Document N2ymR2VdZ9qGDdqkoXGg8Nvjb

Internal Correspondence rc: F. D. Griffith/F. A. Ubel, M.D. - 220-2E-02 ACN: 22452, T - M O l To D. R. Ricker - Industrial Chemical Products - 23&-1B-10 From r . g . Perkins - Medical, Toxicology Services - 220-2E-02 SuDiect Summary of Acute Toxicity Study Report for T-l*101 Date March U, 1908 3M Attached are copies of the acute oral toxicity study in rats, acute dermal toxicity study in rabbits, primary dermal irrittion/corrosion study in rabbits and primary eye irritation/corrosion study in rabbits conducted by Hazleton Laboratories America, Inc., for T--J*101, FC-109 FLUORAD Brand Fluorochemical Surfactant, lot 2, l*l-2601-0l*lU-0. The following studies were conducted according to the Organization for Economic Cooperation and Development's Guidelines for Testing Chemicals. ACUTE ORAL TOXICITY (RATS): SLIGHTLY TOXIC. Ten albino rats (Sprague-Davley strain, 5 males, 5 females) each weighing between 200 and 290 grams each received an oral dose of T-l*101 of either 0.5 grams or 5-0 grams per kilogram of body weight. For the 0.5 gram/kg dose level no clinical signs were observed. Ho deaths occurred and weight gains were noted. At necropsy no visible lesions were observed. For the 5.0 gm/kg dose level clinical signs included hypoactivity, ataxia, red-stained face, absence of pain reflex, miosis, prostration, tremors, diarrhea, cyanosis and yellov-stained genital region. Nine of the 10 dosed animals died between 1 day and 6 days post dose administration. At necropsy lesions included tan stains of perianal area, red and crusty ocular discharge, granular mucosa of stomach diffusely red with brown linear areas, material in the stomach, and gastrointestinal tract severely autolyzed in some animals. The acute oral LD50 in the rat of T-^101 is between 0.5 and 5.0 grams per kilogram of body weight. T-LlOl is considered slightly toxic orally. ACUTE DERMAL TOXICITY (BA BBIT): PRACTICALLY E0ET0X IC. Ten albino rabbits (New Zealand White strain, 5 males, 5 females) weighing between 20Ul and 23^3 grams each received a dermal application of T-hl01 equivalent to 2.0 grama per kilogram of body weight. The area of application was occluded and 2k hours later the wrap and sample was removed. Clinical signs observed included few feces, hypoactivity, loss of appetite and thin D. R. Ri-cker Page 2 March k, 1988 appearance among the female animals only. Dermal irritation consisted of slight-to-moderate erythema and edema and slight atonia and desquamation. No mortalities occurred. An increase in average body weight was observed for the male animals, but a decrease in average body weight was observed for the female animals at the day 7 observation. An increase in average body weight was observed at day 1^*. One female animal showed decreased body weight during the study, while 2 female animals showed decreased body weight at day 7 but had increased body weight by day lU; the remaining 2 females showed increases in body weight during the study. At necropsy no visible lesions were observed in 2 of 5 males and in 3 of 5 females. In one male diffusely dark red auxiliary lymph nodes were observed. Dermal irritation effects were observed in 2 male and 2 female animals. Additionally, one of the latter females was observed to have a thin appearance, red areas and green fluid were noted in the gastrointestinal tract and green perianal stains were observed. Under the conditions of this study T-l*101 has a dermal LD50 in the rabbit of greater than 2.0 grams per kilogram of body weight. T-l*101 is considered practically nontoxic dermally. PRIMARY DERMAL IRRITATION: MU T U A L L Y IRRITATING. Three albino rabbits (New Zealand White strain) each received 0.5 milliliter applications of T-U101 to intact skin test sites. The sites were covered with a semi-occlusive wrap and contact was maintained for k hours. Thirty minutes after removal of the wrap and sample, and 2k, U8, and 72 hours after application of the sample, the sites were evaluated for irritation. Very slight erythema only was observed at one test site at the 2k and 1*8 hour evaluation. No irritation was observed at the site at the 72 hour evaluation. No irritation was observed in the other 2 animals at any of the k evaluation periods. Under the conditions of this study, T--1*101 is considered minimally irritating to the skin. After 2k hour occluded contact, both erythema and/or edema were observed and irritation persisted to day ll* in some animals. PRIMARY OCULAR IRRITATION: MINIMALLY IRRITATING. Three albino rabbits (New Zealand White strain) each received 0.1 milliliters of T-klOl into the conjunctival sac of one eye. The contralateral eyes served as untreated controls. The eyes were evaluated for irritation at 1, 21*, 1*8 and 72 hours after treatment and a sodium fluorescein examination performed at the 72 hour evaluation. At the one hour evaluation, irritation in 2 eyes consisted only of conjunctival irritation including redness, chemosis and/or discharge; iridal effects and conjunctival irritation occurred in the remaining test eye. At the 2k hour evaluation irritation in 2 test eyes now consisted of D. F. Ricker Page 3 March I, 1988 corneal involvement (corneal epithelial peeling) and conjunctival irritation; only conjunctival redness was observed in the remaining teat eye. At the U8 hour evaluation only conjunctival redness was observed in 1 test eye; the 2 remaining test eyes were clear. All test eyes were clear at the 72 hour evaluation and the sodium fluorescein examination was negative. A maximum primary irritation score of 6.3 of a possible 110.0 was assigned for the 1 hour evaluation. T-U101 is considered minimally irritating to the eyes under the conditions of this study. If there are questions, please contact me. RGP:bh (TS113 2.30) Attachments : 1) Acute Oral Toxicity Study in Rats for T-UlOl 2) Acute Dermal Toxicity Study in Rabbits for T-UlOl 3) Primary Dermal Irrittion/Corrosion Study in Rabbit's Foot T-U101 U) Primary Eye Irritation/Corrosion Study in Rabbits for T-UlOl