I'd like to thank the person who provided the Study on Bisphenol A. Although it is nearly 400 pgs long I weeded through it in search of points that would be relevant to daycare centers (in particular) and parents of young children. I have copied the Summaries and Conclusions here, along with several studies that stand out. Should anyone be patient enough to read through the study (a chemist perhaps?) and want to comment on any items of significance your contribution is more than welcome! Please send your opinions via email and I will add them to the bottom of this posting- info@cantondaycare.org
5.1 Developmental Toxicity
No data on the effects of human developmental exposure to Bisphenol A are available. There is a large literature describing studies in rodents and some work in other species. A large experimental animal literature was reviewed, assessed for its utility, and weighed based on the criteria established by this panel.
From the rodent studies we can conclude that Bisphenol A:
• Does not cause malformations or birth defects in rats or mice at levels up to the highest doses evaluated: 640 mg/kg/d (rats) and 1250 mg/kg/d (mice).
• Does not alter male or female fertility after gestational exposure up to doses of 450 mg/kg bw/d in the rat and 600 mg/kg bw/d in the mouse (highest dose levels evaluated).
• Does not permanently affect prostate weight at doses up to 475 mg/kg/d in adult rats or 600 mg/kg/d in mice.
• Does not cause prostate cancer in rats or mice after adult exposure at up to 148 or 600 mg/kg/d, respectively.
• Does change the age of puberty in male or female rats at high doses (ca. 475 mg/kg/d).
Rodent studies suggest that Bisphenol A:
• Causes neural and behavioral alterations related to disruptions in normal sex differences in rats and mice (0.01-0.2 mg/kg/d).
The data on bisphenol A are insufficient to reach a firm conclusion about:
• A change in the onset of puberty in male rats or mice at doses up to 475 – 600 mg/kg/d.
• An acceleration in the age of onset of puberty at a low dose in female mice at 0.0024 mg/kg/d, that Bisphenol A:
• Causes neural and behavioral alterations related to disruptions in normal sex differences in rats and mice. (0.01-0.2 mg/kg/d).
The data on bisphenol A are insufficient to reach a firm conclusion about:
• A change in the onset of puberty in male rats or mice at doses up to 475 – 600 mg/kg/d.
• An acceleration in the age of onset of puberty at a low dose in female mice at 0.0024 mg/kg/d, the only dose tested.
• Whether Bisphenol A predisposes rats toward prostate cancer or mice towards urinary tract deformations.
5.2 Reproductive Toxicity
There are insufficient data to evaluate whether bisphenol A causes male or female reproductive toxicity in humans. A large experimental animal literature was reviewed, assessed for its utility, and weighted based upon the criteria established by this expert panel, including an evaluation of experimental design and statistical procedures. These animal data are assumed relevant for the assessment of human hazard.
Female effects:
There is sufficient evidence in rats and mice that bisphenol A causes female reproductive toxicity with subchronic or chronic oral exposures with a NOAEL of 47.5 mg/kg bw/day and a LOAEL of ≥475 mg/kg bw/day.
Male effects:
There is sufficient evidence in rats and mice that bisphenol A causes male reproductive toxicity with subchronic or chronic oral exposures with a NOAEL of 4.75 mg/kg bw/day and a LOAEL of .47.5 mg/kg bw/day.
Human Exposures
Bisphenol A is FDA-approved for use in polycarbonate and epoxy resins that are used in consumer products such as food containers (e.g., milk, water, and infant bottles) food can linings. Resins, polycarbonate plastics, and other products manufactured from bisphenol A can contain trace amounts of residual monomer and additional monomer may be generated during breakdown of the polymer.
Environmental Exposures
Bisphenol A emitted from manufacturing operations is unlikely to be present in the atmosphere in high concentrations. However, it was found in 31-44% of outdoor air samples with concentrations of <>Exposures through Food
The highest potential for human exposure to bisphenol A is through products that directly contact food such as food and beverage containers with internal epoxy resin coatings and through the use of polycarbonate tableware and bottles, such as those used to feed infants. Studies examining the extraction of bisphenol A from polycarbonate infant bottles in the U.S. found concentrations < 5 ug/L. Canned infant formulas in the U.S. had a maximum level of 13 ug/L in the concentrate that produced a maximum of 6.6 ug/L when mixed with water. Breast milk studies in the U.S. have found up to 6.3 ug/L free bisphenol A in samples. Measured bisphenol A concentrations in canned foods in the U.S are less than 39 ug/kg. Limited drinking water sampling in the U.S. indicates that bisphenol A concentrations were all below the limit of detection (<0.1 ng/L).
Biological Measures of Bisphenol A in Humans
The panel finds the greatest utility in studies of biological samples that use sensitive and specific analytical methods (LC-MS or GC-MS) and report quality control measures for sample handling and analysis. The panel further focused on biological monitoring done in U.S. populations. In the U.S, adult urine concentrations of free bisphenol A are less than 0.6 ug/L and total bisphenol A concentrations are <19.8 ug/L. The 95th percentile total bisphenol A concentration for 394 adult volunteers (males and females; 20–59 years old) from the NHANES III survey was 5.18 ug/L. Girls age 6-9 in the U.S. have concentrations of total bisphenol A < 54.3 ug/L, with median concentrations ranging from 1.8-2.4 analytical methods (LC-MS or GC-MS) and report quality control measures for sample handling and analysis. The panel further focused on biological monitoring done in U.S. populations. In the U.S, adult urine concentrations of free bisphenol A are less than 0.6 ug/L and total bisphenol A concentrations are <19.8 ug/L. The 95th percentile total bisphenol A concentration for 394 adult volunteers (males and females; 20–59 years old) from the NHANES III survey was 5.18 ug/L. Girls age 6-9 in the U.S. have concentrations of total bisphenol A < 54.3 ug/L, with median concentrations ranging from 1.8-2.4 ug/L (86, 97). No U.S. studies have examined blood or semen concentrations of bisphenol A. Amniotic fluid total bisphenol A concentrations in the U.S are less than 1.96 ug/L. Dental sealant exposure to bisphenol A occurs primarily with use of the dental sealant bisphenol dimethylacylate. This exposure is considered an acute and infrequent event with little relevance to estimating general population exposures.
Bisphenol A Intake Estimates:
The panel found that previous oral intake estimates for infants fed formula and breast milk did not use levels reported for the U.S. population, so the panel estimated intake based on typically-used parameters.
The panel found the food intake estimates made by the European Commission used concentrations of bisphenol A comparable to U.S. food concentrations in their intake estimates, so have included these estimates as well. Estimates from duplicate diets in U.S. children found lower bisphenol A concentrations in foods than those estimated by the European Commission, therefore the aggregate estimates of intake by Wilson were somewhat lower than those estimated by the European Commission. However, the aggregate intake estimates by Wilson et al. are in line with the estimates based on urinary metabolite measurements for children described above.
Overall Conclusions
The panel spent a considerable amount of time attempting to interpret and understand the inconsistent findings reported in the “low dose” literature for bisphenol A. Conducting low dose studies can be challenging because the effects may be subtle and small in magnitude and therefore more difficult to statistically distinguish from background variability. The inherent challenge of conducting these types of studies may be exacerbated with bisphenol A because the endpoints of concern are endocrine-mediated and potentially impacted by factors that include phytoestrogen content of the animal feed, extent of bisphenol A exposure from caging or water bottles, and the alleged sensitivity of the animal model to estrogens. The panel believed that high dose studies are less susceptible to these types of influences because the toxicologic response should be more robust and less variable. While the panel did not necessarily expect a specific effect to display a monotonic dose response (e.g., consistently increasing organ size), many members of the panel expected the high dose studies with bisphenol A to detect some manifestation of toxicity (e.g., altered weight, histopathology) in tissues reported to be affected at low doses even if the study could not replicate the reported low dose effect. There are several large, robust, well designed studies with multiple dose groups using several strains of rats and mice and none of these detected any adverse reproductive effects at low to moderate dosage levels of BPA administered via the relevant route of human exposures. Further, none of these studies detected changes in prostate weight, age at puberty (rat), pathology or tumors in any tissue, or reproductive tract malformations. For this reason, panel members gave more weight to studies that evaluated both low and high doses of bisphenol A compared to low-dose-only studies in cases where the target tissues were comparably assessed.
Every chemical that produces low dose cellular and molecular alterations of endocrine function also produces a cascade of effects increasing in severity resulting in clearly adverse alterations at higher doses, albeit the effects can be different from those seen at low doses. With these endocrine disrupters, but not BPA, the low dose effects are often causally linked to the high dose adverse effects of the chemical. This is true for androgens like testosterone and trenbolone, estrogens like DES, 17β-estradiol and ethinyl estradiol, xenoestrogens like methoxychlor and genistein, and antiandrogens like vinclozolin, for example.
Hence, the failure of BPA to produce reproducible adverse effects via a relevant route of exposure, coupled with the lack of robustness of the many of the low dose studies (sample size, dose range, statistical analyses and experimental design, GLP) and the inability to reproduce many of these effects of any adverse effect strains the credibility of some of these study results. They need to be replicated using appropriate routes of exposures, adequate experimental designs and statistical analyses and linked to higher dose adverse effects if they are to elevate our concerns about the effects of BPA on human health.
The lack of reproducibility of the low dose effects, the absence of toxicity in those low-dose-affected tissues at high doses, and the uncertain adversity of the reported effects led the panel to express “minimal” concern for reproductive effects.
In contrast, the literature on bisphenol A effects on neural and behavioral response is more consistent with respect to the number of “positive” studies although it should be noted that the high dose studies that proved to be the most useful for evaluating reproductive effects did not adequately assess neural and behavioral responses. In addition, even though different investigators assessed different neural and behavioral endpoints, the panel concluded that the overall findings suggest that bisphenol A may be associated with neural changes in the brain and behavioral alterations related to sexual dimorphism in rodents. For this reason, the panel expressed “some” concern for these effects even though it is not clear the reported effects constitute an adverse toxicological response.
CONCERNS are expressed relative to current estimates of general population exposure levels in the U.S.
1. For pregnant women and fetuses, the Expert Panel has different levels of concern for the different developmental endpoints that may be susceptible to bisphenol A disruption, as follows:
• For neural and behavioral effects, the Expert Panel has some concern
• For prostate effects, the Expert Panel has minimal concern
• For the potential effect of accelerated puberty, the Expert Panel has minimal concern
• For prostate effects, the Expert Panel has minimal concern
• For the potential effect of accelerated puberty, the Expert Panel has minimal concern
• For birth defects and malformations, the Expert Panel has negligible concern
2. For infants and children, the Expert Panel has the following levels of concern for biological processes that might be altered by Bisphenol A, as follows:
• some concern for neural and behavioral effects
• minimal concern for the effect of accelerated puberty
3. For adults, the Expert Panel has negligible concern for adverse reproductive effects following exposures in the general population to Bisphenol A. For highly exposed subgroups, such as occupationally exposed populations, the level of concern is elevated to minimal.
POINTS WORTH NOTING:
1. Current manufacturers of bisphenol A in the US are Bayer MaterialScience, Dow Chemical Company, General Electric, Hexion Specialty Chemicals, and Sunoco Chemicals. 2003 consumption patterns included 619,000 metric tons [~1.4 billion pounds] used in polycarbonate resins, 184,000 metric tons [~406 million pounds] used in epoxy resins, and 53,000 metric tons [~117 million pounds] used in other applications. The production of bisphenol A is increasing annually in the U.S., while the European Union is phasing out bisphenol A production.
2. Bisphenol A in daycares and home environments:
Two studies examining aggregate exposures in preschool age children in the US used GC/MS to measure bisphenol A concentrations in environmental media. In the first study, bisphenol A concentrations were measured in air outside 2 day care centers and the homes of 9 children. Bisphenol A was detected in 9 of 13 outdoor air samples at daycare centers and at homes. In indoor air from day care centers and homes, bisphenol A was detected in 12 of 13 samples. At those same locations, bisphenol A was detected in all of 13 samples of floor dust and play area soils (25-70% of indoor dust samples). In the second study, bisphenol A concentrations were measured inside and outside at least 222 homes and 29 daycare centers. Bisphenol A was detected in 31–44% of outdoor air samples from each location, and 45% to 73% of indoor air samples contained detectable concentrations of bisphenol A.
3. Potential exposures from food and water:
The European Union noted that the highest potential for human exposure to bisphenol A is through products that directly contact food. Examples of food contact materials that can contain bisphenol A include food and beverage containers with internal epoxy resin coatings and polycarbonate tableware and bottles, such as those used to feed infants.
4. Exposure of Bisphenol A in daycare and home food:
The highest potential for human exposure to bisphenol A is through products that directly contact food such as food and beverage containers with internal epoxy resin coatings and polycarbonate tableware and bottles, such as those used to feed infants. Dietary sources account for 99% of exposure.
A study examining aggregate exposures of US preschool age children measured bisphenol A concentrations in liquid food and solid food served to the children at home and at child care centers. Duplicate plates of food served to 9 children were collected over a 48-hour period. GC/MS analyses were conducted on 4 liquid food samples and 4 solid food samples from the child care center and 9 liquid food samples and 9 solid food samples from home. Bisphenol A was detected in all solid food samples, 3 liquid food samples from the child care center, and 2 liquid food samples from the home. Concentrations of bisphenol A were found in liquid and solid food.
The study examining aggregate exposures of US preschool age children was repeated with a larger sample and again measured bisphenol A concentrations in liquid food and solid food served to the children at home and at child care centers. Bisphenol A concentrations were measured by GC/MS in food served over a 48 hour period to at least 238 children at home and 49 children at daycare centers. Bisphenol A was detected in 83–100% of solid food samples and 61% to 80% of liquid food contained detectable concentrations of bisphenol A. Data were also collected for hand wipes of 193 children at daycare centers and 60 children at home. Bisphenol A was detected in 94–100% of handwipe samples, and food preparation surface wipes. Bisphenol A was detected in 85–89% of food preparation surface wipes from homes.
5. Bisphenol A and chlorine use:
When exposed to chlorine disinfectant, bisphenol A disappears within 4 hours, but the chlorinated bisphenol A congeners that are formed can remain in solution up to 20 hours when low chlorine doses are used. The toxicity of these chlorinated bisphenol A congeners is unknown; however, there is some evidence that estrogenic activity and receptor binding remains after chlorination.
6. Bisphenol A in fetuses:
Schönfelder et al. examined bisphenol A concentrations in maternal and fetal blood and compared bisphenol A concentrations in blood of male and female fetuses. In a study conducted at a German medical center, blood samples were obtained from 37 Caucasian women between 32 and 41 weeks gestation. Bisphenol A was detected in all samples tested. Mean bisphenol A concentrations were higher in maternal than fetal blood. Study authors noted that in 14 cases fetal bisphenol A plasma concentrations exceeded those detected in maternal plasma. Among those 14 cases, 12 fetuses were male, revealing significantly higher mean bisphenol A concentrations in the blood of male than female fetuses.
7. General toxicity:
Gross signs of toxicity observed in rats acutely exposed to bisphenol A included pale livers and gastrointestinal hemorrhage [reviewed by the European Union]. Acute effects of inhalation exposure in rats included transient and slight inflammation of nasal epithelium and ulceration of the oronasal duct. Based on LD50s observed in animals, the European Union concluded that bisphenol A is of low acute toxicity through all exposure routes relevant to humans, however there is evidence that bisphenol A is irritating and damaging to the eye and is irritating to the respiratory tract and possibly the skin.
8. Human developmental effects:
No studies were located on possible human developmental effects of bisphenol A.
National Toxicology Program
U.S. Department of Health and Human Services
SUMMARIES & CONCLUSIONS
From the Expert Panel Report
On the Reproductive and Developmental Toxicity of Bisphenol A
U.S. Department of Health and Human Services
SUMMARIES & CONCLUSIONS
From the Expert Panel Report
On the Reproductive and Developmental Toxicity of Bisphenol A
5.1 Developmental Toxicity
No data on the effects of human developmental exposure to Bisphenol A are available. There is a large literature describing studies in rodents and some work in other species. A large experimental animal literature was reviewed, assessed for its utility, and weighed based on the criteria established by this panel.
From the rodent studies we can conclude that Bisphenol A:
• Does not cause malformations or birth defects in rats or mice at levels up to the highest doses evaluated: 640 mg/kg/d (rats) and 1250 mg/kg/d (mice).
• Does not alter male or female fertility after gestational exposure up to doses of 450 mg/kg bw/d in the rat and 600 mg/kg bw/d in the mouse (highest dose levels evaluated).
• Does not permanently affect prostate weight at doses up to 475 mg/kg/d in adult rats or 600 mg/kg/d in mice.
• Does not cause prostate cancer in rats or mice after adult exposure at up to 148 or 600 mg/kg/d, respectively.
• Does change the age of puberty in male or female rats at high doses (ca. 475 mg/kg/d).
Rodent studies suggest that Bisphenol A:
• Causes neural and behavioral alterations related to disruptions in normal sex differences in rats and mice (0.01-0.2 mg/kg/d).
The data on bisphenol A are insufficient to reach a firm conclusion about:
• A change in the onset of puberty in male rats or mice at doses up to 475 – 600 mg/kg/d.
• An acceleration in the age of onset of puberty at a low dose in female mice at 0.0024 mg/kg/d, that Bisphenol A:
• Causes neural and behavioral alterations related to disruptions in normal sex differences in rats and mice. (0.01-0.2 mg/kg/d).
The data on bisphenol A are insufficient to reach a firm conclusion about:
• A change in the onset of puberty in male rats or mice at doses up to 475 – 600 mg/kg/d.
• An acceleration in the age of onset of puberty at a low dose in female mice at 0.0024 mg/kg/d, the only dose tested.
• Whether Bisphenol A predisposes rats toward prostate cancer or mice towards urinary tract deformations.
5.2 Reproductive Toxicity
There are insufficient data to evaluate whether bisphenol A causes male or female reproductive toxicity in humans. A large experimental animal literature was reviewed, assessed for its utility, and weighted based upon the criteria established by this expert panel, including an evaluation of experimental design and statistical procedures. These animal data are assumed relevant for the assessment of human hazard.
Female effects:
There is sufficient evidence in rats and mice that bisphenol A causes female reproductive toxicity with subchronic or chronic oral exposures with a NOAEL of 47.5 mg/kg bw/day and a LOAEL of ≥475 mg/kg bw/day.
Male effects:
There is sufficient evidence in rats and mice that bisphenol A causes male reproductive toxicity with subchronic or chronic oral exposures with a NOAEL of 4.75 mg/kg bw/day and a LOAEL of .47.5 mg/kg bw/day.
Human Exposures
Bisphenol A is FDA-approved for use in polycarbonate and epoxy resins that are used in consumer products such as food containers (e.g., milk, water, and infant bottles) food can linings. Resins, polycarbonate plastics, and other products manufactured from bisphenol A can contain trace amounts of residual monomer and additional monomer may be generated during breakdown of the polymer.
Environmental Exposures
Bisphenol A emitted from manufacturing operations is unlikely to be present in the atmosphere in high concentrations. However, it was found in 31-44% of outdoor air samples with concentrations of <>
The highest potential for human exposure to bisphenol A is through products that directly contact food such as food and beverage containers with internal epoxy resin coatings and through the use of polycarbonate tableware and bottles, such as those used to feed infants. Studies examining the extraction of bisphenol A from polycarbonate infant bottles in the U.S. found concentrations < 5 ug/L. Canned infant formulas in the U.S. had a maximum level of 13 ug/L in the concentrate that produced a maximum of 6.6 ug/L when mixed with water. Breast milk studies in the U.S. have found up to 6.3 ug/L free bisphenol A in samples. Measured bisphenol A concentrations in canned foods in the U.S are less than 39 ug/kg. Limited drinking water sampling in the U.S. indicates that bisphenol A concentrations were all below the limit of detection (<0.1 ng/L).
Biological Measures of Bisphenol A in Humans
The panel finds the greatest utility in studies of biological samples that use sensitive and specific analytical methods (LC-MS or GC-MS) and report quality control measures for sample handling and analysis. The panel further focused on biological monitoring done in U.S. populations. In the U.S, adult urine concentrations of free bisphenol A are less than 0.6 ug/L and total bisphenol A concentrations are <19.8 ug/L. The 95th percentile total bisphenol A concentration for 394 adult volunteers (males and females; 20–59 years old) from the NHANES III survey was 5.18 ug/L. Girls age 6-9 in the U.S. have concentrations of total bisphenol A < 54.3 ug/L, with median concentrations ranging from 1.8-2.4 analytical methods (LC-MS or GC-MS) and report quality control measures for sample handling and analysis. The panel further focused on biological monitoring done in U.S. populations. In the U.S, adult urine concentrations of free bisphenol A are less than 0.6 ug/L and total bisphenol A concentrations are <19.8 ug/L. The 95th percentile total bisphenol A concentration for 394 adult volunteers (males and females; 20–59 years old) from the NHANES III survey was 5.18 ug/L. Girls age 6-9 in the U.S. have concentrations of total bisphenol A < 54.3 ug/L, with median concentrations ranging from 1.8-2.4 ug/L (86, 97). No U.S. studies have examined blood or semen concentrations of bisphenol A. Amniotic fluid total bisphenol A concentrations in the U.S are less than 1.96 ug/L. Dental sealant exposure to bisphenol A occurs primarily with use of the dental sealant bisphenol dimethylacylate. This exposure is considered an acute and infrequent event with little relevance to estimating general population exposures.
Bisphenol A Intake Estimates:
The panel found that previous oral intake estimates for infants fed formula and breast milk did not use levels reported for the U.S. population, so the panel estimated intake based on typically-used parameters.
The panel found the food intake estimates made by the European Commission used concentrations of bisphenol A comparable to U.S. food concentrations in their intake estimates, so have included these estimates as well. Estimates from duplicate diets in U.S. children found lower bisphenol A concentrations in foods than those estimated by the European Commission, therefore the aggregate estimates of intake by Wilson were somewhat lower than those estimated by the European Commission. However, the aggregate intake estimates by Wilson et al. are in line with the estimates based on urinary metabolite measurements for children described above.
Overall Conclusions
The panel spent a considerable amount of time attempting to interpret and understand the inconsistent findings reported in the “low dose” literature for bisphenol A. Conducting low dose studies can be challenging because the effects may be subtle and small in magnitude and therefore more difficult to statistically distinguish from background variability. The inherent challenge of conducting these types of studies may be exacerbated with bisphenol A because the endpoints of concern are endocrine-mediated and potentially impacted by factors that include phytoestrogen content of the animal feed, extent of bisphenol A exposure from caging or water bottles, and the alleged sensitivity of the animal model to estrogens. The panel believed that high dose studies are less susceptible to these types of influences because the toxicologic response should be more robust and less variable. While the panel did not necessarily expect a specific effect to display a monotonic dose response (e.g., consistently increasing organ size), many members of the panel expected the high dose studies with bisphenol A to detect some manifestation of toxicity (e.g., altered weight, histopathology) in tissues reported to be affected at low doses even if the study could not replicate the reported low dose effect. There are several large, robust, well designed studies with multiple dose groups using several strains of rats and mice and none of these detected any adverse reproductive effects at low to moderate dosage levels of BPA administered via the relevant route of human exposures. Further, none of these studies detected changes in prostate weight, age at puberty (rat), pathology or tumors in any tissue, or reproductive tract malformations. For this reason, panel members gave more weight to studies that evaluated both low and high doses of bisphenol A compared to low-dose-only studies in cases where the target tissues were comparably assessed.
Every chemical that produces low dose cellular and molecular alterations of endocrine function also produces a cascade of effects increasing in severity resulting in clearly adverse alterations at higher doses, albeit the effects can be different from those seen at low doses. With these endocrine disrupters, but not BPA, the low dose effects are often causally linked to the high dose adverse effects of the chemical. This is true for androgens like testosterone and trenbolone, estrogens like DES, 17β-estradiol and ethinyl estradiol, xenoestrogens like methoxychlor and genistein, and antiandrogens like vinclozolin, for example.
Hence, the failure of BPA to produce reproducible adverse effects via a relevant route of exposure, coupled with the lack of robustness of the many of the low dose studies (sample size, dose range, statistical analyses and experimental design, GLP) and the inability to reproduce many of these effects of any adverse effect strains the credibility of some of these study results. They need to be replicated using appropriate routes of exposures, adequate experimental designs and statistical analyses and linked to higher dose adverse effects if they are to elevate our concerns about the effects of BPA on human health.
The lack of reproducibility of the low dose effects, the absence of toxicity in those low-dose-affected tissues at high doses, and the uncertain adversity of the reported effects led the panel to express “minimal” concern for reproductive effects.
In contrast, the literature on bisphenol A effects on neural and behavioral response is more consistent with respect to the number of “positive” studies although it should be noted that the high dose studies that proved to be the most useful for evaluating reproductive effects did not adequately assess neural and behavioral responses. In addition, even though different investigators assessed different neural and behavioral endpoints, the panel concluded that the overall findings suggest that bisphenol A may be associated with neural changes in the brain and behavioral alterations related to sexual dimorphism in rodents. For this reason, the panel expressed “some” concern for these effects even though it is not clear the reported effects constitute an adverse toxicological response.
CONCERNS are expressed relative to current estimates of general population exposure levels in the U.S.
1. For pregnant women and fetuses, the Expert Panel has different levels of concern for the different developmental endpoints that may be susceptible to bisphenol A disruption, as follows:
• For neural and behavioral effects, the Expert Panel has some concern
• For prostate effects, the Expert Panel has minimal concern
• For the potential effect of accelerated puberty, the Expert Panel has minimal concern
• For prostate effects, the Expert Panel has minimal concern
• For the potential effect of accelerated puberty, the Expert Panel has minimal concern
• For birth defects and malformations, the Expert Panel has negligible concern
2. For infants and children, the Expert Panel has the following levels of concern for biological processes that might be altered by Bisphenol A, as follows:
• some concern for neural and behavioral effects
• minimal concern for the effect of accelerated puberty
3. For adults, the Expert Panel has negligible concern for adverse reproductive effects following exposures in the general population to Bisphenol A. For highly exposed subgroups, such as occupationally exposed populations, the level of concern is elevated to minimal.
The findings and conclusions of this report are those of the Expert Panel and should not be construed to represent the views of the National Toxicology Program.
END OF REPORT
END OF REPORT
POINTS WORTH NOTING:
1. Current manufacturers of bisphenol A in the US are Bayer MaterialScience, Dow Chemical Company, General Electric, Hexion Specialty Chemicals, and Sunoco Chemicals. 2003 consumption patterns included 619,000 metric tons [~1.4 billion pounds] used in polycarbonate resins, 184,000 metric tons [~406 million pounds] used in epoxy resins, and 53,000 metric tons [~117 million pounds] used in other applications. The production of bisphenol A is increasing annually in the U.S., while the European Union is phasing out bisphenol A production.
2. Bisphenol A in daycares and home environments:
Two studies examining aggregate exposures in preschool age children in the US used GC/MS to measure bisphenol A concentrations in environmental media. In the first study, bisphenol A concentrations were measured in air outside 2 day care centers and the homes of 9 children. Bisphenol A was detected in 9 of 13 outdoor air samples at daycare centers and at homes. In indoor air from day care centers and homes, bisphenol A was detected in 12 of 13 samples. At those same locations, bisphenol A was detected in all of 13 samples of floor dust and play area soils (25-70% of indoor dust samples). In the second study, bisphenol A concentrations were measured inside and outside at least 222 homes and 29 daycare centers. Bisphenol A was detected in 31–44% of outdoor air samples from each location, and 45% to 73% of indoor air samples contained detectable concentrations of bisphenol A.
3. Potential exposures from food and water:
The European Union noted that the highest potential for human exposure to bisphenol A is through products that directly contact food. Examples of food contact materials that can contain bisphenol A include food and beverage containers with internal epoxy resin coatings and polycarbonate tableware and bottles, such as those used to feed infants.
4. Exposure of Bisphenol A in daycare and home food:
The highest potential for human exposure to bisphenol A is through products that directly contact food such as food and beverage containers with internal epoxy resin coatings and polycarbonate tableware and bottles, such as those used to feed infants. Dietary sources account for 99% of exposure.
A study examining aggregate exposures of US preschool age children measured bisphenol A concentrations in liquid food and solid food served to the children at home and at child care centers. Duplicate plates of food served to 9 children were collected over a 48-hour period. GC/MS analyses were conducted on 4 liquid food samples and 4 solid food samples from the child care center and 9 liquid food samples and 9 solid food samples from home. Bisphenol A was detected in all solid food samples, 3 liquid food samples from the child care center, and 2 liquid food samples from the home. Concentrations of bisphenol A were found in liquid and solid food.
The study examining aggregate exposures of US preschool age children was repeated with a larger sample and again measured bisphenol A concentrations in liquid food and solid food served to the children at home and at child care centers. Bisphenol A concentrations were measured by GC/MS in food served over a 48 hour period to at least 238 children at home and 49 children at daycare centers. Bisphenol A was detected in 83–100% of solid food samples and 61% to 80% of liquid food contained detectable concentrations of bisphenol A. Data were also collected for hand wipes of 193 children at daycare centers and 60 children at home. Bisphenol A was detected in 94–100% of handwipe samples, and food preparation surface wipes. Bisphenol A was detected in 85–89% of food preparation surface wipes from homes.
5. Bisphenol A and chlorine use:
When exposed to chlorine disinfectant, bisphenol A disappears within 4 hours, but the chlorinated bisphenol A congeners that are formed can remain in solution up to 20 hours when low chlorine doses are used. The toxicity of these chlorinated bisphenol A congeners is unknown; however, there is some evidence that estrogenic activity and receptor binding remains after chlorination.
6. Bisphenol A in fetuses:
Schönfelder et al. examined bisphenol A concentrations in maternal and fetal blood and compared bisphenol A concentrations in blood of male and female fetuses. In a study conducted at a German medical center, blood samples were obtained from 37 Caucasian women between 32 and 41 weeks gestation. Bisphenol A was detected in all samples tested. Mean bisphenol A concentrations were higher in maternal than fetal blood. Study authors noted that in 14 cases fetal bisphenol A plasma concentrations exceeded those detected in maternal plasma. Among those 14 cases, 12 fetuses were male, revealing significantly higher mean bisphenol A concentrations in the blood of male than female fetuses.
7. General toxicity:
Gross signs of toxicity observed in rats acutely exposed to bisphenol A included pale livers and gastrointestinal hemorrhage [reviewed by the European Union]. Acute effects of inhalation exposure in rats included transient and slight inflammation of nasal epithelium and ulceration of the oronasal duct. Based on LD50s observed in animals, the European Union concluded that bisphenol A is of low acute toxicity through all exposure routes relevant to humans, however there is evidence that bisphenol A is irritating and damaging to the eye and is irritating to the respiratory tract and possibly the skin.
8. Human developmental effects:
No studies were located on possible human developmental effects of bisphenol A.
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