Table 2.

Study Quality Issues Associated with Studies on BPA^a

study type	number of studies reviewed	studies deemed “useful” for hazard identification and/or risk assessment	study quality issues
Pharmacokinetic	34	3 useful for hazard identification and risk assessment	Study focus was limited Small sample size Inconsistency between study concentrations and those existing in the literature (e.g., controlled human absorption, distribution, metabolism, and excretion (ADME), animal pharmacokinetic (PK), and physiologically based pharmacokinetic (PBPK) modeling) Potential contamination with BPA monomer
Neurotoxicology	36	1 useful for hazard identification and risk assessment; 6 useful for hazard identification	Not designed to establish NOAELs Routes of exposure that were not relevant to human exposure (e.g., subcutaneous, intraperitoneal) No dose confirmation Control issues (e.g., varying degrees of control for environmental exposure; controls were sometimes not reported) Did not account for lactation exposure (i.e., dose in dams may not have been high enough to ensure adequate transfer to pups via lactation) Doses ranged widely Less than 3 doses used No positive control Exposure was not confirmed Human exposures were estimated through single urine samples Did not account for litter effects Overinterpretation of marginally significant results Inappropriate extrapolation of findings to humans
Reproductive and Developmental	5	2 useful for hazard identification	Routes of exposure that were not relevant to human exposure (e.g., subcutaneous, implanted osmotic pumps) Not guideline compliant Reproductive parameters were not evaluated in both sexes Less than 3 doses used Lack of complete reporting in study design and procedures Vehicle used was oil; some of these oils have been shown to have estrogenic constituents
Carcinogenesis	5	None	Routes of exposure that were not relevant to human exposure (e.g., subcutaneous, implanted osmotic pumps) Vehicle used was oil; some of these oils have been shown to have estrogenic constituents Less than 3 doses used Large fold-change in doses used Study design limitations
Other End Points (Systemic effects)	13	2 useful for hazard identification	Routes of exposure that were not relevant to human exposure (e.g., subcutaneous, intraperitoneal) Vehicle used was oil; some of these oils have been shown to have estrogenic constituents Diets contained phytoestrogens Litter effects were not accounted for No positive control Rodent housing information was not provided Exposure was not confirmed BPA in housing materials was not assessed Dosing solutions were not certified
Epidemiology	48	7 useful for hazard identification	Did not account for extraneous contamination of BPA samples by the collecting device Used blood or cord-blood measurements; however, these have been demonstrated to be unreliable metrics, as BPA has a short half-life in plasma Plasma BPA cannot adequately discriminate between true signal and noise Single time points (i.e., mostly cross-sectional studies) Associations were reported for transformed but not original data Use of plastic sample containers but potential for BPA leaching was not assessed Small sample size Single exposure measure Not controlling for confounders Not controlling for multiple hypothesis testing Poor description of sample collection timing No clinical significance for measured outcome Highly variable outcome used as target end point Arbitrary definition of clinical outcome Selective reporting of positive results No dose–response relationship Inconsistent inter- or intrastudy results Lack of generalizability Reverse causality

^aAlthough 142 studies were carried out on BPA, only a select few (21) were deemed “useful” for hazard identification and/or risk assessment. The remaining 121 studies had a number of associated quality issues which prevented them from being included in a hazard or risk assessment.