Evidence of a Dose-Rate Threshold for Life Span Reduction of Dogs Exposed Lifelong to γ-Radiation

Our return to a study on dogs exposed lifelong to cobalt-60 γ-radiation was prompted by a comment that data in dog studies have large statistical errors due to the small number of dogs. We located an earlier article on the same study that had a better mortality curve for the dogs in each dose-rate group. The median life span of the dogs in each group was tabulated, and the standard error of each was calculated. No statistically significant shortening of median life span was observed for the lowest dose-rate group at any reasonable significance level ( P value: .005-.05), whereas for dogs with higher irradiation rates, life span shortening was statistically significant at highest reasonable significance level ( P value: .005). The results were entered on a graph of life span versus dose rate, assuming a threshold dose–response model. The fitted line indicates that the dose-rate threshold for γ-radiation induced life span reduction is about 600 mGy per year, which is close to the value we found previously. Making allowance for the calculated standard errors, we conclude that this threshold is in the range from 300 to 1100 mGy per year. This evidence is relevant for emergency measures actions (evacuation of residents) and for nuclear waste management.

Final Report of the Safety Assessment of Methylisothiazolinone

Methylisothiazolinone (MIT) is a heterocyclic organic compound used as a preservative in cosmetics and personal care products in concentrations up to 0.01%. MIT is a colorless, clear liquid with a mild odor that is completely soluble in water; mostly soluble in acetonitrile, methanol, and hexane; and slightly soluble in xylene. Consistent with its solubility, dermal penetration is low. The Cosmetic Ingredient Review Expert Panel noted the in vitro evidence of neurotoxicity but concluded that the absence of any neurotoxicity findings in the many in vivo studies, including subchronic, chronic, and reproductive and developmental animal studies, suggests that MIT would not be neurotoxic as used in cosmetics. Although recognizing that MIT was a sensitizer in both animal and human studies, the panel concluded that there is a threshold dose response and that cosmetic products formulated to contain concentrations of MIT at 100 ppm (0.01%) or less would not be expected to pose a sensitization risk. Accordingly, MIT may be safely used as a preservative in cosmetics up to that concentration.

Quantification of Hormesis in Anticancer-Agent Dose-Responses

Quantitative features of dose responses were analyzed for 2,189 candidate anticancer agents in 13 strains of yeast ( Saccharomyces cerevisiae). The agents represent a diverse class of chemical compounds including mustards, other alkylating agents, and antimetabolites, inter alia. Previous analyses have shown that the responses below the toxic threshold were stimulatory and poorly predicted by a threshold dose-response model, while better explained by a hormetic dose-response model. We determined the quantitative features of the hormetic concentration-responses ( n = 4,548) using previously published entry and evaluative criteria. The quantitative features that are described are: (1) the width of the concentration range showing stimulation above 10% of the control (mean of 5-fold), (2) the maximum stimulation of the concentration-responses (mean of 27% above the control), and (3) the width from the maximum stimulation to the toxicological threshold (mean of 3.7-fold). These results show that 52.5% of the 2,189 chemicals evaluated display hormetic concentration-responses in at least one of the 13 yeast strains. Many chemicals showed hormesis in multiple strains, and 24 agents showed hormesis in all 13 strains. The data are compared to previously reported quantitative features of hormesis based on published literature.