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International Research and Development Corporation
SPONSOR: TEST MATERIAL: SUBJECT:
3M Company ARZ26-3S5'
Fluorad Fluorochemical Surfactant FC-95
CD
Acute Oral Toxicity (LD.^) Study in Rats.
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Wilson P. Dean, B.A. Director of Acute Toxicology
and Special Studies (Study Director)
& EPA-OTS 000811792S
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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
137-083
Date: Mav 31. 1978
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International Research and Development Corporation
T A B L E OF C O N T E N T S
Page
I. Synopsis.......................................................
1
II. Test M a t e r i a l ................................................. III. M e t h o d ........................................................
2
3
IV. R e s u l t s .................................
A. Mortality and LD^q V a l u e s .................................
4
B. Pharmacotoxic Signs .....................................
4
C. Body Weights............................................. D. Necropsy Findings .......................................
5
6
Table No. 1. Pharmacotoxic Signs ..................................... 2. Summary of Gross Necropsy Observations ...................
7-8 9
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I. SYNOPSIS Based upon the data obtained, the acute oral LD^q values and 95%
confidence limits were calculated to be as follows: Male Rats: 233 (160 - 339) mg/kg, Female Rats: 271 (200 - 369) mg/kg, Combined Male and Female Rats: 251 (199 - 318) mg/kg.
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II. TEST MATERIAL The test material was received from the 3M Company, St. Paul,
Minnesota on October 24, 1977. It was identified as "Fluorad Fluorochemical Surfactant FC-95, 3M Stock No. 98-0207-0103-7, Lot 640, Net wt. 5 lbs. 2.2 kg." and was received as a white powder.
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III. METHOD Twenty male and 20 female rats of the Charles. River CD strain (ob
tained from The Charles River Breeding Laboratories, Inc., Portage, Michigan), weighing from 172 to 212 grams, were used for this study. The rats were housed by sex in groups of 5 rats per cage, 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 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 suspended in a 20% acetone/80% corn oil mix ture and administered orally by gavage at the following dosage levels to male and female rats: 100, 215, 464 and 1000 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 immediately 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 study period.
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IV. RESULTS A. MORTALITY AND LD:o VALUES: Dose - Mortality Data
Dosage Level mg/kg
100
215
1040640
Hrs 0-4 MF
1
MF
Number of Deaths
Days 234 5 MFM FM FM F
6
MF
7-14 MF
112
1 11 11
22 1 1 2
1 1 13
Total Mortalitic s Male Female Total
0/5 0/5 0 /1 0
2/5 5/5 5/5
1/5 5/5 5/5
11 030/// 111000
The Acute Oral LD^q Values and 95% Confidence Limits: Male Rats: 233 (160 - 339) mg/kg, Female Rats: 271 (200 - 369) mg/kg, Combined Male and Female Rats: 251 (199 - 318) mg/kg.
Slope: Male Rats: 1.00, Female Rats: 1.00, Combined Male and Female Rats: 1.00.
Statistical References:
Hieil, C. S. 1952. Tables for Convenient Calculation of Median
8Effective Dose and Instruction in Their Use. Biometrics, : 249-263. 2
Thompson, W. R. and Weil, C. S. 1952. On the Construction of
8Tables for Moving Average Interpolation. Biometrics, : 51-54.
3 Eby, R. 1957. Statistical Tables for Dose Evaluation, Report
No. 5711. Miles-Ames Research Laboratory, Elkhart, Indiana. B. PHARMAC0T0XIC SIGNS:
The following pharmacotoxic signs were observed during the 14 day observation period: (see Table 1):
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C. BODY WEIGHTS:
The following body weights were obtained during the 14 day
observations periods:
Dosage Level (mg/kg)
100
Individual Rat Number
76838 76839 76840 76841 76842
Sex
Male Male Male Male Male
Control Weight (grams)
122710221
179 188
7 Day Weight (grams)
224 250
221080
235
14 Day Weight (grams)
272 291 282 270 276
76818 76819 76820 76821 76822
Female Female Female Female Female
181 179 191 180 184
195 175
221080
129100 224210
178 203
215
76843
Male
182
170 230
76844
Male
177
Died
Died
76845
Male
188
160 244
76846 76847
Male Male
129081
190 Died
218 Died
76823 76824 76825 76826 76827
Female Female Female Female Female
189 188 177 198 179
152 145 150
222100410
180 Died
132 192
464
76848
Male
175
Died
Died
76849
Male
193
Died
Died
76850
Male
183
Died
Died
76851
Male
187
140 Died
76852
Male
178
Died
Died
1000
76828 76829 76830 76831 76832
76853 76854 76855 76856 76857
Female Female Female Female Female
Male Male Male Male Male
209 189 183 183 178
178 180 190 193 197
Died Died 130 Died Died
Died Died Died Died Died
Died Died Died Died Died
Died Died Died Died Died
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Dosage Level (mg/kg)
1000
Individual Rat Number
76833 76834 76835 76836 76837
Sex
Female Female Female Female Female
Control Weight (grams)
185 193 191 183 195
7 Day Weight (grams)
Died Died Died Died Died
14 Day Weight (grams)
Died Died Died Died Died
NECROPSY FINDINGS :
Gross necropsy observations were noted as indicated in Table 2.
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NUMBER OF RATS SNOWING P11ARMACOTOXIC SIGNS AND TIME [HOUR] (DAY) OBSERVED
TABLE - I.
COMPOUND - Fluorad Fluorochemical Surfactant FC-95;
MALES
OBSERVATION
Normal
Diarrhea Hypoactivlty Decreased Limb
Tone Ataxia Corneal Opacity
High Carriage
Death
100 mg/kg
215 mg/kg
464 mg/kg
1000 mg/kg
3(3-11), 5(12-14)
511,2%,4], 5(1-2), 2(3-7), 1(8-9) 1[2 ,4], 3(2) 1[2%,4], 2(1), 3(2) 5(2), 2(3-11)
3(3-7), 2(8), 3(9), 2(10). 3(11-14)
1 (2)
5[1,2%,4], 5(1-2) 2(3-4)
3[2%], 4[4], 3(2)
31[(23%-,44)), 3(2-),
511,2%,4], 5(1-2), 4(3), 3(4), 1(5-7)
3[2%,4], 5(2), 1(7)
3[2%], 4[4], 4(1),
1(3-4)
2 (2)
5(2). 1(3-4)
1(2)
1 (8), 1 (10)
5[1,2%,4], 4(1),
12([12-],3),5
1(4-5) [2%,4],
1 (1-2)
1(5)
11[(12]), 5[2%,4], 4(1),
2(5)
1L((38)), 1(4), 2(5),
11((16)), 2(2), 1(4),
Pag
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NUMBER OF RATS SHOWING PHARMACOTOXIC SIGNS AND T IME [HOUR] (DAY) OBSERVED
TABLE - l.(Cont.)
COMPOUND - Fluorad Fluorochemical Surfactant FC-95:
FEMALES
- OBSERVATION Normal
Ptosis Piloerection Hypoactivity Decreased Limb
Tone Ataxia Prostration Tremors Corneal Opacity High Carriage Death
100 mg/kg
3(3), 4(4-5), 3(6) 4(7-11), 5(12-14)
511,2*5,4], 5(1-2), 1(3-9) 2[2 ,4], 2(1), 3(2) 2[2*5,4], 2(1), 3(2)
215 mg/kg
2(1-2), 5(3-7), 2(8j
464 mg/kg
2(8), 4(9), 2(10),
3(11-13), 4(14)
2(3-4)
1000 mg/kg
1(3-4)
51t(l8,)2*5,4], 3(1-2),
2[2*5], 3[4], 2(2)
2[2h], 3[4], 2 (2)
1 (6)
1 (6)
5[1,2*5,4J, 5(1-2) 5TT,^S,4], '4(1-2)
T T t t T T2(3-4), 3(5-6), 1(7) 2(3-4), 3(5), 1(6)
4[2*5,4], 3(2), 1(7) 4[2*5,4], 2(1), 3(2)
41[(26*)5], 5[4], 1(1-4) 1 (6)
1 (6)
1 (2)
2(2), 1(3-11)
2 (8), 2 (^0),
1(11-13)
1(9)
11((38)), 1(5), 2(7),
1(1), 1(3), 2(6), 1(7)
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0017S2
Flourad Flourochemical Surfactant FC-95:
Acute Oral Toxicity (LD^^) Study in Rats.
TABLE 2.
Summary of Gross Necropsy Observations.
Site Lesion
215 mg/kg MF
Deaths
464 mg/kg MF
1000 JBg/.kg MF
Number necropsied No gross lesions
21
55 1
55
External yellow stained urogential region partially cannibalized broken left front leg red stain around mouth white stain around mouth
21 1
2
1 1
2 11
Stomach distension mucosa, thickened mucosa, hyperemia fluid filled glandular mucosa, hyperemia glandular mucosa, thickened glandular mucosa, erosion glandular mucosa, dark red foci glandular mucosa, ulcerations
11 11 2
1
3
1 34 12
1
31
11 35
1
1 1
Lungs congestion edema
11
42
33 1
Intestines fluid filled contains transparent red mucoid-like material
1
2
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Terminal Sacrifice
100 Mg/kg MF
215 mg/kg MF
55 51
34 32
1 21 2
1
1
