg/day) 61 36

67 53

5 TNT-High 69 46(1 mg/kg/day) 70 47

71 48

6 TNT-Medium 60 42(0.1 mg/kg/day) 62 38

63 52

7 TNT-Low 56 39(0.02 mg/kg/day) 57 44

58 51

C. Diet Preparation and Administration

Preliminary trials in the sponsor's laboratory had indicated that diets

containing the planned concentrations of RDX and TNT were not readily accepted

by dogs. After much consideration of various alternatives, the following procedure

Li3BIONETICSUltton •

-4

was agreed upon. Diluted chow mixes were prepared accuru,,,g to the sponsor's

directions as follows:

Sche- Corn- Animaldule pound Pre-Mix Chow Final Conc. Group No.

gm gil mg/gm/chow

A RDX Undiluted 20.0 2

"B RDX 400 3600 2.0 3

C RDX 40 3960 0.2 4

D TNT Undiluted 2.0 5

E TNT 400 3600 0.2 6

F TNT 80 3920 0.04 7

Each day a food mixture was prepared for each individual dog. This

mixture contained 0.5 gm of the appropriate diluted chow mix (see above) per

kilogram of body weight and about 60 grams of a commercial (meat containing)

canned dog food. The :ontrol group was given normal ground dog chow handled

in the same way. After this had been consumed by the dog, dog chow was provided

ad libitum for the remainder of the working day. Uneaten chow was removed at

the end of normal working hours so that appetite would be good the following

morning. Records were kept of test material consumed daily. Water was avail-

able at all times.

D. Observations

Each dog was observed at least once daily at the time of feeding or

more often if indicated. Records were made of any deviations from normal with

respect to appearance, behavior, appetite and elimination. Signs of toxic or

pharmacologic effects were also recorded daily or more often. Each animal was

weighed weekly.

LU BIONr--TICS

-5-

All dogs were examined by a consultant veterinary ophthalmologist prior

to group assignments and again du: ing the 13th week of the study.

F. L_,oratory Diagnostic Procedures

The following studies were performed on each animal twice during the

quaranti-e period and again during the 4t,., 8th and terminal weeks of the study.

1 Hematology

1 hematocrit total leucocyte counthemoglobin differential leucocyte counterythrocyte count reticulocyte count and Heinz bodies

RBC fragility

L. Clinical Biochemi-try

fasting blood sugar serum chlorideblood urea nitrogen serum glutamic-pyruv" c transaminasetotal sprum protein methemoglobintotal serum bilirubin serum alkaline phosphataseserum sodium serum glutamic-oxaloacetic transaminaseserum potassium sulfobromophthalein liver function test

3. Urinalysis

pH total proteinspecific gravity bilirubinglucose microscopic examination of sedimentketones urine glutamic-oxaloacetic transaminase

F. Termination

At the scheduled time for termination, the dogs were transferred to the

Kensington facility of Litton Bionetics where superior facilities for necropsy

exist. Each animal was killed and immediately subjected to a gross necropsy

under the direction of a Board-Certified Veterinary Pathologist.

The following organs were removed and individually weighed:

heart adrenalskidneys spleenliver testes with epididymisthyroids

I BIONETICS•_ i Utton

-6-

Samples of the following tissues were taken for preservation in 10%

neutral buffered formalin:

brain gallbladder urinary bladderpituitary spleen prostatethoracic spinal cord kidneys ovaryeye adrenals uterusthyroids stomach rib junctionlung pancreas bone marrowheart small intestine nerve with muscleliver mesenteric lymph node any unusual lesions

Approximately 12 selected tissues from each animal in the control and the high

dosage groups for each compound were prepared and examined for histopathologic

alteration:

brain liver stomachthyroid spleen small intestinelung kidney bone marrowheart adrenals lesions

V. RESULTS

A. Observations

During the first two weeks, there were scattered instances of nausea

and vomiting. No single dog was affected for more than a few days and the whole

matter subsided.

One dog (No. 75, male, medium level RDX) died during the fourth week.

At necropsy, a lesion was found, located subcutaneously in the left flank. It

was necrotic and crepitant and appeared to have originuted as an abscess. There

were numerous focal hemorrhages. It was the opinion of the examining pathologist

that this dog died of a bacteremia derived from the lesion mentioned and unre-

lated to the RDX treatment.

Except for this one dog and the few emesis episodes mentioned, there

were no tuxic signs recorded nor were there changes in body weight beyond the

expected fluctuations.

Sm

SBIONETICS

-7-

IOphthalmoscopic examination by Dr. Seth A. Koch, a board-certified

veterinary ophthalmologist, revealed no changes attributable to treatment except

"some increased granularity and mild hyper-reflectivity of the fundus" in high

dosage groups of both RDX and TNT. This could indicate a mild inflammatory

retinopathy but is not considered evidence of important toxicity.

B. Laboratory Diagnostic Procedures

There were no important changes in any of the blood cytology chemistry

measures. There are low values among the blood chemistry determinations at the

eight-week point, but these occurred in control animals as well as in treated

ones. Thus, they probably represent laboratory variants rather than toxic effects.

Similarly, ,;rinalysis failed to reveal abnormalities.

C. Pathology

Necropsies conducted under the supervision of Walter F. Loeb, V.M.D.,

Ph.D., revealed nothing remarkable. The occasional abnormalities are itemized

in the individual report sheets in the Appendix. Organ weights are also recorded.

4I The incidence of microscopic findings is tabulated as part of the signed

summary also incorporated in the Appendix. It seems clear that no important toxic

effects were observed. Renal microcalculi and bone marrow hemosiderosis are both

encountered occasionally in random dog populations. The small group sizes, three

per sex per dosage group, make it precarious to attribute importance to the inci-

F, dences seen in this study.

F

03BIONETICSUtto"

-8-

VI. CONCLUSIONS

Dogs given daily dosages of RDX of 0.1, 1 or 10 mg/kg/day for 90 days


a tolerance apparently developed. One medium level animal died for reasons

unrelated to the study.

Dogs given daily dosages of TNT of 0.02, 0.1 or 1 mg/kg/day for 90 days


tolerance apparently developed.

Laboratory diagnostic procedures and both gross and microscopic post-

mortem examinations revealed no important differences from controls.

Submitted by: ___

E. ROSS H R_ Th.D.Director,Department ofPharmacology and Toxicology

ERH: pp

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A- 34LITTON BIONETICS, INC.

TABLE 3

HEMATOlf" - HEINZ BODIES

WEEKS OFDOG NO. PRE-DRUG DRUG ADMINISTRATIONAND SEX 3 Wks 2 Wks 4 8 13

CONTROL

65 (M) Neg Neg Neg Neg Neg66 (M) Neg Neg Neg Neg Neg72 (M) Neg Neg Neg Neg Neg

37 (F) Neg Neg Neg Neg Pos43 (F) Neg Neg Neg Neg Neg45 (F) Neg Neg Neg Neg Neg

Ii;

L.

A-35

LITTON BIONETICS, INC.

TABLE 3 (continued)

HEMATOLOGY -HEINZ BODIES


RDX - 10 mg/kg


49 (F) Neg Neg Neg Neg Neg50 (F) Neg Neg Neg Neg Neg76 (F) Neg Neg Neg Neg Neg

RDX - 1 mg/kg

64 (M) Neg Neg Neg Neg Pos68 (M) Neg Neg Neg Neg Neg

75 (M) Dead

40 (F) Neg Neg Neg Neg Neg41 (F) Neg Neg Neg Pos Neg54 (F) Neg Neg Pos Neg Neg

RDX - 0. 1 mg/kg


35 (F) Neg Neg Neg Neg Neg36 (F) Neg Neg Neg Pos Neg53 (F) Neg Neg Neg Neg Neg

'7

g 4!~


TABLE 3 (continued)

HEMATOLOGY - HEINZ BODIES

WEEKS OFDOG No. PRE-DRUG DRUG A1E4INISTRATIONAND SEX 3 WI-3 2 Wks 478 3

TNT-i1 mg/kg

69 (m) Neg Neg Neg Neg Negil70 C)Neg Neg Neg Neg Neg71 C)Neg Neg Pos Neg Neg

46 (F) Neg Neg Neg Neg Pos47 (F) Neg Neg Neg Neg Neg48 (F) Neg Neg Pos Neg Neg

TNT - 0.1 mg/kg

60 (m) Neg Neg Nag Neg Pos62 (m) Neg Neg Neg Neg Neg63 (M) Neg Neg Neg Nag Neg

42 (F) Neg Neg Neg Nag Ne~g38 (F) Neg Neg Neg Neg Neg52 (F) Neg Neg Nag Neg Neg

TNT -0.02 mg/kg

56 CM) Neg Neg Neg Neg Neg57 (M) Neg Neg Neg Neg Neg58 CM) Neg Neg Neg Neg Neg

39 (F I e e e e39 (F) Neg Neg Neg Neg Neg51 (F) Neg Neg Neg Neg Neg

A-37


TABLE 4

HEMATOLOGY - RED CELL FRAGILITY

CONTROL

DOG NO.AND SEX % NaCI % HEMOLYSIS

3 •E "S PRE-DRUG

65 (M) Max. .30 100Min. .55 1.0

66 (M) Max. .35 100Min. .55 0.8

72 (M) Max. .35 100Min. .55 4.4

MEAN Max. .33 100Min. .55 2.1

2 WEEKS PRE-DRUG

65 (M) Max. .30 100Min. .65 1.0

66 (K Max. .40 100Min. .55 5.4

72 (M) Max. 0.0 100Min. .60 1.0

MEAN Max. .23 100Min. .60 2.5

•'4

- - r

A- 38


TABLE 4 (continued)


CONTROL

DOG NO.

AND SEX % NaCI % HEMOLYSIS

4-WEEKS

65 CM) Max. .30 100Min. .50 3.7

66 (M) Max. 0.0 100Min. .50 22.0

72 (M) Max. .30 100Mir.. .55 1 .1

MEAN Max. .20 100Min. .52 8.9

8-WEEKS

65 (M) Max. .30 100Min. .50 5.1

66 (M) Max. 0.0 100Min. .55 1.7

72 (M) Max. .35 100Min. .55 2.0

MEAN Max. .22 100

Min. .53 2.9

13-WEEKS

65 (M) Max. 0.0 100Min. .55 2.1

66 (M) Max. .35 100Min. .55 1.8

72 (M) Max. .35 100Min. .65 1.0

MEAN Max. .23 100Min. .58 1.6

A-39t LITTON BIONETIOS, INC.

TABLE 4 (continued)


CONTROL

DOG NO.AND SEX % NaCl % HEMOLYSIS

3 WEEKS PRE-DRUG

37 (F) Max. .35 100Min. .65 1.8

43 (F) Max. .30 100

Min. .65 2.7

45 (F) Max. .35 100Min. .60 1.0

MEAN Max. .33 100Min. .63 1.8

2 WEEKS PRE-DRUG

37 (F) Max. 0.0Min. .55

43 (F) Max. 0.0 100Min. .50 2.2

45 (F) Max. .30 100Min. .55 0.9

MEAN Max. .10 100Min. .53 1.9

[,

.. .. '---

A-40


TABLE 4 (continued)


CONTROL


4-WEEKS

37 (F) Max. 0.0 100Min. .50 9.6

43 (F) Max. .30 100Min. .60 1.7

45 (F) Max. .30 100Min. .60 1.0

MEAN Max. .20 100Min. .57 4.1

8-WEEKS

37 (F) Max. .40 100Min. .55 4.0

43 (F) Max. .40 100Min. .60 2.4

45 (F) Max. .30 100Min. .60 1.0

MEAN Max. .37 100Min. .58 2.5

13-WEEKS

37 (F) Max. .30 100Min. .60 2.1

43 (F) Max. 100Min. .65 1.1

45 (F) Max. .30 100Min. .55 2.1

MEAN Max. .32 100Min. .60 1.8

A- 41LITTON BION•-TICS, [NC.

TABLE 4 (continued)


RDX - 10 mg/kg


3 WE9KS PRE-DRUG

55 (M) Max. .30 100Min. .55 1.8

73 (M) Max. .30 100Min. .60 1.0

74 (M) Max. .35 100Min. .55 2.0

MEAN Max. .32 100Min. .57 1.6

2 WEEKS PRE-DRUG

55 (M) Max. .35 300Min. .50 8.8

73 (M) Max. .30 100Min. .60 0.6

"74 (M) Max. 0.0 100Min. .65 1.0

MEAN Man. .22 10Mi .58 3.5

I-


TABLE 4 (continued)


RDX -10 mgAg


4-WEEK3

55 (M) Max. .35 100Min. .50 3.9

73 (M) Max. .35 100Min. .65 1.9

74 (M) Max. .30 100Min. .60 1.0

Min. .58 2.3

8-WE EKS

55 (M) Max. .35 ICOMin. .65 0.5

73 (14) Max. 0.0 100Min. .60 0.9

74 (M) Max. .35 100Min. .65 2.1

MEAN Max. .23 100Min. .63 1.2

"13-WEEKS

55 (M) Max. .30 100

"Min. .50 1.8

73 (M) Max. .48 100Min. .65 1.0

[I 74 (M) Max. .35 100

Min. .55 3.0

MFAN Max. .38 100

Min. .57 1,3

- I

A-43LITTON BIONETICS, INC.

TABLE 4 (continued)


RDX - 10 mgAcg/k


3 WEEKS PRE-DRUG49 (F) Max. ý35 i00

Min. .55 1.0

50 (F) Max. 0.0 100Min. .60 0.9

76 (F) Max. .35 100Min. .60 1.1

MEAN Max. .23 It'1Min. .58 1.0

2 WEEKS PRE-DRUG

49 (F) Max. .35 100Min. .55 1.0

50 (F) Max. .35 100Min. .60 1.0

76 (F) Max. .30 100Min. .1

WEAN Max. .33 100Min. .60 1.0

17'*1g

- :; -..- --4'


TABLE 4 (continued)


RDX - 10 mg/kg

*• DOG NO.AND SEX % NaCl % HEMOLYSIS

V L4.-WEEKS

A. 49 (F) Max. .30 100Min. .65 1.0

j 50 (F) Max. .35 100Min. .60 1.1

76 (F) Max. .35 100Min. .60 0.9

MEAN Max. .33 100Min. .62 1.0

8-WEEKS

49 (F% Max. .35 100Min. .55 1.0

50 (F) Max. 0.0 100Min. .65 1.0

76 (F) Max. .35 100Min. .65 1.7

MEAN Max. .23 100Min. .62 1.2

13-WEEKS

49 (F) Max. .35 100Min. .55 1.0

50 (F) Max. .35 100Min. .55 2.0

76 (F) Max. .35 100Min. .50 5.4

MEAN Max. .35 100Min. .55 2.8

A-45

LITTON J£ONETICS, INC.

TABLE 4 (continded)

1HEMATOLOGY - RED CELL FRAGILITY

RDX - I mg/kg


3 WEEKS PRE-DRUG

64 (M) Max. .35 100"Min. .60 0.9

68 (M) Max. 0.0 100Min. .55 0.9

75 (M) Max. .35 100Min. .60 0.9

MEAN Max. .23 100Min. .58 0.9

2 WEEKS PRE-DRUG

64 (M) Max. 0.0 100Min. .55 1.0

68 (M) Max. 0.0 100j Min. .60 1.0

75 (M) Max. .35 100Min. .60 1.9

MEAN Max. .12 100Min. .58 1.3

#. ',

.¶}

--- N~

A-46


TABLE 4 (continued)


RDX - 1 mg/kg

lOG NO.AND SEX %NaCI % HEMOLYSIS

4-WEEKS

67 (M) Max. .30 100Min. .50 1.9

68 (M) Max. 0.0 100Min. .55 1.0

75 (M) Max. - -

Min. -

MEAN Max. .15 100Min. .53 1.5

8-WEEKS

64 CM) Max. .30 100Min. .55 0.9

68 (M) Max. .30 100Min. .65 0.9

75 (M) Max.

Miin.

MEAN Max. .30 100

Min. .60 0.9

;•" ,13-WEEKS

S° 64 (M) Max. .30 100SMin. .50 1. 0

!68 (M) Max. .30 100SMin. .60 1.0

S75 (M) Max.S~Min.

SMEAN Max. .30 100SMin. .55 I. 0


TABLE 4 (continued)


RDX - 1 mg/kg


3 WEEKS PRE-DRUG

40 (F) Max. 0.0 100Min. .55 3.4

41 (F) Max. .40 100Min. .65 1.2

54 (F) Max. .30 100Min. .60 0.9

MEAN Max. .23 100Min. .60 1.8

2 WEEKS PRE-DRUG

40 (F) Max. .35 100Min. .55 2.0

41 (F) Max. .35 100Min. .55 5.1

54 (F) Max. .35 100Min. .60 1.0

MEAN Max. .35 100Min. .57 2.7

.-t

A-48


TABLE 4 (continued)


RDX - 1 mgA/g


4-WEEKS

40 (F) Max. .35 100Min. .55 3.9

41 (F) Max. .35 100Min. .55 1.2

54 (F) Max. .40 100Min. .55 3.8

MEAN Max, .37 100Min. .55 3.0

8-WEEKS

40 (F) Max. .35 100

Min. .60 2.2

41 (F) Max. .35 100Min. .65 1.1

54 (F) Max. 0.0 100

Min. .65 1.0

MEAN Max. .23 100Min. .63 1.4

"13 -WEEKS

40 (F) Max. 0.0 100Min. .60 1.9

41 (F) Max. .35 100Min. .50 2.3

54 (F) Max. .35 100Min. .50 15.5

MEAN Max. .23 100Min. .53 6.6

_ _ _-_ _,_ _._. .


TABLE 4 (continued)


RDX - 0.1 mg/kg


3 WEEKS PRE-DRUG

59 (M) Max. .35 100Min. .65 0.4

61 (M) Max. .35 100Min. .55 3.0

67 (M) Max. .35 100Min. .55 1.0

MEAN Max. .35 100Min. .58 1.5

2 WEEKS PRE-DRUG

59 (M) Max. .30 100Min. .60 1.0

61 (M) Max. 0.0 100Min. .65 1.0

67 (M) Max. .30 100

Min. .55 1.2

MEAN Max. .20 100Min. .60 1.1

,41

F54

A- 50


TABLE 4 (continued)


RDX - 0.1 mgAg


4-WEEKS

59 (M) Max. .35 100Min. .55 1.0

61 (M) Max. .40 100SMin. .60 1.9

67 (M) Max. .35 100Min. .55 0.7

MEAN Max. .37 100Min. .57 1.2

8-WEEKS

59 (M) Max. .35 100Min. .60 2.0

61 (M) Max. .30 100Min. .55 3.1

67 (M) Max. 0.0 100Min. .55 2.3

MEAN Max. .22 100min. .57 2.5

13-WEEKS

59 (M) Max. 0.0 100lMin. .55 2.0

61 (M) Max. .40 i00Min. .65 1.0

67 (M) Max. .30 100Min. .55 1.1

MEAN Max. .23 100lMin. .58 1.4


TABLE 4 (continued)


RDX - 0.1 mg/kg

DOG NO.


3 WEEKS PRE-DRUG

35 (F) Max. 0.0 100Min. .60 1.6

36 (F) Max. .30 100Min. .60 0.6

53 (F) Max. .35 100

Min. .60 0.9

MEAN Max. .22 100

Min. .60 1.01...2 WEEKS PRE-DRLTG

35 (F) Max. 0.0 100Min. .55 6.6

36 (F) Max. .35 100Min. .55 2.3

53 (F) Max. .35 100SMin. .60 0.9

MEAN Max. .23 100Min. .57 3.3

i"a

-- 14


TABLE 4 (continued)


RDX -0.1 mg/kg


4-WEEKs

35 (F) Max. 0.0 100Min. .55 1.9

36 (F) Max. .35 100Min. .50 16.3

53 (F) Max. .30 100Min. .50 7.5

MWAN Max. .22 100Min. .52 8.6

8 -WEPFKS

35 (F) Max. .35 100Min. .50 12.0

36 (F) Max. .30 100Min. .55 1.0

53 (F) Max. .35 100Min. .65 1.0

MEAN Max. .33 100Min. .57 4.7

13-WEEKS

"35 (F) Max. .30 100Min. .65 0.9

36 (F) Max. .30 100Min. .45 17.7

53 (F) Max. .35 100Min. .55 2.0

MEAN Max. .32 100Min. .55 6.9

fl *.. ¶

* A-53-.. LITTON BIONETICS, INC.

TABLE 4 (continued)

A HEMATOLOGY - RED CELL FRAGILITY

TNT - 1 mg/kg

DOG NO.

AND SFX % NaCI % HEMOLYSIS

3 WEEKS PRE-DRUG

69 (M) Max. .4u 100Min. .60 1.1

70 (M) Max. .35 100Min. .60 1.8

71 (M) Max. .35 i00Min. .60 1.9

MEAN Max. .37 100Min. .60 1.6

2 WEEKS PRE-DRUG

69 (M) Max. 0.0 100

Min. .65 2.2

70 (M) Max. 0.0 100Min. .55 8.8

71 (M) Max. 0.0 100Min. .65 0.6

MEAN Max. 0.0 100Min. .62 3.9

;LC, • '


TABLE 4 (continued)

HEMATOLOGY R ED CELL FRAGILITY

TNT- 1 mgAg


4-WEEKS

69 (M) Max. .35 100Min. .65 1.0

70 (M) Ma,:. .35 1001bin. .60 1,8

71 (M) Max. .35 100Min. .55 2.0

MEAN Max. .35 100Min. .60 1.6

8-WEEKS

69 (M) Max. .35 100Min. .55 2.1

70 (M) Max. .35 100Min. .55 0.9

71 'M) Max. .30 100Min. .50 4.0

MEAN Max. .33 100Min. .53 2.3

13-WEERKS

69 (M) Max. .30 100Min. .55 1.1

70 (M) Max. .30 100Min. .50 3.0

71 (M) Max. .30 100Min. .55 1.0

MEAN Max. .30 100Min. .53 1.7

...,,


$1 TABLE 4 (continued)


TNT- I mg/kg


3 WEEKS PRE-DRUG

4 (F) Max. .35 100Min. .45 49.0

47 (F) Max. .35 100Min. .65 1.0

48 (F) Max. 0.0 100Min. .55 2.5

MEAN Max. .23 100Min. .55 17.5

2 WEEKS PRE-DRUG

46 (F) Max. 0.0 100Min. .60 1.0

47 (F) Max. 0.0 100Min. .50 6.3

48 (F) Max. .30 100

Min. .50 5.2

MEAN Max. .10 100Min. .53 4.2

4-

A- 56


TABLE 4 (continued)


TNT - 1 mg/kg


4-WEEKS

46 (F) Max. .35 100Min. .60 2.0

47 (F) Max. .30 100Min. .55 2.0

48 (F) Max. .35 100Min. .55 0.8

MEAN Max. .33 100Min. .57 1.6

8-WEEKS

46 (F) Max. .35 100Min. .55 4.4

47 (F) Max. .35 100Min. .60 1.0

48 (F) Max. .35 100Min. .60 0.9

MEAN Max. .35 100Min. .58 1.3

13 -WEEKS

46 (F) Max. .35 100MlBn. .50 2.1

47 (F) Max. 0.0 100

Min. .50 3.5

48 (F) Max. .35 100Min. .55 1.7

MEAN Max. .23 100Min. .52 2.4

-..-,.2.. _________________ _ •_ ;w

A- 56

LITTON BIONETICS, TNC.

TABLE 4 (continued)


TNT - I mg/kg

DOG NO.


4 -WEEKS

46 (F) Max. .35 103Min. .60 2.0

47 (F) Max. .30 100Min. .55 2.0

48 (F) Max. .35 100Min. .55 0.8

MEAN Max. .33 100Min. .57 1.6

8-WEEKS

46 (F) Max. .35 100Min. .55 4.4

L.7 (F) Max. .35 100Min. .60 1.0

48 (F) Max. .35 100Min. .60 0.9

3 MEAN Max. .35 10•SMin. .58 1.3

1' i13 -WEEKS

4,6 (F) Max. .35 100SMin. .50 2.1

47 (F) Max. 0.0 100Min. .50 3.5

48 (F) Max. .35 100

1Min. .55 1.7MEAN Max, .23 100

Min. .52 2.4

A- 57


TABLE 4 (continued)

HEMTOLOGY - RED CELL ,FRAGILITY

TNT - 0.1 mgAg

DOG NO.AND SEX % NaC1 % IIEMOLYSfS

3 WEEKS PRE-DRUG

60 (M) Max. .30 100Min. .55 0.9

62 (M) Max. .35 100Min. .55 2.1

63 (M) Max. .30 100Min. .50 3.0

MEAN Max. .32 100Min. .53 2.0

2 WEEKS PRE-DRUG

60 (M) Max. .35 100Min. .60 2.0

62 (M) Max. .30 100Min. .55 1.5

63 (M) Max. '5 100Min. .65 0.5

MEAN Max. .33 100Min. .60 1.3

|1


TABLE 4 (continued)

HEMATOLOGY - R1D CELL FRAGILITY

T1T - 0.1 mg/kAg

DOG NO.AND SEX %NaCI % HEMOLYSIS

4-WEEKS

60 (M) Max. .35 100Min. .50 6.8

62 (M) Max. .30 100Min. .55 1.0

63 (M) Max. .35 100Min. .60 0.9

MEAN Max. .33 100Min. .55 2.9

8-WEEKS

60 (M) Max. .35 100Min. .50 3.1

62 (M) Max. .30 100Min. .65 1.0

63 (M) Max. 0.0 100SMin. .50 3.9

MEAN Max. .22 100Min. .55 2.7

13-WEEKS

60 (M) Max. .35 100Min. .60 1.1

62 (M) Max. 0.0 100Min. .50 4.3

63 (M) Max. .35 100Min. .65 1.0

SMEAN Max. .23 100SMin. .58 2 .1

A- 59TITJTON i3IrNETICS, INC.

TABLE 4 k-.-ntinued)

IHEMATOLOGY - RED CELL FRAGILITY

TNT- 0.1 mgA/g


3 WEEKS PRE-DRUG

42 (F) Max. .30 100SMin. .55 1.6

38 (F) Max. .35 100Min. .60 2.0

52 (F) Max. .30 100Hi4in. .65 0.9

MEAN Max. .32 100Min. .60 1.5

2 WEEKS PRE-DRUG

42 (F) Max. .30 100Min. .55 2.0

38 (F) Max. 0.0 100Min. .55 1.0

52 (F) Max. .35 100Min. .60 2.2

MEAN Max. .22 100Min. .57 1.7

1i o

r' ...... .• r, '-' ,n-.-r.=r,• i.••II• •• •Sz , f ~ ~ v••• • r .¶. .... .-


TABLE 4 (continued)


TNT - 0.1 mg/kg


4-WEEKS

42 (F) Max. .35 100Min. .55 1.0

38 (F) Max. .40 100Min. .55 4.9

52 (F) Max. .35 100

Min. .60 0.9

MEAN Max. .37 100Min. .57 2.3

8-WEEKS

42 (F) Max. .35 100Min. .60 1.1

38 (F) Max. .35 100Min. .60 1.0

52 (F) Max. .35 100Min. .55 0.5

MEAN Max. .35 100SMin. .58 0.9

13-WEEKS

42 (F) Max. .35 100Min. .60 1..)

38 (F) Max. .35 100Min. .50 4.4

52 (F) Max. .35 100Min. .50 7.5

MEAl, Max. .35 100Min. .53 4.3

A-61


TABLE 4 (continued)


TNT - 0.02 mg/kg


3 WEEKS PRE-DRUG

56 (M) Max. .30 100Min. .55 2.0

57 (M) Max. .40 100Min. .55 2.1

58 (M) Max. .30 100Min. .50 2.2

MEAN Max. .33 100Min. .53 2.1

2 WEEKS PRE-DRUG

56 (M) Max. .35 100Mir . .60 1.0

57 (M) Max. 0.0 100Min. .60 1.1

58 (M) Max. .30 100Min. .50 1.2

MEAN Max. .22 100Min. .57 1.1

A-62

lITTON BIONETICS, INC.

TABLE 4 (continued)


TNT - 0.02 mg/kg

DOG NO.AND SEX % NaCl % HIMOLYSIS

4-WEEKS

56 (M) Max. .35 100Min. .65 1.0

57 (M) Max. .35 100Min. .55 3.1

58 (M) Max. .30 100Min. .55 1.1

MEAN Max. .33 100Min. .58 1.7

8-WEEKS

56 (M) Max. .35 100Min. .60 2.1

57 (M) Max. .35 100Min. .55 7.1

58 (M) Max. .30 100Min. .55 1.1

MEAN Max. .33 100Min. .57 3.4

13-WEEKS

56 (M) Max. .30 100Min. .50 4.3

57 (M) Max. .30 100Min. .65 1.0

58 (M) Max. .30 100Min. .55 2.1

MEAN Max. .30 100Min. .55 2.5

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


TABLE 4 (continued)


TNT - 0.02 mg/kg


3 WEEKS PRE-DRUG

39 (F) Max. .35 100Min. .60 0.9

44 (F) Max. .35 100min. .60 1.1

51 (F) Max. .35 100Min. .55 1.0

MEAN Max. .35 100Min. .58 1.0

2 WEEKS PRE-DRUG

39 (F) Max. .35 100Min. .55 1.0

44 (F) Max. .30 100Min. .55 2.3

51 (F) Max. .35 100Min. .55 1.1

MEAN Max. .33 100

Min. .55 1.5

4-

.

. .~ ._.__._.._.__.__._.._.__._

A-64


TABLE 4 (continued)


TNT - 0.02 mg/kg

DOG NO.

AND SEX % NaCl % HEMOLYSIS

4-WEEKS

39 (F) Max. 0.0 100Min. .55 1.0

44 (F) Max. 0.0 100Min. .60 1.9

51 (F) Max. .35 100Min. .55 1.0

MEAN Max. .12 100Min. .57 1.3

8-WEEKS

39 (F) Max. C L 0 T T E DMin.

44 (F) Max. .30 100Min. .65 2.1

51 (F) Max. .30 100Min. .50 3.2

"MEAN Max. .30 100Min. .58 2.7

13-WEEKS

39 (F) Max. .35 100Min. .60 2.0

44 (F) Max. .35 100Min. .30 19.5

51 (F) Max. .30 100Min. .45 9.3

MEAN Max. .33 100Min. .52 10.3

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00 m 000 cq Enn Ln..- HH .-44 m 4- -'4a' u N4Lfl f14

I <000 0) 000 0l ( Q 0)C) L

Ell'. '0 00N bf)''0 '

S F-4 .

r4 H- to coC: W

1- 0 cq'o0 .I ~ C 4 i N U

S HZ oa 0N r OD t-ti4'%0 '0 ,-4 0 0 1

E4~~~~DC, 140b - 4rIr

r4r-4r-4 ,-4 .ý4 -4 -4 r4-4 -i

c4 .

Co 0 0uLr N %0 00 n %0 Ln U L

r4 -4 r4 r-444 r 4Il' r-4 4 4-4 r4

WHT T r-1 r--4 Dr4

r-4

.Iw r2

Hf-ztrzIno) L l )C) L

A-93 !

LITTON BIONETICS, INrlA.

TABLE 6

SULFOBROMOPHTHALEIN, U.S.P., DYE CLEARANCE TEST (BSP)(% Retention at 30 minutes)


CONTROL

65 (M) 2.0 0.5 2.0 2.5 1.566 (M) 4.2 1.0 2.0 5.0 3.572 (M) 3.0 2.5 2.5 3.5 4.5

MEAN 3.1 1.3 2.2 3.7 3.2

37 (F) 4.0 5.0 2.0 2.5 4.043 (F) 4.0 4.0 3.5 4.0 3.545 (F) 2.5 3.5 2.5 4.0 2.5

MEAN 3.5 4.2 2.7 3.5 3.3

22

HA4

• A- 94


TABLE 6 (continued)


i WEEKS OFDOG NO. PRE-DRUG DRUG ADMINISTRATIONAND SEX 3 Wks 2 Wks 4 8 13

RDX - 10 mg/kg

55 (M) 2.5 2.5 2.5 2.3 3.573 (M) 5.0 3.0 2.0 2.0 2.074 (M) 1.8 0.5 2.5 1.0 2.0

MEAN 3.1 2.0 2.3 1.8 2.5

49 (F) 2.5 3.0 1.5 2.0 4.050 (F) 6.0 4.2 4.6 4.0 4.576 (F) 3.0 2.5 4.0 2.5 3.5

MEAN 3.8 3.2 3.4 2.8 4.8

RDX - 1 mg/kg

64 (M) 2.5 3.0 1.8 4.0 2.568 (M) 4.2 0.2 2.0 2.0 2.575 (M) 3.0 3.5 DEAD - -

MEAN 3.2 2.6 1.9 3.0 2.5

30 (F) 2.5 2.0 1.2 2.5 2.541 (F) 4.0 2.5 1.8 1.0 2.5

A4 (F) 2.7 2.3 2.0 1.0 4.0•'MEAN 2.8 2.1 1.7 1.5 2.8

iRDX - 0.i mg/kg

•oi59 (m) 3.5 0.5 1.2 2.5 4.0Si61 (M) 4.0 1.2 3.6 3.5 4.0

••.'67 (M) 4.0 0.5 1.2 1.5 2.0

SMEAN 3.8 0.7 1.8 2.5 3.3

"••35 (F) 2.5 2.o 1.8 4.5 4.0S,36 (F) 3.0 3.0 2.0 3.5 3.5S53 (F) 2.5 1.8 2.0 2.0 2.5

SMEAN 2.7 2.3 1.9 3.3 3.3


TABLE 6 (continued)



TNT - 1 mg/g

69 (M) 3.0 2.0 2.0 3.5 2.070 (M) 2.5 3.5 4.2 2.5 2.571 (M) 2.5 2.0 1.8 2.5 1.5

MEAN 2.7 2.5 2.7 2.8 2.0

46 (F) 3.0 2.0 3.0 2.5 2.547 (F) 2.5 2.5 2.5 1.5 2.048 (F) 3.5 3.0 2.5 4.5 6.5*

MEAN 3.0 2.5 2.7 2.8 3.7

TNT - 0.1 mg/kg

60 (M) 5.0 3.0 2.5 2.5 2.562 (M) 4.2 1.0 2.0 3.5 3.563 (M) 3.5 1.0 1.0 2.0 2.5

"MEAN 4.2 1.7 1.8 2.7 2.8

42 (F) 2.5 3.5 2.0 3.5 2.538 (F) 2.0 3.5 3.0 4.0 4.052 (F) 2.5 0.5 2.5 2.5 2.5

(t

MEAN 2.3 2.5 2.5 3.3 3.0

TNT - 0.02 mg/^g

56 (M) 4.2 2.5 3.0 3.5 2.557 (M) 3.0 1.0 2.5 2.5 2.558 (M) 1.8 1.8 2.0 2.0 3.5

MEAN 3.0 1.8 2.5 2.7 2.8

39 (F) 4.0 3.5 1.2 3.5 2.044 (F) 3.0 1.2 1.0 4.0 2.051 (M) 1.0 4.2 2.5 1.5 2.5

MEAN 2.7 3.0 1.6 3.0 2.2

iS*Confi~.p.ed by repeat sample.


TABLE 7

METHEMOGLOBIN(% Saturation)

WEEKS OFPRE-DRUG DRUG ADMINISCRATION

DOG NO.AND SEX 3 Wks 2 Wks 4 8 13

CONTROL

65 (M) 0 0 4.0 1.9 066 (M) 6.3 9.7 6.4 5.0 072 (M) 7.0 0 6.0 6.4 4.7

MEAN 4.4 3.2 5.5 4.4 1.6

37 (F) 0 0 7.4 8.7 8.643 (F) 0 0.9 8.0 2.7 045 (F) 0 0 5.7 2.1 0

MEAN 0 0.3 7.0 4.5 2.9

- . . .........

, A-97


TABLE 7 (continued)

METHEMOGLOBINC% Saturation)

WEEKS OFPRE-DRUG DRUG ADMINISTRATION


RDX - 10 mg,,g

55 (5 ) 0 0 1.3 C 3.1-13 (M) 0 0 5.3 2.5 074 (M) 0 0 7.8 2.4 2.3

MEAN 0 0 4.8 1.6 1.8

"49 (F) 0 0 0 0 050 (F) 0 0 1.2 0 076 (F) 0 0 5.9 0 0

MEAN 0 0 2.4 0 0

RDX - 1 mg/kg64 (M) 2.2 0 4.9 1.1 068 CM) 0 2.0 3.4 4.8 6.075 CM) 0 0.2 DEAD - -

MEAN 0.7 0.7 4.2 3.0 3.0

ii40 (F) 0.8 0 7.8 3.8 3.341 (F) 0.7 1.1 4.9 3.7 0

154 (F) 2.0 3.0 6.0 3.2 0

MEAN 1.2 1.4 6.2 3.6 1.1

RDX - 0.1 mg/kg

59 (M) 0 0 5.2 0 0

61 (M) 0 1.6 6.9 1.2 067 (M) 2.6 2.0 9.5 2.0 0

MEAN 0.9 1.2 7.2 1.1 0

3 5 (F) 0 0 4.1 0 036 (F) 1.5 2.3 3.9 0.9 1.3

"" 53 (F) 0 0 2.9 0 0

MEAN 0.5 0.8 3.6 0.3 0.4

ii•


TABLE 7 (continued)

METHEMOGLOBIN

(% Saturation)

WEEKS OFPRE-DRUG DRUG ADMINISTRATION


TNT - 1 mg/'Ag

69 (M) 1.2 0 8.4 4.3 4.170 (M) 0 0 0 2.9 1.871 (M) 11.5 0 6.4 18.7 2.0

MEAN 4.3 0 4.9 8.6 2.6

46 (F) 6.4 0 5.2 3.5 2.047 (F) 0 1.2 6.4 11.5 048 (F) 0 0 0 2.4 0

MEAN 2.1 0.4 3.9 5.8 G.7

TNT - 0.1 mg/kg

60 (M) 0.8 0 7.2 3.2 1.762 (M) 0 0 4.1 2.1 3.163 (M) 0 0 3.6 1.7 0

MEAN 0.3 0 5.0 2.3 1.6

42 (F) 1.8 0 0 7.4 038 (F) 5.1 0 0 2.8 0.8: "52 (F) 0 4.5 8.7 12.4 3.0

" MEAN 2.3 1.5 2.9 6.2 1 .7

•: .'!TNT -0.0O2 mg/kg

;56 (M) 0 0 8.1 4.0 0S .57 (M) 5.5 0 0 10.4 0S58 (m) 0 2.9 2.3 7.9 0

SMEAN 1.81.3. 740

S39 (F) 0 0 0 0

44 (F) 1.8 0 8.4 7.6 4.951 (F) 3.3 0.3 6.5 5.8 0

MEAN 1.7 0.1 7.5 4.5 1.6

A-99


TABLE 8

URINALYSIS

CONTROL 3 WEEKS PRE-DRUG

DOG NO. & SEX65 (M) 66 (M) 72 (M)

UGOT 59 42 86

Specific Gravity 1.035 1.030 1.059

I pH 7.0 6.5 8.0

Protein 30 mg Trace 50 mg

Sugar Neg Neg Neg**

Ketones Neg Neg Neg

Bilirubin Neg Neg Neg

Occult Blood Neg Neg Neg

White Blood Cells* 15-18 Rare 2-3

Red Blood Cells*

Epithelial Cells* Few

Ca Oxalate* Freq Many Occ

Bacteria*

Casts* -

Crystals*:

Uric Acid Occ

Triple Phosphate Occ Many Many

Amorphous Mod Mod Much

Sulfa 2

Remarks

*Microscopic (per higb power field)

**Positive for non-glucose reducing substances.

A-100


TABLE 8 (continked)

URINALYSIS

CONTROL. WEEKS PRE-DRUG

DOG NO. & SEX37 (F) 43 (F) 45 (F)

UGOT 68 68 48


pH 6.0 7.0 7.0

Protein 50 mg 50 mg Neg

Sugar Neg** Neg** Neg**

Ketones Neg Neg Neg


Occult Blood 1+ Neg Neg

White Blood Cells* 5-7 25-30 1-3

Red Blood Cells* Rare -

Epithelial Cells* Many Few

Ca Oxalate*

Bacteria* Small

Casts*

Crystals*:

Uric Acid Freq

Triple Phosphate Freq Few Freq

Amorphous Heavy Mod Little

Sulfa Occ

Remarks

*Microscopic (per high power field)


A-101

LITTON BIONETICS, INC.TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX65 (M) 66 (M) 72 (M)

UGOT 89 80 51

Specific Gravity 1.051 1.q42 1.058

pH 8.0 9.0 9.0

Protein 50 mg 50 mg 30 mg

Sugar Neg** Neg Neg**

Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Occ

Ca Oxalate* Few

Bacteria* Heavy Fnavy Mod

Casts*

Crystals*:

Uric Acid Occ

-" Triple Phosphate Freq Many Many

Amorphous Heavy Heavy Heavy

Sulfa

• -Remarks

*Microscopic (per high power field)**Positive for non-glucose reducing substances.

- , . *% .- I.--t~- --- ~-~

A-102


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX37 IF) 43 (F) 45 (F)

UGOT 68 45 57


pH 7.0 6.5 8.0

Protein 30 mg Trace Trace


Ketones Neg Neg Neg

Bil irubin Neg Neg Neg

Occult Blood Neg Pos Neg


Red Blood Cells* TNTC

* Epithelial Cells* Freq Many

Ca Oxalate* Few Occ

Bacteria* Mod Mod

Casts*

Crystals*:

Uric Acid - Freq

Triple Phosphate Occ Freq

Amorphous Mod Mod

Sulfa

Remarks


A-103


TABLE 8 (continued)

URINALYSIS

CONTROL 4-WEEKS

DOG NO. & SEX

65 (M) 66 (M) 72 (M)

UGOT 54 62 62

Specific Gravity I.066 1.049 1.061

pH 6.0 7.0 7.0


Sugar Neg Neg Neg

Ketones Neg Neg Neg

"Bilirubin Neg Neg Neg


White Blood Cells* 5-25+ 0-3

Red Blood Cells* 0-1

Epithelial Cells* Many Few

Ca Oxalate* Occ Occ

Bacteria* Occ

Gas ts*

Crystals*:

Uric Acid

Triple Phosphate Many Occ

. jAmorphous Little

: I -Sulfa

Remarks


L 3

A-104


TABLE 8 (continued)

URINALYSIS

CONTROL 4-WEEKS

DOG NO. & SEX37 (F) 43 (F) 45 (F)

UGOT 74 62 42


pH 7.0 7.0 7.0

Protein Trace 30 mg Neg

Sugar Neg Neg Neg

Ketones Neg Neg Neg



White Blood Cells* 8-10 3-5 Rare

Red Blood Cells* -

Epithelial Cells* Freq Freq Occ

Ca Oxalate*

Bacteria* 0cc Mod

Casts*

Crystals*:

Uric Acid Freq Occ Freq

* Triple Phosphate Occ Freq Occ

Amorphous Mod Heavy Little

Sulfa

Remarks


A-105


TABLE 8 (continued)

URINALYSIS

CONTROL 8-WEEKS

* •DOG NO. & SEX65 (M) 66 (M) 72 (M)

UGOT 66 62 59

Specific Gravity 1.058 1.0'+8 1.054

pH 7.0 8.0 7.5

Protein Trace 50 mg 50 mg

Sugac Neg** Neg** Neg**

Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Ce]ls* Freq Occ Rare

Ca Oxalate*

Bacteria* Mod Little

Casts* Rare Hyaline

Crystals*:

Uric Acid Freq -

Triple Phosphate Occ Mod Mod

Amorphous Little

Sulfa

Remarks


A-10&


TABLE 8 (continued)

URINALYSIS

CONTROL 8-WEEKS

DOG NO. &SEX

37 (F) 43 (F) 45 (F)

UGOT 70 25 49


pH 8.0 6.0 7.5

Protein Trace Neg Trace

Sugar Neg** Neg Neg

Ketones Neg Neg Neg



White Blood Cells* 0-3 -

Red Blood Cells*

Epithelial Cells* Rare Rare

Ca Oxalate_

Bacteria* Mod Heavy 1.iod

Casts* _

Crystals*:

Uric Acid -

Triple Phosphate Mod Rare Few

Amorphous -

Sulfa

Remarks


A-107


TABLE 8 (continued)

URINALYSIS

CONTROL 13-WEEKS

DOG NO. & SEX65 (M) 66 (M) 72 (M)

UGOT 48 48 37


pH 7.5 7.5 8.0



Ketones Neg Neg Neg



White Blood Cells*

Red Blood Cells*

Epithelial Cells* 0-2 0.1

Ca Oxalate* Many Many Few

SI Bacteria* Slight

Casts* 0-1 0-2

Crystals*:

Uric Acid

Triple Phosphate Many Many Many

Amorphous Mod Mod

Sulfa

SRemarks Waxy casts - Waxy casts


**Positive for non-glucose reducing substances.Snou-lucos

A-108


TABLE 8 (continued)

URINALYSIS

CONTROL 13-WEEKS

DOG NO. & SEX37 (F) 43 (F) 45 (F)

UGOT 55 48 34


pH 9.0 6.5 8.0



Ketones Neg Neg Neg



White Blood Cells* 0-2


Epithelial Cells* 0-2 0-1

Ca Oxalate* Few Many

i) ¶ Bacteria*

Casts* - 0-1 0-1

Crystals*:

Uric Acid Many

Triple Phosphate Many Many 3N

Amorphcus Mod Mod

Sul fa .. _•

Remarks Waxy casts Waxy casts


I • -.4

_ .. I. . . . . .Is - ' I

A-109


TABLE 8 (continued)

URINALYSIS

RDX - 10 mg/kg 3 WEEKS PRE-DRUG

DOG NO. & SEX55 CM) 73 (M) 74~ (M)

UGOT 65 59 54


pH 6.0 7.0 8.0

Protein 30 mg Neg Trace

Sugar Neg** Neg** Neg

Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells*

Ca Oxalate* Occ Occ

Bacteria* Small

GCasts*

Crystals*:

.*ric Acid Many

Triple Phosphate Many Few Many

Amorphous Much Mod

Sulfa

i ~ ~Remarks

•••

i *Microscopic (per high power field)

! **Positive for non-glucose reducing substances.

4

e.R

.M_4

_______________-7 __-_-_-__-

A- 10

LI7TON BIONETICS, INC.

TABLE 8 (continued)

URINALYSIS

RDX - 10 mg//Ag 3 WEEKS PRE-DRUG

DOG NO. & SEX49 (F) 50 (F) 76 (F)

UGOT 36 48 36


pH 7.0 6.1 6.0

Protein Neg Neg Trace


Ketones Neg Neg Neg


Occult Blood Neg 1+ Neg


Red Blood Cells* -2-3

Epithelial Cells* Rare Freq Occ

Ca Oxalate* Occ

Bacteria*

Casts*

Crystals*:

Uric Acid Occ - Freq

S....Triple Phosphate -

Auiorphous Heavy Mucn Little

Sulfa

Remarks

*Microscopic (per high power field)**Positive for zon-glucose reducing substances.

Lt.•,

A-111


TABLE 8 (continued)

URINALYSIS

RDX - 10 mgAg 2 WEEKS PRE-DRUG

DOG NO. & SEX55 CM) 73 (M) 74 'M)

UGOT 22 89 51


pH 7.0 8.0 7.5

Protein Neg 30 mg 30 mg

Sugar Neg Neg** Negk*

Ketones Neg Neg Neg

Bilir b Neg Neg Neg


I White Blood Cells* 1-3 3-4 1-2

j Red Blood Cells*


Ca Oxalate* Freq Freq

Bac ter ia* Much

SI Casts*

Crystals*:

Uric Acid 0cc

Triple Phosphate Freq Freq Occ

Amorphous Much Mod

Sulfa

Remarks

*Microscopic (per high power field) ,W


I -

A-112


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX49 (F) 50 (F) 76 (F)

UGOT 54 36 45


pH 6.5 7.0 6.0

Protein Neg Trace Trace


Ketones Neg Neg Neg




Red Blood Cell *

Epithelial Cells* Many

Ca Oxalate*

Bacteria* Mod Mod

Casts* Occ. Wa%7

Crystals*:

Uric Acid Freq Many

Triple Phosphate Occ Occ Occ

Amorphous Heavy Mod

Sulfa

Remarks


-s. . --- i-?-

A-1 13


TABLE 8 (continued)

URINALYSIS

RDX - 10 mg/kg 4-WEEKS

DOG NO. & SEX55 (M) 73 (M) 74 (M)

UGOT 45 88 190


pH 7.0 9.0 9.0


Sugar Neg Neg Neg

Ketones Neg Neg Neg


Occult Blood Neg Neg 1+



Epithelial Cells* Rare

Ca Oxalate*

Bacteria* Mod Occ HeavyI ! ~Casts*_.

.• Crystals* :

Uric Acid Many

Triple Phosphate Occ

Amorphous Mod Little Heavy

Sulfa -

Remarks


J

A-114


TABLE 8 (continued)

URINALYSIS

RDX- 10 mg/kg 4-WEEKS

DOG NO. & SEX49 (F) 50 (F) 76 (F)

UGOT 45 26 112


pH 6.0 5.0 9.0

Protein Neg Neg 100 mg

Sugar Neg Neg Neg

Ketones Neg Neg Neg



White Blood Cells* Rare Rare 9-11I Red Blood Cells*

Epithelial Cells* Occ Rare

Ca Oxalate*

Bacteria* Mod Heavy Heavy

Casts*

Crystals*:

Uric Acid Freq


Amorphous Little Mod Heavy

Sulfa

Remarks .

*Microscopic (per high puver field)

A-115

LTTTON BIONVTICS, INC.

TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX55 (M) 73 (M) 74 (M)

UGOT 18 34 59


p-pH 6.0 6.5 6.5



Ketones Neg Neg Neg



White Blood Cells* Rare 0-2 5-7

Red Blood Cells*

Epithelial Cells* Occ - Occ

Ca Oxalate*

Bacteria* Heavy Heavy Mod

Casts*

Crystals*:

Uric Acid Occ Occi. Triple Phosphate - Occ

Amorohous Mod Mod Mod

Sulfa

Remarks - Occ MucousThreads


W _ • . .. . . ...

s1i - -

A- 16


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX49 (F) 50 (F) 76 (F)

UGOT 32 38 43


pH 7.0 6.0 7.0

Prote in 30 mg Trace Trace


Ketcnes Neg Neg Neg

Bil irub in Neg Neg Neg

Occult Blood Trace Trace Neg


Red Blood Cells* Rare Rare

Epithelial Cells* Occ Rare Occ

Ca Oxalate*

Bacteria* Occ Heavy Occ

Casts*

Crystals*:

Uric Acid Occ


Amorphous Little Heavy

Sulfa-.

Remarks


A-117


TABLE 8 (continued)

URINALYSIS

RDX - 10 mg/k4g 13-WEEKS

DOG NO. & SEX55 (M) 73 (M) 74 (M)

UGOT 40 37 52


pH 8.0 6.0 6.0



Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Occ - Freq

Ca Oxalate*

Bacteria*

Casts* - 0-1

Crystals*:

Uric Acid - Freq Freq


Amorphous Mod Mod Heavy

Sulfa

Remarks - Coarsely gran.

casts



-7

A-118


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX49 (F) 50 (F) 76 (F)

UGOT 48 21 44


pH 7.5 7.0 6.0



Ketones Neg Neg Neg


Occult Blood Pos Neg Neg



Epithelial Cells* Freq

Ca Oxalate* Occ

Bacteria* Heavy

Casts* 2-3

Crystals*:

Uric Acid Occ Freq


Amorphous Heavy Little

Sulfa

Remarks Finely gran.casts


i -- -

ii A-1 19


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX64 (M) 68 (M) 75 (M)

UGOT 51 62 68


pH 7.0 8.0 8.0

41Protein Trace 50 mg 100 mg

[ Sugar Neg Neg** Neg**

Ketones Neg Neg Neg



II White Blood Cells* 6-8 2-4 5-7

Red Blood Cells*


Ca Oxalate* occ Many occ

Bacteria*

Ii Casts*

Crystals*:

Uric Acid Many Occ

Triple Phosphate - Few Few

Amorphous Heavy Heavy

Sulfa

Remarks C -;t



A-120


TABLE 8 (continued)

URINAL!SIS


DOG NO. & SEX40 (F) 41 (F) 54 (F)

UGOT 36 71 59


pH 6.0 7.0 6.0

Protein Neg Trace Trace


Ketones Neg Neg Neg




Red Blood Cells* _

Epithelial Cells* Freq Freq

Ca Oxalate* - Few

Bacteria* Mod

Casts*

Crystals*:

Uric Acid Freq

Triple Phosphate Freq Many Many

Amorphous

Sulfa

Remarks _


~~Aa

A-1 21


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX64 (M) 68 (M) 75 CM)

UGOT 86 51 68


pH 8.5 7.0 8.5



Ketone: Neg Neg Neg




Red Blood Cells*

Epithelial Cells*

Ca Oxalate*

Bacteria* Mod Occ Heavy

!1. ~ Casts*

Crystals*:

Uric Acid Many Many

Triple Phosphate Occ Many

4 Amorphous Much Mod Heavy

Sulfa

Remarks - -



j A-122


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX40 (F) 41 (F) 54 (F)

UGOT 36 59 59


pH 6.0 6.5 7.0

Protein Trace Trace 30 mg


Ketones Neg Neg Neg

I-Bilirubin Neg Neg Neg


1. White Blood Cells* 4-6 7-10 12-15

,-Red Blood Cells* .

Epithelial Cells* - Freq

[ Ca Oxalate*

Bacteria* Mod - Little

Casts*

Crystals*:

Uric Acid - Freq Occ

I Triple Phosphate Freq Freq Freq Z-

Amorphous Mod - Little

Sulfa

Remarks

;" *Microscopic (per high power field)**Positive for non-glucose reducing substances.

,, '..• .

L1

A-123


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX64 M)68 75)

UGOT 88 74 D E A D

Specific Gravity 1.064 1.049

pH 9.0 9.0

Protein 50 mg 50 mg

Sugar Neg Neg

Ketones Neg Neg

Bilirubin Neg NegOccult Blood Neg Neg

White Blood Cells* 1-2 2-3

Red Blood Cells*


Ca Oxalate*

Bacteria*

Casts*

Crystals*:

Uric Acid Fre. I Freq 3

Triple Phosphate Freq Freq

Amorphous Heavy Heavy

Sulfa

Remarks


A-124

LITTON BIONETICS, [NC.

TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX40 (F) 41 (F) 54 (F)

UGOT 160 62


pH 9.0 6.5

Protein 500 mg Neg

Sugar Neg Neg

Ketones Neg Neg

Bilirubin Neg Neg

Occult Bllood Neg Neg

White Blood Celis* Rare 1-2

Rel Blood Cells*

Epithelial Cells* Rare Occ

Ca Oxalate*

Bacteria* Mod Occ

Casts*

"Crystals*:

Uric Acid

Triple Phosphate

Amorphous Mod Little

Sulfa

Remarks


A-125

LTTTON BIONETICS, INC.

TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX64 (M) 68 (M) 75 (M)

UGOT 78 30 D E A D


PH 9.0 8.0

Protein 1000 mg Trace

Sugar Neg Neg**

Ketones Neg Neg

Bil irubin Neg Neg

Occult Blood Neg Neg


Red Blood Cells*

Ep"thelial Cells* Rare Rare

Ca Oxalate*

Bacteria* Heavy Mod

Casts*

Crystals*:

Uric Acid Occ Freq

Triple Phosphate Many

Amorphous Mod Little

Sulfa

Remarks


A-126

"LITTON BIONETICS, INC.

TABLE 8 (continued)

i•j URINALYSIS

RDX 1 mg/"g 8-WEEKS

DOG NO. & SEX40 (F) 41 (F) 54 (F)

UGOT 22 70 47


pH 6.0 6.0 7.0



Ketones Neg Neg Neg




Red Blood Cells* -

Epithelial Cells* Occ Occ Occ

Ca Oxalate*

Bacteria* Mod

Casts* 0-1

Crystals*:

SI Uric Acid Occ

Triple Phosphate Occ Occ

Amorphous Little Little Little

Sulfa

I .marks Finely gra:..casts



8:

A-127


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX64 (M) "" 68 () 7 M

UGOT 66 21 D E A D


PH 9.0 7.0

Protein 30 mg Trace

Sugar Neg** Neg

Neg Neg

Bil irubin Neg Neg

Occult BloodSNeg Neg

White Blood Jells* 2-3

Red Blood Cells*

Epithelial Cells*

Ca Oxalat-i*

Bacteria* "- Heavy

.. Casts* Occ

• - Crystals*:

Uric Acid- Freq

Triple Phosphate Freq_

Amorphous Mod

Sulfa

SRemarks - Waxy casts

*Microscopic (per high power field) "L **Positive for non-glucose reducing substances.

A-128


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX40 (F) 41 (F) 54 (LF1 °

UGOT 30 62 37


pH 6.0 7.0 6.5

Protein Neg Trace 30 mg


Ketones Neg Neg Neg



4 White Blood Cells* 2-4 Occ Rare

1 Red Blood Cells*

Epithelial Cells* Occ Oce Freq

Ca Oxalate* Occ

Bacteria* Little

C Casts* 0-1 Occ

Crystals*:- IUric Acid Occ Freq


Amorphous Little - Heavy

Sulfa

Remarks Coarsely gran. Waxy castscasts


A-129


TABLE 8 (continued)

URINALYSIS

RDX - 0.1 mg/kg 3 ;KS PRE-DRUG

DOG NO. & SEX59 (M) 61 (M) 67 (M)

UGOT 54 45 51


IPH 8.0 8.0 7.0


Sugar Neg Neg** Neg**

Ketones Neg Neg Neg


Occult Blood Neg Neg Negii White Blood Cells* 0-2 0-3 Rare

Red Blood Cells*

Epithelial Cells*

Ca Oxalate* Few

Bac teria*

Casts*

Crystals*:

Uric Acid Few

Triple Phosphate Many Many

Amorphous Mod

Sulfa -

Remarks


VA-130


TABLE 8 (continued)

URINALYSIS

RDX - 0.1 mg/kg 3 WEEKS PRE-DRUG

DOG NO. & SEX35 (F) 36 (F) 53 (F)

UGOT 39 59 62


pH 5.5 6.5 7.0

Protein Trace Trace Trace


Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Occ Occ

Ca Oxalate*

Bacteria*

j i Casts*

-JCrystals*:

Uric Acid Few

Triple Phosphate Occ Few Many

Amorphous Mod -

Sulfa-

"Remarks


A-131


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX59 (M) 61 (M) 67 (M)

UGOT 59 65 74


pH 6.5 7.0 9.0


Sugar Neg Negk* Neg

Ketones Neg Neg Neg




Red Blood Cells*


Ca Oxalate*

Bacteria* Heavy

Casts*

Crystals*:

Uric Acid Freq Freq Freq

Triple Phosphate Occ Many

Amorphous Little Mod Heavy

Sulfa

Remarks


A-132

~~2 LITTON BIONETICS, INC.V

TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX35 (F) 36 (F) 53 (F)

UGOT 45 77 62


pH 7.0 7.0 7.0



Ketones Neg Neg Neg



White Blood Cells* 2-4 8-10 TNTC

Red Blood Cells* -

Epithelial Cells* Few Occ

Ca Oxalate*

Bacteria*

Casts* 0-1

Crystals*:

Uric Acid Occ

Triple Phosphate Occ Freq Many

Amorphous Mod Mod Little

Sulfa

RRemarks -- Coarsely gran.casts


**Positive for non-.glucose reducing substances.

7"

A-133


TABLE 8 (continued)

URINALYSIS

RDX - 0.1 mg/kg 4-WEEKS

DOG NO. & SEX59 (M) 61 (M) 67 (M)

UGOT 70 78 82


pH 6.0 6.0 7.5


"Sugar Neg** Neg Neg

Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Occ Occ Occ

C a Oxalate* Occ

Bacteria* Occ

"t- I Casts*

Crystals*:

Uric Acid Few Occ

f Triple Phosphate Few Freq Many

Amorphous Heavy Mod Heavy

44 Sulfa

Remarks

*Microscopic (per high power field)**Positive for non-glucosc reducing substances.

4

A-134


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX35 (F) 36 (F) 53 (F)

UGOT 62 78 66


pH 7.0 6.5 7.0

Protein Neg Trace 30 mg

"Sugar Neg Neg Neg

Ketones Neg Neg Neg

Bil irubin Neg Neg ,.



Red Blood Cells*

I-E Epithelial Cells* Many Occ Occ

I ~~Ca Oxalate*

Bacteria* 0cc

J, Casts* 0-1

Crystals*:

Uric Acid Freq Occ Occ

Triple Phosphate Freq Many

A Amorphous Heavy Mod

F. Sulfa

Remarks Finely gran.casts


- I

A-135


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX59 (M) 61 (M) 67 (M)

UGOT 52 62 57

Specific Gravity 1.L044 1.054 1.039

PH 7.0 7.0 7.0



Ketones Neg Neg Neg

Bil irub in Neg Neg



Red W, Lood Cells*

Epithelial Cells* Few Rare

Ca Oxalate* Occ

Bacteria* Occ Little 0cc

Casts* occ

Crystals*:

Uric Acid Occ Freq

Triple Phosphate Freq Occ Occ

Amorphous Mod Mo Little

Sulfa

Remarks Hyaline casts



0

A-136


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX35 (F) 36 (F) 53 (F)

UGOT 36 62 45


pH 7.0 7.0 7.0



Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Occ Occ Rare

Ca Oxalate*

Bacteria* Occ Occ Occ

Casts*

Crystals*:

Uric Acid

Triple Phosphate Freq Freq


Sulfa

Remarks


A-137


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX59 (M) 61 (M) 67 (M)

UGOT 48 78 70


pH 7.0 7.0 8.0



Ketones Neg Neg Neg




Red Blood Cells* -

Epithelial Cell.-*

Ca Oxalate* Occ Occ

Bacteria*

Casts* 0-l1Rare 2

Crystals*: 1-23

Uric Acid Freq Freq

Triple Phosphate Occ F,'eq

Amorphous Heavy Heavy Mod

Sulfa

Remarks Occ leucine ICoarsely gran. castsspheres 2 Waxy casts

3Finely gran. casts


A-138


S~TABLE 8 (contil~ued)

URINALYSIS


DOG NO. & SEX

J5 (F) 36 (F) 53 (F)

UGOT 27 70 40


pH 7.0 6.5 7.0



Ketones Neg Neg Neg


Occult Blood Neg Pos Neg


Red Blood Cells* Rare

Epithelial Cells* OcC Few

Ca Oxalate* Mod Occ

Bacteria*

Cas ts*

Crystals*:

Uric Acid Freq Many

Triple Phosphate Mod

A-orphous Slight Little Little

Sulfa

Re-marks.__

*Microscopic (per high ruwer field)**Positive for non-glucose reducing substances.

S....... ..

A-139


TABLE 8 (continued)

URINALYSIS

TNT- 1 mg/kg 3 WEEKS PRE-DRUG

DOG NO. & SEX69 (M) 70 (M) 71 (M)

UGOT 4 48 48


pH 7.0 7.0 7.5


Sugar Neg** Neg Neg

Ketones Neg Neg Neg



Wnite Blood Cells* 3-5 8-10 18-20

Red Blood Cells*


Ca Oxalate* Occ Rare

Bacteria*

Casts*

Crystals*:

Uric Acid 0cc

Triple Phosphate Few Occ Many

"Amorphous Much Mod

Sulfa Freq

Remarks


A-140


T>.3• 8 (continued)

• 1 URINALYSIS

TNT- 1 mgAkg 3 WEEKS PRE-DRUG

DOG NO. & SEX46 (F) 47 (F) 48 (F)

UGOT 68 71 54


pH 7.5 7.5 6.0

Protein 30 mg 30 mg Trace


Ketones Neg Neg Neg

BilirubLi, Neg Meg Neg

I.. Occult Blood Neg Neg Neg


Red Blood Cells*

Epithelial Cells* Freq Occ Occ

Ca Oxalate*

Bacteria* Mod

Casts*

Crystals*:

Uric Acid

- Triple Phosphate Many Many


Sulfa Occ

* Remarks


A- 141


TABLE 8 (continued)

URINALYSIS

TNT - 1 mg•/g 2 WEEKS PRE-DRUG

DOG NO. & SEX69 (M) 70 (M) 71 (M)

UGOT 71 65 71


pH 7.0 6.5 7.0


Sugar Neg Neg Neg

Ketones Neg Neg Neg


Occult Blood Neg Trace Neg


Red Blood Cells* -

Epithelial Cells* 1-2

Ca Oxalate*

Bacteria* Mod Mod

Casts* 0-1

Crystals*:

Uric Acid Many Freq


Amorphous Mod Heavy Little

Sulfa

Remarks Coarsely gran.

casts


• • -

A- 142


I TABLE 8 (continued)

I URINALYSIS

TNT - 1 mg/kg 2 WEEKS PRE-DRUG

I DOG NO. & SEX46 (F) 47 (F) 48 (F)

UGOT 68 54 57

i Specific Gravity - 1.050 1.048

pH 8.0 7.0 6.5

SProtein 30 mg Trace Trace


Ketones Neg Neg Neg


Occult Blood Pos Neg Neg

I White Blood Cells* 9-12 7-10 4-8

Red Blood Cells* 8-10 -

Epithelial Cells* - Occ

I Ca Oxalate* - -

Bacter ia*

Casts*

Crystals*:{i

Uric Acid - Many Many

Triple Phosphate Freq Few Occ

Amorphous Little Mod Mod

i Sulfa

Remarks

H *Microscopic (per high power field)


[I

A-143


TABLE 8 (continued)

URINALYSIS

TNT - I mg/kg 4-WEEXS

DOG NO. & SEX69 (M) 70 (M) 71 (M)

UGOT 132 202 190


SpH 9.0 9.0 9.0


Sugar Neg Neg Neg

Ketones Neg Neg Neg




Red Blood Cells* - -

Epithelial Cells* - - Occ

Ca Oxalate* - -

ABacter ia* Mod Mod Heavy

Casts* - -

Crystals*:

Uric Acid

Triple Phosphate Occ Freq


Sulfa

Remarks


A-144


TABLE 8 (continued)

URINALYSIS

TNT - 1 mg/kg 4-WEEKS

DOG NO. & SEX46 (F) 47 (F) 48 (F)

UGOT 222 222 62

Sp6Aific Gravity 1.026 1.048 1.074

pH 9.0 9.0 6.0


Sugar Neg Neg Neg**

Ketones Neg Neg Neg



White Blood Cells* 2-5 Rare

Red Blood Cells*


Ca Oxalate*

Bacteria* Mod Mod

Casts*

Crystals*:

Uric Acid

Triple Phosphate Rare


Sulfa

Remarks


A-145


TABLE 8 (continued)

URINALYSIS

TNT - 1 mg/kg 8-WEEKS

DOG NO. & SEX69 (M) 70 (M) 71 (M)

UGOT 59 54 54


pH 6.5 7.0 7.0



Ketones Neg Neg Neg



White Blood Cells* Rare 2-4 1-3

Red Blood Cells*


Ca Oxalate* Occ

Bacteria* Occ

p.* Casts*

Crystals*:

Uric Acid Occ Occ Occ


Amorphous Little Mod

Sulfa

Remarks - Many mucous Many mucous

threads threads


A-146


TABLE 8 (continued)

URINALYSIS

TNT - 1 mgAcg 8-WEEKS

DOG NO. & SEX46 (F) 47 (F) 48 (F)

UGOT 40 49 32


pH 7.0 7.0 6.5

Protein Trace Neg Neg


Ke tones Neg Neg Neg



White Blood Cells* 2-4 Rare Rare

Red Blood Cells*


Ca Oxalate*

Bacteria* Mod

Casts*

Crystals*:

J! Uric Acid Occ Occ


Amorphous Little Little Little

Sulfa

Remarks


A-147


TABLE 8 (continued)

UJRIN{ALYSIS

TNT - I mg/kg 13-WTEEKS

DOG NO. & SEX"__69 (M) 70 (M) 71 (M)

UGOT 48 37 118


pH 6.5 7.0 8.0

Protein Trace Neg 30 mg


Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells*

Ca Oxalate*

Bacteria* Mod Mod Mod

Casts*

Crystals*:

Uric Acid Occ Freq

Triple Phosphate - Freq

i• Amorphous Mod Little Mod

Sulfa

Remarks


. . .... ... - - - -- - -- . .. .. .... .. . . . . .. , il

A-148


TABLE 8 (continued)

URINALYSIS

TNT - I mg/kg 13-WEEKS

DOG NO. & SEX46 (F) 47 (F) 48 (F)

UGOT 55 62 55


pH 8.0 8.0 7.0

Protein Trace Trace Trace


Ketones Neg Neg Neg

ailirubin Neg Neg Neg


White Blood Cells* 2-4 Occ 1-2

Red Blood Cells*

Epithelial Cell2s* Occ

Ca Oxalate* Occ

Bacteria*

Casts*

Crystals*:

° 'Uric Acid Occ

Triple Phosphate Occ 0cc Occ

Amorphous Mod Little Little

Sulfa

Remarks


A-i149


TABLE 8 (continued)

URINALYSIS

TNT - 0.1 mg/kg 3 WEEKS PRE-DRUG

DOG NO. & SEX60 (M) 62 (M) 63 (M)

UGOT 74 62 i43


)H 7.0 8.0 7.0


Sugar Neg Neg** Neg

Ketones Neg Neg Neg



White Blood Cells* 5-8

Red Blood Cells*

Epithelial Cells* Occ

Ca Oxalate* Many Few

Bacteria* Mod

Casts*

Crystals*:

'• Uric Acid

Triple Phosphate Many Many Mod

Amorphous Some Mod

Sulfa

Remarks

*Microscopic (per high power field) t

**Positive for non-glucose reducing substances,.

A-1 50

LITTON BIONETIGS, INC.

TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX42 (F) 3S (F) 52 (F)

UGOT 62 54 83


pH 6.0 7.0 7.0


Sugar Neg** Neg** Trace

Ketones Neg Neg Neg




Red Blood Cells* - -

Epithelial Cells* Freq Few

Ca Oxalate* Occ Occ Few

Bacteria*

Casts*

Crystals*:

"Uric Acid

Triple Phosphate Occ Many Many

Amorphous Heavy

Sulfa

Remarks


A.- 151


TABLE 8 (continued)

URINALYSIS

TNT - 0.1 mgkAg 2 WEEKS PRE-DRUG

DOG NO. & SEX60 (M) 62 (M) 63 (M)

UGOT 95 51


pH 7.0 7.1 7.5

Prote in 50 mg Neg Trace


Ketones Neg Neg Neg




Red Blood Cells*


Ca Oxalate* Occ

Bacteria*

Casts* 0-2

Crystals*:

Uric Acid Many Occ

Triple Phosphate Many Occ Many

Amorphous Mod Mod Mod

Sulfa

Remarks - Finely gran.

casts


•i A-1 52

•I LITTON BIONETICS, INC.

TABLE 8 (continued)

j URINALYSIS

TNT - 0.1 mg/k)g 2 WEEKS PRE-DRUG

DOG NO. & SEX42 (F) 38 (F) 52 (F)

UGOT 51 65 92


pH 6.5 8.0 7.0


Sugar Neg** Neg** Nege*

Ketones Neg Neg Neg




Red Blood Cells" - -

Epithelial Cells* Few Freq

Ca Oxalate*

Bacteria* Small

Casts*

Crystals*:

Uric Acid Freq Many

Triple Phosphate Few Freq

I". Amorphous Little Mod Many

Sulfa Some

Reu".rks


A-153

IlITTON BIONETICS, INC.

TABLE 8 (continued)

URINALYSIS

TNT- 0.1 mg/kg 4-WEEKS

DOG NO. & SEX60 (M) 62 (M) 63 (M)

UGOT 150 102 78

Specific Gravity 1.056 1. 048 1.049

pH 9.0 9.0 9.0


Sugar Neg Neg Neg

Ketones Neg Neg Neg



White Blood Cellsx .I.-6 5-7 8-10

Red Blood Cells*

Epithelial Cells*

Ca Oxalate* Freq

Bacteria* Heavy Heavy Little

Casts*

Crystals*:

Uric Acid


Amorphouq Heavy Heavy Little

Sulfa

Remarks

j *Microscopic (per high power field)

7 • !47• •r o #-'-...• . .. .." -

A-154


TABLE 8 (continued)

URINALYSIS

TNT - 0.1 mg/kg 4-WEEKS

DOG NO. & SEX42 (F) 38 (F) 52 (F)

UGOT 74 8 78


pH 9.0 6.0 9.0

Protein 30 mg Neg 30 mg

Sugar Neg Neg Neg**

Ke tones Neg Neg Neg


Occult Blood 1+


1 Red Blood Cells* Rare


Ca Oxalate*

Bacteria* Occ Heavy Occ

Casts*

Crystals*:

Uric Acid

Triple Phosphate - Occ Few


Sulfa

Remarks


- -. - ~-<

A- 155

LITTON BIONETICS, -4C.

TABLE 8 (continued)

URINALYSIS

TNT - '.l mg/kg S-WEEKS

DOG NO. & SEX60 (M) 62 (M) 63 (M)

UGOT 62 59 78


pH 9.0 7.0 9.0


Sugar Neg Neg** Neg

Ketones Neg Neg Neg


Occult Rlood Neg Neg Neg


Red Blood Cells*


Ca Oxalate* - Mod

Bacteria* Mod - Many

[ Casts* 0-2

Crystals*:

Uric Acid - Occ Occ

Triple Phosphate Freq Occ Occ

Amorphous Mod

Sulfa

Ri arks Hyaline - Motile bact.casts


:."• •.. ...

A-156


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX42 (F) 38 (F) 52 (F)

UGOT 62 59 38


pH 6.0 7.0 7.0

Prote in Trace Neg Trace


Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Rare Rare Rare

"Ca Oxalate*

Bacterlia* Occ Heavy Occ

C Casts*

Crystals*:

SUric Acid Occ Occ

" Triple Phosphate Occ

Amorphous Little Little ittle

Sulfa

"Remarks

,- *Microscopic (per high power field)


-4,

A-157


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX60 (M) 62 M) 63 (M)

UGOT 66 66 37

Specific Gravity 1.O084 1.048 1.032

pH 6.5 7.0 6.5



Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells*

Ca Oxalate* 0cc Freq

Bacteria* _

Casts*

Crystals*:

Uric Acid Freq Freq Few

Triple Phosphate

Amorphous Mod Little Mod

Sulfa

Remarks

*Microscopic (per high power field)S**Positive for non-glucose reducing substances.

A-158


TABLE 8 (continued)

URINALYSIS


DOG NO, &SEX" " F 38 (F) 52 "F)

UGOT 37 66 52


pH 8.0 6.5 7.0


Sugar 1+** Neg** Neg**

Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Few Occ

Ca Oxalate*

Bacteria* 0cc

Casts* 0-2

Crystals*:

Uric Acid Few

Triple Phosphate Freq - Occ

Amorphous Lod Mod Mod

Sulfa

Remarks Coarsely gran.casts


'"*Positive for non-glucose reducing substances.

A-159


TABLE 8 (continued)

URINALYSIS

TNT - 0.02 rig/kg 3 WEEKS PRE-DRUG

DOG NO. & SEX56 (M) 57 (M) 58 (M)

UGOT 62 80 68


pH 6.0 7.0 7.0



Ketones Neg Neg Neg




Red Blood Cells*


Ca Oxalate* Many Many

Bacteria* Some

Casts*

Crystals*:

Uric Acid Occ

Triple PhoLphate Many Many

Amorphous Heavy

Sulfa

Remacrks



:5% F

A-160


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX39 (F) 4-4- (F) 51 (F)

UGOT 86 68 86


pH 7.0 6.0 7.5



Ketones Neg Neg Neg

Bilir in Neg Neg Neg



Red Blood Cells*

Epichelial Cells* Occ Freq Occ

Ca Oxalate*

Bacteria* _

Casts*

a !Crystals*:

Uric Acid Occ

Triple Phosphate Few Many


Sulfa

Remarks


' fr

• • . . ... . . . . • . . . .. _ _

A-161


TABLE 8 (continued)

URIMA.LYSIS


DOG NO. & SEX56 (M) 57 (M) 58 (M)

UGOT 51 62 71


pH 7.0 7.0 9.0

Protein Neg 30 mg 100 mg

Sugar Neg Neg Neg**

Ketones Neg Neg Neg




Red Blood Cells* ....I~4 Epithelial Cells* 0cc

Ca Oxalate* - Occ

I iBacteria* Mod - Mod

Casts*

Crystals*:

Uric Acid - Occ Few

Triple Phosphate - Freq Many


Sulfa

Remarks _


V~

A-162


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX39 (F) 44 (F) 51 (F)

UGOT 68 105 71


pH 7.0 6.0 8.0



Ketones Neg Neg Neg




Red Blood Ce'ls* _ _

Epithelial Cells* Few Few Few

Ca Oxalate* - Occ

Bacteria* .

Casts* _

Crystals*:

Uric Acid - Freq

Triple Phosphate Many - Freq

Amorphous Mod Much

Sulfa


A- 163!


TABLE 8 (continued)

URINALYSIS

TNT - 0.02 mgAcg 4-WEEKS

DOG NO. & SEX56 (M) 57 (M) 58 (M)

UGOI 102 82 142


pH 8.0 9.0 9.0


Sugar Neg** Neg Neg

Ketones Neg Neg Neg




Red blood Cells* _ _

Epithelial Cells* Rare Rare

Ca Oxalate*

Bacteria* Mod Mod

i i" • Crystas*:

•~Crystas*:__

F.• • Uric Acid--.

• • ~Triple Phosphate---

" Amorphous Little Heavy Little

Sulfa

Remarks

*Microscopic (per high power field)**Positive for non-glucose reducing substances.4•

-S

A-164


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX39 (F) 44 (F) 51 (F)

UGOT 126 82 138


pH 9.0 9.0 9.0


Sugar Neg** Neg Neg

Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Rare Rare Rare

Ca Oxalate*

Bacteria* Mod Mod Mod

"Casts*

Crystals*:

Uric Acid -



Sulfa

Remarks


A- 165


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX

56 (M) 57 (M) 58 (M)

UGOT 4/0 47 66

Specific Gravity 1.060 1.049 1,058

pH 7.0 7.0 8°0


Sugar Neg Neg Neg**

Ketones Neg Neg Neg




Red Blood Cells*

Epithelial Cells* Freq Occ

Ca Oxalate* Occ

Bacteria* Mod Occ

Casts*

Crystals*:

Uric Acid Occ Occ Occ


Amorphous Mod Little Mod

Sulfa

Remarl .



- _.- .. -

A-166


-ABLE 8 (continued)

URINALYSIS

TNT 0.02 mg/kg 8-WEEKS

DOG NO. & SEX39 (F) 44 (F) 51 (F)

UGOT 8 66 70


9.0 7.0 7.0


Sugar Neg,ýA Neg Neg**

Ketones Neg Neg Neg

Bilirubin Veg Neg Neg



Red Blood Cells*

Epithelial Cells* Freq Occ

Ca Oxalate*

Bacteria*

Casts*

Crystals*:

Uric Ac'd Occ Occ

Triple Phosphate Occ Occ Rar,

I Amorphous Mod Little LittleS~~Sulfa---

Remark, - Occ ieucene

sipheres

*Microscopic (per high power field)**Positive for non-gltaose reducirs substances.

A-167


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX56 (M) __57 ( _-8 (M•

UGOT 66 62 40


pH 8.0 6.5 7.0

Protein 50 tag 30 mg 30 mg


Ketones Neg Neg Neg

Bil irub in Neg Ncg Neg


White Blood Cells* 2-4 Rare 2--L

Red Blood Cells*

Epithelial Cells*

Ca Oxalate*

Bacteria* Mod

Casts*

Crystals*:

S! Uric Acid Many Occ

Triple Phosphate Freq Occ

•' . Amcrphous Mod Mod

Sulfa

Remarks

J *Microscopic (per high power field)


ii ____ _-_. ..._ _.__ _ _ _ _ -

.--.---. r .k-J-- • _________ -________ ..... _______________ __,___________ ._ _ ......_ rl a i_

A-168


TABLE 8 (continued)

URINALYSIS


DOG NO. & SEX39 (F) 44 (F) 51 (F)

UGOT 58 66 90


pH 8.0 6.0 6.0


Sugar Neg*w Neg** Neg**

Ketones Neg Neg Neg


Occ,,. Blood Neg Neg Neg


Red Blood Cell-*

Epithel ial Cells* Freq

Ca Oxalate* Oce

Bacteria*

Casts*

Crystals*:

Uric Acid - Freq Occ

Triple Phosphate

Amorphous Mod-Heavy Mod Little

Sulfa

Remarks

*Microscopic (per high power field)• [ **Positive for non-glucose reducing substances.

'I.

A-169

PATHOLOGY SUMMARY

No major significant microscopic lesions were observed in either

the high dosage RDX or the high dosage TNT groups which were not observed in

controls. The incidence of microcalculi in the renal pelvis was higher in

4 the test animals, in particular, those treated with RDX. The incidence of

hemosiderosis of the bone marrow was higher in the animals treated with TNT.The small sizes of the groups used in this study make interpretation of the

increases in incidences of renal microcalculi and of bone marrow hemosiderosis

highly precarious.

10 June 1974 WALTER F. LOEB, V.M.D., Ph.D.

I

•LU

BIONETICSUtton

A-1 70


SUMMARY OF MICROSCOPIC LESIONS

RDX TNT, CONTROL 10 mg/kg- 1 mglkg

HeartNo visible lesions (NVL) 5 5 6Medial thickening of muscular arteries 1Focal hyalini zation 1

j ILungNV L 3 2 3*Congestion 3 3Edema 2 2Minera i zati on 1Lymphoid nodules 1Alveolar thickening 1Anthracosis IGranulomas (minute) 11

LiverNVL 3 4 6Extramedullary hematopoiesis 2 1Dilitation and thickening of portal 1

and central veinsMultifocal lymphoreticular infiltrate 1

SpleenNVL 2 3 2Congestion 4 3 4Lymphoid hypoplasia 2 2

IntestineNVL 3 5 6Lymphoid hyperplasia 3 1

a •Kidneys•NML 5 2 4Microcalculi in pelvis 1 4 2

ThyroidNVL 6 5 5C-cell hyperplasia 1 1

Bone MarrowNVL 6 5 3Hemosiderosis 1 3

*Lungs collected from only five dogs.

A-171

Dog No. 65 (Male) Control PM NO. 73/2224

GROSS FINDINGS: Lungs congested, hemorrhage in duodenum about 3 incheslong.

ORGAN WEIGHTS: .82 Thyroid .61 Adrenal Gland, Left(in grams)

67.0 Heart .50 Adrenal Gland, Right

189.0 Liver 7.14 Gunad, Left

41.0 Spleen 6.95 Gonad, Right

21.4- Kidney, Left

21.10 Kidney, Right

MICROSCOPIC:

Heart: No visible lesions (NVL).

L'ngs: Very marked congestion and edema. Foci of mineralization, corporaamylacea, peribronchially.

Liver: Minimal extramedullary hematopoiesis; Gallbladder: NVL.

Spleen: Congestion.

Stomach: Not collected.

Intestine with Peyer's patch: Intestine: NVLPeyer's patch: Reticulum cell hyperplasia;

many macrophages containing necroticcell remnants.

Kidneys: NVL

Adrenals: NVL

'1 Thyroids, Parathyroids: NVL

Bone Marrow: Grade ii, 50%. NVL

Brain: NVL

S/ , , ..

4 June 1974 ,Walter F. Loeb, V.M.D., Ph.D.

2-•

A-1 72


GROSS FINDINGS: No gross lesions.

ORGAN WEIGHTS: .71 Thyroid .47 Adrenal Gland (Left): ORGAN(in grams)WIHS.7

84.0 Heart .32 Adrenal Gland (Right)

1- 230 __ Liver 8.68 Gonad (Left)

83 Splean 8.79 Gonad (Right)

26.54 Kidney (Left)

1 25.70 Kidney (Right)

MICROSCOPIC:


Lungs: NVL

Liver: Extramedullary hematopoiesis. No other iesioils.

Spleen: Congestion.

Stomach: NVL

Intestine: NVL

Kidney: Protein droplets present in Bowman's spaces.

Adrenals: NVL

Thyroid: Missing.

Bone Marrow: Grade II, 25%. NVL

Brain: NVL

4 June 1974 ". / ..Walter F. Loeb, V.M.D., Ph.D.

tob V.•

.. *:

G .7- ;:; •._-,__.. .. .__'-_

A-173


GROSS FINDINGS: Congestion of the pelvic urethra.

ORGAN WEIGHTS: .71 Thyroid .81 Adrenal Gland,Left(in grams)

65 Heart .74 Adrenal Gland,Right

227 Liver 8 Gonad, Left

18 Spleen 6 Gonad, Right

25 Kidney, Left

25 Kidney, Right

MICROSCOPIC:

Heart: No visible lesions (fIVL).

Lung: Marked congestion, slight edema.

Liver: NVL

Spleen: NVL

Stpmach: NVL

Intestine: Marked hyperplasia of Peyers patches with increased mitoticfigures.

Kidneys: NVL

Adrenals: NVL

Thyroid: NVL

Bone Marrow: Grade II, 5r%. NVL

Brain: NVL

Prostate: NVL

SBladder: NVL

4 June 1974"Walter F. Loeb, V.M.D.,Ph.D.

'4,I

A-174

Dog No. 37 (Female) Control PM NO. 73/2227

GROSS FINDINGS: Lungs are congested severely.

ORGAN WEIGHTS: .88 Thyroid 1.73 Adrenal Gland, Left('. n grams)

69 Heart 1.62 Adrenal Gland, Right

301 Liver .71 Gonad, Left-

34 Spleen .73 Gonad, Right

24.22 Kidney, Left

24.04 Kidney, Right

MICROSCOPIC:


Lung: Extreme congestion. Few small lymphocytic nodules.

Liver: NVL

Spleen: Contracted.

Stomach: NVL

Intestine: NVL

Kidney: NVL

Adrenals: NVL

Thyroid, Parathyroid: NVL


Brain: NVL

June 1974

Walter F. Loeb, V.M.D., Ph.D.

A-l 75





204.0 Liver .36 Gonad, Left

36.0 Spleen .46 Gonad, Right

17.01 Kidney, Left

17.84 Kidney, Right

MICROSCOPIC:

Heart: No visible lesions: NVL

Lung: There is one microscopic granuloma present. The etiologic agentis not evident.

Liver: Cross sections of individual portal veins and central veins (perhaps10-20% of tota,) reveal very marked dilitation. These vesselshave ,ery thick fibrous or fibromuscular media and adventitia.

Sp .n.: Congested.

Stomach: NVL

Intestine: NVL

Kidney- NVL

Adrenals: NVL

Thyroid: In a portion of one thyroid, the acini are devoid of colloid,but contain material morphologically suggestive of serum.


Brai n: NVL

!• , •June 19741Jne Walter F. Loeb, V.M.D., Ph.D.

A-176


GROSS FINDINGS: No gross lesions. One ascarid noted in small intestine.

ORGAN WEIGHTS: .6%, Thyroid .77 Adrenal Gland, Left(in grams)


253.0 Liver 1.00 Gonad, Left

71.0 Spleen ,79 Gonad, Right

26.78 Kidney, Left

I 26.0 Kidney, Right

MICROSCOPIC:

4. Heart: Medial thickening of some muscular arteries.

Lung: No visible lesions (NVL).

Liver: NVL

Spleen: Red pulp congested.

Stomach: NVL

Intestine: Lymphoid hyperplasia of Peyers patches.

Kidneys: Mineral deposits (microcalculi) in tubules of renal pelvis.

Adrenals: NVL


Brain: NVL

Bone Marrow: Grade I!, 40%. NVL

/

4 June 1974__ _ _:_'


~:i.

A-177

Dog No. 73 (Male) RDX-High PM NO. 73/225610 mg/kg

GROSS FINDINGS: Mesenteric lymph nodes hemorrhagic.


91. Heart .64 Adrenal Gland, Right

275. Liver 11.97 Gonad, Left

89. Spleen 12.11 Gonad, Right

32.58 Kidney, Left

32.46 Kidney, Right

MICROSCOPIC:


Lung: Anthracosis.

Liver: NVL

Spleen: NVL

Stomach: NVL

Intestines: Lymphoid hyperplasia of Peyer's patch.

Mesenteric Lymph Node: Longestion and edema.

Kidneys: Foci of mineralization in pelvis.

Adrenals: NVI.

Thyroid and Parathyroid: NVL

Bone Marrow: Grade II, 30%. Depletion of mature granulocytes.

Brain: NVL

• , /6 June 1974 . •

" !-Iter F. Loeb, V.M.D., Ph.D.

A-178

Dog_ No. 74 (Male) RDX-High PM NO. 73/225710 mg/kg


ORGAN WEIGHTS: 1.0 Thyroid .70 Adrenal Gland, LeftI, _ _(in grams)_( r87. Heart .65 Adrenal Gland, Right

415. Liver 12.28 Gonad, Left

995. Spleen 11.38 Gonad, Righ't

30.64 Kidney, Left

32.17 Kidney, Right

MICROSCOPIC:


* Lung: NVL

Liver: Cells contain glycogen. NVL.

Spleen: Congestion, lymphocytic depletion. Necrosis of individual cellsin center of lymphocytic nodules.

Stomach: NVL

Small Intestine: Cells of lamina pro ria are principally plasma cellsrather than lymphocytes.

Kidneys: NVL

Adrenals: NVL

Thyroid: NVL

Bone Marrow: Grade II, 50%. Excess hemosiderin-filled macrophages.SNo other lesions.

Brain: NVL

6 June 1974 / /" - /Walter F. Loeb, V.M.D., Ph.D.

i "

- {

A-179

Dog No. 55 (Male) RDX-High PM NO. 73/225910 mg/kg


ORGAN WEIGHTS: 1.19 Thyroid .81 Adrenal Gland, Left(in gram)




36.21 Kidney, Left

35.71 Kidney, Right

MICROSCOPIC:


Lung: Carbon filled macropnages around bronchioles; foamy macrophages in andaround bronchioles. Some mucus in bronchioles.

Liver: NVL

Spleen: Congestion, depletion of lymphocytes (marked).

Stomach: NVL

p Intestine: NVL

Kidney: NVL

[I Adrenal: NVL

Thyroid and Parathyroid: NVL

[ Bone Marrow: Grade I1, 40%, NVL.

Brair: (Cerebrum, cerebellum, brain stem, meninges, choroid plexus) - NVL

6 June 1974 '..Walter F. Loeb, V.M.D., Ph.D.

L ,-

A-180

Dog No. 76 (Female) RDX-High PM NO. 73/225810 mg/kg

GROSS FINDINGS: Small intestine - diffuse congestion, focal hemorrhage,moderate. Mesenteric node enlarged.

ORGAN WEIGHTS: .94 Thyroid .81 Adrenal Glaid, Left(in grams)




19.23 Kidney, Left

19.93 Kidney, Right

MICROSCOPIC:


Lung: Congestion; some interstitial cellular infiltration.

Liver: Multifocal lymphoreticular infiltrate unrelated to lobular architecture,slight.

Spleen: Congestion.

Stomach: Missing

Intestine: NVL

S~Lymph Node (Mesenteric ?:Lymphoid hyperpla.sia and edema.

SKidney: Foci of mineralization in interstitium of renal medulla.

" Adr-Enal s: NVL

"" ~Thyroid: Diffuse C-cell hyperplasia, marked.*301Bone Marrow: Grade II, 40%. Erythroid hyperplasia.

Brain: :.4VL

o/ I

6 June 1974 -

Walter F. Loeb,V.M.D., Ph.D.

7111 _---

A-181

Dog No. 49 (Female) RDX-High PM NO- 73/2253

10 mg/kg

GROSS FINDINGS: No gross iesions.

ORGAN WEY'HTS: .59 Thyroid .64 Adrenal Gland, Left(in gran. j


300. Liver .67 Gonad, Left

28. Spleen .73 Gonad, Right

20. Kidney, Left

20. Kidney, Right

MICROSCOPIC:

Heart: Area of hy:'inization (amyloid?) under endocardium of papillary muscle,left ventr',Ie.

Lung: Congestion and edema.

Liver: Liver parenchyma cells filled with glycogen.

Spleen: No visible lesions (NVL).

Stomach: NVL

Intestine: NVL

Kidney: Mineralized deposits (microcalculi) in tubules of pelvis.

Adrenal : NVLK' Thyroid.and Parathyroid: NVL

Brain: NVL


, /

6 June 1974 . Walter F. Loeb, V.M.D., Ph.D.

K Y.l

A-182

Dog No. 50 (Female) RDX-High PM NO. 73/2254

10 mg/kg




225. Liver .44 Gonad, Left

35. Spleen .36 Gonad, Right

16. Kidney, Left

16. Kidney, Right

MICROSCOPIC:


Lung: Edema, congestion.

Liver. Focal extramedullary hematopoiesis. Liver parenchyma cells filledwith glycogen.

Spleen: NVL

Stomach: NVL

Intestine: NVL

Kidneys: Mineralized deposits (microcalculi) in tubules of renal pelvis

Adrenals: NVL

Thyroid: NVL. Parathyroid: One cyst (less than 1 mm diameter) present.

Brain: NVL

Bone Mirrow: Grade II, 50%, NVL

6 June 1974 . , -I -Walter F. Loeb, V.M.D., Ph.D.

i• I

A-183

D__o__N 69 (Male) TNT-High PM NO. 73/22621 mg/kg






25.56 Kidney, Left

24.77 Kidney, Right

MICROSCOPIC:


Lung: NVL

Liver: Liver parenchyma cells filled with glycogen.

Spleen: NVL

Stomach: NVL

Intestine: NVL

Kidneys: NVLii . .Adrenals: NVL


Brain: NVL


,I, / ,I' ( ,- f

6 June 1974 / , . _ __" / , "."Walter F. Loeb-, V.M.D., Ph.D.S• • .

i

g :

A-184

Dog No. 70 (Male) TNT-High PM NO. 73/22631 mg/kg


ORGAN WEIGHTS: 1.22 Thyroid .58 Adrenal Gland, Left(in grams)




25.23 Kidney, Left

24.79 Kidney, Right

MICROSCOPIC:


Lung: Alveolar walls are thickened by amorphous eosinophilic proteinaceousmaterial and congestion.

Liver: NVL

Spleen: Congestion.

Stomach: NVL

Intestine and Pancreas: NVL

Kidneys: NVL

Adrenals: NVL


"Bone Marrow: Grade II, 40% NVL

Brain: NVL

6 June 1974 "- -"


S, _

• .

A-185

Dog No. 71 (Male) TNT-High PM NO. 73/2264

1 mg/kg

GROSS FINDINGS: Parasite in small intestine.

ORGAN WEIGHTS: 1.08 Thyroid .75 Adrenal Gland, Left(in grams)


"313.0 Liver 11.20 Gonad, Left


23.78 Kidney, Left

23.42 Kidney, Right

MICROSCOPIC:


Lung: Not collected at necropsy.

Liver: NVL

Spleen: NVL

Stomach: NVL

Intestine: NVL

Kidneys: Mineralized deposits (microcalculi) in pelvi'ses of kidneys.

Adrenals: NVL


Brain: NVL

Bone Marrow: Grade II, 40%. Normocellular bone marrow with hemosiderosis.

6 JLne 1974 -Walter F. Loeb, V.M.D., Ph.D.

t..

A-186

Dog No 46 (Female) TNT-High PM NO. 73/22551 mg/kg

GROSS FINDINGS: Mesenteric nodes are hemorrhagic.2





25.79 Kidney, Left

22.48 Kidney, Right

MICROSCOPIC:

Heart: No visible lesion (NVL).

Lung: NVL

Liver: NVL

Spleen: Congestion. Lymphoid depletion.

Stomach: NVL

Intestine: NVL

Mesenteric Lymph Node: Areas of lymphoid hyperplasia and areas of congestion.

Kidneys: NVL

Adrenals: NVL

Thyroid: Diffuse C-cell hyperplasia, mild. Parathyroid: NVL

Bone Marrow: Grade II, 65% Increase in hemosiderin. Hyperplasia.

Brain: NVL

/ / .- /

7 June 1974 '/ . "Walter F. Loeb, V.M.D., Ph.D.

LFI

A-187

Dog No. 47 (Female) TNT-High PM NO. 73/2260"1 mg/kg






20.36 Kidney, Left

21.4_t Kidney, Right

MICROSCOPIC:

Heart: No visible lesion (NVL).

Lung: NVL

Liver: NVL

Spleen: 'Congestion. Some of the lymphoid follicles are hypoplastic.

Stomach: NVL

Intestine: NVL

Kidneys: NVL

Adrenals: NVL


Brain: NVL


7 June 1974 K. ?/" " 'Walter F. Loeb, V.M.D., Ph.D.

t 4•

S• ,

A-188

Do9 No. 48 (Female) TNT-High Pr. NO. 73/22611 mg/kg


ORGAN. WEIG,'iS: .97 Thyroid .54 Adrenal Gland, Left




"23.0 Kidney, Left

21.0 Kidney, Right

• '.:art: No visible lesion (NVL).

Lung: Two minute gr-nulomas containing isotropic pigment.

Liver: Liver cells are swollen with finely vacuolated cytoplasm, probablyglycogen. Kuppfer cells contain bilirubin.

Spleen: Congestion. Bile pigmen* in macrophages. 9

Stomach: NVL

Intestine: Plasma cells and eosinophils very abundant in lamina propria.

Kidney: Excessive protein in Bowman's spaces. Very minute mineral depositsin loops of Henle.

* Adrenals: NVL

Thyroid: NVL

"Bone Marrow: Grade II, 40% Excess hemosiderin-filled macrophages. Erythroidhyperpl asia.

Brain: Some vacuolation of h4:ppocampus.

I / * I*

7 June 1974 ..Walter F. Loeb, V.M.D., Ph.D.

., '( A

iirenal microcalculi and bone marrow hemosiderosis are both encountered occasionally in random dog...

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