Endocrine Disruptive Activity of Bisphenol A and its Relationship to Metabolic Syndrome: Explaining Ubiquitous Exposures and Elusive Effects through Animal Studies Open Access
Hesla, Kirsten Faith (2010)
Published
Abstract
Abstract
Endocrine Disruptive Activity of Bisphenol A and its Relationship
to Metabolic
Syndrome: Explaining Ubiquitous Exposures and Elusive Effects
through Animal Studies
By Kirsten Hesla
The pathways and processes of endocrine disrupting chemicals are
extremely
species specific (Ben-Jonathan et al, 2009). The ubiquitous
chemical and endocrine
disruptor bisphenol A (BPA) has been implicated in several
exposure-disease
relationships. There is substantial research suggesting that BPA
has the potential to alter
metabolic processes. In vivo and in vitro
experimental studies isolate specific variables
and explore exposure pathways in different taxonomic groups; they
provide a basis for
determining an exposure-disease causal relationship and insight
into relevant doses and
molecular mechanisms of operation. This meta-analysis integrates
the findings from
multiple in vivo and in vitro animal studies to
provide a probability estimate of an
association between exposure dose of BPA, and the symptoms
characteristic of metabolic
syndrome. The results indicate that low-dose exposures are
significantly more likely to
result in a metabolic effect that is deleterious to health (NTP,
2001; The Endocrine
Society, 2009). The probability coefficient that determined the
relationship between dose
and metabolic effect was statistically significant (p=0.033) and
demonstrated that that
probability of a metabolic effect is higher in the low dose range.
The probability that
BPA will induce insulin resistance is more likely at low-doses but
the probability of
adipose tissue development is higher than insulin resistance at
every dose level. BPA at
low-doses was also shown to have a greater variety of metabolic
effects as opposed to
high-doses. The results of this meta-analysis suggest that there is
a correlation between
BPA and metabolic syndrome, especially at low-dose exposures.
Table of Contents
Table of Contents
INTRODUCTION
BACKGROUND
Endocrine Disrupting Potential of Bisphenol A
Characteristics of Metabolic Syndrome
HYPOTHESES
METHODS
Literature Review and Study Selection
Article Content and Quality Review
Statistical Methods
RESULTS
Metabolic Effect
Figure 1. The Probability of Metabolic Effect at a Given Dose
Figure 2. Distribution of Metabolic Effect Probabilities at a Given Dose
Endpoints
Figure 3. Probability of Adipose Tissue Development versus Insulin Resistance
Given a Positive Metabolic Effect Dose
DISCUSSION
Determining a New "Safe Dose"
Modes of Endocrine Action Inducing Metabolic Syndrome
Considerations
Study Comparisons
Human Evidence
Future Research
Table 1. Summary Data of Studies Evaluated for BPA
Exposure and Metabolic Effects
Table 2. Dose-Conversion and Specific Endpoint Data Based on Study
Table 3. Dose Specific Probit Regression of Metabolic Effect
Table 4. Probit Regression of Positive Metabolic Effect
Doses and Specific Endpoints
REFERENCES
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