Approaches to carcinogenic risk assessment for polycyclic aromatic hydrocarbons: a UK perspective.
This paper reviews the approaches to carcinogenic risk assessment of polycyclic aromatic hydrocarbons (PAHs) in air pollution with emphasis on high potency PAHs such as dibenzo[a,l]pyrene (DB[a,l]P). The potency of DB[a,l]P may be 100-fold greater than benzo[a]pyrene (B[a]P); thus the B[a]P surrogate approach currently used to monitor for compliance with UK air pollution standards may not be appropriate. It is suggested that an approach based on potency equivalency factors (PEFs) could be developed to include highly potent PAHs provided an appropriate reference data set for relevant PAHs using a route acceptable for inhalation risk assessment is selected. Available data suggest that intratracheal administration of low doses of PAHs to rats is likely to simulate the kinetics of inhalation exposure to PAHs in a feasible manner. The use of a measure of total DNA adducts as an endpoint, which correlates well with lung tumourigenicity, would provide surrogate data for setting PEFs without the need for long-term bioassays in rodents. Further, dose-response studies using intratracheal administration of a range of PAHs singly and in combination to assess additivity are required to develop a PEF system for inhalation PEFs derived from DNA adduct measurements.
Pufulete
M
M
Nutrition, Food and Health Research Centre, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, UK.
Battershill
J
J
Boobis
A
A
Fielder
R
R
D000393:Air Pollutants / Q000592:standards / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000592:standards / Q000633:toxicity*; D018736:DNA Adducts; D019570:Inhalation Exposure; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D011084:Polycyclic Aromatic Hydrocarbons / Q000592:standards / Q000633:toxicity*; D051381:Rats; D018570:Risk Assessment / Q000379:methods*; D006113:United Kingdom
D000393:Air Pollutants; D002273:Carcinogens; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons