Document NGrk5d2VvjQgMgOrmwjVk7M8b
AR226-2830 m
Material Tested: Material Submitted by:
Copies
E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine
HASKELL LABORATORY REPORT NO. 245-71
rganic Chemicals Department Jackson Laboratory
Haskell No.: 6918 Other Codes :
ACUTE ORAL TEST
Procedure: The test material, as an aqueous suspension, was administered by intragastric intubation to young adult ChR-CD male rats in single doses. Survivors were sacrificed 14 days later; the livers were removed for gravimetric analysis.
Results:
Suspension ___ C/o)
Dose (mg/kg)
Mortalitv*
Weieht When Killed (g)
Body
Liver
25
ll,000t
S - 14 d.
325
25
7,500t
S - 14 d.
330
25
5,000
S - 14 d.
334
25
3,400
S - 14 d.
343
15
2,250
S - 14 d.
345
25
1,500
S - 14 d.
318
25
1,000
S - 14 d.
331
15
670 S - 14 d.
364
* S - ( ) d. -- Sacrificed ( ) days after dosing t Administered in divided doses
16.20 16.38 15.27 16.18 14.62 13.22 13.65 16.00
L.W./B.W. X 100
5.0 5.0 4.6 4.7 4.2 4.2 4.1 4.4
Clinical Signs None
ALP > 11,000 rag/kg
Aueduia
jgo VOCI imuoo tau wuu
2
TEN-DOSE ORAL SUBACUTE test
Procedure: The test material was administered by intraeastrio nf k *
srx young adult ChR-CD male rats, five times a week fo^two eeksanoi^; " 3 15* aqueous " P-- ion. to
and was intubated with water. Three test and three control rata fro ^ k grUP f Six rats served as controls
four hours and 14 days after the last dose.
1 f e3Ch 8roup were sacrificed approximately
Results:
Dose (mg/ke/day)
2200
0 (Control)
Mortality 0/6
0/6
Weight of Liver (e>)
Animals Killed
After
14 Days
After 10th Dose
14.3 17.6 18.2
17.1 13.3 18.1
W. A IUU
Animals Killed:
After 14 Days
10 th
After
Dose 10th Dose
5.9
6.0
7.2
4.2 4.2. 3.6
3.6 4.8 5.4
4.3 4.0 4..1-
Gross Pathology*
on Liver
Animals Killed;
After 14 Days
10th
After
Dose 10th Dose
1112
--
Histopathology*
on Liver
Animals Killed:
After 14 Days
10th
After
Dose 10th Dose
BB BB BB
BE
histologic changes were observed in any of these organs.
* Gross and histopathologic code
No abnormality detected
21
Large and heavy Slightly ' rge and heavy
B
^ X w rrlobuUtE
S> tracheaJ no compound-related
f\
. low toxicity when administered orally to voune adult ChR-rn
male rat1; its Approximate Lethal Dose (ALD) ft greater than 11,000 mg/kg of body weight. Theresas neither
gross nor gravimetric evidence of liver enlargement 14 days after dosing.
S
neither
i . Repeated administration of the test compound to rats at a rate of 2200 mg/kg/day for ten doses produced
haVy llVer at Cha end of the test Phase, but these livers were within the normal range at the^nd of e 14 day recovery phase. Histologically, the compound caused a reduction of the number of centrilobular cytoplasmic vesicles after the tenth dose and after the 14-day recovery period. This type of liver change is considered reversible; this reversibility probably would have been manifest with a longer recovery periol!*
JAD:pgh
*
Date: July 20. 1971
I
) /Report by:
Joan A. Dimeler Oral Toxicology Section
Approved by:
jdhu-i.a, , ..lt
' John^. A./'Zg'pp^ Jr. Director
