Oncogenic response of strain A/J mice to inhaled chemicals

Abstract

Strain A/J mice were exposed by inhalation for 6 h/d, 5 d/wk, for 6 mo to carbon disulfide, 1,2-dibromoethane, ethylene oxide, naphthalene, nitrogen dioxide, or vinyl chloride. Significant increases in pulmonary adenoma formation were observed following exposure to 300 ppm carbon disulfide; 20 and 50 ppm 1,2-dibromoethane; 70 and 200 ppm ethylene oxide; 10 ppm nitrogen dioxide; and 50, 200, and 500 ppm vinyl chloride compared to control animals. Repeated studies with 1,2-dibromoethane, ethylene oxide, and vinyl chloride gave similarly significant results. Exposure of mice to 30 ppm naphthalene did not elicit a significant adenoma response. Histopathological examination of lungs from animals in these studies revealed multiple alveolar adenomas. Results from earlier studies with these chemicals, using strain A mice and Swiss mice, and bioassay information with rats and mice were compared with these data. These results provide further information for the validation of this in vivo model as a tool for predicting oncogenic potential following chemical exposure.

Naphthalene metabolism in relation to target tissue anatomy, physiology, cytotoxicity and tumorigenic mechanism of action

“…There were increased incidences of alveolar/bronchiolar adenomas or carcinoma in female (but not male) B6C3F1 mice exposed to 30 (but not to 10) ppm naphthalene for 2 years (NTP, 1992;Abdo et al, 1992). A previous study found increased tumor multiplicity in tumor-bearing A/J strain mice exposed to 10 or 30 ppm for 6 months (Adkins et al, 1986). The few case reports of cancer in naphthalene-exposed humans involve four laryngeal cancer cases among smokers in workers at an East German naphthalene purification plant (Kup, 1978;Wolf, 1976Wolf, ,1978, and a series of 11 colorectal carcinoma patients 18 to 30 years old admitted to a Nigerian hospital, "half" of whom "gave a definitive history of ingesting" the "naphthalene compound" kafura used as part of "local indigenous treatment for 'piles' or any anorectal problem" (Ajao et al, 1988).…”

Characterization of the toxicological hazards of hydrocarbon solvents

“…More recently, the toxicology database on naphthalene was substantially expanded through the publication of chronic toxicity/carcinogenicity studies in mice and rats in which naphthalene was administered by inhalation (Abdo et al 1992, Adkins et al 1986, NTP 1992, 2000. Of particular importance were the statistically significant increases in incidence of pulmonary alveolar/bronchiolar adenomas in female mice and nasal tumors in rats.…”

Naphthalin [MAK Value Documentation in German language, 1995]

“…In einer nicht validierbaren Studie war nach 6monatiger inhalativer Exposition gegenüber 10 und 30 ml Naphthalin/m 3 , 6 Stunden pro Tag und 5 Tage pro Woche, bei 30 weiblichen A/J-Mäusen die Rate maligner Lungentumoren nicht erhöht (Tabelle 3; Adkins et al 1986). Die Inzidenz alveolärer Adenome betrug bei den Kontrolltieren 21%, bei den mit 10 ml/m 3 behandelten Tieren 35% und bei den mit 30 ml/m 3 behandelten 37 % und war damit nicht signifikant erhöht.…”