POLYCYCLIC AROMATIC HYDROCARBONS

1
POLYCYCLIC AROMATIC HYDROCARBONS
2
What Are They?

• PAHs are a group of chemicals that are formed
  during the incomplete burning of coal, oil and
  gas, garbage, or other organic substances.
• PAHs can be formed through natural processes or
  those related to human activities.
• There are more than 100 different PAHs. Most
  PAHs do not occur alone in the environment.
  Rather they are found as mixtures of two or more
  PAHs.

3
What Are They? (Continued)

• PAHs can occur in the air attached to organic
  particles, in the soil, or in the sediments as
  solids.
• They can also be found in substances such as
  crude oil, coal, creosote, and road / roofing
  tar.
• Evaporation into air does occur very easily.
  Global transport occurs.

4
What Are They? (Continued)

• Examples of Polycyclic Aromatic Hydrocarbons are
  on overhead.
• Examples Acenaphthene, Anthracene,
  Benzaanthracene, Benzoapyrene,
  Benzobfluoranthene, Benzoghipyrene,
  Benzokfluoranthene, Chrysene,
  Dibenza,hanthracene, Fluoranthene, Fluorene,
  Indeno1,2,3-cdpyrene, Phenanthrene, and Pyrene

5
Toxicity

• Although unmetabolized PAHs can have toxic
  effects, the major concern in animals is the
  ability of reactive metabolites to bind to
  proteins and DNA.
• Four, five and six ring PAHs have greater
  carcinogenic potential than do two, three or
  seven ring PAHs.
• The addition of alkyl groups to PAHs enhances the
  carcinogenic potential of these compounds.

6
Exposure

• Some exposure to PAHs comes through inhalation
• In the environment you are exposed to PAH vapors
  or PAHs attached to dust and other particles in
  the air. These can come from vehicle exhausts,
  coal burning, wildfires, agricultural burning,
  and hazardous waste sites.
• Other inhalation exposures come from PAHs present
  in tobacco smoke, smoke from wood burning
  fireplaces, and creosote-treated wood products.

7
Exposure (Continued)

• Some exposure to PAHs by ingestion
• Cooking meat or other foods at high temperatures
  that results in charring of the food increases
  the amount of PAHs in the food.

8
Animal Exposure

• Exposures to animals are
• Fish - from light MW forms in the water from
  higher MW forms in the sediment.
• Birds - mainly through the exposure of birds to
  oil spills.
• Mammals - also through oil spills.

9
Absorption, Distribution, Excretion

• These are highly lipophilic compounds so they are
  absorbed quickly by all routes of exposure.
• Storage is mostly in kidneys, liver and fat
  tissue.
• PAHs do not have long half-lives. Usually
  measured in days. Excretion is primarily by
  urine and feces.

10
Metabolism

• Important regions of PAH molecules are
• Bay Region - there is a terminal ring on one side
  of the bay region
• L Region - this is a site between two ring fusion
  points, it is alpha to two fusion points.
• K Region - this is a region of high electron
  density in all resonance structures.
• All of these regions are highly reactive.
  Epoxides can be formed at all three regions.

11
Metabolism (Continued)

• Bay region dihydrodiol epoxides are the main
  carcinogenic species.
• Bay region metabolites represent only a small
  fraction of the total metabolism of the parent
  hydrocarbon since metabolism occurs at many sites
  on the molecule.

12
Metabolism (Continued)

• What makes the bay region metabolite unusual and
  the most carcinogenic?
• Bay region dihydrodiol epoxides are particularly
  resistant to enzymatic detoxification. The bay
  region epoxides are not good substrates for
  epoxide hydrolase or for glutathione conjugation.
• The resistance is presumably due to the steric
  inaccessibility of the bay region.

13
Benzoapyrene

• Benzoapyrene diol epoxides show a strong
  preference for reaction with purine residues,
  particularly guanine.
• BPa is one of the most intensely studied PAHs as
  it is an extremely potent carcinogen.
• Metabolic transformations catalyzed by the CYPs
  are mainly hydroxylations occurring at the
  various available sites on the aromatic rings
  (phase I reactions), and conjugations of the
  hydroxyl groups with glucuronic acid, sulphate,
  or glutathione (phase II reactions).

14
Benzoapyrene

• It now seems that the ultimate carcinogen is an
  epoxide of a dihydrodiol metabolite where the
  epoxide is adjacent to the bay region. Although
  a number of the epoxides are mutagenic, the
  7,8-dihydrodiol, 9,10 epoxide is believed to be
  the ultimate carcinogen.
• The diasteroisomer believed to be the ultimate
  carcinogen is shown in Figure 7.2.

15
Benzoapyrene

• Other metabolites are BPa known to be produced
  are the 3,6-quinone and semiquinone. These
  metabolites are cytotoxic and cause DNA strand
  breaks. They are also mutagenic.