Document 5O92DE5Gq12xpYmdKeK2qO7e

AR226-2895 i E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, Newark, Delaware 19711 Study Initiated/Completed 10/6/80-12/15/80 iterial Submitted by; Chemicals & Pigments Department Technical Laboratory INHALATION APPROXIMATE LETHAL CONCENTRATION (ALC) Ijitredu^^or^^Tlieiiurpose this study was to determine inhalation ALC's f o r l | | H H ^ ^ H ^ H Q l n male CrlrCD rats. After conducting i n i t i a L , ^ ^ ^ % , gxperlaCTt s ^ ^ ^ a n t e d difference was observed between the ALC's fiijlH|Hmnd f ^ M B H f t i l s p e r s l o n determined at their respective process temperatures of"250 " ^ n d 100C. Further experiments were conducted to evaluate the temperature- toxicity relationship of these materials. Procedure: Groups of 6 male C r ^ C D ^ r a t ^ ^ 7 - 8 weeks old and weighing 236-291 grams, were exposed to e i t h e r W [ J J ^ [ ^ [ J l F a p o r s for single A hour periods. Prior to and post-exposure, r a t ^ w e r e housed in suspended stainless steel, wire mesh cages. Except during exposure, Purina Certified Rodent Chow #5002 and water were supplied ad libitum. During exposure rats were observed and clinical signs noted. Following exposure rats were weighed and observed daily (excluding weekends) for a 14-day recovery period. CO' 1 Saw Does notcofcn Generation: --- ------------------------ i 3 vapis ere generated at 2 temperatures - 250 and 300C. First, the sample was melted at 1 0 0"C and loaded into a heated syringe (9U*C). It was then syringe driven into a heated quartz tube furnace (250 or 300C). Houseline air circulated through the furnace and carried the vapors directly into the top of a 30-liter glass exposure chamber. C Vapors offjHflf'tere generated at 2 temperatures - 100 and 2 5 0 "C. First, the test material was svringe driven through a Spraying Systems nebulizer onto the heated (100C) surface of a three-neck flask. Houseline air carried the xanor^directly into the top of a 30-liter glass exposure chamber. S e c o n d , a s syringe driven into a heated quartz tube furnace (250C) and h o u s l S ! n ^ 5 l , circulated through the furnace, carried the vapors directly into the top of a 30-liter glass exposure chamber. Chamber temperature was monitored continously and maintained at < 2 8 C. Chamber air was exhausted through a MSA charcoal filter. Analytical: Chamber atmosphere samples were collected at 1/2 hour intervals. Known volumes of atmosphere were drawn through Gelman glass fiber filters (Type A/E, 25 mm). Filters were weighed, dried overnight in CaSO, dessicators, and weighed again. The atmospheric concentration of test material was determined from the dry weight gain of tne filters. Oxygen (0^) concentration was monitored and maintained at >20%. Results: Dose-response data fo: Chamber Concentration (ag/1) Mean Range [ at 100C Standard Deviation 0.08 0.03-0.17 0.05 0.25 = ALC 0.05-1.09 0.35 0.27 0.10-0.51 0.13 0.41 0.19-0.75 0.18 r< at 250C U. 40 U. 74 0.74 2. uu ALC 0.20-0.72 0.33-1.;7 U.43-1.25 1.47-2.64 0.15 0.45 0.27 0.50 re presented below: Dose-Response (6 Deaths/# Exposed) 0/6 5/6 6/6 6/6 0/6 * 0/6 4/6 5/6 250C 0.32 0.60 <= ALC 0.64 1.20 0.01-0.47 0.34-1.2 0.14-1.41 0.79-1.58 0.23 0.23 0.54 0. 29 0/6 6/6 4/6 6/6 0.72 0.91 1.30 1.54 .3.12 = ALC 0.53-0.99 0.67-1.04 0.69-3.39 0.85-1.98 0.48-6.80 0.54 0.11 0.98 0.64 2.46 0/6 0/6 0/6 0/6 5/6 Clinical Signs: Clinical signs increased with dose and were essentially the same for both test materials. During exposure rats exhibited ocular and nasal discharge, gasping, salivation, spasmodic movement, reduced response to sound and labored breathing. Post-exposure signs included dark red eyes, weakness, lethargy, pallor, wet perineal area, and brown stained fur. Negligible to severe weight loss was observed 24-48 hours post-exposure, followed by resumption of a normal rate of gain in the surviving rats.t Deaths occurred during exposure and up to 72 hours post-exposure. t One rat had weight loss until death at the 13th day post-exposure. -3- n0i contain lttlzed-Does Co*nPany San Summary:^ Groups of 7-8 week old male Orl:CD rats were exposed to vapors of o r H ^ ^ ^ M i n air for single 4-hotir periods Approximate Lethal -oneentrations for the materials were determined at various temperatures: Material Generation Temp. (C) ALC (mg/1) 0.25 0.74 0.60 3.1 ; * Clinical signs observed during exposure were ocular and nasal discharge, gasping, salivation, spasmodic movement, reduced response to sound and labored breathing. Post-exposure signs included dark red eyes, weakness, lethargy, pallor, wet perineal area, and brown stained fur. Work by: iL, Q Rayanne L. Ferenz J Toxicologist Work and Report by: Biochemist Approved by: Chief, Acute Investigations Section PA:vim Study Director: Date Issued: F B. A. Burgess r u a r y ^ 5 , 1981 =Po: Com p** Sanftlzed. Does not contain TSC A Cfii 4