5-메톡시소라렌

log Kow = 2.0

2.0

less than 1 mg/mL at 66 °F (NTP, 1992)

In water, 5 ug/mL

Practically insoluble in boiling water

Slightly soluble in glacial acetic acid, chloroform, benzene, warm phenol; soluble in absolute alcohol: 1 part in 60

Hazardous decomposition products formed under fire conditions. - Carbon oxides

When heated to decomposition it emits acrid smoke and irritating fumes.

370 °F (sublimes) (NTP, 1992)

188 °C (sublimes)

188 °C

Grayish-white microcrystalline powder or yellow fluffy solid. (NTP, 1992)

Grayish-white or yellow solid; [CAMEO] White powder; [MSDSonline]

Solid

Danger

H317 (43.7%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P318, P321, P333+P317, P342+P316, P362+P364, P403, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 71 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

Hazard Traits - Carcinogenicity

Regulation (EC) No 1831/2003 (amended)

SYMPTOMS: Symptoms of exposure to this compound include erythema, marked pigmentation, dermatitis, patchy hyperpigmentation of the face and neck, and keratomas or epitheliomas of the skin. Corrosion may occur. It may also cause phototoxic reactions of the skin. Symptoms of exposure to a related compound include extreme destruction of tissue of the mucous membranes and upper respiratory tract, eyes and skin, photosensitization, burning sensation, coughing, wheezing, laryngitis and shortness of breath. Inhalation may be fatal as a result of spasm, inflammation and edema of the larynx and bronchi, chemical pneumonitis and pulmonary edema. Other symptoms include headache, nausea, vomiting and allergic skin reactions. It has also caused dizziness, nervousness, insomnia, pruritus, mental excitation, mental depression, acute vesicular cutaneous photosensitization, blistering and, rarely, hypertrichosis, hyperpigmentation, cataracts, liver injury, onycholysis, nail pigmentation, bullous pemphigoid and acneform eruptions. Chronic exposure may cause alteration of genetic material.

A phototoxic agent; Emergency treatment: Psoralens; Combining psoralens and UV light is called PUVA therapy; Therapeutic doses are 0.6 mg/kg; Toxic hepatitis has been reported after PUVA therapy; [HSDB] An irritant; Effects in high-dose animal studies include, convulsions, photosensitivity (after systemic exposure), and hepatitis; May cause cancer; May cause heritable genetic damage; [MSDSonline]

Skin Sens. 1 (43.7%)

Germ cell mutagenicity - Category 2

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Keep container tightly closed in a dry and well-ventilated place. Light sensitive. Store under inert gas. Keep in a dry place. Storage class (TRGS 510): 6.1D: Non-combustible, acute toxic Cat.3 / toxic hazardous materials or hazardous materials causing chronic effects

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for 5-Methoxypsoralen (7 total), please visit the HSDB record page.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for 5-Methoxypsoralen (14 total), please visit the HSDB record page.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Sunscreens containing 5-methoxypsoralen (5-MOP) are being promoted commercially to incr suntanning & sun protection. The sunscreen, Sun System III (SS III) which contains 5-MOP plus 20 Joules/sq cm of UV radiation (UVA) caused erythema & delayed pigmentation in the skin. No photoxicity was seen unless the solar simulator output was filtered through water to reduce infrared radiation. This indicates that cutaneous phototoxic reactions to 5-MOP plus UVA are diminished by heat. Use of phototoxic psoralens in sunscreens is inappropriate because of the risk of incr uv-induced skin cancer.

PURPOSE: This study was designed to investigate the potential effect of bergapten on lipopolysaccharide (LPS)-mediated osteoclast formation, bone resorption and osteoclast survival in vitro. METHODS: After osteoclast precursor RAW264.7 cells were treated with bergapten (5, 20, 40 umol/L) for 72 hours in the presence of LPS (100 ng/mL), osteoclastogenesis was identified by tartrate-resistant acid phosphatase (TRAP) staining, and the number of TRAP-positive multinucleated cells [TRAP(+)MNCs] per well were counted. To investigate the effect of bergapten on osteoclastic bone resorption, RAW264.7 cells were treated with bergapten for six days in the presence of LPS, and the area of bone resorption was analyzed with Image Pro-Plus. Next, we examined apoptosis of RAW264.7 cells after bergapten incubation for 48 hours by flow cytometer using annexin V/propidium iodide (PI) double labeling. Finally, osteoclast survival was observed by Hoechst 33342 labeling and Western blotting after bergapten treatment for 24 hours. RESULTS: Data showed that bergapten (5-40 umol/L) dose-dependently inhibited LPS-induced osteoclast formation and bone resorption. Treatment with bergapten triggered apoptotic death of osteoclast precursor RAW264.7 cells in a dose-dependent manner. Furthermore, bergapten significantly reduced the survival of mature osteoclast, as demonstrated by emergence of apoptotic nuclei and activation of apoptotic protein caspase 3/9. CONCLUSIONS: These findings suggest that bergapten effectively prevents LPS-induced osteoclastogenesis, bone resorption and survival via apoptotic response of osteoclasts and their precursors. The study identifies bergapten as an inhibitor of osteoclast formation and bone resorption and provides evidence that bergapten might be beneficial as an alternative for prevention and treatment of inflammatory bone loss.

PURPOSE: Melanoma is an aggressive form of skin cancer. The aim of the study was to evaluate the influence of UVA radiation and psoralens: 5-methoxypsoralen (5-MOP) or 8-methoxypsoralen (8-MOP) on melanoma cells viability. MATERIALS AND METHODS: The amelanotic C32 and melanotic COLO829 human melanoma cell lines were exposed to increasing concentrations of psoralens (0.1-100 uM) in the presence or absence of UVA radiation. Cell viability was evaluated by the WST-1 assay. RESULTS: We demonstrated that 8-MOP, in contrast to 5-MOP, has no cytotoxic effect on both melanoma cell lines. Simultaneous exposure of cells to 8-MOP and UVA radiation caused significant cytotoxic response in C32 cells where the EC50 value was estimated to be 131.0 uM (UVA dose: 1.3 J/sq cm) and 105.3 uM (UVA dose: 2.6 J/cm2). The cytotoxicity of 5-MOP on both C32 and COLO829 cells was significantly augmented by UVA radiation - the EC50 was estimated to be 22.7 or 7.9 uM (UVA dose: 1.3 J/sq cm) and 24.2 or 7.0 uM (UVA dose: 2.6 J/sq cm), respectively. CONCLUSIONS: The demonstrated high cytotoxic response after simultaneous exposure of melanoma cells to psoralens and UVA radiation in vitro suggests the usefulness of PUVA therapy to treat melanoma in vivo.

AIM: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses. METHODS: C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg. The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP. Twenty-four hours after APAP administration, blood samples of mice were analyzed for serum enzyme alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) levels, and malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of liver tissues were measured and histopathologic changes of the liver were observed. RESULTS: Compared with the vehicle control group, the serum levels (IU/L) of ALT, AST and LDH were all increased significantly in APAP group (8355 +/- 3940 vs 30 +/- 21, P < 0.05; 6482 +/- 4018 vs 146 +/- 58, P < 0.05; 24627 +/- 10975 vs 1504 +/- 410, P < 0.05). Compared with APAP group, the serum ALT levels (IU/L) (1674 +/- 1810 vs 8355 +/- 3940, P < 0.05; 54 +/- 39 vs 8355 +/- 3940, P < 0.05; 19 +/- 9 vs 8355 +/- 3940, P < 0.05), AST levels (IU/L) (729 +/- 685 vs 6482 +/- 4108, P < 0.05; 187 +/- 149 vs 6482 +/- 4108, P < 0.05; 141 +/- 12 vs 6482 +/- 4108, P < 0.05) and LDH levels (IU/L) (7220 +/- 6317 vs 24 627 +/- 10 975, P < 0.05; 1618 +/- 719 vs 24 627 +/- 10 975, P < 0.05; 1394 +/- 469 vs 24 627 +/- 10 975, P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups. Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP, including hepatocellular necrosis and infiltration of inflammatory cells, and the effect was dose-dependent. MDA levels (nmol/mg) were decreased by 5-MOP in a dose-dependent manner (0.98 +/- 0.45 vs 2.15 +/- 1.07, P > 0.05; 0.59 +/- 0.07 vs 2.15 +/- 1.07, P < 0.05; 0.47 +/- 0.06 vs 2.15 +/- 1.07, P < 0.05). The pretreatment of 5-MOP could also increase the GSH/GSSG ratio (3.834 +/- 0.340 vs 3.306 +/- 0.282, P > 0.05; 5.330 +/- 0.421 vs 3.306 +/- 0.282, P < 0.05; 6.180 +/- 0.212 vs 3.306 +/- 0.282, P < 0.05). In the group treated with 5-MOP but without APAP, the serum enzyme levels, the liver histopathologic manifestation, and the values of MDA and GSH/GSSG ratio were all normal. CONCLUSION: 5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity, and does not cause liver injury at the protective doses.

For more Interactions (Complete) data for 5-Methoxypsoralen (9 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 96(SRC), determined from a log Kow of 2.0(2) and a regression-derived equation(3), indicates that 5-methoxypsoralen is expected to have high mobility in soil(SRC). Volatilization of 5-methoxypsoralen from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.0X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). 5-Methoxypsoralen is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.5X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2019).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 96(SRC), determined from a log Kow of 2.0(2) and a regression-derived equation(3), indicates that 5-methoxypsoralen is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 4.0X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). According to a classification scheme(5), an estimated BCF of 9(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2019).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 5-methoxypsoralen, which has an estimated vapor pressure of 7.5X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 5-methoxypsoralen is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 4 hours(SRC), calculated from its rate constant of 1.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Vapor-phase 5-methoxypsoralen is degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 13 hours(SRC), calculated from its rate constant of 2.1X10-17 cu cm/molecule-sec at 25 °C(SRC) derived using a structure estimation method(2). Particulate-phase 5-methoxypsoralen may be removed from the air by wet and dry deposition(SRC). 5-Methoxypsoralen absorbs UV light at wavelengths of 312 nm(2) and, therefore, is expected to be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC).

As a component of bergamot oil, 5-methoxypsoralen is present in some food products. Bergamot oil has been reported as an additive in nonalcoholic beverages (8.9 ug/g), ice cream (7.9 ug/g), sweets (27 ug/g), baked goods (29 ug/g), gelatins and puddings (ug/g), chewing-gum (ug/g) and icings (ug/g)(1).

IDENTIFICATION AND USE: 5-Methoxypsoralen (5-MOP) is a furocoumarin. As a component of bergamot oil, 5-MOP is present in some perfumes and fragrances, sunscreen preparations and food products. It has been used to promote tanning in suntan preparations. 5-MOP, in combination with UVA, is commonly used as a photochemotherapeutic agent for the treatment of psoriasis. HUMAN STUDIES: Photochemotherapy is very effective for the treatment of skin diseases such as psoriasis, as well as for the prophylactic 'hardening' therapy of patients suffering from polymorphic light eruption. The photosensitizers most widely used for oral photochemotherapy are the furocoumarins. Beside light-induced phototoxic reactions due to the photosensitizing activity of psoralens, side-effects after the oral intake of psoralens are nausea and vomiting, headaches, anxiety and sleeplessness. Anaphylaxis to 5-MOP has been reported. A 55-year-old woman with psoriasis vulgaris was treated with oral 5-MOP and UVA photochemotherapy. After 40 treatments over 3 months she became unwell with hepatitis attributable to the psoralen. 5-MOP caused chromosomal damage in human cells in vitro. ANIMAL STUDIES: When 5-MOP was given orally to beagle dogs at daily doses of 100 or 400 mg/kg (8 days), 60 mg/kg (28 days) or 48 mg/kg (26 wk), at the highest doses tested there were delayed signs of behavioral toxicity, bullous dermatitis, bilateral keratitis, decreased food consumption and decreased weight gain. The cutaneous lesions were reversible, whereas the ocular lesions were not. Hepatomegaly, necrosis and hepatic inflammation occurred in the 48-mg/kg dose group. 5-MOP plus UVA and 12-O-tetradecanoylphorbol 13-acetate induced skin carcinomas in mice. Rats were dosed daily with 5-MOP (75 or 150 mg/kg, p.o.), or vehicle control. Treated males had significantly smaller pituitary glands, fewer sperm per ejaculate, and fewer sperm in the vasa deferentia and epididymides than controls. Dosing significantly elevated levels of testosterone and increased relative testis weight, but did not directly affect testicular weight. Females bred to dosed males required more time to become pregnant, and these males required more breeding attempts. Female rabbits were given 5-MOP orally at daily doses of 0, 70 or 560 mg/kg bw on days 7-18 of gestation. With 560 mg/kg, there was maternal toxicity and a dose-dependent increase in fetal abnormalities. 5-MOP formed a noncovalently-bound complex with DNA in vitro in the dark. It photobound covalently to DNA in vitro in Saccharomyces cerevisiae and in Chinese hamster V79 cells. It photoinduced interstrand cross-links in DNA in vitro and in Chinese hamster V79 cells. 5-MOP alone was reported to be mutagenic to Salmonella typhimurium TA100 in the presence or absence of metabolic activation and to Escherichia coli lac- z (ND160). 5-MOP plus UVA reduced survival of repair-deficient mutants of Bacillus subtilis and E. coli, addition of metabolic activator inhibited the lethal activity.

5-Methoxypsoralen naturally occurs in plants and plant extracts of Angelica seed and root (Ammi majus), bergamot oil (Citrus bergamia), celery, (Apium graveolins), Lime oil (C. Aurantifolia), and parsnip (Pastinaca sativa) at concentrations of 400, 1000, 1100-1500, 0-3700, 3000-3900, 0.04-0.69, 1700-3300, and 3-4 ug/g, respectively(1).

Bioassay guided fractionation of an antimycobacterial extract of Arracacia tolucensis var. multifida (Umbelliferae) led to the isolation of isoimperatorin (1), osthol (2), suberosin (3), 8-methoxypsoralen (8-MOP) (4), herniarin (5), scoparone (6), umbelliferone (7), dihydroxypeucedanin (8), 5-methoxypsoralen (5-MOP) (9), isoscopoletin (10) and scopoletin (11).

5-Methoxypsoralen concentrations in various plants(1).

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for 5-methoxypsoralen is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

The Koc of 5-methoxypsoralen is estimated as 96(SRC), using a log Kow of 2.0(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 5-methoxypsoralen is expected to have high mobility in soil.

5-Methoxypsoralen is a naturally occurring analog of psoralen and isomer of methoxysalen found in a various plants(1). 5-Methoxypsoralen has been isolated from oil of bergamot Citrus bergamia and Fagara xanthoxyloides(1). Furocoumarins including 5-methoxypsoralen are reported in the essential oil of bergamot oil at approximately 0.4%(2). 5-Methoxypsoralen is found in oil of bergamot, which is derived from the rind of the orange-like Mediterranean fruit Citrus bergamia; natural bergamot oil typically contains 3000-3900 ug/g 5-methoxypsoralen(3). 5-Methoxypsoralen naturally occurs in plants and plant extracts of Angelica seed and root, ammi majus, celery, (Apium graveolins), Lime oil, and parsnip (Pastinaca sativa)(3).

/HUMAN EXPOSURE STUDIES/ ... In comparative clinical trials of parallel design, psoriasis clearance rates of > 90% or > 97% were observed in similar numbers of patients (60 to 77%) receiving oral PUVA 5-methoxypsoralen (typically 1.2 mg/kg) or oral PUVA 8-methoxypsoralen (0.6 mg/kg) treatment. ... The incidence and severity of adverse events was generally lower in PUVA 5-methoxypsoralen 1.2 mg/kg than in PUVA 8-methoxypsoralen 0.6 mg/kg recipients. Nausea and/or vomiting, pruritus and erythema were the most commonly reported adverse events in the short term; they occurred about 2 to 11 times more frequently in 8-methoxypsoralen than 5-methoxypsoralen recipients within clinical trials. Adverse hepatic events after oral administration of the drug were uncommon. Long term tolerability data for PUVA 5-methoxypsoralen are scarce; however, carcinogenicity was not reported during a 14-year observation period of 413 patients with psoriasis. ...

/HUMAN EXPOSURE STUDIES/ Application of 4-200 ug/2.5 sq cm 5-methoxypsoralen to human skin and irradiation with UVA induced erythema 22 min to 36 hr after irradiation, followed by marked pigmentation 7 to 15 days later ... .

/HUMAN EXPOSURE STUDIES/ ... Performed photoepicutaneous tests with psoralens isolated from the umbelliferous plant Heracleum laciniatum on normal volunteers. 5-Methoxypsoralen was the most strongly phototoxic, being active at 0.001% in ethanol. Reactions reached their max 75 hr after exposure. The action spectrum of 5-methoxypsoralen was determined, and max photosensitivity was seen at 330-335 nm. Phototoxicity could also be produced in a patient with vitiligo ... .

/SIGNS AND SYMPTOMS/ Phytophotodermatitis of Heracleum laciniatum is quite common in Tromso during the summer months. The clinical picture varies from mild to severe erythematous reactions with or without vesicles or bullae on the exposed parts of the body. Phototoxic reactions of Heracleum laciniatum are reported. The influences on phototoxic reactions by bergapten (5-methoxypsoralen) and UV-A by treating the skin with a membrane labilizing agent, dimethyl sulphoxide (DMSO), and a membrane stabilizing agent, the steroid desoximethasone, are evaluated.

For more Human Toxicity Excerpts (Complete) data for 5-Methoxypsoralen (22 total), please visit the HSDB record page.

5-Methoxypsoralen's production and use in suntan preparations(1) and its administration in photochemotherapy of psoriasis(1) may result in its release to the environment through various waste streams(SRC). 5-Methoxypsoralen has been identified as a constituent of tobacco and tobacco substitute smoke(3).

D - Dermatologicals

QD - Dermatologicals

Micronized bergapten in capsules was absorbed slowly by volunteers (time to max serum concn 3.2 hr; elim half-time about 1 hr).

When injected iv into rabbits, elim half-time 1-2 min (alpha-phase) & 15 min (beta-phase).

PURPOSE: To discuss the contribution of psoralen and bergapten metabolites on psoralens toxicity. METHODS: Computational chemistry prediction of metabolic reactions and toxicophoric groups based on the expert systems Derek and Meteor. RESULTS: a total of 15 metabolites were suggested for both psoralen and bergapten based on phase 1 and 2 biotransformations until the 3rd generation. Five toxicophoric substructures were shared among psoralen, bergapten and their corresponding metabolites; one toxicophoric marker (resorcinol) was only identified in bergapten and its biotransformation products. CONCLUSION: Although the toxic effects of psoralens are well known and documented, there is little information concerning the role of their metabolites in this process. We believe this work add to the knowledge of which molecular substructures are relevant to the process of metabolism and toxicity induction, thus guiding the search and development of more effective and less toxic drugs to treat vitiligo.

A number of studies have demonstrated that cytochrome P450 (P450) converts furanocoumarin derivatives into reactive molecules, which form covalent bonds to biomolecules. 5-Methoxypsoralen (5-MOP) is a natural furanocoumarin from apiaceous plants. In this study, we examined the effect on 5-MOP metabolism of single nucleotide polymorphisms (SNPs) in CYP2A13. We used Escherichia coli-generated recombinant enzymes of wild-type CYP2A13*1 and five variants, CYP2A13*4 (R101Q), CYP2A13*5 (F453Y), CYP2A13*6 (R494C), CYP2A13*8 (D158E), and CYP2A13*9 (V323L). In high-performance liquid chromatography analyses of 5-MOP metabolic products, CYP2A13*1 converted 5-MOP into 5-MOP dihydrodiol; K(m) and V(max) values of the reaction were 1.44 +/- 0.17 uM and 4.23 +/- 0.36 nmol/(min x nmol P450), respectively. The generation of a dihydrodiol from 5-MOP implies that conversion by CYP2A13 causes toxicity due to the formation of covalent bonds with DNA or proteins. Most of the CYP2A13 variants could metabolize 5-MOP; K(m) values for CYP2A13*5, *6, *8, and *9 were 1.63 =/- 0.12, 1.36 +/- 0.10, 0.85 +/- 0.09, and 0.58 +/- 0.06 uM, respectively, and V(max) values were 3.20 +/- 0.13, 4.69 +/- 0.13, 2.34 +/- 0.07, and 1.84 +/- 0.09 nmol/(min x nmol P450), respectively. However, the processing of 5-MOP by CYP2A13*4 was not detectable. Based on this data, we hypothesize that SNPs within the CYP2A13 gene affect metabolism of 5-MOP in humans.

Bergapten has known human metabolites that include Unii-3abk64HG9O.

Substances that reduce or suppress INFLAMMATION.

Drugs used to treat or prevent skin disorders or for the routine care of skin.

Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms.

Micronized bergapten in capsules was absorbed slowly by volunteers (time to max serum concn 3.2 hr; elim half-time about 1 hr). When injected iv into rabbits, elim half-time 1-2 min (alpha-phase) & 15 min (beta-phase).

5-Methoxypsoralen showed a high binding affinity to serum proteins & 98-99% was protein bound. Its high binding affinity resulted in higher tissue concn. In the epidermis, it appeared to be bound to independent & noninteracting sites.

Enrichment in epidermis of 5-methoxypsoralen was measured. It was concentrated by human epidermis & concn reached within the tissue was 10-500 times higher than concn of substance in surrounding buffer. The partitioning distribution among tissue components could account for its behavior.

In young adult Hartley guinea-pigs, a linear relation was found between serum and epidermal concn of 5-methoxypsoralen, and the observed skin phototoxicity correlated with the serum 5-methoxypsoralen concn ... .

For more Absorption, Distribution and Excretion (Complete) data for 5-Methoxypsoralen (11 total), please visit the HSDB record page.

Used to promote tanning in suntan preparations and to treat psoriasis; Present in some perfumes, fragrances, sunscreen preparations, and food products (as a component of bergamot oil); [HSDB]

As a component of bergamot oil, 5-methoxypsoralen is present in some perfumes and fragrances, sunscreen preparations and food products.

Has been used to promote tanning in suntan preparations.

MEDICATION

... Isolated from oil of bergamot from Citrus bergamia Risso, Aaurantiodiae .. . Isolation from Fagara xanthoxyloides Lam., Rutaceae.

5-Methoxypsoralen was first synthesized in 1937 ... by the condensation of 3,4,6-triacetoxycoumaran with ethyl sodium formyl acetate and methylation of the resulting product. Other synthetic routes have been described which use 6-formyl-7-hydroxy-5-methoxycoumarin-7-O-acetic acid, ... the methyl ester of 2,6-dioxy-4-methoxybenzoic acid ... and 5-allyloxy-7-hydroxycoumarin ... as precursors.

Cosmetics product ingredient: 5-Methoxypsoralen with ultraviolet A therapy

Information on 1 consumer products that contain 5-Methoxypsoralen in the following categories is provided:

Psoralens are natural furocoumarins well-known for their photosensitizing potential. Porphyrins, including hematoporphyrin derivatives (HPD), are also potent photosensitizers. ... Psoralens ... have an action spectrum in the UV-A range. /Psoralens/

Natural bergamont oil typically contains 3000-3600 ug/g 5-methoxypsoralen. Nearly all bergamot oil sold in the USA for use in consumer products has been steam-distilled, which reportedly removed 5-methoxypsoralen and any other furocoumarins.

Concentrations of 5-methoxypsoralen in perfumes have been reported to range from 0-100 ug/mL ... while sunscreen preparations with bergamot oil contain 10-50 ug/mL 5-methoxypsoralen.