Toxicokinetics - trdoer40169

Hamsters were chronically exposed to B(a)P by inhalation (IRIS 1992) and

were shown to develop respiratory tract tumors. Those hamsters in the highest

dose group developed upper digestive tract tumors.

USEPA has classified B(a)P as a Group B2, or probable human carcinogen.

The oral cancer slope factor is based on a dietary study in mice.

Toxicokinetics

There are no toxicokinetic data for B(a)P in humans (USEPA 1980). Animal

data indicate that B(a)P is readily absorbed after exposure by inhalation or oral

intake and distributes to many tissues in the body (USEPA 1980). B(a)P in itself

is not believed to be carcinogenic, but metabolized by the cytochrome P-450

dependent mixed function oxidase system, often referred to as the aryl

hydrocarbon hydroxylase (AHH) system. The metabolism results in a more

hydrophilic compound which is easier to excrete, although is carcinogenic. The

hepatic metabolic pathway for B(a)P metabolism is readily inducible by

exposure to a variety of chemicals, including B(a)P, and is found in most

mammalian tissues. It catalyzes the formation of reactive epoxide intermediates

as well as the ultimate carcinogenic form of B(a)P: the B(a)P-7,8-diol-9,10-

epoxide (USEPA 1982) which is capable of forming covalent bonds with cellular

macromolecules such as DNA, RNA, and proteins. This covalent binding and

subsequent alteration of structure and function may result in tumor formation.

Because of their high lipid solubility, PAHs are believed to be distributed

throughout the body. Relative to other tissues, they tend to localize in body fat

and fatty tissues.

Ecological effects

The reader is requested to review the toxicity profile for PAHs for

information regarding ecological effects.

References

Integrated Risk Information System (IRIS) on-line database. (1992).

International Agency for Research on Cancer (IARC). (1973). "Certain

monographs on the evaluation of carcinogenic risk to humans." Polycyclic

aromatic hydrocarbons and heterocyclic compounds. Vol 3. World Health

Organization, Lyon, France.

International Agency for Research on Cancer (IARC). (1983). "IARC

monographs on the evaluation of the carcinogenic risk of chemicals to

humans." Volume 32: Polynuclear aromatic compounds, Part 1, Chemical,

environmental and experimental data. World Health Organization, Lyon,

France.

D17

Appendix D Toxicological Profiles