Document oDemR499p1yr3ggEYpb0jyqGo

AR226-2749 Copies to: E. I. du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine HASKELL IABOBATORY REPORT NO. Material Tested: Ammonium Perfluorooctanoate Material Submitted by: ^Plastics Department W_as_hi_ng_ton riant, Parkersburg, West Virginia Haskell No.: Other Codesd 6001 ACUTE INHALATION DUST TOXICITY Procedure: Two different types of dust generators were used to generate ammonium perfluorooccanoa (1) DeVilbis Dust Generator: A heavy dust cloud was generated by blowing ~ 30 L/mlnute velocity Cu-tubing jet submerged in a mechanically stirred reservoir of the test material. The ai particles into an 8-liter exposure chamber. Suitable diluting air was introduced between the gene achieve lower concentrations. This generator did not fractionate the dust and all particle sizes, delivered into the exposure chamber. ^54 (2) Hornberger Dust Generator: This generator was used for low atmospheric dust concen generator, a falling stream of dust particles from a stirred reservoir impinged on a pneumatic jet this jet carried the particles to a cyclone head where the larger ones were returned to the reserv achieved some particle size fractionation and the rats received mainly particles mass median DeVilbis generator, the generator itself was run under constant conditions and dust concentrations diluting the stream with air between the generator and the exposure chamber. Six racs of 250-270 grams body weight were used per exposure. Only their heads were exp were four hours. The eyes were stained with fluoroscein immediately after exposure to check on e material. Rats were sacrificed for hiscopathologic examination at 1, 7, 14, 27, and 42 days post from two rats dying during exposure were also examined microscopically. In both methods, the airborne solids were measured in the exposure chamber by collecting air volume on a filter of known pore size. The concentration was determined five times during ea the mid-point of each exposure, a particle size distribution measurement was made with a Monsanto Company Sanitized. Does not contai <(D - 2 - Results: Generat 1 Average Dust Concentracion (mg/L) 5.7 Mortality Ratio 6/6 Mass Median Diameter (u) 6.4 t 3.2 4.8 2.2+ 0.83* 6/6 16 t 3.4 6/6 7.6 t 3.8 176 1.8 t 2.5 O.BL- 0.38 2/6 1/6 1.8 2.8 2.4 + 2.4 Clinical Observations During Exposure Gaining, irregular breathing, red discharge around eyes and nose, salivation, death (1/6) Death from (5/6) Same as above, but no deaths Some ruptu eyes opaqu Same as above Same as ab confirmed Gasping, irregular breathing, red discharge around eyes and nose Same as above except one death Same as above Severe wei loss the n thereafter opaque and external d fluorescei 2nd night Same as ab normal aft Severe we normal gro t Whole body control exposure. * Sacrificed at 1, 7 and 14 days. i Sacrificed at 27 and 42 days. Death not related to test material. It Pathology: Rats dying during exposure had hyperinflated lungs. Some of the test materiel was pr They also had a foamy white exudafe in the trachea. The ratio of liver weight to body weight was normal range one day after exposure. increased to a maximum (two times normal) at 7-14 days a decreased to the high end of the normal range at the last sacrifice, 42 days post-exposure. C'6h'!?3ny "Sanitized. Does Pathology (Cont'd.): Microscopic tissue examination* indicated that acute pulmonary edema developed promptly b a week, leaving no residual injury. No dust particles were seen in the lungs microscopically. Ther the stomach which cleared in two weeks and irritation of the eyes which was still present when the sacrificed 42 days after exposure. The liver tissue appeared microscopically normal at all times a enlargement was not apparent. Discussion: The time paj-tern and magnitude of rat liver enlargement caused by inhalatio- ______ IIBBHBHHHHRBU^^HBp./Inhalation oS^HIf^HUMWSHW} caused changes in liver *CCT^morp HH^BHHNHI^H^Bmi^ut inhalation ofj----1----idjjl not. However, the exposures to thetwo strictly comparable, since eKposure tc^l------mH------gwas whole body, whereas exposure teg---- MMWW----WlM---- Thus effects from the( sxposureS" would reflect ingestion of greater amounts o material fro. pattern comparison caiT e made for liver enlargement caused by^. inhala^ on of]------f versus ingesti recovery studies hav< of been carried out after ingestion ovMSm^ However, 14 days after inh lethal dose o^~ liver to body weight ratio was two timeS norm Fourteen days after inge sublethal oral ver to body weight ratio was < 1.5 times normal A study of rat liver enlargement versus time afterJ.ngestion has been carried out for the the ratio of liver weighCtobody weight reached a maximum yiO days after ingestion of 1/5 of the (ALD; dose was 12 mg/kg) ar stayed relatively constant for the rest of the study (last sacrifice I^EMHiJwould be considered highly toxic by inhalation administration as judged by four-h Orally, it would be considered to have only moderate acute toxicity. Summary: The Approximate Lethal Concentration (ALC) of ammonium perfluorooccanoate is 0.8 mg/L fo exposure. It is considered lilgnly toxic by inhalation. O.ily the rat heads were exposed to minimi by ingesting the test material. Inhalation of the test material caused liver enlargement which re times normal) 7-14 days after exposure. Liver weights returned to the normal range 42 days after in liver cell morphology were observed. The small amount ingested caused irritation of the stomac The material also caused corneal opacity and ulceration which were still microscopically evident 4 * Lungs, liver, trachea, gastrointestinal tract were the only tissues examined microscopically. Company Sanitized. Does nol co - 4 Summary (Cont'd.): ^Hmfijshould be handled with at least the same care asjitf^J any spilled on the skin or eyes should be washed off immediately, ^here contact. Ingestion should be and inhalation sh medical follow-up Report by: Approved by: g^i Q 0 Figen 0 Inhalation To ^ -Hichard- Chief, Inh'alation ^L (a. /y7JohJnoh^n^ -- D Company Sanitized. Does no