Document dnxDp1X3VMNa3bgqaGZLjxpKb

InternaClorrespondence rc: ACN: F. D. Griffith/F. A. Ubel, M.D. - 220-2E-02 22452,T-4101 To D. R. Ricker - Industrial Chemical Products - 236-lB-10 Fro- R. G. Perkins - Medical, Toxicology Services - 220-2E-02 Subiect lily-aryof Acute Toxicity Study Report for T-4101 Daie March 4, 1988 Attached are copies of the acute oral toxicity study in mts, acute dermal toxicity study in rabbits, primary dermal irritation/corrosionstudy in rabbits and primary eye irritation/corrosion study in rabbits conducted by Hazleton Laboratories America, Inc..for T-4101, FC-109 FLUORAD Brand Fluorochemical Surfactant, lot 2, 41-26ol-o4l4-o. The following studies were conducted according to the Organization for Economic Cooperation and Development's Guidelines for Testing Chemicals. ACM ORAL TOXICM (RATS): SLIGNMY TOXIC. Ten albino mts (Sprague-Davley strain, 5 males, 5 females) each weighing between 200 and 298 grwa each received an oral dose of T-4101 of either 0.5 grw--qor 5.0 grams per kilogram of body weight. For the 0.5 gram/kg dose level no clinical signs were observed. No 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 bywactivity, 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 oml LD50 in the rat of T-4101 is between 0.5 and 5.0 gra= per kilogram of body weight. T-4101 is considered slightly toxic orally. ACUTZ DERMAL TOX3[CITr (RA rT): PRACTICALLY NONMXXC. Ten albino rabbits (New Zealand White strain, 5 males, 5 females) weighing between 2041 and 2343 gram each received a dermal application of T-4101 equivalento 2.0 gramsper kilogramof body weight. The area of application was occluded and 24 hours later the wrap and sample van removed. Clinical signs observed included few feces, hypoactivity, loss of appetite and thin D. R. Ri-cker Page 2 March 4, 1988 appearance among the female animals only. Dermal irritation consisted of slight-to-moderate erythemn 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 14. One female animal shoved decreased body weight during the study, while 2 female animals showed decreased body weight at day 7 but had increased body veight by day 14; the remaining 2 females shoved 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-4101 has a dermal LD50 in the rabbit of greater than 2.0 grams per kilogram of body weight. T-4101 is considered practically nontoxic dermL3.1y. PPJDMY DERKAL IRMATION: NINMKAMY IRRITATM. Three albino rabbits (New Zealand 'White strain) each received 0.5 milliliter applications of T-4101 to intact skin test sites. The sites were covered with a semi-occlusive wrap and contact was maintained for 4 hours. Thirty minutes after removal of the wrap and sample, and 24, 48, and T2 hours after application of the sample, the sites were evaluated for irritation. Very slight er3rthemsonly was observed at one test site at the 24 and 48 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 4 evaluation periods. Under the conditions of this study, T-4101 is considered minimally irritating to the skin. After 24 hour occluded contact, both er3rthems and/or edema were observed and irritation persisted to day 14 in some animals. PRDLAW OCULAR IRRITATION: M33DIALLY ITA=AYM. Three albino rabbits (New Zealand White strain) each received 0.1 milliliters of T-4101 into the conjunctival sac of one eye. The contralateral eyes served as untreated controls. The eyes were evaluated for irritation at 1, 24, 48 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 24 hour evaluation irritation in 2 test eyes now consisted of D. R. Ricker Page 3 March 4, 1988 corneal involvement (corneal epithelial peeling) and conjunctival irritation; only conjunctival redness was observed in the remaining test eye. At the 48 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-4101 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-41ol 2) Acute Dermal Toxicity Study in Rabbits for T-4101 3) Primary Dermal Irritation/Corrosion Study in Rabbit's Foot T-41ol 4) Primary Eye Irritation/Corrosion Study in Rabbits for T-41oi