Polycyclic aromatic compounds (PACs) are widespread environmental contaminants. There are many different types of PACs, including polycyclic aromatic hydrocarbons (PAHs), which are discussed below. PACs can occur in complex mixtures or be synthesized as individual chemicals.

PACs are found naturally in fossil fuels (petroleum and coal). The release of PACs can occur through natural events such as volcanic eruptions and forest fires. They are also created and released into the environment by burning organic material such as fuels, garbage, and wood. Some PACs stay in the environment for a long time and do not break down easily. Polycyclic aromatic hydrocarbons were a particular concern following the Deepwater Horizon oil spill (see NIEHS Gulf Oil Spill Response Efforts).

How People are Exposed to PACs

People are rarely exposed to a single PAC. They are more often exposed to complex mixtures of PACs. The mixture depends on the source of the exposure, as well as other factors such as sunlight or weathering of contaminated materials.

People can be exposed to PACs in various ways, including:

• Eating certain foods such as chargrilled meat or smoked fish
• Breathing contaminated air
• Drinking contaminated water
• Absorbing PACs through the skin from tainted soil
• Exposure in workplaces which use petroleum or coal
• Exposure in workplaces that burn organic material such as wood, oil, garbage, or plants

For example, workers who produce tar or asphalt, or use these substances in roofing and paving, may be exposed to PACs.

Health Concerns Associated with Exposure to PACs

Some PACs are known carcinogens. Animal experiments have shown that certain PACs can cause damage to the immune and reproductive systems. However, the majority of PACs have not been evaluated for potential health effects, and research is needed to understand the combined effects of multiple PACs. NTP is currently studying PACs to learn more about the effects of individual PACs and PAC mixtures.

About Polycyclic Aromatic Hydrocarbons

PAC is a broad term which describes a large group of chemicals, including PAHs. PAHs are made up of only carbon and hydrogen atoms within their ring structure. PAH ring structures may have other atoms attached to the rings, creating alkyl-PAHs, nitro-PAHs, and oxy-PAHs.

Heterocyclic PACs contain other atoms besides carbon and hydrogen, such as nitrogen, oxygen, or sulfur within the ring structure. NTP is studying both PAHs and other PACs, so the broader term PACs is used to describe the range of compounds which are part of our research effort.

One of NTP's study efforts is the Polycyclic Aromatic Compounds Mixtures Assessment Program (PAC-MAP). This program aims to increase our understanding of the toxicity of PACs and PAC mixtures. In December 2012, NTP presented the research concept for PAC-MAP to the NTP Board of Scientific Counselors. In 2012, NTP Board members gave the approval for NTP research.

Under this program, NTP will use a wide range of tests in cells and rodents to assess the toxicity of individual PACs and PAC mixtures, and to identify potential health hazards.

See the table for a list of the studies and their descriptions.

PACs Tested in Rat Immunotoxicity Study

Below is a list of PACs tested in the rat immunotoxicity (28-day) study:

Cookstove Activities

The burning of solid fuels such as wood, charcoal, and dung results in a significant global health burden with over four million premature deaths per year attributed to indoor air pollution from inefficient use of solid fuels.

NTP is involved in studies to analyze the release of PACs associated with cookstove activities. Indoor air pollution caused by biomass burning is one of the five focus areas of environmental health concern for the Collaborating Centre for Environmental Health Sciences of World Health Organization (WHO), of which NIEHS is a partner. This formal partnership provides new opportunities for translating research findings into effective global public health interventions.

As an initial step, NTP held the Symposium on Assessing Exposures and Health Effects Related to Indoor Biomass Fuel Burning at NIEHS, Research Triangle Park, NC. This symposium brought together researchers to discuss policies and the way forward.

The 2012-2017 NIEHS strategic plan also identified Global Environmental Health as a priority research area with a focus on cookstoves and indoor air pollution.

Other NTP Evaluations

NTP has published a variety of technical reports, toxicity reports, immunotoxicological studies, and developmental toxicity abstracts for PACs and/or mixtures that contain PACs.

• NTP Technical Reports for PACs or Mixtures that Contain PACs

  NTP Technical Reports for PACs or Mixtures that Contain PACs by Report Number

  Report	Description
  Anthraquinone (TR-494)	In this study, anthraquinone (a substance used to make dyes and paper and as a bird repellant) was laced in feed to determine anthraquinone's potential to cause cancer
  Marine Diesel Fuel and JP-5 Navy Fuel (TR-310)	This study evaluated the toxicological and cancer-causing potential of marine diesel fuel and JP-5
  Naphthalene (TR-410 and TR-500)	Napthalene (a white crystalline powder used as a moth repellent and in manufacturing substances) was tested for its cancer-causing potential via this inhalation study
  5-Nitroacenaphthene (TR-118)	A bioassay of 5-Nitroacenaphthene to test for possible carcinogenicity was conducted and administered in feed

• NTP Toxicity Reports for PACs or Mixtures that Contain PACs

  NTP Toxicity Reports for PACs or Mixtures that Contain PACs by Report Number

  Report	Description
  Black Newsprint Inks (TOX-17)	Topical administration of black newsprint inks was used to assess the toxicological potential of particular inks
  1-Nitropyrene (TOX-34)	1-Nitropyrene, a byproduct of combustion, was administered by inhalation to determine possible carcinogenic effect

• Immunotoxicology Studies on 1,2:5,6-Dibenzanthracene

  Immunotoxicology Studies on 1,2:5,6-Dibenzanthracene

  Report	Description
  NTP Range-Finding Report: Immunotoxicity of 1,2:5,6-Dibenzanthracene in Female B6C3F1/N Mice	This dose range-finding study was conducted to establish the potential effects of DBZA (a PAH class substance) on the immune system
  NTP Report on the Immunotoxicity of 1,2:5,6-Dibenzanthracene in Female B6C3F1/N Mice	1,2:5,6-dibenzanthracene (DBZA) is a substance belonging to the PAH class. This study involved subcutaneous treatment of DBZA for 28-days
  NTP Report on the Developmental Immunotoxicology Evaluation of 1,2:5,6-Dibenzanthracene in Female B6C3F1 Mice	This developmental immunotoxicology study evaluated the effects of perinatal exposure to DBZA

• Developmental Toxicity Abstract Studies on Naphthalene

  Developmental Toxicity Abstract Studies on Naphthalene

  Report	Description
  Developmental Toxicity Studies of Naphthalene in Sprague-Dawley CD Rats	Naphthalene (NAP) is a substance widely used in the manufacture of dyes, synthetic tanning agents, and lubricants, as well as in mothballs. A developmental toxicity study of NAP was conducted to determine potential maternal signs of toxicity
  Developmental Toxicity of Naphthalene in New Zealand White Rabbits	NAP was administered in this developmental toxicology study, following which clinical signs of toxicity were evaluated

• Report on Carcinogens (RoC) PAH Studies

  Report on Carcinogens (RoC) PAH Studies

  The 15 individual PAHs are reasonably anticipated to be human carcinogens based on sufficient evidence of carcinogenicity from studies in experimental animals.

  List of Report on Carcinogens (RoC) PAH Studies

  PAH	CASRN	Test Results
  Benz[a]anthracene	56-55-3	Caused tumors at several different tissue sites and by more than one route of exposure
  Benzo[b]fluoranthene	205-99-2	Evidence of tumors by two different routes of exposure
  Benzo[j]fluoranthene	205-82-3	Dermal exposure resulted in benign and/or malignant skin tumors
  Benzo[k]flouranthene	207-08-9	Caused tumors in more than one species, at two different tissue sites and by two routes of exposure
  Benzo[a]pyrene	50-32-8	Resulted in tumors in eight species at several tissue sites, by several routes of exposure
  Dibenz[a,h]acridine	226-36-8	Studies resulted in tumors at various tissue sites by several routes of exposure
  Dibenz[a,j]acridine	224-42-0	Dermal exposure and subcutaneous injection resulted in cancer and lung tumors
  Dibenz[a,h]anthracene	53-70-3	Caused tumors in several species, through a variety of tissue sites, and several routes of administration
  Dibenzo[c,g]carbazole	194-59-2	Administration resulted in tumors among several species. Numerous tissues sites and routes of exposure were studied.
  Dibenzo[a,e]pyrene	192-65-4	Caused tumors at two separate tissue sites
  Dibenzo[a,h]pyrene	189-64-0	Several routes of administration and exposure resulted in tumors
  Dibenzo[a,i]pyrene	189-55-9	Tumors resulted from studies of different routes of administration and exposure
  Dibenzo[a,l]pyrene	191-30-0	Caused tumors at two different tissue sites, by two routes of exposure
  Indeno[1,2,3-cd]pyrene	193-39-5	Caused tumors at two different tissue sites and by two different avenues of exposure
  5-Methylchrysene	3697-24-3	Administration resulted in tumors at two tissue sites and by two separate routes of exposure

  Nitroarenes are a large class of structurally related chemicals found in particulate emissions from a variety of combustion sources, most notably, diesel exhausts. These molecules are nitro-substituted derivatives of PAHs. Both 1,6-Dinitropyrene and 1,8-Dinitropyrene are reasonably anticipated to be human carcinogens based on sufficient evidence in experimental animals.

  List of Report on Carcinogens (RoC) Nitroarene Studies

  Report	CASRN	Results
  1,6-Dinitropyrene	42397-64-8	1,6-Dinitropyrene evidenced genotoxicity in a wide variety of bacteria and mammalian cells. Exposure resulted in gene mutations and tumors among experimental animals.
  1,8-Dinitropyrene	42397-65-9	1,8-Dinitropyrene evidenced genotoxicity in a wide variety of bacteria and mammalian cells. Exposure resulted in tumors in experimental animals.

• PAH Studies on Inflammation and Atherosclerosis

  PAH Studies on Inflammation and Atherosclerosis

  NTP is conducting a systematic review to evaluate whether environmental substances contribute to inflammation that leads to atherosclerosis and to evaluate key biomarkers of the associated inflammation. During scoping activities, polycyclic aromatic hydrocarbons were identified as a potential focus for the evaluation.

NTP Future Research

In the future, NTP will design experiments to see if we can predict the toxicity of PAC mixtures using our understanding of individual PACs. Data will also be gathered on environmental mixtures that contain PACs and used to predict the toxicity of untested mixtures.

Results from PAC-MAP will help address knowledge gaps identified in the 2011 NIEHS workshop Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health Effects.

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