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AR226-2987
Study TAtte
Approxluate Lthil Doac (ALP) of H-19913 in Raf
Autboy
Curol Fiftlay
Mtrch 3, 1993
Peirforain^ Laboratory
HaakrIT
I. E.
du it d IIRnirs and Coaipany
Laboratory
ToxicolOBy and Zn^ustrial
Elkton Road, P. 0. Box 50
Nevirk, DIvare 19714
Medicine
La&oratogy Peojcct IB Haakell L^wratoty Beport o< 13-93
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Appgoxi--f Ulthal Poe ^ALO) of H-19913 in Rat*
SUMHAItY
DuPont RLR 13-93
f t , H-19913 was dlni8tered ic lnci oral done by incrc--tric intubation
1to ! rt. No death* occurred durinf the tudy. Diarrhea vaa obairvd in
aaiial. Undr the 11,000 nc/kf of body
conditions of vaifht. i Thia
thil
auhctanca
th* AU> vac (rafr than ia conaldrd to b* vry low
in
toxic! ty
dose.
(ALD greater
thin
5000 Kf/kc)
vhn drinifrd
a
cinfl
oral
Vork by
^ ^ M i y 1 Toxicology Aiiocfate
Approved by<
Revieved and Approved for Inc^ei CI?/lrr
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DuPont HLR 13-93
DociETATION
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DatesofInspection:
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Conduct - 12/30/92
Records, ows - 343m :
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Date(s)FindingsBaporeadto: |
9
SiidyDsator = 2/5/93
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Reported bys
Chg
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1 Servesnes dnitor fee
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Cai CompanySenitized.Does notcontainTSCA CBI
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Duront RUt 13-93
iw The purpose of this test vas to dt<FrlR ti pproxitt* letbfti
of
H-19913 vhen adminisi^Fed i t ltg^ oral dor to Male raf The ALO vat
defined a the loveat doa a<ji !lnitMd Khich cu>(( death ither on th day
of dosing or within 14 days pi ' Mponure. This study vac conducted according
to the applicable EPA Sood tafrera"fo'-r^y PTacUco Stn<Sar<S,
HATEKIALS ANP MKTKODS
A. Anial Husbandry
^ Hale CrItCOtR rats, aj>^roxiatiy 7 weeks old, vere received fror
Charles River Breedi?ig JVl bora^iN* '1fN||lf-ffii New York* Rats vere
housed singly IB'V B '" di tiailjiNIa liffallf^^^^
cages. Bach rat
va assigned
ntliAeadon nuiS>er v*ich was recorded on a card
ffixed to the
ina Certified KtMient Chow* #5002 and water vere
available ad 11
ts were qvrantiwd, 'velghed, and obscrvad for
general health"
llMfly 1 vsek prior to teating. Animal roors
were --inCftinod ^(i1
r-eonsrolltd, 12-hcyr llght/12-hour dark cycle*
Enviroirentel conditloJtl of the roo-- Wr* Stretd for a tenprature of
23'C * 2*C and igelattw^^uinidlty of SO? iOX, Bxeuraions outside these
rancci vere of SMil uu?nniltucS and/or brief fsiurmt Ion and did not
adversely affect the vaiitH)dHy of law stwiy.
B. Protocol
The teat aubatanee a dispenred in d|iilniced vater and administered
to 1 rat per doe rate ty iTttragaatric intubation. In the absence of
visible evidence to the cco| ntrary, the test subatanet vaa asaunied to be
stable under the conditionisa of adeinittratlon. Dose rates adRinistered
ranged froR 2300 to 11,00" t/ke of bwly weight in inerenents of
epproxinately 50X. Addit cnnlly, 1 rat VCB dolsed at 670 g/kg. The
dosing day was test
ppstexposur dy N was test day 15.
Following adrlnictFation f the tost u&Btanc, rats vere observed for
clinical signs of toxicit^ . the rats ver weighed and observed daily
until signs of tosicity iisbsided, and then; at feast 3 tiMes per veek
throughout the 14-day rec<|>very period (holl<iy excluded). Observations
Cor ortality vere ade d) ily throughout the study. Patholoffleal
examinations of teat anil ils veee not .perforaaid.
DuPont HLR 13-93
C. Reeord Retention
All raw data and the final report vill be stored in th archives of
Haskell Laboratory for Toxicology and Industrial Medicine, E. Z. du Font
de NMOjrs and Company, ^avark. Dataware or in the DuPont Record* Hanageient Center, VilRington, Delaware.
RESULTS
A. Dosage and Mortality Data
The dosage regimen ^nd the Mortality resulting over the 15-day test period are detailed belotf. No deaths occurred during the study.
Dosage (mg/kg)
Dose
VoluBe
(L)
Eculsion
Concentration
(M/L)
Initial Body
tfeight (g)
Mortality
670
1.2
ISO
275
No
2300
3.9
ISO
254
No
3400
2.9
300
254
(to
5000
4.7
300
280
No
7500
7.0"
300
279
No
11,000
9.9*
300
271
No
Administered in 2 portions, approximtely 15 minutes apart.
B. Clinical Signs
No clinical signs of toxicity were observed in rats dosed at 670, 2300, 3400, 7500, or 11,900 /k: The rat dosed at 5000 ffig/kg had diarrhea the day after dosing.
CONCLUSION
Under the conditions of this study, the ALD for H-19913 was greater than 11,000 ig/kg of body weight. This substance Is considered to be very low in toxicity (ALD greater than 5000 ng/kg) when administered as a single oral dose to aale rats.
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