The relevance of the rat lung response to particle overload for human riskassessment: A workshop consensus report

On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science institute convened a workshop entitled "Relevance of the Rat Lung R esponse to Particle Overload for Human Risk Assessment." The workshop addre ssed the numerous study reports of lung tumors in rats resulting from chron ic inhalation exposures to poorly soluble, nonfibrous particles of low acut e toxicity and not directly genotoxic. These poorly soluble particles, indi cated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nona sbestiform talc, and titanium dioxide), elicit tumors in rats when depositi on overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload. " These PSPs have been shown not to induce tumor s in mice and hamsters, and the available data in humans are consistently n egative. The objectives were twofold: (I) to provide guidance for risk asse ssment on the interpretation of neoplastic and nonneoplastic responses of t he rat lung to PSPs; and (2) to identify important data gaps in our underst anding of the lung responses of rats and other species to PSPs. Utilizing t he five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participa nts are presented in this report. Because it is still not known with certai nty whether high lung burdens of PSPs.