Bisphenol A

Flammable agents - 2nd degree

Bisphenol

Waste-water effluent contaminant and(or) Hormone

log Kow = 3.32

3.32

3.32

3.41

Mild phenolic odor

Weak medicine odor

1.195 at 77 °F (USCG, 1999) - Denser than water; will sink

1.195 at 25 °C/25 °C

Relative density (water = 1): 1.2 (25 °C)

1.195 at 77 °F

1.195 @25 °C

Crystallizes as prisms from dil acetic acid and as needles from water

White flakes

Crystals or flakes

White to light brown solid flakes or powder

less than 1 mg/mL at 70.7 °F (NTP, 1992)

In water, 300 mg/L at 25 °C

In water solubility, 120 mg/L at 25 °C

Insoluble in water

Very soluble in ethanol, ether, benzene, alkali; soluble in acetic acid

Soluble in aqueous alkaline solution, alcohol, acetone; slightly soluble in carbon tetrachloride.

175 °F (NTP, 1992)

175 °F

227 °C (closed cup)

227 °C c.c.

175 °F

428 °F at 4 mmHg (NTP, 1992)

360.5 °C at 760 mm Hg

BP: 220 °C at 4 mm Hg

at 1.7kPa: 250-252 °C

428 °F

Danger

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P261, P264+P265, P271, P272, P273, P280, P302+P352, P304+P340, P305+P354+P338, P317, P318, P319, P321, P333+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for < 0.1% (1 of 2613) of reports.

Danger

H317 (99.9%): May cause an allergic skin reaction [Warning Sensitization, Skin]

Chemical: Phenol, 4,4'-(1-methylethylidene)bis-

Hazard Traits - Developmental Toxicity; Endocrine Toxicity; Reproductive Toxicity

Regulation (EC) No 178/2002 (amended)

Phenol, 4,4'-(1-methylethylidene)bis- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Phenol, 4,4'-(1-methylethylidene)bis- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 30-08-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/15752

Restricted substance: 4,4'-isopropylidenediphenol

This chemical is combustible. This compound may form explosive dust clouds. Static electricity can cause its dust to explode. (NTP, 1992)

Combustible. Finely dispersed particles form explosive mixtures in air.

A skin, eye, and respiratory tract irritant; Repeated or prolonged contact may cause skin sensitization. [ICSC] Reports of sensitization are rare; A possible sensitizer in vinyl gloves; [Kanerva, p. 1759] Danger of photo-contact sensitization; [MAK]

DHHS/NTP; Center for the Evaluation of RIsks to Human Reproduction (CERHR); NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A. 321 pp. NIH Pub. No. 08-5994 (September 2008) gives the results of the NTP CERHR evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. This Monograph includes the NTP Brief and the Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Printed copy avaialble from CERHR.[Available from, as of October 20, 2017: https://ntp.niehs.nih.gov/ntp/ohat/bisphenol/bisphenol.pdf]

DHHS/NTP; Toxicology & Carcinogenesis Studies of Bisphenol A in F344/N Rats and B6C3F1 Mice (Feed Study) Technical Report Series No. 215 (1982) NIH Publication No. 82-1771[Available from, as of October 20, 2017: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr215.pdf]

European Chemicals Bureau; European Union Risk Assessment Report, 4,4'-Isopropylidenediphenol (Bisphenol-A) (CAS# 80-05-7) 302 pages (2003).

European Food Safety Authority (EFSA); Bisphenol A (Last updated October 2016). Website providing information and links to research, reports, studies, and analysis regarding Bisphenol A.[Available from, as of October 20, 2017: http://www.efsa.europa.eu/en/topics/topic/bisphenol.htm]

For more Special Reports (Complete) data for Bisphenol A (8 total), please visit the HSDB record page.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Bisphenol A is included on this list. Effective date 6/28/1984; Sunset date 6/28/1994.

Fire Extinguishing Agents: Foam, dry chemical, carbon dioxide (USCG, 1999)

Use water spray, foam, powder, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Fresh air, rest. Seek medical attention if you feel unwell.

Remove contaminated clothes. Rinse and then wash skin with water and soap. Seek medical attention if you feel unwell.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Give one or two glasses of water to drink. Refer for medical attention .

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.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Use water spray, foam, powder, carbon dioxide.

In case of fire: keep drums, etc., cool by spraying with water.

Use dry chemical, carbon dioxide, water spray, or foam extinguishers. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. ... From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. ... The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode.

Keep container tightly closed in a dry and well-ventilated place.

Safe Storage: Separated from acid anhydrides, acid chlorides, strong oxidants, strong bases and food and feedstuffs. Store in an area without drain or sewer access.

Store away from heat and strong oxidizers ... .

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. Discharge into the environment must be avoided. 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.

Evacuate and restrict persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Vacuum cleaning is preferable to sweeping to keep dust levels down. Use special HEPA vacuum, not a shop vacuum. Ventilate area of spill or leak after cleanup is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.

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.

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.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

Spillage Disposal: Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into sealable containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into sealable containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

In a study conducted 2003-2004 by the National Health and Nutrition Examination Survey, bisphenol A was detected in 86 of 916 urine samples(1). Bisphenol A was detected in 38 of 50 and of 50 of 56 urine samples collected from university student in Japan in 1992 and 1999 at respective mean concentrations of 2.5-19 and 0.8-2 ug/g creatine, according to a survey conducted in Japan(2). In urine samples collected May-Oct 2012 from 34 Tunisian women, bisphenol A was detected at <0.2-8.1 ng/mL with a median concentration of 0.35 ng/mL(3). In 116, 22 and 20 urine samples collected July-August 2014 from people living in an electronic waste dismantling, rural reference and urban reference area of China, respective bisphenol A concentrations were 0.233-27.6, <LOQ-4.12 and <LOQ-4.07 ng/mL(4). In 85 second term termination umbilical cord blood samples collected 2010-2012 from San Francisco General Hospital, CA, bisphenol A, and metabolism products bisphenol A glucuronide and bisphenol A sulfate were detected at <0.05-52.26, <0.05-5.41 and <0.025-12.65 ng/mL, respectively(5). Bisphenol A was detected at 2.02-6.52 ng/mL in 98% of 1016 serum samples collected from 70 year old residents of Uppsala, Sweden(6). Bisphenol A was detected in 9 of 12 serum samples collected from firefighters in 2009 from San Francisco, CA at 0.03-1.2 ng/mL(7).

Bisphenol A was detected in 62% of breast milk samples collected from 21 nursing mothers in the US at 0.22-10.8 ng/mL (median 0.68 ng/mL, mean 3.13 ng/mL)(1). Bisphenol A was detected in the colostrum of 101 human breast milk samples collected within three days after delivery in Shizuoka prefecture, Japan, during 2000-2001 at 1-7 ng/mL with a mean concentration at 3.41 ng/mL(2). The mean bisphenol A concentration in breast milk samples collected from 23 healthy lactating women was 0.61 ng/mL(3). Bisphenol A was detected in 11 of 20 adipose tissue samples collected from women in Southeast Spain at a mean of 5.83 ng/g(4). Bisphenol A was detected in adipose, brain and liver tissue of 11 autopsy patients collected in 2002 from University Hospital of Antwerp, Belgium at 1.12-12.28, <0.4-2.36 and 0.77-3.35 ng/g wet weight, respectively(10).

Consider dilution immediately after ingestion. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. In case of inhalation, move patient to fresh air and monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. In case of eye contact, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. Decontaminate skin or mucous membranes immediately with water and a soft sponge. (T36)

We investigated the possible transmission of heritable changes via the sperm, following preconceptional exposure of mice to bisphenol A (BPA), either alone or in combination with X-irradiation. Males were exposed for 8 weeks to BPA, X-rays or both agents, and mated to unexposed females. Pre- and postnatal development of the offspring of exposed males was examined. Both BPA alone and the combined exposure slightly affected postnatal development. Combined exposure induced two-fold higher postnatal mortality than BPA the alone, whereas BPA exposure caused reduced body weight and diminished sperm quality in F1 generation.

This study was designed to investigate the effects of 2 weeks of exposure of male mice to bisphenol A (BPA) alone or in a combination with X-rays on the sperm count and quality as well as induction of DNA strand breaks in somatic and germ cells. Pzh:SFIS male mice were exposed to X-rays (0.05 and 0.10 Gy) or BPA (5, 10, 20, and 40 mg/kg) or to a combination of both (0.05 Gy + 5 mg/kg body weight of BPA and 0.10 Gy + 10 mg/kg of BPA). Both X-rays and BPA administered alone decreased sperm count and quality. X-rays induced DNA strand breaks in spleen cells, whereas BPA induced DNA strand breaks in lymphocytes and in cells from spleen, kidneys, and lung and in germ cells. After combined exposure to both agents, sperm count and quality were similar as after exposure to each agent alone and significantly reduced, compared to control. Levels of DNA damage in somatic and germ cells after combined exposure to lower, as well as higher, doses were significantly reduced, compared to the effects of BPA alone. Results confirmed the mutagenic ability of BPA. Combined exposure to X-rays and BPA leads to the prevention of DNA damage in somatic and germ cells of mice.

Bisphenol A (BPA) is employed in the manufacturing of epoxy, polyester-styrene, and polycarbonate resins, which are used for the production of baby and water bottles and reusable containers, food and beverage packing, dental fillings and sealants. The study was designed to examine the effects of 8-week exposure (a full cycle of spermatogenesis) to BPA alone and in a combination with X-irradiation on the reproductive organs and germ cells of adult and pubescent male mice. Pzh:Sfis male mice were exposed to BPA (5, 10, and 20 mg/kg) or X-rays (0.05 Gy) or to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The following parameters were examined: sperm count, sperm motility, sperm morphology, and DNA damage in male gametes. Both BPA and X-rays alone diminished sperm quality. BPA exposure significantly reduced sperm count in pubescent males compared to adult mice, with degenerative changes detected in seminiferous epithelium. This may suggest a higher susceptibility of germ cells of younger males to BPA action. Combined BPA with X-ray treatment enhanced the harmful effect induced by BPA alone in male germ cells of adult males, whereas low-dose irradiation showed sometimes protective or additive effects in pubescent mice.

... The aim of the present study was to investigate if bisphenol A induces oxidative stress in the liver of rats and if co-administration of vitamin C, an antioxidant, can prevent oxidative stress. Bisphenol A (0.2, 2.0 and 20 ug/kg body weight per day) and bisphenol A + vitamin C (0.2, 2.0, 20 ug + 40 mg/kg body weight per day) was orally administered to rats for 30 days. After 24 hr of the last treatment, rats were killed using overdose of anesthetic ether. Body weights of the animals and the weights of liver showed no significant changes. The activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were decreased in mitochondrial and microsome-rich fractions of liver. The levels of hydrogen peroxide and lipid peroxidation increased in the treated rats when compared with the corresponding group of control animals. Activity of alanine transaminase, a marker enzyme of hepatic injury remained unchanged in the treated rats as compared with the corresponding control rats. Co-administration of bisphenol A and vitamin C showed no changes in the activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase and in the levels of hydrogen peroxide and lipid peroxidation as compared with the corresponding control groups.

For more Interactions (Complete) data for Bisphenol A (12 total), please visit the HSDB record page.

Permanent changes to genital tract, changes in breast tissue that predispose cells to hormones and carcinogens, increased prostate weight 30%, lower bodyweight, increase of anogenital distance in both genders, signs of early puberty and longer estrus, decline in testicular testosterone, breast cells predisposed to cancer, prostate cells more sensitive to hormones and cancer, decreased maternal behaviors, reversed the normal sex differences in brain structure and behavior, U.S. human exposure limit (not a result from an animal study, but a guideline set by EPA). (L953)

LC50; Species: Eisenia andrei (Earthworm) adult age <2 months, well developed clitellum; dipped or soaked (filter paper) 0.017 mg/sq cm /99% purity/

LC50; Species: Xenopus laevis (African Clawed Frog) 46 stage tadpole; Conditions: freshwater, renewal, 23 °C; Concentration: 9090 ug/L for 96 hr (95% confidence interval: 8600-9640 ug/L) /formulation/

LC50; Species: Xenopus laevis (African Clawed Frog) 8-11 stage embryo late blastula; Conditions: freshwater, renewal, 23 °C; Concentration: 5790 ug/L for 96 hr (95% confidence interval: 5310-6180 ug/L) /formulation/

LC50; Species: Menidia menidia (Atlantic silverside); Conditions: saltwater, flow through, 22 °C, salinity 20 ppt; Concentration: 12000 ug/L for 24 hr (95% confidence interval: 9800-16000 ug/L) /polycarbonate grade, 99.93% purity/

For more Ecotoxicity Values (Complete) data for Bisphenol A (58 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 251-3886(2-3), indicate that bisphenol A is expected to have moderate to slight mobility in soil(SRC). Most of the measured Koc values suggest that Bisphenol A may have moderate to low mobility in soil(SRC). Volatilization of bisphenol A from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.0X10-11 atm-cu m/mole(SRC), based upon its vapor pressure, 4.0X10-8 mm Hg(4), and water solubility, 300 mg/L(4). Bisphenol A is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Although Bisphenol A has been found to be non-biodegradable in various studies and screening tests, other studies have found bisphenol A to be readily biodegradable or inherently biodegradable, especially after short lag periods of acclimation(4).

TERRESTRIAL FATE: In loamy sand soil, after a 10 year simulation of turf grass irrigation using reclaimed water, bisphenol A was 64.33% degraded, 1.36% evaporated <0.01% leached and 34.34% was absorbed to soil(1). In sandy loam soil the respected percentages were 78.16%, 1.42%, <0.01% and 20.45%. The degradation half-life for bisphenol A in soil was reported as follows(1):[Table#1429]

AQUATIC FATE: Based on a classification scheme(1), Koc values of 115-3886(2-4), indicate that bisphenol A is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(5) based upon an estimated Henry's Law constant of 4.0X10-11 atm-cu m/mole(SRC), derived from its vapor pressure, 4.0X10-8 mm Hg(6), and water solubility, 300 mg/L(6). Bisphenol A is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(5). According to a classification scheme(7), BCFs of 5.1-73.4, measured in a variety of fish(6,8), suggest bioconcentration in aquatic organisms is low to moderate. Phenols can undergo sensitized photooxidation in surface waters exposed to sunlight via reaction with hydroxyl and peroxy radicals with half-lives on the order of days to weeks at the water surface(9). Irradiation studies in water have demonstrated that photodegradation occurs readily with the addition of sensitizing agents such as algae, humic acid and Fe+3 ions(10-11). Although bisphenol A has been found to be non-biodegradable in various studies and screening tests, other studies have found bisphenol A to be readily biodegradable or inherently biodegradable, especially after short lag periods of acclimation(6). Bisphenol A was found to degrade in natural waters with half-lives of 2.5-4 days(12).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bisphenol A, which has a vapor pressure of 4.0X10-8 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase bisphenol A may be removed from the air by wet or dry deposition(SRC). Bisphenol A absorbs at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The bisphenol A concentration in canned infant formula, mushrooms, green beans and mixed vegetables were 0.1-13.2, 9.4-12.5, 6.1 and 9.1-38.7 ng/mL, respectively(1). In 84 of 99 baby food products sold in glass jars with metal lids purchased from local stores in Ottawa, Canada, August 2008, bisphenol A was detected at 0.18-7.2 ng/g with an average of 1.1 ng/g(2). Bisphenol A was detected in 22 of 42 peeled canned tomatoes samples collected from Italian supermarkets at 20.5-115.3 ug/kg(3). Bisphenol A was detected 71 of 78 canned food samples collected at grocery stores in Washington DC and Maryland areas at 2.6-730 ng/g(4). Bisphenol A was detected in 63 of 105 US food samples including fresh turkey, canned green beans and canned infant formula at levels of 0.23 to 65.9 ng/g(5). The concentration of bisphenol A in foods sold in cans, glass, paper and plastic were reported as <0.01-146, <0.01-4.16, <0.01-2.37 and <0.01-20.8 ng/g, respectively(6).

In 267 food samples divided into nine categories collected 2008, 2011 and 2012 from retail grocery stores in Albany, NY, bisphenol A was detected at the following concentrations(1):[Table#1431]

Bisphenol A was detected in food products sampled in 2012 from China(1).[Table#1432]

The substance can be absorbed into the body by inhalation of its aerosol.

Oral (L953) ; inhalation (L953) ; dermal (L953)

ENVIRONMENTAL: Bisphenol A was measured in the colostrum of 101 human breast milk samples collected within three days after delivery in Shizuoka prefecture, Japan, during 2000-2001. Levels ranged from 1-7 ng/mL with the mean concentration at 3.41 ng/mL. There was no apparent correlation between bisphenol A concentrations and age and post partum (within 3 days) of the mothers(1).

ENVIRONMENTAL: A highly sensitive HPLC method was developed for the determination of xenoestrogenic compound, bisphenol A (BPA) in human breast milk samples. ...Twenty-three breast milk samples of healthy lactating women were analyzed for the BPA concentration; the mean value was 0.61 +/- 0.20 ng/mL, with no correlation to the lipid content of milk samples.

Five brands of Spanish commercial whole milk processed and packed in different ways were analyzed for bisphenol A. Average concentrations in two brands of ultrahigh-temperature sterilized milk available in a carton-based package composed of a laminate of paper, polyethylene, and aluminum foil were 0.99 and 2.64 mg/kg. Average concentration in two brands of in-bottle sterilized milk packaged in high-density polyethylene bottles were 2.88 and 1.23 mg/kg. The average concentration in powdered milk infant formula packed in tin cans was 1.18 mg/kg(1).

This investigation describes a reliable and sensitive method for simultaneously determining bisphenol A (BPA) and two major phytoestrogens, daidzein and genistein, in powdered milks and infant formulas by gas chromatography-mass spectrometric analysis after trimethylsilylation. To reduce the matrix interference associated with the constituents of the formulas, the dissolved formula solutions were firstly ultra-centrifuged and the analytes in the supernatant were then extracted using a C18 solid-phase extraction column. The accuracy and precision of the method were determined and the technique was successfully employed to measure trace concentrations of BPA, daidzein and genistein in powdered formulas. The results show that BPA, daidzein and genistein were detected in all the testing samples (n = 6) at concentrations from 45 to 113 ng/g (except one infant formula), 20 to 2050 ng/g and 21 to 6510 ng/g, respectively. ...

IDENTIFICATION AND USE: Bishphenol A (BPA) is a solid. It is used in the manufacture of epoxy resins and polycarbonates for food packaging. HUMAN STUDIES: Allergic contact dermatitis caused by polyvinyl chloride gloves is rarely reported, and in only 2 cases was BPA considered to be the responsible sensitizer. A clinical report describes photoallergic contact dermatitis to BPA in a group of eight outdoor workers. Urinary BPA may be associated with declined semen quality and increased sperm DNA damage. A correlation was observed between environmental exposure to BPA and the genesis of fetal malformations. Maternal conjugated BPA was also associated with a higher risk of aneuploid and euploid miscarriage. BPA is an endocrine disruptor with estrogenic properties that can adversely affect meiotic spindle assemblies. Data indicate that BPA exposure in female patients may interfere with oocyte quality during in vitro fertilization (IVF). Male BPA exposure may affect embryo quality during IVF. BPA was found to be cytotoxic, but not genotoxic in human cell lines. ANIMAL STUDIES: BPA caused serious damage to the eyes of rabbits, but demonstrated negligible skin irritation potential in rabbits. The effect of BPA on fertility was evaluated in an extensive oral two generation reproduction toxicity study in rats. No clinical signs of toxicity or effects on body weight gain during lactation were observed in F1 and F2 pups. No treatment-related changes were seen in the litter size, survival, sex ratio, anogenital distance and reflex ontogeny. BPA significantly accelerated mammary tumorigenesis in a transgenic mouse model that spontaneously develops tumors. In mice, exposure to a low dose of BPA, only during gestation, had immediate and long-lasting, transgenerational effects on mRNA in brain and social behaviors. Prenatal exposure to BPA mainly affected male rats and abolished sex differences in rearing behavior in the open-field test and struggling behavior in the forced swimming test. In mice, prenatal exposure to BPA affected pituitary gonadotroph development in females. BPA was not mutagenic using tester strains of Salmonella typhimurium (TA 98, TA 100 and TA 102) in the presence and absence of metabolic activation. However, in vivo BPA exposure in rats caused a significant increase in the frequency of micronucleus in polychromatic erythrocytes, structural chromosome aberrations in bone marrow cells and DNA damage in blood lymphocytes. Exposure to BPA in rodents was shown to induce obesity. Furthermore, feeding Drosophila melanogaster males with BPA significantly inhibited the expression of insulin-like peptides. ECOTOXICITY STUDIES: BPA demonstrated sex reversal effects on the gonads in F1 Japanese quail (Coturnix japonica) embryos. Vitellogenin induction in rainbow trout described after intraperitoneal injection of BPA. Japanese medaka (Oryzias latipes) was exposed to BPA at the sublethal concentrations of 2.28, 13.0, 71.2, 355, and 1,820 ug/L in the early life stage from fertilized eggs to 60-days posthatch. When observed for their external secondary sex characteristics, no males were identified in the 1,820-ug/L treatment. In addition, histological examination showed that 32% of fish in the 1,820-ug/L group had testis-ova composed of both testicular germ cells and oocytes. The effect of BPA on gene expression in Arabidopsis thaliana was determined using microarray analysis and quantitative gene PCR. Many hormone responsive genes showed changes in expression after BPA treatment. BPA disrupted flowering by a mechanism that may involve disruption of auxin signaling.

Bisphenol is an endocrine disruptor. Low doses of bisphenol A can mimic the body's own hormones, possibly causing negative health effects. There is thus concern that long term low dose exposure to bisphenol A may induce chronic toxicity in humans (L705).

The primary source of exposure to bisphenol A for the general populations is via ingestion; bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes occur in infants and children(1).

The average daily intake of bisphenol A for different age groups was calculated using food concentrations from a survey collected 2008, 2011 and 2012 in Albany, NY (Albany), from a 2010 joint meeting of the Food and Agriculture Organization (FAO) and World Health Organization (WHO), and the Scientific Committee of European Commission (SCEC) with the following results in ng/kg body weigh/day(1):[Table#1424]

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Bisphenol A is included on this list. Effective date 6/28/1984; Sunset date 6/28/1994.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Bisphenol A is produced, as an intermediate or a final product, by process units covered under this subpart.

This study evaluated the effects of bisphenol A (BPA) on human endometrial stromal fibroblast (ESF) differentiation and expression of genes involved in estrogen metabolism. Human ESF from eight hysterectomy specimens were cultured and treated with 5-100 umol/L of BPA + or - estradiol or 8-br-cAMP for 48 hr. mRNA expression was analysed by real-time reverse-transcription PCR. 8-br-cAMP-induced human ESF decidualization was confirmed by expression of insulin-like growth factor binding protein-1 (IGFBP1) and prolactin secretion. Short-term exposure (48 hr) decreased human ESF proliferation (P<0.04) not due to apoptosis. High doses of BPA significantly induced IGFBP1 mRNA and protein, decreased P450scc mRNA, reversed the 8-br-cAMP-induced increase in HSD17B2 (estradiol to estrone conversion) in a dose-dependent manner and down-regulated HSD17B1 expression (oestrone to estradiol conversion; P = 0.03). 8-br-cAMP significantly potentiated this effect (P=0.028). BPA had no significant effect on aromatase and PPAR gamma expression. The estrogen-receptor antagonist ICI had no effect on gene expression in BPA-treated cells, and estrogen receptor a, but not estrogen receptor beta, was significantly down-regulated by high doses of BPA (P=0.028). BPA has an endocrine-disrupting effect on human ESF function and gene expression but the underlying mechanisms appear not to involve estrogen-mediated pathways.

... Following a single oral or intravenous (iv) dose of 100 ug/kg (ring-(14)C(U)) radiolabeled bisphenol A ((14)C-BPA) to male and female cynomolgus monkeys ... the terminal elimination half-life was larger post-iv dose (t(1/2iv) = 13.5 to 14.7 hr) than post-oral dose (t(1/2oral) = 9.63 to 9.80 hr). After iv dose, the fast-phase half-life (t(1/2f)) of total radioactivity was 0.61 to 0.67 hr. The t(1/2f) of unchanged (14)C-BPA for females (0.39 hr) was smaller than that for males (0.57 hr).

...The oral bioavailability was determined after administration of relatively low iv (0.1 mg/kg) and oral (10 mg/kg) doses of bisphenol A to rats. ... The apparent terminal elimination half-life of bisphenol A (21.3 +/- 7.4 hr) after oral administration was significantly longer than that after iv injection

... Bisphenol A was injected intravenously to mouse, rat, rabbit and dog (1-2 mg/kg doses). The obtained serum concentration-time profiles were best described by bi-exponential equations in all these animal species, with the mean ... t(1/2) of 39.9 min in mouse, 37.6 min in rat, and 40.8 min in rabbit, and 43.7 min in dog, respectively. ... The simple allometric scaling and different time transformation methods predicted the human t(1/2) ranging from 43.6 to 196.2 min. ...

The toxicokinetics of bisphenol A (BPA) in F344 rats, cynomolgus monkeys and chimpanzees /were examined/. ...After the oral administration of 10 mg/kg BPA, both C(max) and AUCs of BPA metabolites were ranked in the following order: cynomolgus monkeys>chimpanzees>rats, and the terminal elimination half-life (T(1/2)) in rats was greater than that in cynomolgus monkeys and chimpanzees, suggesting the enterohepatic circulation of BPA in rats. ...

... The metabolism of bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA) by CD1 mice liver microsomal and S9 fractions was investigated. Nine metabolites were isolated and characterized using HPLC and mass spectrometry. Many of these metabolites were characterized for the first time in mammals, namely isopropyl-hydroxyphenol (produced by the cleavage of BPA), a bisphenol A glutathione conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, and BPA dimers.

... In this study, bisphenol A (BPA) levels in 30 healthy Koreans (men, N=15, 42.6 +/- 2.4 years; women, N=15, 43.0 +/- 2.7 years) were analyzed from urine treated with/without beta-glucuronidase and/or sulfatase by an RP-HPLC with fluorescence detection. The total BPA concentrations including free BPA and the urinary conjugates were similar in men and women (2.82 +/- 0.73 and 2.76 +/- 0.54 ng/mL, respectively), but gender differences were found in the levels of urinary BPA conjugates. Men had significantly higher levels of BPA-glucuronide (2.34 +/- 0.85 ng/mL) than women (1.00 +/- 0.34 ng/mL), whereas women had higher levels of BPA-sulfate (1.20 +/- 0.32 ng/mL) than men (0.49 +/- 0.27 ng/mL).

... The objective of this study was to determine if a route dependency exists in the pharmacokinetics and metabolism of (14)C-labeled bisphenol A (BPA) following single oral (po), intraperitoneal (ip), or subcutaneous (sc) doses of either 10 or 100 mg/kg to Fischer 344 rats. Results indicated a marked route dependency in the pharmacokinetics of BPA. The relative bioavailability of BPA and plasma radioactivity was markedly lower following oral administration as compared to sc or ip administration. The major fraction of plasma radioactivity following oral dosing was the monoglucuronide conjugate of BPA (68-100% of plasma radioactivity). BPA was the major component in plasma at Cmax following sc or ip administration exceeded only by BPA-monoglucuronide in females dosed ip. Up to four additional unidentified metabolites were present only in the plasma of animals dosed ip or sc. One of these, found only following ip administration, was tentatively identified as the monosulfate conjugate of BPA. The monoglucuronide conjugate was the major urinary metabolite; unchanged BPA was the principal component excreted in feces. ...

Previous studies demonstrated the rapid clearance of bisphenol A (BPA) from blood following oral administration to adult rats with the principal metabolite being BPA-monoglucuronide (BPA-glucuronide). Since the ontogeny of glucuronyl transferases (GT) differs with age, the pharmacokinetics of BPA were studied in neonatal animals. (14)C-BPA was administered via gavage at 1 or 10 mg/kg body weight to rats at postnatal day (pnd) 4, pnd 7, pnd 21, or to 11 week old adult rats (10 mg/kg dose only). Blood (neonates and adults) and selected tissues (neonates) were collected at 0.25, 0.75, 1.5, 3, 6, 12, 18, and 24 hr postdosing. BPA and BPA-glucuronide in the plasma were quantified by high-performance liquid chromatography; radioactivity in the plasma and tissues was quantified by liquid scintillation spectrometry. The data indicate that neonatal rats at all three ages metabolized BPA to BPA-glucuronide, although an age dependency in the number and concentration of plasma metabolites was observed, consistent with the ontogeny of GT. BPA-glucuronide and BPA concentrations in the plasma were greater in neonates than in adults, except at 24 hr postdosing, suggesting an immaturity in the development of hepatic excretory function in neonatal rats. ... A dose dependency in the metabolism and pharmacokinetics of BPA administered to neonates was also observed with nearly complete metabolism of BPA to BPA-glucuronide (94-100% of the plasma radioactivity) at a dose of 1 mg/kg. This was in contrast to finding up to 13 different plasma metabolites observed at the 10 mg/kg dose. ...

For more Metabolism/Metabolites (Complete) data for Bisphenol A (8 total), please visit the HSDB record page.

Bisphenol A has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[4-[2-(4-hydroxyphenyl)propan-2-yl]phenoxy]oxane-2-carboxylic acid.

Toxic air-borne matter related to work performed They are usually produced by the specific nature of the occupation.

Non-steroidal compounds with estrogenic activity.

Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY.

This research examined the distribution of low dietary doses of bisphenol A (BPA). When female rats received 50 ug/kg (14)C-BPA orally, radioactivity was distributed throughout the body, with especial presence in the uterus. Pre-treatment with estradiol or the estrogen antagonist ICI 182,780 significantly reduced radioactivity in the uterus. The majority of BPA at the uterus was determined to be aglycone (receptor-active) via GC-MS. Subsequently, mice given 0.5, 5, or 50 ug/kg (14)C-BPA showed more radioactivity in the uterus than in other non-metabolic tissues. When female mice received 1, 7, or 28 daily doses of 50 ug/kg (14)C-BPA, then were measured 24 hr after the last dose, significantly more radioactivity was detected in the uterus, liver, and kidney following repeated doses. Collectively, these data provide evidence for the in vivo interaction of BPA with estrogen receptors. They also indicate elevated presence of BPA in reproductive tissues after repeated low doses.

The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G.

When administered as a single dose by gavage to male CFE rats, 28% of the (14)C-labeled bisphenol A was excreted in the urine (primarily as the glucosamide) and 56% in the feces (20% as free bisphenol A, 20% as a hydroxylated bisphenol A, and the rest as an unidentified conjugate). No carbon-labeled residues were detected in animals killed after 8 days.

Toxicokinetics of radiolabeled (14C) bisphenol A was studied in the common frog (Rana temporaria) at two experimental temperatures (7 and 19 °C). The growth rate of the tadpoles during the 96-hr experiment was very slow at 7 °C, but the weight of tadpoles almost tripled at 19 °C. At all tested exposure concentrations (0.2, 1.5, 10, and 100 ug/L), conditional uptake rate constants (ku) were 69 to 82%, and elimination rates (ke) 79 to 90% lower, at 7 °C than at 19 °C. On the contrary, bioconcentration factors (BCFs) were higher at 7 °C than at 19 °C. Total accumulated bisphenol A per individual was higher at 19 °C, which is in agreement with higher ku at 19 °C. Exposure concentrations did not have any constant effect on BCFs at the two temperatures. The results of the current experiment suggest that higher temperature increases uptake and total amount of chemical in frog tadpoles but does not necessarily lead to higher BCFs. High temperature may have increased the growth rate more than the uptake rate, resulting in a net dilution of bisphenol A in tadpole tissues. The observed difference in BCFs also could be a result of temperature-induced changes in allometric relationships (increased surface area to volume ratio) and/or more effective elimination in more developed tadpoles at high temperature.

For more Absorption, Distribution and Excretion (Complete) data for Bisphenol A (27 total), please visit the HSDB record page.

Used as a chemical intermediate, mainly for epoxy resins and polycarbonate resins; [HSDB] Used with epichlorohydrin to produce epoxy resins; [Kanerva, p. 1759]

Semiconductor Manufacturing [Category: Industry]

The largest use for bisphenol A is polycarbonate ... followed by epoxy resins. Other uses are flame retardants, unsaturated polyester resins and polyacrylate, polyetherimide, and polysulfone resins.

... Used for a wide range of products such as aromatic polyesters with phthalic acid; polysulfones; polyetherketones; unsaturated, hydrolysis-resistant polyesters; antioxidants; phenoxy resins from bisphenol A and epichlorohydrin; and phenolic resins elastified by incorporation of bisphenol A. However, the majority is used for flame retardants, especially tetrabromobisphenol A.

Manufacture of thermal papers

Fungicide /Former USA/

(1972) AT LEAST 7.26X10+9 G

(1984) 1.92X10+10 g

US exports in 1999 amounted to 169 million pounds; in 2000 amounted to 255 million pounds

US exports in 2002 amounted to 113 million pounds; in 2003 amounted to 153 million pounds

(1972) NEGLIGIBLE

(1975) 6.07X10+7 G (PRINCPL CUSTMS DISTS)

US imports in 1999 amounted to 18 million pounds; in 2000 amounted to 6 million pounds

US imports in 2002 amounted to 9.4 million pounds; in 2003 amounted to 2.1 million pounds

2023: 1,000,000,000 - <2,500,000,000 lb

(1972) 1.16X10+11 G

(1975) 1.33X10+11 G

(1984) 3.46X10+11 g

(1991) 1.37X10+9 lbs

For more U.S. Production (Complete) data for Bisphenol A (10 total), please visit the HSDB record page.

53% AS A CHEM INT FOR EPOXY RESINS; 31% AS A CHEM INT FOR POLYCARBONATE RESINS; 16% IN MISC APPLICATIONS INCL AS A CHEM INT FOR PHENOXY & POLYSULFONE RESINS (1973)

Polycarbonate Resins, 52%; Epoxy Resins, 41%; Tetrabromobisphenol A, 2%; Miscellaneous, 5% (1984)

US Consumption Pattern (1986)

US Consumption Pattern (2000)

For more Consumption Patterns (Complete) data for Bisphenol A (9 total), please visit the HSDB record page.

... Hydrogen chloride or sulfonated cross-linked polystyrenes are used as the catalyst which are usually arranged as a fixed bed over which the reaction mixture is passed. The reaction of phenol with acetone takes place at 50 - 90 °C, the molar ratio phenol - acetone is up to 15:1. Bisphenol A crystallizes as an adduct with 1 mol phenol, after separation of the hydrogen chloride by distillation or neutralization. The use of ion exchangers is preferred to that of hydrogen chloride because they are less corrosive. The yield is normally 80-95%.

Manufacture from phenol and acetone: Jansen, United States of America patent 2468982 (1949).

Condensation of two equivalent amounts of phenol with an aldehyde or ketone.

Bisphenol A is manufactured by the condensation of phenol and acetone in the presence of an acid catalyst or in recent plants by using a cation-exchange resin.

... 4,4'-Dihydroxydiphenyldimethylmethane is generally available as thin plates and has the following properties: bisphenol content greater than 99%; phenol content less than 0.1%; water content less than 1%; ash less than 0.02%; and iron less than 0.001%.

Available as flake, crystalline or prilled material

Cosmetics product ingredient: Bisphenol A (BPA) (4,4'-isopropylidenediphenol)

Information on 8 consumer products that contain 4,4-Isopropylidenediphenol in the following categories is provided:

Paint and Coating Manufacturing

Phenol, 4,4'-(1-methylethylidene)bis-: ACTIVE

Impurities of phenol-acetone condensation can be removed by distillation and extractive crystallization under pressure.