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Material Tested; Material Submitted by
Copies co:
E. I, du Font de Nemours and Company
Haskell Laboratory for Toxicology and Industrial Medicine
HASKELL LABORATORY REPORT NO. 244-71
irganic Chemicals Department fJackson Laboratory
Haskell No.: Other Codes:
6917
AR226-2829
ACUTE ORAL TEST
Procedure; The test material, as an a ~)UB suspension, was administered by intragastric intubati ChR-CD male rats in single doses. Cjrv.i.vors were sacrificed 14 days later; the livers were remove analysis,
Results:
Suspension (%)
25 25 25 25 25
Dose
(me/ka)
11,000+ 7,500+ 5,000 3,400 2,250
Mortality*
14 d. 14 d. 14 d. 14 d. 14 d.
Weight When Killed (a)
Body
Liver
301
12.68
31)
14.15
352
15.65
328
14.55
312
13.79
* S - ( ) d. = Sacrificed ( ) days after dosing
+ Administered in divided dose
L.W./B.W.
X 100
4.2 4.4 4.4 4.4 4.4
Clinical
None
TEN-DOSE ORAL SUBACUTE TEST
Procedure: The test material was administered by intragastric intubation, as a 15% aqueous suspen of six young adult ChR-CD male rats, five times a week for two weeks; an additional group of six ra
controls and was intubated with distilled water. Three control and three test rats from each group appioximately four hours and 14 days after the last dose.
Results:
Dose ('Pfi/kg/day.?
Mortality
Weight of Liver (g)
Animals, Killed:
After
14 Days
10th
After
Dose
10th Dose
L,W,/B.W. X 100
Animals Killed:
After 14 Days
10th
Dose
After
10th Dose
Gross Pathology^
on Liver
Animals Killed:
After 14 Days
10th
After
Dose 10th Doae
2250
0
(Control)
0/6
23.0
17.8
27.0
18.6
21.9
16.8
0/6
13.0
17.1
13.9
13.3
8.4
18.1
7.8
5.6
8.2
4.8
7.9
4.9
4.2
4.3
4.2
4.0
3.6
4.1
In addition, the following organs were examined histologically: brain, eyes, stomach, d spleen, bone marrow, pancreas, adrenal, kidney, testia, epididymis, lung and trachea; no compoun
changes were observed in any of these organs.
No clinical signs were observed during the first week of the test phase. During the sec recovery period, the test animals gained weight at a rate slightly less than that of the controls
Gross
1 A B C +
and histopathologic code:
No abnormality detected Large and heavy Degeneration and necrosis of isolated hepatocytes Reduction in number' of centrilobular cytoplasmic vesicles
Focal RE cell hyperplaaia Slight degree of change
I^UUBI^UHjhas ^unma^y:
low acute fcoxicity when adKa-uistered orally to young adult ChR-
its Appro&inate Lethal Dose (KBD) is greater than 11,000 ing/kg of body weignt. There was neither
gravimetric evidence of liver enlargement 14 days after dosing.
The repeated administration of th" test compound to rats at 2250 mg/kg/day for ten doses
heavier liver weights and larger liver/body weight ratios at the end of the test phase. These va
to the normal range after the 1^-day recovery period. The histologic effect which was present at
if test period and after the 14-da^ recovery period was characterized by a depletion of cytoplasm^-c
which are usually found in centrilobular hepatocytes of control male rats of this age group. Rec
this type of liver change probably would have occurred
the recovery period had been longer.
KSC:pgh
Date: July 20, 1971
Report ;; ____^j^&^ag7
Kathlee Oral Tox
^'"John Approved by: _____^jV ^> --'
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