Dinitro derivatives of pyrene and fluoranthene in diesel emission particulates and their tumorigenicity in mice and rats.

A number of mutagens/carcinogens in diesel emission particulates are produced and distributed into the atmosphere. On the basis of the results of chemical analysis, it was found that most of the mutagenicity in diesel particulate extracts is due to super-mutagens such as 1,3-, 1,6- and 1,8-DNP, and 3,7- and 3,9-DNF. 3,7- and 3,9-DNF are new mutagens which were isolated in this study and they induced a frameshift type mutation in the Salmonella microsome test. Each derivative of DNP and DNF was detected at a concentration of 0.01 to 0.03 ppm in the particulates while the diesel engine was used under the condition of idling. 1,6- and 1,8-DNP were tumorigenic at the injection site in BALB/c male mice when a total of 2 and 1 mg, respectively, of the compounds was given subcutaneously. The incidences for tumors by 60 weeks were at a ratio of 50 and 30%, respectively, for 1,6- and 1,8-DNP-treated mice. 4-NQO and BaP, as positive control, induced tumors at the injection site in BALB/c mice when a total of 2 and 1 mg, respectively, of the compound was given. The incidences of tumors were observed at a high ratio of 90 and 93.4%, respectively, for 4-NQO- and BaP-treated mice. Histologically the tumors were diagnosed as malignant fibrous histiocytomas in all the tumors which developed. No tumors occurred at the injection site in mice given injections of 1,3-DNP. Tumorigenicity tests of 3,7- and 3,9-DNF are now being attempted using F344/DuCrj male rats. This animal experiment is now in progress. In the 3,9-DNF-treated rats (a total of 1 mg per rat), subcutaneous tumors developed in 8 of 11 rats up to 150 days after injection, and a part of a tumor resected from a rat showed the typical features of rhabdomyosarcoma.