According to Jason Aungst, division of food contact notifications, Office of Food Additive Safety (OFAS), Center for Food Safety and Applied Nutrition (CFSAN), the FDA’s BPA Joint Emerging Science Working Group that previously identified NOAEL (No observed adverse effect level) of 5 mg/kg bw/day for systemic toxicity from subchronic/multigenerational studies using rodents is the most appropriate NOAEL for a safety assessment of oral or dietary exposures.
'Margins of safety exceed uncertainty factor'
“Available pharmacokinetic data and comparisons between ages and species further support use of this NOAEL as very conservative in extrapolating to humans,” he said.
“Compared to the 90th percentile exposures cited for populations of less than two years old and greater than two years old, the margins of safety exceed the uncertainty factor of 1,000.”
Aungst added a number of additional research studies are currently in progress, including NCTR two year rodent chronic toxicity study on BPA, NCTR development of PBPK models, and NIEHS human pharmacokinetic studies.
Recent pharmacokinetic data and physiologically-based pharmacokinetic models as evaluated by the Working Group suggest the magnitude of the uncertainty factors provide an overly-conservative safety margin in extrapolating from a rat study to the human scenario.
For interspecies variability, rats and neonatal rodents have been shown to metabolize BPA much less efficiently than primates. The available data suggest all ages of primates have multiple forms of enzymes capable of metabolizing BPA; Physiologically Based Pharmacokinetic (PBPK) models predict and biomonitoring data support the conclusion that serum levels of the active form of BPA in primates (including humans) of all ages will be approximately 1000-fold less than the ingested dose.
Minor impact of rodent enterohepatic recirculation
The decreased metabolic capacity in rodents with a minor impact of rodent enterohepatic recirculation results in higher internal exposure levels in rodents than primates when given the same oral dose.
This suggests the rat as the more “sensitive” species, diminishing the support for the full interspecies variability factor of 10x. However, as an additional conservative measure in deference to hazard endpoints identified by the Working Group, the interspecies uncertainty factor was not modified herein.
This safety assessment may be revised pending completion, review, and identification of data from these or other studies relevant to a dietary safety assessment.
In response to the findings, Dr. John Rost, president, The North American Metal Packaging Alliance said he welcomed the assessment.
“It should put to rest once and for all concerns about its (BPA) safe use in canned foods,” he added.
“FDA researchers could not have been more clear or definitive in their conclusion that an adequate margin of safety exists for BPA at current levels of exposure from food contact uses.
“FDA scientists reviewed the most current animal and human studies on BPA and determined that there was no new information that would suggest the need for any changes to current exposure guidelines.”
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SOURCE: 2014 Updated safety assessment of Bisphenol A (BPA) for use in food contact applications.
REFERENCE: DYPI 4570
DATE: June 17, 2014
AUTHOR: Jason Aungst, Division of Food Contact Notifications, Office of Food Additive Safety (OFAS), Center for Food Safety and Applied Nutrition (CFSAN, HFS-275).