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AR226-2895 FOR DU POUT USE ONLY Copies Co E. I. du Font 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 aubrnltted by 'Chemicals & Pigments Department: Technical Laboratory INHALATION APPROXIMATE LETHAL CONCENTRATION (ALC) ^'{URnd Intr.oduction: The aurpose of this study was to determine Inhalation ALC'B 7oTwHI|^^1^1jI.n male Crl:CD rats. After conducting initial^,^,^ ,expertoent^^^narKed difference was observed between the ALC's ^BBHRiisperslon determined at their respective process temperatures of'"250 ^nd 100C. Further experiments were conducted to evaluate the temperaturecoxicity relationship of these materials. Procedure: Groups of 6 male Ci.^CQ^jats.7.8 weeks old and weighing 236-291 grams, were exposed to elcheir|H|H^^HB|9apors for single 4 hour periods. Prior to and post-exposure,ratswere housed in suspended stainless sceel, wire mesh cages. Except during exposure, Purina Certified Rodent Chow ^5002 and water were supplied ad llbitum. 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. ilSW^- poes notcot^ 1 - Generation: 0--1 Vapors G^^IB'6^ generated at: 2 temperatures - 250 and 300C. First, thee sample wwas melted at l1O0O0-C and loaded into a heated syringe (90*0). It was then syringe driven into a heated quartz Cube furnace (250 or 30UC). Houseliae air circulated through the furnace and carried the vapors directly into the top of a 30-liter glass exposure chamber. H--^ |Vapors o^uHBv jere generated ie test mnaterlial was syringe driven through a Spraying Systems nebulizer onto the heated (100C) surface of a three-neck flask. Cop of a 30-liter glass eHxopuosseulirnee chaaimr bcear.rrieSdecthoendjt,a||aHo^r^^^^pAarsecstylyrinignetodtrhiveen into a heated quartz cube furnace (250C) and housi3m^a, 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 <28C. 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%. ^ ^ ^ .^^ooe" Results; Dose-response data foo^^Jend ______Chamber Concentration (ag/1) Mean Range Standard Deviation re presented below: Dose-Response (9 Deaths/*? Exposed) 0.03-0.17 0.05 0/6 0.05-1.09 0.35 5/6 0.10-0.51 0.13 6/6 0.19-0.75 0.18 6/6 0.20-0.72 0.15 0/6 U.33-1.;7 0.45 0/6 U.4^-1.25 0.27 4/6 1.47-2.64 0.50 5/6 0.01-0.47 0.23 0/6 0.34-1.2 0.23 6/6 0.14-1.41 0.54 4/6 0.79-1.58 0.29 6/6 0.53-0.99 0.54 0/6 0.67-1.04 0.11 0/6 0.69-3.39 0.98 0/6 0.85-1.98 0.64 0/6 0.48-6.80 2.46 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. CoWP3'^ ^ . -- " 0 > W " - 3 - Groups of 7-B week old male .'rl:CD rats were exposed to vapors of ^^Jin air for single ^-hour periods' Approximate Lethal ons for the materials were determined ac various temperatures: Material Generation Temp. 1UO 250 250 JOO (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 perinea! area, and brown stained fur * Composition: Synonyms: Work by: j( 0^(7^ [UCL S^ULf- (vJyHaTyaonxniecoLl.ogFisertenz ^ ^PoM^f6LJjtjU4- Work and Report by: ----------^/Poliy-Ashley ^---- Biochemist Approved by; ^ ^Ge ^ . rald t. L . ^ K e n n e a y Chief, Acute Investigations Section PA:vim Study Director: B. A. Burgess .Date Issued: February 25, 1981 C^^-.D.e.no.c.^CACtf