Document wg2ZDmyeyra82d0EdMajGZKoJ

AR226-2884 E. I . du Pont de Nemours and Company H askell Laboratory fo r Toxicology and I n d u s tr ia l M edicine E lk to n Road, Newark, Delaware 19711 HASKELL LABORATORY REPORT NO. 494-80 M aterial Tesi H askell No. "137553 .O ther Codes/Synonyms" Study T nltlated/C om pleted 4/21/80 - 4/29/80 TTM a te ria l Subm itted GD&P D@pt Jackson Lab INHALATION MEDIAN LETHAL CONCENTRATION (LC50) In tr o d u c tio n ; The purpose o f t h i s study was to d eterm in e th e LC50 forj z' P ro ced u re: Groups o f 10 ChR-CDG r a t s , 8 weeks old and w eighing 235-282 g , were exposed to vapor atm ospheres of the te s t m a te ria l fo r s in g le 4 -h r. p e rio d s. Except during ex p o su re, r a t s were housed in suspended s t a i n l e s s - s t e e l w ire mesh cages. P u rin a C e r t i f i e d Rodent Chow* #5002 and w ater were s u p p lie d ad l i b i t u m . During exposure, a l l r a ts were observed and c lin ic a l sig n s n oted. Follow ing exposure, ra ts were weighed and observed d a ily (excluding weekends) fo r a 14-day recovery period. G eneration; Vapor atm ospheres of the te s t m ate ria l were generated by syringe d riv in g th e compound through a Spraying Systems n e b u liz e r . The s y rin g e and n e b u liz e r were h e a te d to a tem p eratu re of app ro x im ately 50C. The a e ro s o l was then -sprayed onto the heated surface of a 3-neck round-bottom fla s k . H ouseline a ir swept the vapors in to a 20 1 g lass b a tte ry j a r . Dry ic e was p lac e d on top of chamber to keep te m p e ra tu re 28C. Oxygen and chamber tem perature were m onitored throughout each exposure. A n a ly tic a l; Chamber sam ples were c o lle c te d a p p ro x im ately ev ery 30 m in u tes by drawing a known volume of chamber atmosphere through 2 tandem m idget im pingers contain* 'M jM IflR n s a trap p in g solvent. These samples were analyzed using a Hewlett ia c k a x d n o a e l 5710 gas chromatograph equipped w ith a flame io n iz a tio n d e te c to r . The column used was a 6* x 1/4" 0D g la s s c o l l packed w ith a 202 SE30 on - 1- gmpany Sanitized. Does not contain TSCA CBI 80/100 mesh chromosorb W-HP. The GC was ten mature programed w ith an I n i t i a l hold a t 50aC fo r 2 m inutes, Increased a t 32 In to 200*C, and held th e r e f o r 2 m inutes. GC a n a ly s is was based n the C-8 jpmponent. Chamber c o n c e n tra tio n s a re expressed as the equivalen fl concentration (mg/1). R e su lts: Six exposures were conducted. O ccasslonally, during exposures, low b o ilin g components caused f la s h ev ap o ratio n and high b o ilin g s o lid s caused plugging of the n eed le. These problems account fo r the high standard d e v ia tio n for the exposure concentrations. C o n cen tratio n mg/1 51.2 66.7 70.9 76.9 110 123 S. D. 13.4 41.6 22.7 29.8 14.0 30.0 Fractional M ortality t deaths/ # exposed 0 10 1 10 0 10 7 10 4 10 6 10 O bservations: Labored b reath in g , reduced response to sound, and s a liv a tio n were observed d u rin g a l l exposures except one. Mild to severe w eight lo s s 24 hours p o st-e x p o su re follow ed by norm al h e ig h t g a in was observed in le v e ls 70.9 m g/1. G asping, severe w eight lo s s 48 hours p o st-ex p o su re followed by normal w eight g a in was observed a t 7 6 .9 mg/1. In le v e ls ^ 110.0 m g/1, severe w eight lo s s 48-72 hours p o st-e x p o su re follow ed by norm al w eight g a in was observed. A ll deaths occurred 24-48 hours post-exposure. Summary: Groups o f 8 w eek-old ChR-CD male r a t s were exposed to vapors o f `^ g H E o r s in g le 4 - h r . p e rio d s . The LC5Q** was e stim a ted to be 107 mg/1. n i n e t y - ' `f i v ^ p e r c e n t confidence in te r v a l s could not be c a lc u la te d due to in c o n s is te n c y of dose-response. .. . C lin ical signs observed during exposure included labored breaching, sa liv a t io n , and reduced response to sound. Mild to sev ere w eight lo s s was observed 24--72 hours p o s t--exposure b u t normal w eight g a in was achieved t h e r e a f t e r . - 2- Company Sanitized. Does not contain TSCA cr Report by: J js/z .- - Z ). Stephen D. Nash T e c h n ic ian Approved by : - J -3*. G erald L. Kennedy C hief, Acute In v estig a tio n s Section SDNsjrg Study D ire c to r: Sayanne L. Feremz Date Issu ed : August 21, J.980 R eport No. 494-80 Company Sanitized. Does not contain TSC CB 3