3,3-Bis(4-hydroxyphenyl)phthalide

318.32

318.32

284423

201-004-7

6QK969R2IF

757271|215214|10464

1993

DTXSID0021125

C29359

White or yellowish-white minute, triclinic crystals, often twinned|White rhombic needles|Pale yellow powder

A - Alimentary tract and metabolism

29322910

66.8

3.6

White to yellow-white Solid

1.277 g/cm³ @ Temp: 32 °C

262.5 °C

557.8±50.0 °C at 760 mmHg

24 °C

1.693

H2O: <0.1 g/100 mL;soluble in alcohol. Slightly soluble in ether. Slightly soluble in dimethyl sulfoxide and insoluble in benzene or hexane.

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.

6.7X10-13 mm Hg @ 25 deg C /Estimated/

ODORLESS

9.7(at 25 °C)

Henry's Law constant = 9.0X10-16 atm-cu m/mol @ 25 °C /Estimated/

9.7 (at 25 °C)|pKa = 9.7 at 25 °C

172.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Solutions are colorless to pH 8.5; pink to deep-red, above pH 9|Forms an almost colorless solution in neutral or acid solution, pink to deep red in presence of alkali, but colorless in the presence of large amounts of alkali.|Hydroxyl radical reaction rate constant = 8.4X10-11 cu cm/molecule-sec @ 25 °C /Estimated/

Insoluble in water.

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

PHENOLPHTHALEIN is incompatible with alkaloids. (NTP, 1992)

3

UN 1993

3

40-22-10-36/38-23/25-11-36/37/38-68-62-45-39/23/24/25-23/24/25

45-36/37-33-24-16-7-36-26-53

SM8380000

Xn,T,F,Xi

Stable. Incompatible with strong oxidizing agents, alkalies.

P201-P210-P280-P308 + P313-P337 + P313-P403 + P235

H225-H319-H341-H350

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.|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 PHENOLPHTHALEIN (6 total), please visit the HSDB record page.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Danthron phenolphthalein is included in laxative drug products.

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Phenolphthalein (77-09-8) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s145phen.pdf]

Literature sources indicate that this compound is nonflammable. (NTP, 1992)

|Danger|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]|P201, P202, P281, P308+P313, P405, and P501|H341 (99.62%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]|Aggregated GHS information provided by 1066 companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|P201, P202, P260, P264, P270, P281, P308+P313, P314, P405, and P501|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P201, P202, P260, P261, P264, P270, P272, P280, P281, P302+P352, P305+P351+P338, P308+P313, P314, P321, P333+P313, P337+P313, P363, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]: As an immediate precautionary measure, isolate spill or leak area for at least 50 meters (150 feet) in all directions. LARGE SPILL: Consider initial downwind evacuation for at least 300 meters (1000 feet). FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol 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. STORAGE PRECAUTIONS: You should store this material at ambient temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)|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/

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/

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.|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/|PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. 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. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for PHENOLPHTHALEIN (10 total), please visit the HSDB record page.

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/

Pretreatment of rats with sodium methotrexate (1 mg, orally, daily for 5 days) or vincristine sulfate (0.03 mg/kg, iv, weekly for 3 wk) markedly reduced biliary excretion of phenolphthalein (10 mg/kg, iv) indicating that hepatic function was decreased.

... Male and female F344/N rats and B6C3F1 mice were exposed to phenolphthalein (98% to 99% pure) in feed for ... 2 years. ... 2 YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were given 0, 12,000, 25,000, or 50,000 ppm phenolphthalein (equivalent to average daily doses of approximately 500, 1,000, or 2,000 mg phenolphthalein/kg body weight to males and 500, 1,000, or 2,500 mg/kg to females) in feed for 2 yr. 2 YEAR STUDY IN MICE: Groups of 50 male and 50 female B6C3F1 mice were given 0, 3,000, 6,000, or 12,000 ppm phenolphthalein (equivalent to average daily doses of approximately 300, 600, or 1,200 mg phenolphthalein/kg body weight to males and 400, 800, or 1,500 mg/kg to females) in feed for 2 yr. CONCLUSIONS: Under the conditions of these 2 yr feed studies, there was clear evidence of carcinogenic activity of phenolphthalein in male F344/N rats based on markedly increased incidences of benign pheochromocytomas of the adrenal medulla and of renal tubule adenomas and adenomas or carcinomas (combined). There was some evidence of carcinogenic activity of phenolphthalein in female F344/N rats based on the increased incidences of benign pheochromocytomas of the adrenal medulla in the 12,000 ppm group and of benign or malignant pheochromocytomas (combined) in the 12,000 and 25,000 ppm groups. There was clear evidence of carcinogenic activity of phenolphthalein in male B6C3F1 mice based on increased incidences of histiocytic sarcomas and of malignant lymphomas of thymic origin. There was clear evidence of carcinogenic activity of phenolphthalein in female B6C3F1 mice based on increased incidences of histiocytic sarcomas, malignant lymphomas of all types, lymphomas of thymic origin, and benign sex cord stromal tumors of the ovary.|Phenolphthalein administered via feed was tested for its effects on fertility & reproduction in Swiss CD-1 mice according to the Continuous Breeding protocol. A dose-finding study was not conducted; rather based on information available in the literature, 0.1, 0.7, & 3.0% levels were tested in the reproductive study. For F0 evaluation, male & female mice were continuously exposed for a 7 day precohabitation & a 98 day cohabitation period (Task 2). Subsequently, the control & 0.7% groups were used in a cross-over mating trial (Task 3) to determine the sex affected by chemical treatment. The F1 generation from control, 0.1, & 0.7% groups were also evaluated (Task 4). Phenolphthalein with increasing dose & duration of exposure, caused a significant reduction in fertility, with a decr in the number of litters/fertile pair in the 0.7 & 3.0% groups. Parental body weights were not affected by phenolphthalein treatment. The cumulative days to litter values were also increased in the 0.7 & 3% treated animals. In the cross-over mating trial, the treated females mated with control males delivered fewer live pups. There were no adverse effects in the litters from treated males mated with control females. At terminal necropsy, male kidneys were enlarged & right epididymis & testis weights were significantly lower than controls. Sperm morphology & vaginal cytology evaluation (SMVCE) results were parallel to subchronic study results in B6C3F1 mice; both sperm count (Task 3) & incidence of abnormal sperm (Tasks 3 & 4) were adversely affected. Reproductive performance of treated males, however, was similar to the corresponding control males. The middle dose group was chosen for Task 3 crossover in the expectation (based on several previous RACB studies) that use of the high dose would indicate that both sexes were affected. Similar to Task 2 results, fertility declined in F1 mice receiving 0.7% phenolphthalein. The number of live F2 pups/litter decreased as well. Also, in the F1 males in the 0.7% group, testis & epididymis weights were decreased, & the incidence of abnormal sperm was increased. Pathologic lesions in F1 males were similar to those found in the parental males. Thus, phenolphthalein, administered in the feed at concns up to 3.0%, was clearly toxic to murine reproduction in both generations of treated mice.

Phenolphthalein is not known to occur as a natural product(1).

Phenolphthalein's production and use an acid/base indicator, as a laboratory reagent, and its former use as a laxative(1), may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 490(SRC), determined from a log Kow of 490(2) and a regression-derived equation(3), indicates that phenolphthalein is expected to have moderate mobility in soil(SRC). Volatilization of phenolphthalein from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.0X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Phenolphthalein is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.7X10-13 mm Hg(5).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 490(SRC), determined from a log Kow of 2.41(2) and a regression-derived equation(3), indicates that phenolphthalein is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 9.0X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 14(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), phenolphthalein, which has an estimated vapor pressure of 6.7X10-13 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase phenolphthalein may be removed from the air by wet and dry deposition(SRC).

The rate constant for the vapor-phase reaction of phenolphthalein with photochemically-produced hydroxyl radicals has been estimated as 8.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1).

An estimated BCF of 14 was calculated for phenolphthalein(SRC), using a log Kow of 2.41(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of phenolphthalein is estimated as 490(SRC), using a log Kow of 2.41(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that phenolphthalein is expected to have moderate mobility in soil.

The Henry's Law constant for phenolphthalein is estimated as 9.0X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that phenolphthalein is expected to be essentially nonvolatile from water surfaces(2). Phenolphthalein's Henry's Law constant indicates that volatilization from moist soil surfaces may not occur(SRC). Phenolphthalein is not expected to volatilize from dry soil surfaces(SRC) based uponan estimated vapor pressure of 6.7X10-13 mm Hg(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 73,297 workers (18,309 of these are female) are potentially exposed to phenolphthalein in the US(1). Occupational exposure to phenolphthalein may occur through inhalation and dermal contact with this compound at workplaces where phenolphthalein is produced or used(SRC).

Used for over a century as a laxative.

Cathartics; Indicators and Reagents|...Has...been widely employed as cathartic. ... /it/ is avail...in numerous proprietary preparations.|Since ... laxative effects are not usually produced in less than 6 hr after oral administration, they are often taken at bedtime, to produce their effect next morning. Because of adverse effects, use of these agents should be limited to 10 consecutive days. /diphenylmethane derivatives/|(VET): Has been used as a laxative.|Cathartic drug in laxatives; acid-base indicator

Use of phenolphthalein by women during breast-feeding may cause diarrhea in their infants.|Patients should be warned of possible coloring of urine and feces.

Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant and Hackh's Chemical Dictionary, 5th ed, p301, p499) (See all compounds classified as Indicators and Reagents.)

Up to 15% of therapeutic dose of phenolphthalein is absorbed and eliminated by kidney, most of it in conjugated form.|Urine becomes pink or red if it is sufficiently alkaline (pH 7or more). Some absorbed drug is also exreted in the bile, and the resulting enterohepatic cycle may contribute to prolongation of laxative effect.|Biliary excretion of metabolites of...phenolphthalein...in rats was shown...to be increased by pre-treatment with hepatic-microsomal-enzyme inducers, and to be decreased by enzyme inhibitors after dosing with parent compound, but no effect was observed after dosing with metabolites.|Phenolphthalein glucuronide (I) excreted more rapidly than phenolphthalein (II) following iv injection, suggesting that uptake of (I) from blood imposes rate limitation which outweighs the lack of conjugation before excretion.|For more Absorption, Distribution and Excretion (Complete) data for PHENOLPHTHALEIN (14 total), please visit the HSDB record page.

Phenolphthalein that had undergone conjugation, but no unmetabolized phenolphthalein, was excreted into breast milk in concentrations up to 1.0 ug/mL after a single 200-800 mg dose in 22 lactating women. Bowel movements occurred in 16 of the women after the dose, but none of the nursing infants had diarrhea.|Yields phenolphthalein-beta-d-glucuronide in rat, in mouse. /from table/|Phenolphthalein is absorbed in the intestine and is almost completely converted to its glucuronide during extensive first-pass metabolism in the intestinal epithelium and liver via uridine diphosphate glucuronosyltransferase (UDPGT) in rodents and dogs. In guinea-pigs, small amounts of sulfate-conjugated metabolites have been detected in isolated mucosal sheets originating in the jejunum and colon. Fecal excretion is the major route of elimination of phenolphthalein in rats, while in mice both urinary and fecal elimination are important. The metabolites identified in urine and feces are phenolphthalein glucuronide, phenolphthalein sulfate and phenolphthalein hydroxide.|...The major metabolite was PHTH glucuronide. Three minor metabolites were detected. A sulfate conjugate and and a hydroxylated metabolite were identified by comparison of retention times and 1H NMR and/or mass spectra with synthetic standards. A diglucuronide conjugate was tentatively identified. Biliary elimination was extensive in rats (35% of dose within 6 hr); the only product detected in bile was phenolphthalein glucuronide

Classical compartmental pharmacokinetics model developed to describe systemic blood concentration-time profile of phenolphthalein following single iv bolus injection; used to simulate 24-hr time course of blood concentration. Indication that long t/2 are artifacts of recirculation.

Stimulant drugs alter fluid and electrolyte absorption, producing net intestinal fluid accumulation and laxation. Increased concentrations of cyclic 3'-5'-adenosine monophosphate (CAMP) occurring in clonic mucosal cells may alter the permeability of these cells leading to net fluid accumulation and laxative action. Phenolphthalein also acts directly or reflexly to increase the the activity of the small intestine. Phenolphthalein acts mainly on the colon about 6 hours after ingestion.|When taken orally, it is thought to be dissolved by intestinal juices and bile and to stimulate intestinal musculature, chiefly that of colon.|Phenolphthalein increased intestinal fluid volume in rat colon in situ, apparently via stimulation of prostaglandin E biosynthesis in colon.|Water absorption from intestines of 6 pt with ileostomies and from rats was measured after administration of phenolphthalein. Results indicate that some laxative effects result from inhibition of water absorption in large and small intestines.|.... A catechol metabolite of PT, hydroxyphenolphthalein (PT-CAT), was recently identified and may be the molecular species responsible for at least part of the toxicity/carcinogenicity of PT. We hypothesize that PT-CAT inhibits the enzyme catechol-O-methyltransferase (COMT) and therefore potentiates genotoxicity by either PT-CAT itself or the endogenous catechol estrogens (CEs) in susceptible tissues. The present studies were conducted to determine the effects of PT treatment and PT-CAT itself on the COMT-mediated metabolism of 4- and 2-hydroxyestradiol both in vitro and in vivo. Female mice were treated with PT (50 mg/kg/d) for 21 days and then euthanized. PT-CAT concentration in urine reached plateau levels by 7 days of exposure. An O-methylated metabolite of PT-CAT was detected in feces. In vitro experiments demonstrated that PT treatment resulted in an increase in free CEs, which are normally cleared by COMT and a concurrent decrease in the capacity of hepatic catechol clearance by COMT. In vitro, PT-CAT was a substrate of COMT, with kinetic properties within the range measured with endogenous substrates. PT-CAT was an extremely potent mixed-type inhibitor of the O-methylation of the catechol estrogens, with 90-300 nM IC50s.

SYMPTOMS: Exposure to this compound may cause purging, collapse and erythematous, itching skin rash that may progress to persistent ulceration. Acute exposure may cause hypotension, vomiting, watery or bloody diarrhea, pallor, rapid heart rate, coma and death. Other symptoms include burning pain in the mouth and stomach and tenesmus. Eye contact may result in edema of the eyelids and conjunctival ecchymoses. It may also result in irritation, redness and pain. It has occasionally caused albuminuria and hemoglobinurea. It may also cause skin rash. Other symptoms include pink coloring of the urine and feces, allergic reactions including fixed-drug eruption, Stevens-Johnson syndrome (resembles lupus erythematosus), osteomalacia, protein-losing gastroenteropathy, and fluid and electrolyte deficits. Exposure has also caused cerebral and pulmonary edema, oliguria and severe acidosis. Hypothermia has also been reported. Other symptoms include abdominal cramps, cardiac and respiratory distress, lack of sphincter control, flaccid paralysis, fixed mydriasis, intense cyanosis, undetectable blood pressure or pulse, toxic epidermal necrolysis, and bullous lesions on the hands, lips, mouth and tongue. ACUTE/CHRONIC HAZARDS: This compound may cause skin, eye and gastrointestinal tract irritation. When heated to decomposition it emits acrid smoke and fumes. (NTP, 1992)|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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/HUMAN EXPOSURE STUDIES/ Only ocular complications reported have been edema of eyelids and conjunctival ecchymoses accompanying widespread reactions of skin, which may be severe.|/HUMAN EXPOSURE STUDIES/ ... Major danger /from/ overdosage ... is fluid and electrolyte deficits resulting from excessive laxative effect. However, allergic reactions, including fixed-drug eruption, stevens-johnson syndrome, and a syndrome that resembles lupus erythematosus, have been reported ... /diphenylmethane derivatives/|/HUMAN EXPOSURE STUDIES/ Phenolphthalein was used by 236 mother-child pairs during the first trimester and 806 anytime during pregnancy...No evidence was found to associate the use of this drug with major or minor malformations.|/HUMAN EXPOSURE STUDIES/ A retrospective study of 172 phenolphthalein ingestions, ranging from 32.5 to 1620 mg... in children indicated that about 20% had no symptoms. Most had minor symptoms that resolved within 24 hours.|For more Human Toxicity Excerpts (Complete) data for PHENOLPHTHALEIN (12 total), please visit the HSDB record page.

Ap-La-Day

TABLETS NF: 60 & 120 MG|GRADES: Techinical, pure reagent; NF|Available in white or yellow forms; the monosodium salt is the most common form sold commercially.

1(3H)-Isobenzofuranone, 3,3-bis(4-hydroxyphenyl)-: ACTIVE|A 1% alcoholic solution as an indicator in titrations of mineral and organic acids and most alkalies.|... Not suitable for /titration of/ ammonia. Very sensitive to CO2, and in estimating carbonates liquid must be boiled. Borax can be titrated with phenolphthalein as indicator only when glycerol is present, because color gradually fades away as acid is added. Usable with few alkaloids.|Color loss of phenolphthalein in 1% wt/vol sodium carbonate and saturated lime water solution due to decomposition to 2-(4-hydroxybenzoyl)benzoic acid and phenol. Ideal sodium carbonate concentration was 0.05 n in basic solution for storing phenolphthalein samples as possible evidence in criminal cases.

SPECTROPHOTOMETRIC DETERMINATION OF PHENOLPHTHALEIN WITH SULFURIC ACID.|HIGH PRESSURE LIQUID CHROMATOGRAPHY OF PHENOLPHTHALEIN IN ANTHELMINTIC TABLETS.

SPECTROPHOTOMETRIC ASSAY OF PHENOLPHTHALEIN IN INTESTINAL PERFUSATE, SERUM & URINE.

Health Hazards -> Carcinogens