Considerations for deriving a safe intake of propylene glycol.

The use of propylene glycol (PG) in food and other applications is widespread, and some estimates of dietary exposure to PG approach or exceed the Acceptable Daily Intake (ADI) of 25 mg/kg bw-day. The current ADI for PG applies a cumulative uncertainty factor of 100, which includes factors of 10 for both interspecies and intraspecies differences. Available toxicology studies and human data, however, indicate a plausible mode of action (MoA) that would support a chemical-specific adjustment factor (CSAF) of 1 for interspecies toxicodynamic differences, reducing the total uncertainty factor from 100 to 40. The MoA involves an increase in serum PG concentrations after metabolic saturation, leading to serum hyperosmolarity, which can ultimately cause hemolytic changes and red blood cell damage. Therefore, the species similarities in toxicodynamic response for this critical effect could support increasing the ADI from 25 to 62.5 mg/kg bw-day, applicable to both children and adults.

A critical review of talc and ovarian cancer.

The association between perineal talc use and ovarian cancer has been evaluated in several epidemiology studies. Some case-control studies reported weak positive associations, while other case-control and three large prospective cohort investigations found this association to be null. A weight-of-evidence evaluation was conducted of the epidemiology, toxicity, exposure, transport, in vitro, and mechanistic evidence to determine whether, collectively, these data support a causal association. Our review of the literature indicated that, while both case-control and cohort studies may be impacted by bias, the possibility of recall and other biases from the low participation rates and retrospective self-reporting of talc exposure cannot be ruled out for any of the case-control studies. The hypothesis that talc exposure induces ovarian cancer is only supported if one discounts the null results of the cohort studies and the fact that significant bias and/or confounding are likely reasons for the associations reported in some case-control investigations. In addition, one would need to ignore the evidence from animal experiments that show no marked association with cancer, in vitro and genotoxicity studies that did not indicate a carcinogenic mechanism of action for talc, and mechanistic and transport investigations that did not support the retrograde transport of talc to the ovaries. An alternative hypothesis that talc does not produce ovarian cancer, and that bias and confounding contribute the reported positive associations in case-control studies, is better supported by the evidence across all scientific disciplines. It is concluded that the evidence does not support a causal association between perineal talc use and ovarian cancer.