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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
50 mg/kg bw/day
Additional information

The No-Observed-Adverse-Effect-Level (NOAEL) for both parental and reproductive adverse effects in the rat three-generation reproduction feeding study was approximately 50 mg Bisphenol A/kg/day. Generally, any evidence of adverse reproductive effects was only observed in the presence of parental toxicity at oral dose levels of 500 mg/kg/day and higher in rodents. The NOAEL of approximately 50 mg/kg/day for both parental systemic effects and reproductive effects in the rat three-generation reproduction study is the most appropriate value upon which to derive worker and general population DNELs. This NOAEL value of 50 mg/kg/day is supported by NOAEL for both parental systemic and reproductive effects observed in the mouse two-generation reproduction study. Similar findings may be anticipated for BPA-Tars.

Following E.C.H.A. guidance (Guidance on information requirements and chemical safety assessment, Chapter R.8: May 2008) the Assessment Factors (AF) applied for derivation of the DNELs were: Interepecies, 4-fold rat scalling, Intraspecies, 3-fold (worker) and 5-fold (general population), Study duration, subchronic to chronic, 2 -fold and use of read-across data, 2-fold. Interspecies scalling was not applied in derivation of the inhalation DNELS. The oral rodent NOAEL dose was first adjusted to a human inhalation dose. The Total AFs applied in derivation of oral and dermal DNELs were 48-fold (worker) and 80-fold (general population). Total AFs used for derivation of inhalation DNELs were: 12-fold (worker) and 20-fold (general population). The resulting long-term systemic DNELs are as follows: DNEL oral (general population) = 0.625 mg.kg/day, DNEL dermal (worker) = 1.0 mg/kg/day, DNEL dermal (general population) = 0.625 mg/kg/day, DNEL inhalation (worker) = 3.65 mg/m3, DNEL inhalation (general population) = 2.2 mg/m3.


Short description of key information:
Bisphenol A, a structural analog for 2-Acetone polymer with phenol (BPA-Tars) was evaluated for reproductive toxicity in O.E.C.D. Test Guideline 416 studies conducted by the oral route of exposure (dose-feed) in a rat three-generation reporduction study and a mouse two-generation study. In addition a U.S. National Toxicology Program mouse continuous breeding study was conducted.

Effects on developmental toxicity

Description of key information
Bisphenol A (BPA) was assessed for potential developmental toxicity in O.E.C.D. Test Guideline No. 414 Prenatal Developmental Toxicity Studies conducted by the oral gavage route of administration in rats and mice.  No evidence of teratogenicity was observed in any of these studies.  
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
640 mg/kg bw/day
Additional information

No evidence of teratogenicity (malformations) induced by BPA was observed in three independent rodent studies conducted upto maternally toxic doses. Generally, any evidence of adverse developmental effects was observed only at dose levels that resulted in significant maternal toxicity including mortality in the mouse study and severe dehydration at the high dose of BPA in a rat study. Dose levels of > 600 mg/kg/day were necessary to see adverse developmental effects.

Justification for classification or non-classification

There is sufficient evidence to "cause concern for human fertility" based on findings of significantly reduced group mean testes weights with accompanying histopthology in F1 rats and sigficantly reduced litters/pair and live pups/litter in the mouse continuous breeding study. Findings from multiple rodent developmental toxicity studies suggesting adveres effects only at dose that were significantly toxic to the dams do not support a concern for possible adverse developmental effects.