Document o67a6z6Gkv8B1VM1yb5wnRME
InternatioRneaslearcahndDevelopmenCtorporation
SPOLNSOR: TEST -M&TERI-kL: SUBJECT:
3M Company (D
Fluorad Fluorochemical Surfactant FC-95 Acute Oral Toxicity (LD50) Study in Rats.
Wilson P. Dean, B... Director of Acute Toxicology
and Special Studies (Studv Director)
D. 1'-l-f-ffo'Jdessup n.D. Associat Directo @xresearch
Collaborators: Gary Thompson, B.S.
Group Technical Supervisor Greg Romig, B.S.
Unit Technical Supervl@sor David Powell, B.A.
Unit Supervisor, Report Preparation, Acute and Special Studies Department
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Date: Ma7 31, 1978
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TA BLE 0F C0NTENT S
I. Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . Il. Test Material . . . . . . . . . . . . . . . . . . . . . . . . . III. Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . .
A. Mortality and LD Values . . . . . . . . . . . . . . . . . 50
B. Pharmacotoxic Signs . . . . . . . . . . . . . . . . . . . . C. Body Weights . . . . . . . . . . . . . . . . . . . . . . . . D. Necropsy Findings . . . . . . . . . . . . . . . . . . . . .
Page 1 2 3 4 4 4 5 6
Table No. 1. Pharmacotoxic Signs . . . . . . . . . . . . . . . . . . . . 7-8 2. Sl--gry of Gross Necropsy Observations . . . . . . . . . . . 9
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Page 1 SYNOPSIS
Based upon the data obtained, the acute oral LD values and 95% 50
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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Page 2 TEST MATERIAL
The test material was received from the 3M Company, St. Paul, QD
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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Page 3
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 mixture 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 weiahts 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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Page 4
IV. RESULTS A. MORTALITY AND-lL5n VALUES: Dose - Mortality Data
Dosage Level mg/kg
100 215 464 1000.
Hrs 0-4 MF
1 MF
Number of Deaths
Days
2
3
4
5
M FM FMFMF
6 MF
7-14 M F'
112
111 11
2
1
21
13
12
1
Total Mortalitiqs Male Female Total
0/5
0/5
0/10
2/5
1/5
3/10
5/5
5/5 10/10
5/5
5/5 10/10
The Acute Oral LD Values and 95% Confidence 5n
Male Rats: 233 (160 - 339) mg/kg,
Female Rats: 271 (200 - 369) mg/kg,
Limits:
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:
'Weil, C. S. 1952. Tables for Convenient Calculation of Median Effective Dose and Instruction in Their Use. Biometrics, 8: 249-263.
2 Thompson, W. R. ane Weil, C. S. 1952. On the Construction of
Tables for Moving Average In@erpolation. Biometrics, 8: 51-54.
3 Eby, R. 1957. Statistical Tables for Dose Evaluation, Report No. 5711. Miles-Ames Research Laboratory, Elkhart, Indiana.
B. PHAMIACOTOXIC SIGNS: The following pharmacotoxic signs were observed during the 14 day
observation period: (see Table 1).
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Page 5
C. BODY WEIGHTS: The following body weights were obtained during the 14 day
observations periods:
Dosage Level (mg/kg)
Individual.
Rat Number
Sex
100
76838
Male
76839
Male
76840
Male
76841
Male
76842
Male
76818 76819
76820 76821 76822
Female Female Female Epmale Female
215
76843
Male
76844
Male
76845
Male
76846
Male
76847
Male
76823 76824 76825 76826 76827
Female Female Female Female Female
464
76848
Male
76849
Male
76850
Male
76851
Ma*le
76852
Male
76828 76829
76830 76831 76832
Female Female Female Female Female
1000
76853 76854 76855 76856 76857
Male Male LMale Male Male
Control Weight (grams)
172 212 201 179 188
181 179 191 180 184
182 177 188 198 201
189 188 177 198 179
175 193 183 187 178
209 189 183 183 178
178 180 190 193 197
7 Day Weight (grams)
224 250 218 200 235
195 175 190 210 178
170 Died 160 190 Died
152 145 150 180 132
Died Died Died 140 Died
Died Died 130 Died Died
Died Died Died Died Died
14 Day Weight (jzrams)
272 291 282 270 276
218 200 241 220 203
230 Died 244 218 Died
214 201 200 Died 192
Died Died Died Died Died
Died Died Died Died Died
Died Died Died Died Died
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Page 6
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
D. NECROPSY FIINDINGS: Gross necropsy observations were noted as indicated in Table 2.
137-083
TABI,E - 1. CO@IPOUND - Fluorad
NUMBER OF RATS SIIO141NG PlIAltMACOTOXIC .SIGNS AND TIME [HOUR) (DAY@_OBSERVED
Fluorochemical Surfactant FC-95:
MALES
ORSI?@ltVAI'ION Normal
HypoacLivity Decreased Linib
Toiie Ataxia Corneal Opacity Iligh Carriage Death
100 mg/kg
215 mg/kg
464 mg/kg
1000 mg/kg
3(3-11), 5(12-14)
3(3-7),2(8), 3(9), 2(10)..3(11-14)-
1(2)
5[1,2@,41, 5(1-2)9 2(3-7), 1(8-9)
1[2 41, 3(2) 1[2@,4], 2(l),.3(2)
5[192,11941,5,(1-2) 2(3-4)
3[2@l, 4[41, 3(2) 1(3-4)
3[2@,4], 3(2T.-
.1(3-4)
5[1,211,41, 5(1-2), 5[1,211,41,4(l) 4(3), 3(4),--1(5-7) 2(2-3), 1(4-5)
1[11, 5[2@,41, 3[2@,41, 5(2), 1(7) 1(5
3[2@]. 4[4]. 4(l),
5[2@,-41.-
5(2)
1(2)
5(2), 2(3-11)
2(2)
1(2)
1(8), 1(10) 2(5)
1(3),1(4), 2(5), L(8)
IL(l),2(2), 1(4 1(6)
Study No.:_ 137-083
'RABLE - 1.(Cont.) COTIPOUND - Fluorad
NtJtIBER OF RATS SIIOWING PHARNACOTOXIC SIGNS AND TDIE [HOUR) (DAY) OBSERVED
Fluorochemical Surfactant FC-95:
FEMALES
OIISI?RVATION Normal
Ptosis
Piloerection
flypoactivity
Decreased
- Tone
Ataxia
Limb
Prostration
Tremors
Corneal Opacity High Carriage
Death
100 mg/kg
3(3). 4(4-5),3(6) 4(7-11.),5(12-14)
215 mg/kg
4 4 mg/kg
2 (1- 2) , 5 (7!@-)-, @2 (-81
2(8), 4(9), 2(10),
3(11-13), 4(14)
2(3-4)
1000 mg/kg 1(3-4)
1(6)
5 [1, 2!1,4 j 1(3-9) 2[2 41, 2(l), 3(2)
2[211,4],2(l), 3(2)
5[1,2@1,41, 3(1-2), 1(8) 2[211], 3[41. 2(2)
2[2@], 3[41, 2(2)
1(6)
-511,211,4j,5(1--ZT- JL1,zq,4j, 4(1-2' 2(3-4),3(5-6), 1(7) 2(3-4),3(5),1(
4 [211,4
3(2), 1(7)
5M I 1TI:
1(6)
4[211,4],2(l), 3(2) 4[211),5[41, l(l 1(6)
1(6)
1(2)
2(2), 1(3-11)
1(9)
1(3), 1(5) 2(7), 1(8)
l(l),1(3),2(6) 1(7)
StiidyNo.: 117-ogl
0 Flourad Flotirochemical surfactant FC-95: TABLE 2.
Site Lesion
Number necropsied No gross lesions
Acute Oral Toxicity (LD ) Study in Rats. 50
Summary of Gross Necropsy Observations.
215 mg/kg
m
F
2
1
Deaths
464 mg/kg
m
F
5
5
1
1000 mg/kg
m
F
5
5
External yellow stained urogential region partially cannibalized broken left front leg red stain around mouth white stain around mouth
2
1
I
2
1 1
2
1
1
Stomach distension mucosa, thickened mucosa, hyperemia fluid filled glandular mucosa, glandular mucosa, glandular mucosa, glandular mucosa, glandular mucosa,
hyperemia thickened erosion dark red foci ulcerations
1
1
1
1
2
I
3
1
3
4
1
2
1
3
1
1
1
3
5
1
1 1
Lungs congestion edema
Intestines fluid filled contains transparent red mucoid-like material
1
1
1
4
2
3
3
1
2
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