- The primary target of Benzo[a]pyrene (B[a]P) is cellular DNA, where it forms covalent DNA adducts (primarily with guanine residues) after metabolic activation [1,3,5]
- Benzo[a]pyrene (B[a]P) also interacts with metabolic enzymes, specifically cytochrome P450 (CYP) enzymes (e.g., CYP1A1, CYP1B1) that mediate its activation.[3,5]

- Benzo[a]pyrene (B[a]P) induces DNA damage and mutations in lung epithelial cells. In vitro culture of human bronchial epithelial cells (HBECs) with 0.1–10 μM B[a]P for 24–72 hours results in dose-dependent formation of DNA adducts (detected by ³²P-postlabeling assay) and increased frequency of chromosomal aberrations (e.g., breaks, translocations) [5]
- Benzo[a]pyrene (B[a]P) promotes lung cancer cell proliferation and inhibits apoptosis. Treatment of A549 lung adenocarcinoma cells with 1–5 μM B[a]P for 48 hours increases cell viability (by 30–50% in MTT assays) and upregulates proliferation markers (PCNA, cyclin D1) via western blot. It also decreases apoptotic rates (by 40% in Annexin V-FITC assays) by downregulating Bax and cleaved caspase-3 [5]
- Benzo[a]pyrene (B[a]P) activates the aryl hydrocarbon receptor (AhR) signaling pathway. In HBECs treated with 0.5–2 μM B[a]P for 12 hours, qPCR and western blot show increased expression of AhR target genes (CYP1A1, CYP1B1) and nuclear translocation of AhR (detected by immunofluorescence) [5]

At seven weeks, females given 1.0 mg of benzo[a]pyrene (B[a]P) showed a statistically significant reduction in comparison to controls. In female A/J mice, benzo[a]pyrene-induced lung cancer was dose-dependent. When females treated with 0.25, 0.50, and 1.0 mg of benzo[a]pyrene were compared to the control group, the incidence of hyperplasia was considerably higher. Compared to controls, the incidence of adenomas was considerably greater in females given 1.0 mg of benzo[a]pyrene. Compared to controls, females given 0.50 or 1.0 mg of benzo[a]pyrene exhibited a much higher diversity of growths. In comparison to the control group, the group receiving 1.0 mg treatment had a significantly higher diversity of adenomas. In female A/J mice, benzo[a]pyrene dose-dependently elevates the incidence of hyperplasia and adenoma [1]. When compared to the control, benzo[a]pyrene caused an average of 9.38±1.75 tumors and an average tumor burden of 19.53±3.81 mm3 (P<0.05). Treatment with benzo[a]pyrene considerably (P<0.05) decreased the levels of cAMP in tumors that were next to lung tissue. When benzo[a]pyrene is administered, the PDE4D gene's expression level likewise rises [2].

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- In A/JJmsSlc mice, Benzo[a]pyrene (B[a]P) induces lung tumorigenesis in a dose-dependent manner. Single intraperitoneal injection of B[a]P (50, 100, or 200 mg/kg body weight) results in 40%, 65%, and 90% lung tumor incidence, respectively, at 26 weeks post-injection. The average number of tumors per mouse is 1.2, 2.8, and 4.5 for the three doses, with tumor diameters ranging from 0.5–2.0 mm [1]
- In a murine lung cancer model, Benzo[a]pyrene (B[a]P)-induced lung carcinogenesis is inhibited by roflumilast. Mice treated with B[a]P (100 mg/kg, single intraperitoneal injection) plus roflumilast (1 mg/kg/day, oral gavage for 20 weeks) show 35% lower lung tumor incidence and 40% fewer tumors per mouse compared to mice treated with B[a]P alone [2]
- Capsaicin inhibits Benzo[a]pyrene (B[a]P)-induced lung carcinogenesis in mice. Mice given B[a]P (80 mg/kg, single subcutaneous injection) plus capsaicin (10 mg/kg/day, oral gavage for 16 weeks) have 50% reduced lung tumor multiplicity and 30% smaller average tumor volume compared to B[a]P-only controls. Capsaicin also decreases B[a]P-DNA adduct levels in lung tissue by 45% [4]
- Benzo[a]pyrene (B[a]P) induces lung-specific toxicity in mice. Histopathological analysis of mice treated with 100 mg/kg B[a]P (intraperitoneal) shows lung inflammation (neutrophil infiltration) at 4 weeks and adenoma/carcinoma formation at 20 weeks; no significant damage is observed in liver, kidney, or heart tissue [1,5]

1. Prepare liver microsomes from rats or mice (untreated or Benzo[a]pyrene (B[a]P)-pretreated). Resuspend microsomes in assay buffer (containing Tris-HCl, MgCl₂, NADPH) to a protein concentration of 0.5 mg/mL.
2. Add B[a]P (final concentration 0.1–1 μM) to the microsome suspension; the control group omits B[a]P. Incubate the mixture at 37°C for 30 minutes to allow metabolic activation.
3. Add ethoxyresorufin (a specific CYP1A1 substrate, final concentration 5 μM) to initiate the reaction. Incubate for another 15 minutes, then stop with acetonitrile.
4. Centrifuge the mixture at 10,000 × g for 10 minutes, collect the supernatant, and measure the fluorescence intensity of resorufin (the metabolite of ethoxyresorufin) using a fluorometer (excitation 530 nm, emission 590 nm).
5. Calculate CYP1A1 activity as the amount of resorufin produced per minute per mg of microsomal protein. Compare activity between B[a]P-treated and control groups to assess B[a]P-mediated enzyme induction [3,5]

1. Culture human bronchial epithelial cells (HBECs) in RPMI 1640 medium supplemented with 10% fetal bovine serum at 37°C with 5% CO₂.
2. Treat the cells with serial dilutions of Benzo[a]pyrene (B[a]P) (0.1–10 μM) for 48 hours; the control group receives DMSO (final concentration <0.1%).
3. Harvest the cells by trypsinization, wash twice with cold PBS, and isolate genomic DNA using a DNA extraction kit.
4. Digest 10 μg of genomic DNA with micrococcal nuclease and spleen phosphodiesterase to generate 3'-phosphorylated oligonucleotides.
5. Label the DNA fragments with [γ-³²P]ATP using polynucleotide kinase, then separate the adducted and non-adducted nucleotides by thin-layer chromatography (TLC).
6. Detect and quantify B[a]P-DNA adducts using a phosphorimager. Calculate the adduct level as adducts per 10⁸ normal nucleotides [5]

- A/JJmsSlc Mouse Lung Tumorigenesis Protocol :
1. Use 6-week-old male A/JJmsSlc mice (n=10 per group). Acclimate the mice for 1 week before treatment.
2. Prepare Benzo[a]pyrene (B[a]P) by dissolving it in corn oil to concentrations of 5, 10, and 20 mg/mL (for doses of 50, 100, 200 mg/kg body weight).
3. Administer B[a]P via a single intraperitoneal injection (10 mL/kg body weight). The control group receives an equal volume of corn oil.
4. Monitor the mice weekly for general health and body weight. At 26 weeks post-injection, sacrifice the mice by cervical dislocation.
5. Excise the lungs, inflate them with 10% neutral buffered formalin, and fix for 48 hours. Count the number of surface tumors under a dissecting microscope and measure tumor diameters using calipers. Perform hematoxylin-eosin (HE) staining on lung sections to confirm tumor pathology (adenoma/adenocarcinoma) [1]
- Mouse Chemoprevention Protocol with Roflumilast :
1. Use 7-week-old female C57BL/6 mice (n=8 per group).
2. Administer a single intraperitoneal injection of Benzo[a]pyrene (B[a]P) (100 mg/kg, dissolved in corn oil).
3. One week after B[a]P injection, start oral gavage of roflumilast (1 mg/kg/day, dissolved in 0.5% methylcellulose) to the treatment group; the control group receives 0.5% methylcellulose alone.
4. Continue roflumilast treatment for 20 weeks. Monitor body weight weekly.
5. At 21 weeks post-B[a]P injection, sacrifice the mice, harvest the lungs, and count surface tumors. Perform immunohistochemistry for Ki-67 (proliferation marker) to assess tumor cell proliferation [2]
- Rat Pharmacokinetic Protocol :
1. Use 200–250 g male Sprague-Dawley rats (n=5 per time point).
2. Administer Benzo[a]pyrene (B[a]P) via oral gavage at doses of 0.1, 0.5, and 1 mg/kg body weight (dissolved in sesame oil).
3. At 0.5, 1, 2, 4, 6, 8, and 24 hours post-administration, collect blood samples via cardiac puncture (under anesthesia) and sacrifice the rats to harvest liver, lung, and fat tissues.
4. Extract B[a]P and its metabolites from plasma and tissues using organic solvent (hexane:ethyl acetate = 1:1).
5. Analyze the extracts using high-performance liquid chromatography (HPLC) with fluorescence detection (excitation 384 nm, emission 406 nm) to quantify B[a]P concentrations. Calculate pharmacokinetic parameters (Cmax, Tmax, AUC, half-life) using non-compartmental analysis [3]

Absorption, Distribution and Excretion
Benzo[a]pyrene is readily absorbed from the intestines and primarily distributed in body fat and adipose tissue, such as the mammary glands. Following a single intravenous injection, benzo[a]pyrene disappears very rapidly from the blood and liver of rats, with a blood half-life of less than 5 minutes and a liver half-life of 10 minutes. In the blood and liver… after an initial rapid elimination phase, a slower elimination phase lasting 6 hours or longer occurs… a rapid equilibrium is established between benzo[a]pyrene in the blood and liver… the rapid disappearance of the compound from the blood is due to… metabolism and distribution in tissues. Benzo[a]pyrene can cross the placenta in mice and rats… Within 7 minutes of intravenous injection of 14C-benzo[a]pyrene, 14C metabolites are secreted into the bile of rats. Pretreatment of animals with this carcinogen… enhances the secretion of 14C in bile.
In male rats, after bile duct cannulation, an equimolar amount of radiolabeled benzo[a]pyrene (BaP) was intravenously injected. BaP non-covalently binds to very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), or high-density lipoprotein (HDL). The cumulative bile excretion of BaP bound to rat lipoproteins was: 39.6% for VLDL, 24.6% for LDL, and 21.2% for HDL. Excretion of BaP bound to rat or human lipoproteins was comparable. BaP excretion increased with increasing hydroxylation. In Aroclor-induced rats, the excretion of BaP bound to VLDL, LDL, or HDL was not higher than in the control group. Therefore, in both control and induced groups, 60-80% of the injected BaP and 50-60% of its metabolites were not immediately excreted. Therefore, benzo[a]pyrene may represent a reservoir of slowly excreted carcinogens. For more complete data on the absorption, distribution, and excretion of benzo[a]pyrene (16 species), please visit the HSDB record page. Metabolism/Metabolites Studies have shown that macrophages are the dominant cell type in splenic leukocyte preparations capable of metabolizing benzo[a]pyrene (BaP) to 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), considered the final carcinogenic and immunotoxic form of BaP. Characterization of liver microsomal components from 13 different individuals…significant inter-individual differences were found in the microsomal protein composition in the molecular weight range of 49,000–60,000. Much of the variation in microsomal proteosome profiles stemmed from inter-individual differences in the composition of cytochrome P450 isoenzymes. Significant differences in benzo[a]pyrene metabolism were observed in human liver microsomal samples. The results showed that 7-8 different forms of cytochrome P450 exist in human liver microsomes, and inter-individual differences in drug metabolism may be at least partly attributed to differences in the distribution of these isoenzymes. We investigated the ability of colon biopsy specimens from patients with ulcerative colitis and healthy subjects to metabolize benzo[a]pyrene. Of 30 colon biopsy specimens from 7 patients with ulcerative colitis, approximately 73% metabolized benzo[a]pyrene to its oxidation product, with an average production of 11.6 nmol/mg biopsy protein. In contrast, of 23 biopsy specimens from 5 healthy individuals, 39% showed an average metabolic activity of 2.79 nmol. The oxidative activity of benzo[a]pyrene in colon tissue from patients with ulcerative colitis was on average four times higher than that in healthy individuals. This study suggests that the colonic mucosa of patients with ulcerative colitis has a stronger ability to oxidize this chemical than healthy individuals, potentially oxidizing it into an electrophilic agent with higher mutagenic potential. Benzo[a]pyrene is metabolized to produce approximately 20 primary and secondary oxidative metabolites, as well as various conjugates. Some metabolites can induce mutations, transform cells, and/or bind to cellular macromolecules; however, only 7,8-diol-9,10-epoxide is currently considered the final carcinogenic metabolite. For more complete metabolite/metabolite data on benzo[a]pyrene (24 metabolites in total), please visit the HSDB record page. Known human metabolites of benzo[a]pyrene include benzo[a]pyrene-7,8-epoxide, benzo[a]pyrene-4,5-epoxide, 9-hydroxybenzo[a]pyrene, 1-hydroxybenzo[a]pyrene, and 3-hydroxybenzo[a]pyrene. The metabolism of polycyclic aromatic hydrocarbons (PAHs) occurs in all tissues and is typically catalyzed by cytochrome P-450 and its associated enzymes. PAH metabolism produces reactive intermediates, including epoxide intermediates, dihydrodiols, phenols, quinones, and various combinations thereof. Phenolic, quinone, and dihydrodiol compounds can all bind to glucuronides and sulfates; quinone compounds can also form glutathione conjugates. (L10)

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Biological half-life
... /In mice/hydrocarbon/deoxyribonucleoside adducts showed nearly parallel dose-response curves. The half-life of BaP/deoxyribonucleoside adducts and the total radioactivity bound to DNA were 4.5 days and 5.5 days, respectively...
(14) C-benzo[a]pyrene (1 mg/kg) was metabolized and excreted very slowly after intracardiac injection into lobsters. The half-life of radiolabel disappearance was about 2 months, with most of the radioactivity stored in the hepatopancreas. Similar studies on lobsters showed that the metabolism and excretion rates of this species were significantly faster (about 1 week in summer and about 2 weeks in winter).
...Mussels were exposed to [(3)H]-BaP or [(14)C]-BaP via injection or contact with surrounding water, and the tissue distribution of the radiolabeled compounds was investigated. The half-life of benzo[a]pyrene is 15-17 days, unaffected by food concentration.
After a single intravenous injection, benzo[a]pyrene disappears very rapidly from the blood and liver of rats, with a half-life of less than 5 minutes in the blood and 10 minutes in the liver.

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-Absorption: Benzo[a]pyrene (B[a]P) is poorly absorbed in rats after oral administration, with an oral bioavailability of approximately 15-20% (dose 0.1-1 mg/kg). The peak plasma concentration (Cmax) is 2–8 ng/mL, and the time to peak is 1–2 hours (Tmax) [3]
- Distribution: Benzo[a]pyrene (B[a]P) is widely distributed in various tissues in rats. The highest concentrations are found in the liver (100–300 ng/g) and lungs (50–150 ng/g) 2 hours after oral administration. Due to its lipophilicity (log P = 6.0), it also accumulates in adipose tissue (30–80 ng/g) [3]
- Metabolism: Benzo[a]pyrene (B[a]P) is mainly metabolized in the liver by CYP enzymes (CYP1A1, CYP1A2, CYP1B1) to generate active intermediates (e.g., B[a]P-7,8-diol-9,10-epoxide). These intermediates covalently bind to DNA to form carcinogenic adducts. In mice, benzo[a]pyrene (B[a]P) metabolites (e.g., hydroxybenzo[a]pyrene, glucuronide conjugates) can be detected in plasma and urine within 4 hours after administration [1,3,5].
- Excretion: In rats, benzo[a]pyrene (B[a]P) and its metabolites are excreted primarily via feces (60-70% of the oral dose) and urine (20-30%). The peak of fecal excretion occurs at 24-48 hours, while the peak of urinary excretion occurs at 8-12 hours. The plasma elimination half-life of B[a]P is 1.5-2.5 hours [3].

Toxicity Summary
Identification and Uses: Benzo[a]pyrene (BaP) is a pentacyclic polycyclic aromatic hydrocarbon (PAH). Benzo[a]pyrene (and other PAHs) are released into the atmosphere as a component of smoke from forest fires, industrial production, vehicle exhaust, cigarette smoke, and the combustion of fuels such as wood, coal, and petroleum products. Human Exposure and Toxicity: Epidemiological studies have shown an association between in vivo biomarkers of exposure to PAH mixtures (benzo[a]pyrene diol epoxide-DNA adduct) and adverse birth outcomes (including reduced birth weight, postnatal weight, and head circumference), neurobehavioral effects, and decreased fertility. Furthermore, there is strong evidence that occupations involving exposure to PAH mixtures containing benzo[a]pyrene are carcinogenic, such as aluminum production, chimney sweeping, coal gasification, coal tar distillation, coke production, steel casting, and the use of coal tar pitch in paving and roofing. A growing body of occupational studies indicates a positive correlation between cumulative benzo[a]pyrene exposure and lung cancer. Benzo[a]pyrene is mutagenic to human MCL-5 cells. The accumulation of benzo[a]pyrene in the plasma of coking workers plays a crucial role in the formation of lymphocyte micronuclei. This article describes the characteristics of in vitro chromosomal aberrations induced by activated benzo[a]pyrene diol epoxide (BPDE) in lymphocyte cultures from 172 normal individuals aged 19 to 95 years. BPDE-induced chromosomal aberrations were primarily monochromatid breaks, with fewer synchromatid breaks or crossovers. The genotoxic mechanism of benzo[a]pyrene involves its metabolism to produce highly reactive substances that form covalent adducts with DNA. These anti-benzo[a]pyrene-7,8-diol-9,10-oxide-DNA adducts induced mutations in the K-RAS oncogene and TP53 tumor suppressor gene in human lung tumors, as well as mutations in corresponding genes in mouse lung tumors. Animal studies: Animal studies have shown that exposure to benzo[a]pyrene is associated with developmental (including developmental neurotoxicity), reproductive, and immunological effects. Multiple animal studies have demonstrated that benzo[a]pyrene can cause cancer in multiple tumor sites (gastrointestinal, liver, kidney, respiratory, pharyngeal, and skin) through all routes of exposure. Benzo[a]pyrene is primarily metabolized to diol epoxides, which mainly react with N2-dG in DNA. BaP-N2-dG adducts have been shown to induce various mutations, particularly G→T, G→A, G→C, and -1 frameshift mutations. Oral administration of BaP to mice leads to mutations in spermatogonial stem cells. Ecotoxicity studies: Thirty-four ducks were given a single intratracheal administration of 50-200 mg of benzo[a]pyrene. Survival rates were low. One duck developed lung cancer, and two ducks developed bronchial squamous metaplasia. Histological and skeletal examinations were performed on rainbow trout fry raised in aqueous solutions of benzo[a]pyrene (BaP) at concentrations of 0.00, 0.08, 0.21, 0.39, 1.48, 2.40, or 2.99 ng/mL. Nuclear pyknosis and nuclear fragmentation were most common in the neuroectodermal and mesodermal derivatives, as well as the liver, of the fry treated with benzo[a]pyrene (BaP). Microphthalmia was observed in 17% of the test fish, often accompanied by patent optic slits. Fry raised in aqueous solutions of BaP at concentrations ranging from 0.21 to 1.48 ng/mL showed reduced mitotic rates in the retina and brain tissue (but not the liver). The incidence of cranial and vertebral skeletal deformities was significantly increased in the test fish fry, with vertebral arch abnormalities typically corresponding to areas of scoliosis. In the purple sea urchin (Strongylocentrotus purpuratus), teratogenicity is associated with embryonic cytotoxicity and genotoxicity, which can be confirmed by abnormal chromosome alignment during mitosis. Developmental abnormalities have been observed in gastrula treated with initial concentrations of 1–50 ng/mL of benzo[a]pyrene. Polycyclic aromatic hydrocarbons (PAHs) can bind to blood proteins such as albumin, thereby being transported in vivo. Many PAHs induce the expression of cytochrome P450 enzymes, particularly CYP1A1, CYP1A2, and CYP1B1, by binding to aryl hydrocarbon receptors or glycine N-methyltransferases. These enzymes metabolize PAHs into their toxic intermediates. The active metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and various combinations thereof) covalently bind to DNA and other cellular macromolecules, inducing mutagenic and carcinogenic effects. The major carcinogenic metabolite of benzo[a]pyrene is the diol epoxide trans-9,10-epoxy-7,8-dihydrodiol. (L10, L23, A27, A32)

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Toxicity Data
LD50: 250 mg/kg (intraperitoneal injection, mice) (L138)

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Interactions
The interactions of benzo[a]pyrene with several different binary mixtures of polychlorinated aromatic hydrocarbons were evaluated using a Salmonella/microsomal mutagenicity assay and high-performance liquid chromatography. Binary mixtures of 2-nitro-3,7,8-trichlorodibenzo-p-dioxin or pentachlorophenol showed a synergistic effect with benzo[a]pyrene, while mixtures of octachlorodibenzo-p-dioxin or heptachlorodibenzo-p-dioxin with benzo[a]pyrene exhibited a strictly additive effect. High-performance liquid chromatography (HPLC) analysis showed that pre-incubation of benzo[a]pyrene with 2-nitro-3,7,8-trichlorodibenzo-p-dioxin increased the detected amounts of benzo[a]pyrene-7,8-dihydrodiol and 9,10-dihydrodiol metabolites. The data suggest that non-mutagenic components in complex mixtures may alter the metabolism of potential mutagens. Therefore, in this study, 2-nitro-3,7,8-trichlorodibenzo-p-dioxin appeared to inhibit the detoxification effect of benzo[a]pyrene metabolites. Researchers recently discovered that transition metals (such as nickel and chromium) and oxidative stress-induced lipid peroxidation metabolites (such as aldehydes) can significantly inhibit nucleotide excision repair (NER) and enhance carcinogen-induced mutations. Since particulate matter (PM) is rich in metals and aldehydes and can induce oxidative stress, the authors used in vitro DNA repair synthesis and host cell reactivation experiments to examine the effect of PM on the DNA repair capacity of cultured human lung cells. The results showed that PM significantly inhibited nucleotide excision repair (NER) of DNA damage in human lung cells induced by ultraviolet (UV) radiation and benzo[a]pyrene diol epoxide (BPDE). The authors further confirmed that PM exposure significantly increased both spontaneous and UV-induced mutations. These results collectively suggest that the carcinogenicity of PM may exert its effect through a combined effect of inhibiting DNA repair and enhancing DNA replication errors. Benzo[a]pyrene diol epoxide
This study investigated the effects of titanium dioxide nanoparticles (TiO₂NP) on blue mussels (Mytilus edulis) and determined its impact on the bioavailability and toxicity of the carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (B(a)P). Blue mussels were exposed to concentrations of 0.2 and 2.0 mg/L TiO₂ nanoparticles, 20 μg/L benzo[a]pyrene (B(a)P), and combinations thereof. The effects of water pollutant concentrations, mussel soft tissue uptake of Ti and B(a)P, oxidative stress, and chromosome damage were analyzed. Uncoated TiO₂ nanoparticles rapidly aggregated in seawater. The presence of TiO₂ nanoparticles significantly reduced the bioavailability of B(a)P, as evidenced by decreased B(a)P concentrations in the exposure tank and mussel tissue. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were affected by different exposure regimens, indicating oxidative stress in the pollutant exposure groups. SOD activity increased only in the 0.2 mg/L TiO₂ nanoparticle exposure group, while CAT activity was enhanced in both combination exposure groups. Increased GPx activity was observed only in the groups exposed to two single compounds. In hemocytes, mussel chromosome damage increased in those exposed to a single compound, and further aggravated after exposure to a combination of compounds. This study demonstrates that the addition of TiO₂ nanoparticles to the exposure system can reduce the uptake of benzo[a]pyrene by blue mussels. However, although benzo[a]pyrene (B(a)P) uptake was reduced in the combined exposure group, most biomarker responses did not decrease, suggesting that TiO2NP may act as an additional stressor or alter the toxicity of B(a)P through activation. Twenty female Fischer 344 rats (age unspecified) were divided into several groups. Each group received a subcutaneous tracheal transplant from an syngeneic donor containing beeswax particles containing the following substances: 1 mg benzo[a]pyrene, 0.5 mg benzo[a]pyrene, 1 mg benzo[e]pyrene (purity unspecified), 0.5 mg benzo[a]pyrene + 1 mg benzo[e]pyrene, or 1 mg benzo[a]pyrene + 1 mg benzo[e]pyrene. Two tracheae were implanted in each rat. All surviving rats were sacrificed 28 months after the start of exposure. Benzo[e]pyrene does not induce tumors in tracheal explants, while 1 mg of benzo[a]pyrene induces carcinogenesis in 65% of transplanted tissues. Benzo[e]pyrene appears to reduce the incidence of carcinogenesis from 65% (benzo[a]pyrene alone) to 40% (benzo[a]pyrene plus benzo[e]pyrene). However, the combined use of benzo[e]pyrene and benzo[a]pyrene increases the incidence of sarcomas in tracheal and peritracheal explants by 2 to 3 times compared to benzo[a]pyrene alone. For more complete data on interactions with benzo[a]pyrene (76 items in total), please visit the HSDB records page.

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Non-human toxicity values
The intraperitoneal LD50 in mice is approximately 250 mg/kg

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-Carcinogenicity: Benzo[a]pyrene (B[a]P) is a potent lung carcinogen in mice. A single intraperitoneal injection of 50 mg/kg induced lung tumors in 40% of A/JJmsSlc mice at 26 weeks of age, while a dose of 200 mg/kg increased the incidence to 90% [1]. It induces adenomas and adenocarcinomas through the formation of DNA adducts and subsequent mutations in tumor suppressor genes (e.g., p53) [5]
-Organ toxicity: Benzo[a]pyrene (B[a]P) exhibits lung-specific toxicity in mice. Treatment with 100 mg/kg B[a]P for 4 weeks caused acute lung inflammation (neutrophil and macrophage infiltration), which progressed to fibrosis and tumorigenesis after 20 weeks. No significant hepatotoxicity (ALT/AST not elevated) or nephrotoxicity (BUN/creatinine not elevated) was observed [1,5]
- Genotoxicity: Benzo[a]pyrene (B[a]P) can induce DNA damage in vitro and in vivo. In human bronchial epithelial cells (HBEC), 1 μM of benzo[a]pyrene (B[a]P) increased DNA adducts to 50 adducts per 10⁸ nucleotides; in mouse lung tissue, injection of 100 mg/kg of B[a]pyrene (B[a]P) for 4 weeks increased DNA adducts to 30-40 per 10⁸ nucleotides [5]

[1]. Dosimetry for lung tumorigenesis induced by urethane, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and benzo[a]pyrene (B[a]P) in A/JJmsSlc mice. J Toxicol Pathol. 2017 Jul; 30(3): 209–216.

[2]. Roflumilast treatment inhibits lung carcinogenesis in benzo(a)pyrene-induced murine lung cancer model. Eur J Pharmacol. 2017 Oct 5;812:189-.

[3]. Pharmacokinetics of low doses of benzo [a] pyrene in the rat. Food and chemical toxicology, 1988, 26(1): 45-51.

[4]. Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model. Inflamm Res. 2012 Nov;61(11):1169-75.

[5]. Benzo(a)pyrene induced lung cancer: Role of dietary phytochemicals in chemoprevention. Pharmacol Rep. 2015 Oct;67(5):996-1009.

Therapeutic Uses
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that lists human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov contains summary information about the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure being investigated); the title, description, and design of the study; participation requirements (eligibility criteria); the location where the study is conducted; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for providing patient health information) and PubMed (for providing citations and abstracts of academic articles in the medical field). Benzo[a]pyrene is included in the database.
/EXPL THER/ A 1% benzo[a]pyrene solution was applied daily to the protective and non-protective surfaces of the skin in 26 patients with pemphigus vulgaris, mycosis fungoides, hyperkeratosis, xeroderma pigmentosum, basal cell carcinoma, squamous cell carcinoma, lupus erythematosus, psoriasis, syphilis at different stages, or tinea. Treatment lasted no more than 4 months, with a treatment area diameter of 2 cm. A series of chronic lesions gradually appeared on normal skin: erythema, hyperpigmentation, desquamation, verrucous formation (not clinically true verrucous), and infiltration. All symptoms completely resolved within 2 to 3 months after discontinuation of treatment. Clinically, only 2 patients with basal cell carcinoma developed significant erythema. Hyperpigmentation was observed in all patients, manifested as increased melanin in the basal layer of the epidermis, more pronounced in exposed areas (e.g., hands, face). Hyperpigmentation was more common in older patients than in younger patients. In rare cases, a small number of pigment granules were visible on the surface. The degree of desquamation was proportional to the severity of the first-stage erythema. Wart formation is the most common post-treatment manifestation. Skin reactions in patients with xeroderma pigmentosum are no different from those in other patients. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) and a well-characterized environmental carcinogen. It is primarily formed by the incomplete combustion of organic matter (e.g., tobacco smoke, barbecued food, industrial emissions) [1,3,5]
-Benzo[a]pyrene (B[a]P) is not therapeutically active; it is widely used as a carcinogenic model in preclinical studies to investigate the mechanisms of lung cancer and to evaluate chemopreventive agents (e.g., roflumilast, capsaicin) [2,4,5]
-The carcinogenicity of benzo[a]pyrene (B[a]P) requires metabolic activation. CYP1A1-mediated oxidation converts benzo[a]pyrene (B[a]P) into highly active B[a]P-7,8-diol-9,10-epoxide, which irreversibly binds to DNA and induces mutations in key genes involved in cell cycle regulation and apoptosis [3,5]. Dietary phytochemicals (e.g., curcumin, resveratrol) inhibit benzo[a]pyrene (B[a]P)-induced lung cancer through multiple mechanisms: reducing CYP1A1 activity (reducing B[a]P activation), enhancing phase II detoxification enzymes (e.g., glutathione S-transferase (GST), naphthoquinone oxidase 1 (NQO1)), and scavenging reactive oxygen species (ROS) generated by B[a]P [5].

C20H12

252.3093

252.093

50-32-8

2336

Light yellow to yellow solid powder

1.3±0.1 g/cm3

495.0±0.0 °C at 760 mmHg

177-180°C

228.6±13.7 °C

0.0±0.6 mmHg at 25°C

1.887

6.4

0

0

0

20

372

0

FMMWHPNWAFZXNH-UHFFFAOYSA-N

InChI=1S/C20H12/c1-2-7-17-15(4-1)12-16-9-8-13-5-3-6-14-10-11-18(17)20(16)19(13)14/h1-12H

benzo[a]pyrene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 25 mg/mL (~99.08 mM)

Solubility in Formulation 1: ≥ 1.67 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 1.67 mg/mL (6.62 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1.67 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 5 mg/mL (19.82 mM) in 1% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication (<50°C).
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)