A Combined 28-Day Oral Toxicity Study of HFPO-Amidol (CASRN 75888-49-2) With Reproductive/Developmental Toxicity Screening Test in Wistar Han Rats.

HFPO-Amidol (CAS # 75888-49-2) is a new hexafluoropropylene oxide (HFPO)-based intermediate developed as an alternative to longer chain perfluorinated compounds. The repeated-dose toxicity of this material was evaluated in an Organization for Economic Cooperation and Development 422-compliant, 28-day oral exposure study with a concurrent reproductive/developmental toxicity screening test. Wistar rats received doses of 0, 30, 300, or 1000 mg/kg/d by oral gavage. Statistically significant changes in body weight gain of 1000 mg/kg/d females during the postcoitum period were possibly related to treatment but were considered not adverse, given the slight nature of the changes. The lower food consumption of 300 mg/kg/d females during the postcoitum and lactation period was not considered treatment related given the absence of a time- and dose-related trend and because food intake was generally similar to control levels after allowance for body weights. Statistically significant changes in motor activity (total movements and total ambulations) were noted in 1000 mg/kg/d main male and female rats. The changes observed in female rats were considered not treatment related in the absence of a dose-response trend. The higher motor activity of high-dose males was primarily apparent within the first 10 minutes of the 60-minute measurement period and was suggestive of temporary hyperreactivity to a new environment/stimulus. This increased peak motor activity remained present although at an apparent lower magnitude when measured 13 days after withdrawal of treatment. Because the possible toxicological relevance of the temporarily increased motor activity observed in 1000 mg/kg/d males could not be excluded, these changes were considered possibly adverse in nature. No treatment-related or toxicologically relevant effects were noted on the other parental, reproductive, and developmental parameters investigated in this study. The parental systemic no observed adverse effect level (NOAEL) for this study is 300 mg/kg/d (based on increased motor activity in males), while the reproductive and developmental NOAEL is 1000 mg/kg/d.

Reproductive toxicity evaluation of the dental resin monomer triethylene glycol dimethacrylate (CASRN 109-16-0) in mice.

The reproductive toxicity potential of the resin monomer triethylene glycol dimethacrylate (TEGDMA; Chemical Abstracts Service Registry Number 109-16-0) was investigated in male and female Crl:CD1(ICR) mice, 4 dosage groups, 25 mice/sex/group. Formulations of TEGDMA (0, 0.01, 0.1, or 1.0 mg/kg/d) in reverse osmosis-processed deionized water were intubated once daily beginning 28 days before cohabitation and continuing through mating (males) or through gestation day 17 (females). The following parameters were evaluated: viability, clinical signs, body weights, estrous cyclicity, necropsy observations, organ weights, sperm concentration/motility/morphology, cesarean-sectioning and litter observations, and histopathological evaluation of select tissues. No deaths or clinical signs related to TEGDMA occurred. No significant changes in male and female body weights and body weight gains were recorded for any of the administered dosages of TEGMDA. All mating and fertility parameters and all litter and fetal data were considered to be unaffected by dosages of TEGMDA as high as 1 mg/kg/d. Gross or histopathologic tissue changes attributable to the test article were not observed. Reproductive and developmental no observed adverse effect levels (NOAELs) for TEGMDA were 1.0 mg/kg/d, the highest dose tested. Comparison of conservatively estimated TEGDMA exposures from dental treatments to the NOAEL of 1.0 mg/kg/d identified in this study indicates margins of exposure of at least 120- to 3000-fold depending on the exposure scenario. The results of this study support the continued safe use of TEGDMA in polymeric dental products applied according to the manufacturers' instructions.

Reproductive toxicity evaluation of the dental resin monomer bisphenol a glycidyl methacrylate (CAS 1565-94-2) in mice.

The reproductive toxicity potential of the dental resin monomer bisphenol A glycidyl methacrylate (BisGMA; CASRN 1565-94-2) was investigated in male and female Crl: CD1(ICR) mice, 4 dosage groups, and 25 mice/sex/group. Formulations of BisGMA (0, 0.008, 0.08, or 0.8 mg/kg/d) in 0.8% ethanol in deionized water were intubated once daily beginning 28 days before cohabitation and continuing through mating (males) or through gestation day 17. The following parameters were evaluated: viability, clinical signs, body weights, estrous cyclicity, necropsy observations, organ weights, sperm concentration/motility/morphology, cesarean sectioning and litter observations, and histopathological evaluation of select tissues. No deaths or clinical signs related to BisGMA occurred. No significant changes in male and female body weights and body weight gains were recorded at any of the administered dosages of BisGMA. All mating and fertility parameters, and all litter and fetal data, were considered to be unaffected by dosages of BisGMA as high as 0.8 mg/kg/d. Gross or histopathologic tissue changes attributable to the test article were not observed. Reproductive and developmental no observed effect levels (NOAELs) for BisGMA were 0.8 mg/kg/d, the highest dose tested. Comparison of this NOAEL value to published probabilistic estimates of human BisGMA exposure from dental products suggests a margin of safety of at least 280- to nearly 2000-fold. Under the conditions of this study, BisGMA is not a reproductive toxicant.

Potential confounders of bisphenol-a analysis in dental materials.

OBJECTIVES: In the published literature, a variety of analytical methods have been used to quantify and report bisphenol A (BPA) release from dental resins. The objective of this study was to compare results obtained for quantification of BPA in dental resin extracts using an LC/UV analytical method and an LC/MS/MS method. METHODS: A cured Bis-GMA-based resin representative of commercial dental products was extracted according to ISO 10993 guidelines for medical devices. d16BPA was included as an internal standard. Sample processing followed expert recommendations for minimizing BPA sample contamination. Extracts were separated using HPLC methods and analyzed for BPA using LC/UV and LC/MS/MS detection methods. RESULTS: The reported BPA concentrations were about 30-fold higher using LC/UV vs. LC/MS/MS. Full scan LC/MS/MS in both positive and negative modes showed that the apparent high BPA values seen with LC/UV were caused by co-elution of a previously unidentified chemical, thought to arise from one of the polymerization initiators. SIGNIFICANCE: These results emphasize the potential difficulties in obtaining accurate analyses of BPA in complex mixtures such as dental resins and their extracts. Both good separation methodology and a detection method with high specificity and sensitivity are important to avoid incorrect identification of extractables, and consequent incorrect quantitative assignments for species of interest. Reliable methods are essential for accurate estimation of patient exposure to BPA and development of meaningful health risk assessments.