Exp. Anim. 39(2), 239-248,

Spontaneous

Lesions

Hideki

in Beagle

MORISHIMA,

Dogs Used

Takashi NONOYAMA, and Hiroaki MIYAJIMA

Drug Safety Research Laboratories, Takeda 6-10-1 Himuro-cho, Takatsuki-shi, (Received 26 September

in Toxicity Satoshi

1 December

Studies

SASAKI,

Chemical Industries, Osaka 569, Japan

1989/Accepted

1990

Co., Ltd.,

1989)

Spontaneous histopathologic lesions were examined in 276 young beagle dogs (8 to 15 months old) used in toxicity studies. Mononuclear cell infiltration in the liver was observed with the highest incidence (more than 95%). Calcium deposition in the kidney, mononuclear cell infiltration in the salivary glands, pigmentation in the spleen, and cortical atrophy in the thymus were seen with relatively high incidences (more than 30%). The incidence of mononuclear cell infiltration in the gallbladder, vacuolization of the tubular epithelium in the kidney, and vacuolization of the zona glomerulosa cell in the adrenal gland showed differences between the sexes. No abnormalities were seen in the spinal cord, sternum, and femur. Although most lesions observed are considered to be age-related, several were considered to be due to congenital anomalies observed in some organs.

The importance of beagle dogs as experimental animals in toxicologic and medical studies is well established. Background information on this breed has been extensively accumulated [1, 5, 10, 13, 14]. Although the recognition of subclinical spontaneous lesions in dogs used in drug-safety evaluation studies and the differentiation of these lesions from drug-induced alterations are very important, only a few histopathologic surveys of spontaneous lesions in beagle dogs are found in the literature [7, 8,11,12,15], but control data may take many forms and include variables such as the source and age of animals and diet. In this report, the histopathology of spontaneous subclinical lesions found in young beagle dogs (8 to 15 months old) used in drugsafety evaluation studies is described.

and

leptospirosis,

serologically

and

Methods

were

proved

Brucella

canis

to

be

by

the

After the animals arrived at our laboratory, they were quarantined and acclimatized to the environmental conditions for at least one month before they were used in the studies. During this period, all animals were considered to be normal on the basis of body weight, heart rate, body temperature, ophthalmoscopy, hematology, blood chemistry, examination for Brucella canis in the serum, examination for salmonellosis and the eggs of parasites in the feces, and the absence of clinical signs of disease. The metal

10-20

animals

cages

ditioned

tion

1. Animals : Two hundred and seventy-six beagle dogs (144 males and 132 females) used in drug-safety evaluation studies are the subjects of this report. The animals were obtained from Japan Experimental Dog and Monkey Co., Ltd. or White Eagle Laboratories, Inc. at 5-6 months of age. The animals were vaccinated against canine distemper, infectious hepatitis,

from

breeder.

were

housed

(650•~580•~800mm)

room

a relative

Materials

and

free

with

humidity

times/hr, light/dark

a temperature of

and

in in

55•}15%,

a 12 hr

individual an of

air-con23•}3•Ž,

air-changes

fluorescent

of

illumina-

cycle.

Each animal was fed daily a mixture of 260g of a pellet diet (CD-5, CLEA Japan, Inc. ), 100g of a canned meat (Kal Kan (R), Kal Kan Foods Co., U. S. A.), and 360g of warm tap water in the afternoon. They were allowed free access to tap water. The ages of the from 8 to 15 months.

dogs

at

autopsy

ranged

240

2.

Histopathologic

mination was

Procedures

of

each

anesthetized

sacrificed and

with

by

of

and

f ormalin

the

fixed

10

uterus,

testis/ovary,

gallbladder, lymph node, glands

at

ixed in specimens

sectioned with

at

cord,

pH

formalin,

tract and

for

about

of eosin

infiltration•h

of •gMononuclear in

beagle

cell

dogs

and for

stained histopa-

sternum, by

and

f ormalin. paraffin,

in

(H-E)

The

were

15 min

4 ƒÊm,

decalcified they

Table

mesenteric salivary sublingual

thickness

were

colon),

mammary

a

before

para-

and trachea. The phosphatebuffered

7.1

examination. trachea

dogs

liver,

skin,

neutral buffered were embedded

and

Incidence

in beagle

prostate/

and

5%

hematoxylin

thologic

lung,

ileum,

femur, in 4%

2.

lesions

were

thyroid,

gland

sternum, were fixed

glutaraldehyde postf All

heart, kidney,

spinal

Common

buffered

bone marrow (femur), urinary bladder, tongue,

esophagus,

gland, eyeballs

organs neutral

duodenum,

(submaxillary

gland),

1.

artery,

gastrointestinal

pylorus,

Table

sodium,

carotid

vagina,

adrenal,

(fundus,

%

thymus,

ter-

animal

immediately.

pituitary,

pancreas,

thyroid,

the

following

in

: brain,

spleen,

and

of

examined

portions

obtained

the

each

thiopental

incision

macroscopically

Small

After

experiment,

femur, formic

embedded

acidin

para-

ffin.

If there was any suspicion that a lesion might be related to drug-treatment, it was not considered to be spontaneous. Differences between the sexes in the incidence of each lesion were statistically analyzed using the Chi-square test. Results Various observed spinal

histopathologic in

cord,

all

organs

sternum,

lesions examined

and

except

were the

femur.

Table 1 shows the common lesions that were observed in several organs. Mononuclear cell infiltration was the most common lesion observed in 21 organs (Fig. 1, 2) ; the incidence in each organ was relatively high (Table 2), but the severity was minimal to mild. In the salivary glands, most of the mononuclear cell infiltration observed was in the sublingual gland. The cells which infiltrated the sublingual gland had abundant basophilic cytoplasm, a wheel-like nucleus, and resembled plasma cells (Fig. 3, 4). In the gallbladder, the incidence of mononuclear cell infiltration in males (20.8%) was significantly higher than that in females

* : Significant

difference

male and female

in incidence

between

(P

Spontaneous lesions in beagle dogs used in toxicity studies.

Spontaneous histopathologic lesions were examined in 276 young beagle dogs (8 to 15 months old) used in toxicity studies. Mononuclear cell infiltratio...
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