Document z6MKdxgLZN7KKo4j1B1Ej1D3
InternatioRneaslearcahndDevelopmenCtorporation
SPONSOR: I"-7STXATERT-U: SUBJECT:
3M Company
FM-3422
Acute Oral Toxicity (LD
Study in Rats.
50
Wilson P. Dean, B.A. Director c@4 Acute
and Spec4-ai St,-d4-as (Stl-ldvD,;-rec:o,-)
D.
Jessuv,,/7*,,.D.
Assoc4az D.:rec:o
Researzh
CoLlaborators: Gary Thompson, B.S.
Group Technical Supervisor Gre,0, Romig, B.S.
Un4-t Technical- Superv4-sor David Powell, B.A.
Un4-t Supervisor, Report Preparat-Lon, Acute and Special Studies Department
137-084
Date: June 7, 1978
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T A B L E 0 F C 0N T EN T S
I II. III. IV.
Page
Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . 1
Test Material . . . . . . . . . . . . . . . . . . . . . . 2
Method . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Results . . . . . . . . . . . . . . . . . . . . . . . . . 4
A. Mortality and LD Values 50
.. . .. . . . . . . . .. 4
B. Pharmacotoxic Signs . . . . . . . . . . . . . . . . . 4
C. Body Weights . . . . . . . . . . . . . . . . . . . . . 9-10
D. Necropsy Findings . . . . . . . . . . . . . . . . . . 10
Table No.
1. Number of Rats Showing Pharmacotoxic Signs and Time [Hour] (Day) Observed (Males) . . . . . . . . 5-6
2. Number of Rats Showing Pharmacotoxic Signs and Time [Hour] (Day) Observed (Females) . . . . . . . 7-8
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Page I I. SYNOPSIS
Based upon the data obtained, the acute oral LD values and 50
95% confidence limits were calculated to be as follows: Male Rats: 1615 (818 - 3188) mg/kg, Fpmale Rats: 1333 (715 - 2487) mg/kg, Combined Male and Fpmale Rats: 1467 (923 - 2332) mg/kg.
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Page 2 TEST MATERIAL
The test material was received from the 3LM Company, St. Paul, Minnesota on October 28, 1977. It was identified as "F.4-3422,41-27003422-0, Lot 784/Net-35, RR-1" and was received as an off-white to tan waxy substance.
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Page 3
METHOD Twenty-five male and 25 f,-Tnalreats of the Charles River CD strain
(obtained from Charles River Breeding Laboratories, Inc., Portage, '@fichigan),weighing from 171 to 259 grams, were used for this studv. The rats were housed by sex in arcups of 5 rats per ca-e, in hanging wire-mesh cages in temperature and humidity controlled quarters. They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and Use of Laboratory Animals". Water and Purina Laboratorv Chow were available ad libitum, except for an overnight period immediately preceding oral administration during which food, but not water, was withheld.
The test material was administered orally by -.avaeeas an emulsion in 40@'a.cetone/60% corn oil at the following dosage levels to male and female rats:
464, 1000, 2130, 4640 and 10000 mg/kg. Five rats of each sex were used at each dosage level. Volumes of 10 ml/kg of body weight were administered at all dosage levels with the exception of the 10000 mg/ka dosage level which was administered at a volume of 20 ml/kg. All rats were observed for mortalitv and pha-.-nacctcxicsigns during the first four hours after dosing, at 24 hours and dai-lvthereafter for a total of 14 days. Body weiahts were recorded i=ediately prior to dosing (control weight) and at 7 and 14 davs. All rats which died an study were subjected to gross necropsy examinations as were all sur-vivorsat the end of the 14 day study period.
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Page 4
IV. RESULTS A. IIORTALITY AND LD 5n VALUES: Dose - Mortalit7 Data
Dosage Level m g/k9
2150 4640 10000
@Hrs 10-4 1 1 F-Fl M F
Number of Deaths
Days
2
3
4
5
M FMFM FM F
11
1
2 21
6 MF
1 1 11
Total
7-14
Mortalities
M F Male I Female' Total
1
1/5
2 2/5
1 2 2/5
2 3 5/5
2 2 1 5/5
0/5
1/10
4/5
6/10
2/5
4/10
4/5
9/10
5/5
10/10
The Acute Oral_LD 50 Values and 95/'.Cc-ifidence Limi,-z: 'faleRats: 1615 (u'18 - 3188) mg/kg,
FpynnleRats: 1333 (715 - 2487) mg/kg, Combined i4ale and Female Rats: 146/' (97-3- 2332) mg/kg.
SloT)e: Male Rats: 0.80, Fp-nle Rats: 0.80, Combined Male and Fpynale Rats:
Statistical References:
0.80.
1'weil,C. S. 1952. '@rablesfor Convenient Calculation of Median Effective Dose and Instruction in Their Use. Biometrics, 8: 249-263.
2Thompson, W. R. and Weil, C. S. 1952. On the Construction of Tables for Moving Average Interpolation. Biometrics, 8: 51-54.
3 Eby, R. 1957. Statistical Tables for Dose Evaluation, Re-
port No. 5711. Miles-.AmesResearch Laboratory, Elkhart, Indiana.
B. PHARMACOTOXIC SIGINS: The following pharmacotoxic signs were observed during the 14 day
observation period: (see Table 1).
137-084
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Page 9
C. BR)DYWEIGHTS: The following body weights were obtained during the 14 day
observation period:
Dosac,e Level mc,,/kg
Individual Rat No.
464
77218
77219
77220
77221
77222
77223 77224 77225 77226 77227
1000
77060 77061 77062 77063 77064
77065 77066 77067 77068 77069
2150
76858 76859 76860 76861 76862
76873 76874 76875 76876 76877
4640
76863 76864 76865 76866 76867
Sex
Male Male Male Male Male
Female Female Female Female Female
Male Male Male li4ale Male
Female Female Female Female Female
Male Male @iale Male Male
Female Female Female Female Female
Male Male @@le LMale Male
Control Weight (grams)
220 214 228 234 236
232 216 230 224 224
258 225 259 221 254
202 209 213 200 201
196 193 185 192 183
194 185 183 174 200
182 182 182 191 195
7 Day Weight (grams)
Died 185 257 263 259
204 216 237 220 221
220 209 Died Died 249
156 Died Died 186 150
Died 140 140 Died 140
170 160 142 130 @50
Died Died Died 154 Died
14 Day Weight (grams)
Died 236 298 284 304
240 228 242 238 250
280 268 Died Died 310
Died Died Died 231 Died
Died 248 190 Died 218
215 202 176 Died Died
Died Died r)ied Died Died
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Page 10
Dosage Level (mg/kg)
4640
10000
Individual Rat No.
76878 76879 76880 76881 76882
76868 76869 76870 76871 76872
76883 76884 76885 76886 76887
-Sex
Female Female Female Female Female
Male Male Male Male Male
Female Female Female Female Female
Control Weight (grams)
176 184 176 178 185
171 191 192 190 178
192 197 176 172 173
7 Day Weight (grams)
120 140 Died Died 148
Died Died Died Died Died
Died 145 Died 138 Died
14 Day Weight (?,rams)
130 Died Died Died Died
Died Died Died Died Died
Died Died Died Died Died
D. NECROPSY FINDINGS: Gross necropsy observations were noted as indicated on Table 2.
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