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I FOR DU PONT USE ONLY AR226-2934 Du Pont HLR 624-87 Study T it le In h a la tio n Approximate Lethal Concentration of Author Rudolph V a le n tin e Study Completed On November 10, 1987 Performing Laboratory E . I . du Pont de Nemours and Company, In c . H a ske ll Lab o rato ry fo r Toxicology and In d u s t r ia l M edicine Elkto n Road, P. 0 . Box 50 Newark, Delaware 19714 Medical Research No. Laboratory P ro je ct ID H a ske ll Laboratory Report No. K24-87 Page 1 of 10 ^ p a n y Sanitized. Does not contain TSCA CBf M aterial Tested: Medical Research No. H askell No.: P h ysical Form: Synonyms : P u rity: C o m p o sitio n : General information (c o n t'd ) Composition (C o n t'd ): Du Pont HLR 624-87 Contaminants: Other Code: S ta b ility : Sponsor: The te s t m aterial was assumed to be stab le throughout the exposure phase of the study. Chemicals and Pigments Department E . I . du Pont de Nemours and Company, In c. Wilmington, Delaware M aterial Submitted By J . R. Alender Chemicals and Pigments Department E. I . du Pont de Nemours and Company, In c . Jackson Laboratory Deepwater, New Je rse y In - L ife Phase In it ia t e d - Completed: 10/15/87 - 11/3/87 Notebook: There are 10 pages in t h is report. D istribution: 3- , Sng?, ri9 eeplsn TSCA C81 *> Du Pont HLR 624-87 In h ala tio n Approximate Lethal Concentration (ALC) o SUMMARY Groups of male Crl:CD*BR ra ts were exposed to aerosol/vapor atmospheres ^nr a s in g le . 4ahour period Under the conditions o f t h is F o r | i H f l H v as 21 mg/nr. At an atmospheric concentration of 230 mg/mJ o f a e i^ ^ ^ t n ^ m in ospherlc co n c e n tra tions o f acetone and of these below those associated w ith animal m o rta lity . A ll deaths occurred e it h e r during exposure or w ith in 24 hours o f exposure. No common c l in i c a l sig ns of t o x ic it y were observed 1n s u rv iv in g ra ts during the 14-day recovery p erio d . Based on the atmospheric co ncentration o f the a e ro so l, ------- ------ l i s considered to be extrem ely t o x ic on an acute In h ala tio n b a s is . h Work by: RtvfLi ^ ^fX A JV y A A / _____ 11 / ^ --------- Robert T . TurneT Technician Study D ire cto r: n /o /e* Rudolph V a le n tin e , Ph.u. Research Toxicologist Approved by: d 0AUU( (L ( L f a t w j . ////d /f? Narrfty C . ChromeyU Ph.D. Section Supervisor, Acute and Developmental Toxicology Section RV:smk:HLR71.8 - 4- Company Sanitized. Does not contain TSC CB! STUDY Du Pont HLR 624*87 QUALlfY ASSURANCE DOCUMENTATION Inhalation Approximate Lethal oncentration ioff Because snort-term studies are numerous and routine in natu re, rep resentative stud ies from t h is te s t type are audited q u a rte rly to ensure the studies are designed and conducted in compliance with the Good Laboratory P ra c tice Standards. Reported by: Kathleen L . Reed Q uality Assurance Auditor //WO-S7Date Company Sanitized. Does not contain TSCA CBI 5 Du Pont HLR 624-87 INTRODUCTION J h e purpose of t h is study was to determine a 4-hour In h alatio n ALC fo r J n male r a t s . The AL(J was defined as the lowest atmospheric lu rice n tratid h tested th at caused the death of 1 or more ra ts e ith e r on the day o f exposure or w ith in 14 days post exposure. Except as documented In the study reco rd s, t h is study was conducted according to the ap p lica b le Good Laboratory P ractice Regulations. MATERIALS AND METHODS A. Animal Husbandry Young adult male Crl:CD*BR rats were received from Charles R iv e r Breeding L a b o ra to rie s, Kingston, New York. Each ra t was assigned a unique 6 - d ig it id e n t ific a t io n number which corresponded to a numbered card a ffix e d to the cage. Rats were quarantined fo r one w eek.p rio r to t e s t in g , and were weighed and observed tw ice during the quarantine p erio d . During the t e s t , ra ts were housed 1n p a irs in 8" x 14" x 8" suspended, s t a in le s s s t e e l, wire-mesh cages. The ra t assigned the lower number in each cage was id e n tifie d by a sla sh in the rig h t e a r . P rio r to exposure, r a t s ' t a i l s and cage cards were color-coded with waterin so lu b le markers so that in d ivid u a l ra ts could be id e n tifie d a f t e r exposure. Except during exposure, Purina C e rtifie d Rodent Chow* #5002 and water were a v a ila b le ad lib itu m . Animal rooms were maintained on a tim e r-c o n tro lle d , 12 hour/12 hour lig h t/d a rk c y c le . Environmental conditions o f the rooms were targeted fo r a temperature of 23 + 2C and r e la t iv e humidity of 50* + 10*. Excursio ns outside these ranges were judged to have been of in s u ff ic ie n t magnitude and/or duration to have adversely affe cted the v a lid it y of the study. B. Exposure Protocol Groups of 6 r a t s , 8 weeks old and weighing between 230 and 277 grams, were re stra in e d in p e rfo rated , s ta in le s s s te e l c y lin d e rs with co n ical nose p ie ce s. Each group was exposed n o s e - o n l^ fo ^ ^ s in g le , 4-hour period to an aerosol/vapor atmosphere o f f f l H J H H H i n a i r . Rats were weighed p rio r to exposure, u id were o b s e rv e ^ ro ^ c m fic a l signs of t o x ic it y during exposure. Survivin g ra ts were weighed and observed d a ily fo r 14 days post exposure, weekends included when warranted by the ra ts ' c o n d itio n . - 6- company Sanlftzsd. Does r,m confab T&C& <">?? Du Pont HLR 624-87 C. Atmosphere Generation Mixed aerosol/vapor atmospheres o f A f g g f f f U r e Senerated w lth a Spraying Systems a ir atomizing nozzle k i n g a n ig n ^ e s s u r e a lr stream. The t e s t m aterial was'metered in to the spray nozzle w ith a Harvard Model 975 compact in fu sio n pum# and atomized with high pressure (approxim ately 24 L/m1n). The spray nozzle was *to c y lin d r ic a l, glass 38-L exposure chamber th a t was f it t e d w U ^ ^ a f f l e t o enhance aerosol d isp e rsio n . Atmospheric concentrations were co n tro lle d by varying the t e s t m aterial feed r a t e . Cnamoer atmospheres were exhausted through a dry 1ce cold tra p and a msa ca rtrid g e f i l t e r p rio r te discharge In to a fume hood. D. A n a ly tic a l sin ce the process j>f atmosphere generation produced a e ro so ls of ' |fand vapors of acetone and ethylene g lc o l, two j i r f erent~anaTyt1cal procedures were used. The atmospheric concentration of a e ro so lize d polymer w*s determined by g ra vim etric * " chromatographic method w*s used to monitor the atmospheric co ncentration of acetone and ethylene g ly c o l. The atmospheric concentrations of aerosolized polymer were determined at approximately 30-m1nute in te r v a ls by g ra vim e tric a n a ly s l* ach exposure. Known volumes of chamber atmospheres were drawn rh preweighed Gelman g lass fib e r f i l t e r s . F i l t e r s were "elghed on a Cahn . Model 28 Automatic Electro b alan ce . Atmospheric concentrations of [ M | t e r e ca lcu late d from the f i l t e r weight g ain , determined from post-sampl 1ng f i l t e r w eights. The atmospheric concentrations of acetone and ethylene g lyco l were determined at approximately 60-mln In t e rv a ls during s me Samples were co llected by bubbling known volumes f chamber } * J spJ ? r * s through tandem midget impingers containing w ate r. A liq uots from both Implngers were analyzed With a Hewlett Packard 5790A gas chromatograph equipped a w ith a flame io n iz a tio n d e te c to r. Samples were rnlljmn chromatographed Iso therm ally at 125 C on a 3 x Z m 1 .d . g la ss packed w ith 80/100 mesh Porapak 0 . The atmospheric concentrations of acetone and ethylene glycol were determined by response o f the samples with standard cu rv e s. Acetone and ethy n g lyco l standards were prepared as needed by the q u a n tita tiv e d ilu tio n o acetone and ethylene glycol in w ater. P a r t ic le s iz e (mass median aerodynamic diameter and percent p a rtic le s le s s than 10 um) was determined w ith a S ie rra S e rie s 210 cascade lipp*cto during each exposure.1 During each exposure, chamber teTMpeTM t ^ e w a s h measured w ith a mercury thermometer, r e la t iv e humidity w a s i 1th a Bendlx Model 566 psychrometer, and chamber oxygen concentration was measured w ith a Biosystem s, I n c ., Model 3100 oxygen a n a ly ze r. - 7 - Company Sanitized. Does not contain TSCA CB! Du Pont HLR 624-87 I E. Records Retention A il raw data and the fin a l report w ill be stored In the arch ive s o f Haskell Laboratory fo r Toxicology and In d u stria l Medicine, Newark, Delaware, or 1n the Dii Pont Records Management C enter, E . I . du Pont de Nemours and Company, I n c ., Wilmington, Delaware. RESULTS A. Exposure Conditions and Associated M o rta lity Chamber temperatures ranged from 22-24C, r e la t iv e humidity varied from 34-46*, and chamber oxygen concentration was 21*. Atmospheric c h a ra c te riz a tio n and associated ra t m o rta lity data are summarized In Table 1. Atmospheric Concentrations of acetone and ethylene g lyco l are presented In Tables 2 and 3, re s p e c tiv e ly . Table 1 Characterization o f *tmospheres and Associated Rat M o rta lity Concentration (mg/m^)a Me*n S .D . Range n 11 10 21 17 63 39 230 17 0.34 - 24 0 -4 2 1 .4 - 96 210 - 260 5 6 5 S * Particles. < 10 um AD MMD(um)c 95 2.3 94 2 .8 99 1.6 97 1.8 M ortality (# deaths/# exposed) 0/6 1/6 4/6 6/6 a Values shown represent the mean, standard d eviation ( S .D .) , range and number l of observations (n) fo r each exposure. Percent by weight of p a rtic le s with aerodynamic diameter le s s than 10 um. c Mass median aerodynamic diameter. i - 8- ompany 8iilitzadf. 5>oes onte5?! TSCA e w r-'' Du Pont HLR 624-87 Table 2 Atmospheric Concentrations of Acetone Aerosol Concentration 11 mg/m^ 21 mg/mf 63 mg/mf 230 mg/nr __________ Acetone Concentration (ppm)a Mean S .D . Range NM NM NM NM 66 31 150 19 M NM 27 - 100 120 - 160 n NM NM 4 5 3k a Values shown represent the mean, standard d eviation ( S .D .) , range and number o f observations (n) fo r each exposure. Table 3 Atmospheric Concentrations of Ethylene Glycol Aerosol Concentration 11 mg/m^ 21 mg/mf 63 mg/mf 230 mg/nr Ethylene. Glycol Concentration (ppm)a Mean S.D. Range n NM NM NM NM NM NM 9.4 5.0 NM NM NM 5 .0 - 18 NM NM NM 5 a Values shown represent the mean, standard deviation ( S .D .) , range and number of observations (n) fo r each exposure. B. C lin ic a l Observations Deaths occurred follow ing exposure t o p H j m F j a t concentrations of 21, 63 o r 230 mg/m . C lin ic a l signs of 't o x ic it y observed e ith e r during exposure or upon release from the animal re s tra in e rs among ra ts from these groups Included diminished aco u stic s t a r t le response, compound-covered fa c e s , red nasal or o cu lar d isch arg es, and labored or rapid breathing. . A ll deaths occurred w ith in 24 hours of exposure. Rats exposed to 11 mg/mJ exh ib ited red nasal and o cular discharges during or immediately a fte r - 9 - Company Sanitized. Does not contain TSCA CBt Du Pont HLR 624-87 exposure. With the exception of s lig h t to severe (up to 9% of I n i t i a l body weight) weight lo sses w ith in 24 hours o f exposure In some r a t s , no c lin ic a l sig ns of t o x ic it y were observed during the 14-day recovery period. . DISCUSSION AND CONCLUSION Under the conditions of th is stu d y, the ALC fo r ^ m w a s 21 mg/m123. The amounts-of acetone, .and ethylene, g lyco l detected TrOneTexposure charabe'- at an aerosol concentration of 230 mg/nr were 150 and 9.4 ppm, re s p e c tiv e ly . Although e xte n sive In h ala tio n t o x ic it y data fo r acetone and ethylene g lyco l are not a v a ila b le In the lit e r a t u r e fo r comparison, r a t deaths have been reported a ft e r a 4-hour exposure to 16,000 ppm acetone , no deaths were reported in ra ts a fte r repeated exposure to ethylene glycol vapors at approximately 150 ppm fo r 8 hr/day fo r 16 weeks . The concentrations o f these solvents observed 1n t h is study were co nsid erab ly le ss than those associated w ith le t h a lit y or adverse e f f e c t ^ n r a t s . Based on the atmospheric concentration of the a e ro so l, consldered^to be extremely to x ic on an acute in h a la tio n b asis (ALC le s s than 80 mg/nr). 1 Calculation described in S ie rra Instrum ents, I n c ., B u lle tin 7-79-219IM, In stru ctio n Manual: S e ries 210 Ambient Cascade Impactors and Cyclone Preseparators. 2 Smyth, H . F . , Carpenter, C . P . , Well, C . S . , Pozzani, U . C ., and S t r ie g e l, B.S. Amer. Ind . Hyg. Assoc. J . , 23, 95, 1962. 3 Wiley, F . J . , Heuper, W.C., and von O etcinger, W.F. J . Ind. Hyg. T o x ., 1 8 , 123, 1936. 10 - 'Senffpany Ssnfffeeif. Boss m i contain TSCA C'P