Document MMoG17G1BNGzxZYXgLdKjevBk
InternatioRneaslearcahndDevelopmenCtorporation
SPONSOR: TEST MATERIAL: SUBJECT:
3M Company
Fluorad Flucrochemical FC-143
Acute Oral Toxicity (LD
Study in Rats.
50
Wilson P Dean, B.A.
Director of Acute Tox4-coloaay and Special Studies
(Study Director)
t--liffod Jessup /-/Iii.-D. Associ-at Directo f Researzh
Collaborators:
Gary Thompson, B.S. Group Technical Supervisor
Greg Romig, B.S. Unit Technical Supervisor
David Powell, B.A. Unit Supervisor, Report Preparation, Acute and Special Studies Department
Date: May 5, 1978
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TABLE 0F C0N TEN TS
I. Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . II. Test Material . . . . . . . . . . . . . . . . . . . . . . . . . III. Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . .
A. Mortality and LD 50 Values . . . . . . . . . . . . . . . . . B. Pharmacotoxic Signs . . . . . . . . . . . . . . . . . . . . C. Body Weights . . . . . . . . . . . . . . . . . . . . . . . . D. Necropsy Findings . . . . . . . . . . . . . . . . . . . . .
1. Rats which died during the study period . . . . . . . . 2. Rats which were sacrificed following 14 days of
observation . . . . . . . . . . . . . . . . . . . . . . Table No.
1. Pharmacotoxic Signs . . . . . . . . . . . . . . . . . . . .
Page 1 2 3 4 4 4 7 8 9
11
5- 6
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SYNOPSIS
Based upon the data obtained, confidence limits were calculated
the acute oral LD values 50
to be as follows:
and 95%
Male Rats: 680 (399 - 1157) mg/kg. Female Rats: 430 (295 - 626) mg/kg. Combined Male and Female Rats: 540 (389 - 749) mg/kg.
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Page 2 TEST MATERIAL
The test material was received from the 3M Company, St. Paul, Minnesota ou October 24, 1977. It was identified as "Fluorad(D Fluorochemical FC-143, 3M Stock No. 98-0211-0008-0, Lot 340" and was received as a white powder.
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METHOD Twenty-five male and 25 female rats of the Charles River CD strain
(obtained from Charles River Breeding Laboratories, Inc., Portage, Michigan), weighing from 180 to 221 grams, were used for this study. The rats were housed by sex in groups of 5 rats per cage, in hanging wiremesh 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 Laboratory 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 gavage as an emulsion in 40% acetone/60% corn oil at the following dosage levels to male and female rats: 100, 215, 464, 1000 and 2150 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.
All rats were observed for mortality and pharmacotoxic signs during the first four hours after dosing, at 24 hours and daily thereafter for a total of 14 days. Body weights were recorded i=ediately prior to dosing (control weight) and at 7 and 14 days. All rats which died on study were subjected to gross necropsy examination as were all survivors at the end of the 14 day observation period.
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IV. RESULTS
A. MORTALITY AND LD VALUES@50 Dose - Mortality Data
Dosage Level mg/kg
Hrs ' 0-4
MF
1 MF
Number of Deaths
Days
2
3
4_ 5
MFMFMFMF
6 MF
7-14 MF
Total Mortalities Male Female Total
100 215 464 1000 2150
22 2 22 1 314 2
1 11
1
1/5
0/5
1/10
0/5
0/5
0/10
2/5
3/5
5/10
3/5
5/5
8/10
5/5
5/5 10/10
The Acute Oral LD Values and 95% Confidence Limits 50
Male Rats: 680 (399 - 1157) mg/kg. Female Rats: '430 (295 - 626) mg/kg. Combined Male and Female Rats: 540 (389 - 749) mg/kg.
Slo_pe
Male Rats: 1.00. Female Rats: 1.00. Combined Male and Female Rats:
1.00.
Statistical References
1Weil, C. S. 1952. Tables for Convenient Calculation of Median Effective Dose and Instruction in Their Use. Biometrics, 8: 249-263.
2 Thompson, W. R. and Weil, C. S. 1952. On the Construction of Tables for Moving Average Interpolation. Biometrics, 8: 51-54.
3Eby, R. 1957. Statistical Tables for Dose Evaluation, Report No. 5711. Miles-Ames Research Laboratory, Elkhart, Indiana.
B. PRARMACOTOXIC SIGNS:
The following pharmacotoxic signs were observed during the 14 day
observation period: (see Table 1).
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TABLE COTIPOUND
FC-143:
NUMBER OF RATS SliOWING PitAPJIACOTOXIC SIGNS AND TIME [IIOURI.@DAY) OBSERVED
@IALES
OBSERVATION Normal Ptosis --@iPlioleoreerce@cttlionn@@ Hypoactivity
Decreased Tone
Ataxia
Limb
Corneal Opacity Death
100 mg/kg
4 (13 - 14) 2 (1)
215 mg/kg
5 (6 - 14) 2 (1)
464 mg/kg -5T,3 (6 - 14)
3 (1)
[1, 2 IT2, 4],, 5 (1)
5 [1. 2 1/2, 41,
5 [1, 2 11T,41,-
5 (1),1 (2 - 3) 5 (1), 1 (2 - 3)
3 [1], 4 [2 1/2, 41,
3 (1)
4
5:)1,2:111 2
212(11'[41
4 [1, 2 1/2), 3 [41,F-[1[12,@13/2),
3 (1)3 12 1 2, 4
5 [4)2. 52 (117)2, 4
22 (1 - 66 ), 1 ((77@ 122)) 2 (1), 1 (2 5) 2 (1),1 (2 5)
1 (7)
2 (2)
1000 mg/kg 2 (6- 14)
1 [11, 3 (1)
1 (1)
-5-[1J/,@22,
41,
5 (1), 3 (2 - 3),)
2 (4 - 5)
2 [1, 2 1/i4l-,[41, 5
5 (1), 1 (2 - 3)
2 [1
2-,-4
5 (1), 1 (2 3)
4 (1)
2 (2),1 (4)
StutlyNo. :_j. U7:9@
TABLE - 1.(Cont.) COMPOUND - FC-143:
NUMBER OF RATS SIIOWINC PitARMACOTOXIC SIGNS AND TIME- [HOUR] (DAY) OBSERVED
OBSERVATION Normal Ptosis Piloerection H othermic
to Touch llypoactivity Decreased
Limb Tone
Ataxia Corneal Opacity
100 mg/kg 5 (2 14)
FEMALES
215 mg/kg 5 (2 - 14)
464 mg/kg 2 (4 14)
3 (1)
1000 mg/kg
2 (1) 3 (1),1 (2)
5 1 2 1)2, 5
5 [1 .--@-I2@, 4 5 (1)
4 [1, 2 1/21, 3 [4), 1 [11, 2 [2 1/21,
3 (1)
3 [4), 3 (1)
1-5/2[12, 3 [41
4 [1, 2 1/2,4
1 (2 3) 1-. 2--172--4 -j-
5 (1), 3 (2 - 3) 1 [1), 12-/[221,
5 [41, 5 (1), 2 (2 - 3)
2-172,-4T3 (1),1 (2) [2-1], 4 [2 1121. 5 [41, 3 (1), 1 (2)
2 [1, i--f/2-31-,[41 3_(I).2 2 - 3)
4 [1. 2 1/2f,5-[4), 3 (1),1 (2)
Death
2 (2),1 (4)
2 (1),2 (2),1 (3)
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C. BODY WEIGHTS:
The following body weights were obtained during the 14 day observa-
tion period:
Dosage Level (mg/kg)
Individual Rat Number
100
76888
76889
76890
76891
76892
76908 76909 76910 76911 76912
215
76893
76894
76895
76896
76897
76913 76914 76915 76916 76917
464
76898
76899
76900
76901
76902
76918 76919 76920 76921 76922
1000
76903 76904 76905 76906 76907
Sex
Male Male Male Male Male
Female Female Female Female Female
Male Male Male Male Male
Female Female Female Female Female
Male Xale Male Male Yale
Female Female Female Female Female
Male Male Male Male Male
Control Weight (grams)
194 189 210 190 198
198 192 186 204 188
214 213 212 210 203
195 182 190 185 182
215 202 216 218 200
180 180 182 192 194
188 194 192 186 192
7 Day Weight (grams)
242 228 Died 240 246
217 212 208 225 191
266 267 254 252 234
218 203 209 205 203
Died 249 239 Died 245
200 Died 204 Died Died
208 Died Died Died 223
14 day Weight (.grams)
296 275 Died 285 304
240 226 227 244 212
318 330 312 290 298
243 23'@' 230 222 236
Died 330 296 Died 302
227 Died 223 Died Died
270 Died Died Died 290
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Dosage Level (mg/kg) 1000
2150
D. NECROPSY
Individual Rat Number
76923 76924 76925 76926 76927
77208 77209 77210 77211 77212
77213 77214 77215 77216 77217
FIINDINGS:
Sex
Female Female Female Female Female
Male Male Male ',4ale Male
Female Female Female Female Female
Control Weight (grams)
202 180 184 198 196
206 213 208 211 213
221 213 217 219 206
7 Day Weight (grams)
Died Died Died Died Died
Died Died Died Died Died
Died Died Died Died Died
14 Day Weight (grams)
Died Died Died Died Died
Died Died Died Died Died
Died Died Died Died Died
Gross necropsy observations were noted as indicated on pages 9, 10 and ii.
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1. Rats which died during the study period:
Dosage Level (mg/kg) Number Exhibiting Sign/Number Necropsied
Gross Necropsy Observations:
Yellow stained urogenital region
Lungs, congestion
Lungs, pitted
Lungs, red foci
Stomach, distension
Stomach, fluid filled
Stomach, mucosa, hyperemia
Stomach, mucosa, thickened
Stomach, contains dark red fluid
Stomach, glandular mucosa, erosion
Stomach, contains dark red particulate material
Stomach, red fluid filled
100
215
464
1000
2150
Male Female Male Female Male Female Male Female Male Female
2/5 3/5, 2/5
1/1
2/21 1/3 2/3 4/5 4/5 5/5
2/5
1/5
1/3 1 2/3 4/5 5/51 3/5
1 1/3
5/5 4/5
3/3 1/3 1/5 4/51 1/5
2/3 2/3
1/3
1/3
1/5 1/5
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Dosage Level (mg/kg) Number Exhibiting Sign/Number Necrapsied
Gross Necropsy Observations:
Intestines, red fluid filled
Liver, pale coloration
Partially, cannibalized
Red ttain around nose/ mouth
100 Male Female
1/1
215 Male Female
464 Male Female
1000 Male Female
2150 ixale Femalp
2/5 1/5 1/5
3/5 4/5
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tion:
2. Rats which were sacrificed following 14 days of observa-
Dosage Level (mg/kg) Number Exhibiting Sign/Number Necropsied
Gross Necropsy Observations:
No gross lesions
Lungs, foci
Stomach, mucosa, thickened
Stomach, glandular mucosa, hyperemia
Uterus, hydrometra
Kidneys, mottled coloration
100
215
464
1000
Male
Female Male
Female 1/5
Male Female I
1/3
1/2
Male Female 1/2 -
4/4
5/5
5/5
4/5
2/3, 1/2
1/2,
1/4
2/5
1/5
1/5
1/2
1/5
2/5
2/4
2/5
3/5
4/5 1 1/3
1/2
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