A SAFETY ASSESSMENT FOR THE USE OF POLYCARBONATE PLASTIC WATER CONTAINERS
Quang Q. Bui, Ph.D
Diplomate, American Board of Toxicology
Palo Alto, CA 94304

INTRODUCTION 

Bisphenol A (BPA; CAS # 80-05-7) is an industrial chemical used in the production of polycarbonate plastics, epoxy resins and other products. Polycarbonate plastics are used in food and drink packaging.  BPA is also found as a residue in paper and cardboard food packaging materials.   

Concerns were raised by employees at our facility in Palo Alto relating to the potential exposure to BPA from commercial 5-gallon polycarbonate bottles.
 

RISK ASSESSMENT 

This risk assessment follows the basic steps outlined by the US National Research Council (NRC): hazard identification, dose-response assessment, exposure assessment and risk characterization.  These steps lead to a final risk management and judgement concerning risk acceptability.

1. Hazard Identification

The objective of the hazard identification is to qualitatively identify the health effects that may be associated with exposure to BPA.

1. Reproduction and Developmental Toxicity

Although there is no direct evidence that exposure of people to BPA adversely affects reproduction or development, studies with laboratory rodents show that exposure to high dose levels of bisphenol A during pregnancy and/or lactation can reduce survival, birth weight, and growth of offspring early in life,            and delay the onset of puberty in males and females. These effects were seen at maternally toxic doses.  Studies show that bisphenol A does not reduce fertility in laboratory animals exposed in adult­hood and/or during development at dose levels up to 500 mg/kg bw/day in rats.

2. Carcinogenicity

No human data examining the carcinogenicity of BPA were identified.

The carcinogenic potential of BPA was investigated in F344 rats and B6C3F1 mice.  It was concluded that under the conditions of these studies, there was no convincing evidence that BPA was carcinogenic in F344 rats or B6C3F1 mice.  There was suggestive evidence of increased cancer in the hematopoietic system based on marginally significant increases in leukemia in male rats, non-statistically significant increases in leukemia in female rats, and a marginally significant increase in combined incidence of lymphoma and leukemia in male mice. A statistically significant increase in testicular interstitial cell tumors in aging F344 rats was also found but the effect was not considered conclusive evidence because of the high incidence of the testicular neoplasm in aging F344 rats (88% incidence in historical controls). The European Union (2003) concluded, ‘‘Overall, all of these [tumor] findings in rats and mice are not considered toxicologically significant. Consequently, it is concluded that BPA was not carcinogenic in both species.’’

3. Genotoxicity

There is no evidence to suggest that BPA is either a mutagen or clastogen from the published in vivo and in vitro assays.

4. Low-Dose Hypothesis

In recent years, a hypothesis has been advanced claiming that exposure to extremely low doses of certain substances could cause adverse health effects in humans, including disruption of normal hormonal functions. According to this "low-dose hypothesis", health effects occur at doses far below levels previously determined to be safe using well-established toxicological procedures and principles. The low-dose hypothesis is largely based on several small-scale experimental studies that report reproductive or developmental effects in mice or rats from low doses of BPA. Several attempts to confirm the hypothesis by repeating these initial experiments have shown that the results cannot be replicated, which indicates that the hypothesis is not valid. More importantly, definitive large-scale experiments using accepted protocols have also found no evidence for reproductive or developmental effects from low doses of BPA. Consequently, a number of independent scientific bodies, after reviewing all available evidence, have concluded that the low-dose hypothesis is unproven. 

The US National Toxicology Program (US NTP) and the Center for the Evaluation of Risks to Human Reproduction (CERHR) Expert Panel on BPA conclude that:

·         There is negligible concern that exposure of pregnant women to BPA will result in fetal or neonatal mortality, birth defects or reduced birth weight and growth in their offspring

·         There is negligible concern that exposure to BPA will cause reproductive effects in non-occupationally exposed adults

2. Dose-response Assessment

The objective of the dose response assessment is to define the relationship between exposure level and frequency and severity of any health effects associated with exposure to BPA.

Based on the results of the lifetime exposure cancer studies conducted by the US NTP, the US EPA (Environmental Protection Agency) has established the NOAEL (no observed adverse effect level) at 50 mg/kg bw/day. 

                  Systemic toxicity NOAEL = 50 mg/kg bw/day

Based on the two multi-generation reproductions studies (Ema et al., 2001; Tyl et al., 2002), a reproductive NOAEL is also established at 50 mg/kg bw/day

                  Reproductive NOAEL = 50 mg/kg bw/day

Using a 1000X margin of safety, the US EPA has established a reference dose at 0.05 mg/kg bw/day or 50 µg/kg bw/day.

The European Union concurs with the selection of 50 mg/kg bw/day as the NOAEL for both systemic toxicity and reproductive toxicity.

3. Exposure Assessment

The sources of exposure to BPA include dietary (primary), air, dust, and drinking water.  In this assessment, the primary source of concern is exposure to BPA via drinking water contained in polycarbonate plastic bottles.

Studies conducted by the US Food and Drug Administration (FDA), the United Kingdom Ministry of Agriculture, Fisheries and Food (MAFF), the Japanese National Institute of Health Sciences (NIHS) and the United Kingdom Department of Trade and Industry (DTI) show that, under typical use conditions, the potential migration of BPA into water/food is generally less than 5 parts per billion (ppb). In the FDA study, water from several 5-gallon polycarbonate bottles was analyzed after being stored in the bottles for up to 39 weeks.  BPA was found a levels ranging from 0.1 to 4.7 ppb.  Based on these results and using procedures recommended by the US FDA and US EPA, the estimated intake of BPA from polycarbonate plastic water bottles is calculated as:

      Average water intake per day = 2 liters

      Concentration of BPA in water = 5 ppb (maximum) = 5 µg

      Estimated daily intake of BPA = 2 L x 5 µg = 10 µg

      Estimated daily intake of BPA from water bottles = 0.2 µg/kg bw/day

                  (using 60 kg as the default body weight)

4. Risk Characterization

The objective of the risk characterization is to determine if the potential exposure to BPA from water bottles will result in any risk to human’s health.  A margin of exposure is calculated based on the NOAEL (discussed above) and the estimated daily intake:

                              NOAEL (mg/kg bw/day______________

                              Estimated daily exposure (mg/kg bw/day

Margin of Safety for Systemic Toxicity:

                              50 mg/kg bw/day or 50,000 µg/kg bw/day_ = 250,000

                                                      0.2 µg/bw/day

Margin of Safety for Reproductive Toxicity:

                              50 mg/kg bw/day or 50,000 µg/kg bw/day_ = 250,000

                                                      0.2 µg/bw/day

Even under the worst case scenario that a person is drinking only water from polycarbonate plastic containers, a 250,000X fold margin of safety still exists between daily exposure and the NOAEL.

RECOMMENDATION AND CONCLUSION 

The US EPA has established a reference dose at 50 µg/kg bw/day, which is defined as a daily oral exposure that is likely to be without deleterious effects to human during a life time exposure.  This reference dose is calculated by dividing the NOAEL (50 mg/kg bw/day) by a safety factor (1000). 

The European Union Scientific Committee on Food (SCF) set a Tolerable Daily Intake (TDI) for BPA at 10 µg/kg bw/day.  The TDI represents a lifetime exposure level that is considered to be safe. 

The estimated maximum daily intake of BPA from consumption of water from polycarbonate plastics is 0.2 µg/kg bw/day which is well below the US EPA reference dose of  50 µg/kg bw/day and the EU SCF tolerable daily intake of 10 µg/kg bw/day.  The potential exposure to BPA from water in polycarbonate plastic containers is 250 times lower than the US EPA reference dose and 50 times lower than the EU SCF tolerable daily intake. 

To echo the US EPA, US FDA and the European Food Safety Authority (EFSA), it is also this reviewer’s professional opinion that products made from materials based on BPA, such as polycarbonate or epoxy resins, can be used safely and the very low levels of exposure from food contact applications like baby bottles, water bottles, water plastic containers or epoxy coated cans do not pose any health concern when used as intended. 

Palo Alto, CA 94304

June 01, 2009
Quang Q. Bùi, Ph.D.

Diplomate, American Board of Toxicology