A review of whole animal bioassays of the carcinogenic potential of naphthalene.
This report provides a summary of deliberations conducted under the charge for members of Module A participating in the Naphthalene State-of-the-Science Symposium (NS3), Monterey, CA, October 9-12, 2006. Whole animal bioassays have been performed by the National Toxicology Program in mice and rats to ascertain the carcinogenic potential of naphthalene by inhalation exposure. A statistically significant increased incidence of pulmonary alveolar/bronchiolar adenoma (a benign lesion), was observed among female mice; an observed increase among the males did not reach statistical significance. No nasal tumors were observed in either sex. A tumorigenic response was observed in both sexes of rats, in males an increased incidence of nasal respiratory epithelium adenoma (a benign rather than malignant lesion) and in females, olfactory epithelial neuroblastoma. Interpretations of these studies vary. On the one hand, evidence of extensive non-neoplastic response in both sexes of both species indicates cytotoxicity occurred at all doses, and strongly suggests that cytotoxicity played a significant role in the tumor responses observed in the target tissues. On the other hand, olfactory epithelial neuroblastoma has rarely been observed in NTP bioassays. This review seeks to develop a consensus understanding of the scientific evidence provided by these studies, taking into account that they have been used as the basis for quantitative human cancer risk assessment, and suggests scientific studies that, if performed, could resolve scientific uncertainties.
North
D Warner
DW
NorthWorks, Inc., 1002 Misty Lane, Belmont, CA 94002-3651, USA. northworks@mindspring.com
Abdo
Kamal M
KM
Benson
Janet M
JM
Dahl
Alan R
AR
Morris
John B
JB
Renne
Roger
R
Witschi
Hanspeter
H
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D015197:Carcinogenicity Tests / Q000379:methods*; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000145:classification / Q000633:toxicity*; D018304:Esthesioneuroblastoma, Olfactory / Q000139:chemically induced / Q000473:pathology; D005260:Female; D019570:Inhalation Exposure; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage / Q000145:classification / Q000633:toxicity*; D009296:Nasal Cavity / Q000187:drug effects / Q000473:pathology; D009669:Nose Neoplasms / Q000139:chemically induced / Q000473:pathology; D009831:Olfactory Mucosa / Q000187:drug effects / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats
D002274:Carcinogens, Environmental; D009281:Naphthalenes