Comparative pulmonary toxicities and carcinogenicities of chronically inhaled diesel exhaust and carbon black in F344 rats.
Diesel exhaust (DE) is a known pulmonary carcinogen in rats, and the carcinogenic response is known to require the presence of soot. Many estimates of human lung cancer risk from inhaled DE have been developed from rat bioassay data or from the comparative mutagenic potencies of DE soot extract and known human chemical carcinogens. To explore the importance of the DE soot-associated organic compounds in the lung tumor response of rats, male and female F344 rats were exposed chronically to diluted whole DE or aerosolized carbon black (CB) 16 hr/day, 5 days/week at target particle concentrations of 2.5 mg/m3 (LDE, LCB) or 6.5 mg/m3 (HDE, HCB) or to filtered air. The CB served as a surrogate for the elemental carbon matrix of DE soot. Considering both the mass fraction of solvent-extractable matter and its mutagenicity in the Ames Salmonella assay, the mutagenicity in revertants per unit particle mass of the CB was three orders of magnitude less than that of the DE soot. Both DE soot and CB particles accumulated progressively in the lungs of exposed rats, but the rate of accumulation was higher for DE soot. In general, DE and CB caused similar, dose-related, nonneoplastic lesions. CB and DE caused significant, exposure concentration-related increases, of similar magnitudes, in the incidences and prevalences of the same types of malignant and benign lung neoplasms in female rats. The incidences of neoplasms were much lower in males than females, and the incidences were slightly higher among DE- than CB-exposed males. Survival was shortened in the CB-exposed males, and the shortened survival may have suppressed the expression of carcinogenicity as measured by crude incidence. Logistic regression modeling did not demonstrate significant differences between the carcinogenic potencies of CB and DE in either gender. The results suggest that the organic fraction of DE may not play an important role in the carcinogenicity of DE in rats.
Nikula
K J
KJ
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185, USA.
Snipes
M B
MB
Barr
E B
EB
Griffith
W C
WC
Henderson
R F
RF
Mauderly
J L
JL
D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001822:Body Burden; D001835:Body Weight / Q000187:drug effects; D002244:Carbon / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D016017:Odds Ratio; D009929:Organ Size; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms; D018675:Toxicity Tests; D001335:Vehicle Emissions / Q000633:toxicity*
D001335:Vehicle Emissions; D002244:Carbon