Document rxQ6Y4X8ZVm2pXvVaY2dBgY3q

TUESDAY 1073 MAY 1973 s M TWT F S 123 4 5 6 7 8 9 10 11 12 13 14 15316 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 15 MAY 1973 ?,j cAs DENTIAL irmarville \ ttsburgh 12, 1974 r%ry- 'r i date April 23, 1974 REFERENCE 100B1-5.2.0 ML (A-" JiA C<` LA- A dum from SPI (Society of Plastics Industries) C (Polyvinyl Chloride) and its precursor VCM nimal experiments appears very extensive, ficient for a valid statistical evaluation, r safety for the PVC use as food containers, idy occupational preventive measures in the 11^ u~7 \AJ /, <4 c ^ 4s]15|73 a- 135 TUES., MAY 15, 1973 AdcJA n I'o - iuiiu uis oncogenic Dasis. A ^ 230 h- literature references concerning the ind VCM through the mammalian system. It itions of inhaled or directly absorbed VCM thus also rapidly excreted. Higher con tuse oxygen deficiencies or in general Under such conditions different chemical formation of potential carcinogenic or . The mammalian system, in attempts to ,e them in the liver and skeleton, i.e. . Especially when hepatic pathways are jay interfere with DNA synthesis, and thus Similarly, during industrial processes synthetic and degradative inter mediates may be formed which could directly act as dermal, respiratory or hepatic carcinogens. However, as above, at low concentrations the mammalian system may readily metabolize, hydroxylate and excrete such products without detrimental effects. The following reaction may be postulated to occur under certain indus trial or biological conditions: CH =CH-C1 ^i H 0\i vinyl chloride CH-CH -Cl lL OH HC1 high temperatures y CH3-CH0 \ Acetaldehyde 1-chloro, 3-hydroxyethane lower temperatures on certain biological conditions CH,,-CH 2 \V 0 Ethylenoxide CUSAROSS 02186 t f-'''' L RN AL_QR R L5PON DENCE L .1_'0 CONFIDENTIAL rX9^- FROM TO E. E. Sandmeyer Mr. R. E. Rutherford at Harmarville V at Pittsburgh SUBJECT CONFIDENTIAL MEMO FROM SPI OF MARCH 12, 1974 date April 23, 1974 REFERENCE 100B1-5.2.0 I have reviewed the memorandum from SPI (Society of Plastics Industries) counsel Mr. J. Heckman concerning PVC (Polyvinyl Chloride) and its precursor VCM (Vinyl Chloride Monomer). The protocol for proposed animal experiments appears very extensive, and the number of animals appear sufficient for a valid statistical evaluation. This may suffice to evaluate consumer safety for the PVC use as food containers, but it would not cover aspects to study occupational preventive measures in the production of such containers. So far I have not found any literature references concerning the metabolic and catabolic fate of PVC and VCM through the mammalian system. It is highly probable that low concentrations of inhaled or directly absorbed VCM are readily oxidized, conjugated and thus also rapidly excreted. Higher con centrations on the other hand, may cause oxygen deficiencies or in general decrease the rate of detoxification. Under such conditions different chemical reactions may occur and lead to the formation of potential carcinogenic or carcinogen potentiating intermediates. The mammalian system, in attempts to detoxify such products, may accumulate them in the liver and skeleton, i.e. at sites distant to the port of entry. Especially when hepatic pathways are involved, the accumulated compounds may interfere with DNA synthesis, and thus form the oncogenic basis. Similarly, during industrial processes synthetic and degradative inter mediates may be formed which could directly act as dermal, respiratory or hepatic carcinogens. However, as above, at low concentrations the mammalian system may readily metabolize, hydroxylate and excrete such products without detrimental effects. The following reaction may be postulated to occur under certain indus trial or biological conditions: CH =CH-C1 ^i h2o\I V CH-CH.-Cl i^ OH vinyl chloride 1-chloro, 3-hydroxyethane HC1 high temperatures' \ \ CH3-CHO Ace taldehyde lower temperatures on certain biological conditions CH -CH \/ 0 Ethylenoxide CUSAROSS 02187 date 4/23/74 from E. E. Sandmeyer to Mr. R. E. Rutherford SHEET NO 2 Acetaldehyde (dermal and respiratory irritant and sensitizer) Ethylenoxide (highly irritant to eyes, can cause pulmonary edema, potent nutagen; possible carcinogen) In order to investigate these reactions, acetaldehyde in the light of the "Meat cutter's syndrome" and the ethylenoxide and chloro-hydroxy-ethane in view of the incidence of angiosarcoma, the experimental protocol might include the study of all of these compounds. However, as preventative measures, good industrial hygiene and adequate local ventilation should prevent any health hazard. E. E. Sandmeyer EES/sma cc: Dr. F. D. Gassaway - Pittsburgh Dr. R. L. Gibson - Pittsburgh * SllOi'DlARv cr G.-Jl f oil CORPORATION CUSAROSS 02188