Benzo[''a'']pyrene (BaP or B[a]P) is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between 300°C and 600°C. The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, especially grilled meats. The substance with the formula C20H12 is one of the benzopyrenes, formed by a benzene ring fused to pyrene. Its diol epoxide metabolites, more commonly known as BPDE, react with and bind to DNA, resulting in mutations and eventually cancer. It is listed as a Group 1 carcinogen by the IARC. In the 18th century a scrotal cancer of chimney sweepers, the chimney sweeps' carcinoma, was already known to be connected to soot.
Benzo[''a'']pyrene (BaP) is a polycyclic aromatic hydrocarbon found in coal tar with the formula C20H12. The compound is one of the benzopyrenes, formed by a benzene ring fused to pyrene, and is the result of incomplete combustion at temperatures between 300°C and 600°C.
The main source of atmospheric BaP is residential wood burning.[1] It is also found in coal tar, in automobile exhaust fumes (especially from diesel engines), in all smoke resulting from the combustion of organic material (including cigarette smoke), and in charbroiled food.A 2001 National Cancer Institute study found levels of BaP to be significantly higher in foods that were cooked well-done on the barbecue, particularly steaks, chicken with skin, and hamburgers: Cooked meat products have been shown to contain up to 4 ng/g of BaP,[2] and up to 5.5 ng/g in fried chicken[3] and 62.6 ng/g in overcooked charcoal barbecued beef.[4]
BaP is discharged in wastewater by industries such as smelters, particularly iron and steel mills[5] and aluminium smelters.[6]
In the 18th century, young British chimney sweeps who climbed into chimneys suffered from chimney sweeps' carcinoma, a scrotal cancer peculiar to their profession, and this was connected to the effects of soot in 1775,[7] in the first work of occupational cancer epidemiology and also the first connection of any chemical mixture to cancer formation. Frequent skin cancers were noted among fuel industry workers in the 19th century. In 1933, BaP was determined to be the compound responsible for these cases, and its carcinogenicity was demonstrated when skin tumors occurred in laboratory animals repeatedly painted with coal tar.[8] BaP has since been identified as a prime carcinogen in cigarette smoke.[9]
Prenatal exposure of BaP in rats is known to affect learning and memory in rodent models. Pregnant rats eating BaP were shown to negatively affect the brain function in the late life of their offspring. At a time when synapses are first formed and adjusted in strength by activity, BaP diminished NMDA receptor-dependent nerve cell activity measured as mRNA expression of the NMDA NR2B receptor subunit.[10]
BaP has an effect on the number of white blood cells, inhibiting some of them from differentiating into macrophages, the body's first line of defense to fight infections. In 2016, the molecular mechanism was uncovered as damage to the macrophage membrane's lipid raft integrity by decreasing membrane cholesterol at 25%. This means less immunoreceptors CD32 (a member of the Fc family of immunoreceptors) could bind to IgG and turn the white blood cell into a macrophage. Therefore, macrophage membranes become susceptible to bacterial infections.[11]
In experiments with male rats, subchronic exposure to inhaled BaP has been shown to generally reduce the function of testicles and epididymis with lower sex steroid/testosterone production and sperm production.[12]
BaP's metabolites are mutagenic and highly carcinogenic, and it is listed as a Group 1 carcinogen by the IARC. Chemical agents and related occupations, Volume 10, A review of Human Carcinogens, IARC Monographs, Lyon France 2009 [13]
In June 2016, BaP was added as benzo[''def'']chrysene to the REACH Candidate List of Substances of very high concern for Authorisation.[14]
Numerous studies since the 1970s have documented links between BaP and cancers.[15] It has been more difficult to link cancers to specific BaP sources, especially in humans, and difficult to quantify risks posed by various methods of exposure (inhalation or ingestion).[16] A link between vitamin A deficiency and emphysema in smokers was described in 2005 to be due to BaP, which induces vitamin A deficiency in rats.[17]
A 1996 study provided molecular evidence linking components in tobacco smoke to lung cancer. BaP was shown to cause genetic damage in lung cells that was identical to the damage observed in the DNA of most malignant lung tumours.[18]
Regular consumption of cooked meats has been epidemiologically associated with increased levels of colon cancer[19] (although this in itself does not prove carcinogenicity),[20] A 2005 NCI study found an increased risk of colorectal adenomas was associated with BaP intake, and more strongly with BaP intake from all foods.[21]
The detoxification enzymes cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) are both protective and necessary for benzo[''a'']pyrene toxicity. Experiments with strains of mice engineered to remove (knockout) CYP1A1 and CYP1B1 reveal that CYP1A1 primarily acts to protect mammals from low doses of BaP, and that removing this protection accumulates large concentrations of BaP. Unless CYP1B1 is also knocked out, toxicity results from the bioactivation of BaP to benzo[''a'']pyrene -7,8-dihydrodiol-9,10-epoxide, the ultimate toxic compound.[22]