History of vinyl chloride carcinogenicity studies 

in Carcinogenicity bioassays of vinyl chloride monomer: a model of risk assessment on an experimental basis. 
Environmental Health Perspectives v.41, 1981

Maltoni-C; Lefemine-G; Ciliberti A; Cotti-G; Carretti-D

1961          VC was found to produce liver enlargement and 
              microscopic hepatic degenerative changes (5)

1970          Zymbal gland carcinomas were reported in rats exposed 
              to 30,000 ppm of VC, by inhalation (6)

1970          An increase in atypias in respiratory cells was observed 
              among workers heavily exposed to VC (7)

July 1971     A vast project of long-term carcinogenicity bioassays on VC 
              was started in Bentivoglio, near Bologna, Italy (BT project)

August 1972   Zymbal gland carcinomas, nephroblastomas and 
              liver angiosarcomas were observed in rats exposed 
              to VC by inhalation (Maltoni, BT project)

April 1973    The first data of the BT project were released to the 
              scientific community: the oncogenic effect was observed 
              up to 250 ppm (4)

1973          Splenomegalic liver disease was found among 
              poly(vinyl chloride) production workers (8)

December 1973 For the first time a case of liver angiosarcoma in a 
              poly(vinyl chloride) production worker was correlated to 
              VC exposure (9)

February 1974 On the basis of the BT project data indicating a carcinogenic 
              effect at 250 ppm, OSHA proposed a TLV of 50 ppm

February 1974 The BT project data showed that VC is a multipotential carcinogen, 
              producing a variety of tumors, in different animal species

1974          The BT project data indicated a carcinogenic effect at 50 ppm (10); 
              OSHA proposed new stricter rules

1974          Early epidemiological observations (paralleling the experimental 
              information) indicated an increase in tumors other than liver 
              angiosarcomas (of brain, lung, liver, hemolympho reticular tissues) 
              among workers of VC-PVC industries (11)

1974-75       BT project data showed that VC had carcinogenic effects in rats 
              also when given by ingestion (1l)

1976          In rats of the BT project exposed to VC by inhalation, 
              angiosarcomas were observed down to the level of 25 plan, 
              and Zymbal gland carcinomas down to the level of 10 plan (13)