Derivation of a No-significant-risk-level (NSRL) for dermal exposures to diethanolamine

AbstractDiethanolamine (DEA) has been found to produce liver and kidney tumors in mice following lifetime dermal exposures. Data regarding the mode of action by which DEA produces these tumors were used to support a dose-response assessment that resulted in a no-significant-risk-level (NSRL) for dermal exposures to DEA. DEA and its metabolites are structural analogs to endogenous agents important to choline homeostasis. Sufficient information is available to support an epigenetic MOA involving the perturbation of choline homeostasis and hepatic methylation reactions in the formation of mouse liver tumors. This MOA may also apply to mouse kidney tumors, but direct measurements for key events in kidney are lacking. For both tumor types, dose-response data were pooled across four cancer bioassays conducted for DEA and DEA-containing condensates in order to provide a more robust characterization of the dose-response relationships. Doses were expressed in terms of dermally absorbed dose so that the dose-dependency and species differences in the dermal absorption of DEA were addressed. The resulting NSRL value of 3400 ug/day for dermal exposures to DEA is considered to be protective of human health for both tumor endpoints

Derivation of inhalation toxicity reference values for propylene oxide using mode of action analysis: Example of a threshold carcinogen.

Propylene oxide (PO) is an important industrial chemical used primarily in the synthesis of other compounds. Inhalation carcinogenesis studies in rodents, with no-observed-adverse-effect levels (NOAELs) of 100 and 200 ppm, have revealed that chronic, high exposure to PO can induce tumors at the site of contact. Despite these characteristics, there is no evidence that typical environmental or occupational exposures to PO constitute a health risk for humans. The nongenotoxic effects of PO (glutathione depletion and cell proliferation) that augment its DNA-reactive and non-DNA-reactive genotoxicity are expected to be similar in humans and rodents. Available evidence on mode-of-action suggests that cancer induction by PO at the site of contact in rodents is characterized by a practical threshold. Human toxicity reference values for potential carcinogenic effects of PO were derived based on nasal tumors identified in rodent studies and specified uncertainty factors. The 95% lower confidence limit on the dose producing a 10% increase in additional tumor risk (LED10) was calculated using the rat and mouse data sets. The human reference values derived from the rat and mouse LED10 values were 0.7 and 0.5 ppm PO, respectively. A similar noncancer reference value, 0.4 ppm, was derived on the basis of non-neoplastic nasal effects in rats

Learning in a Network Economy

We model a simple communication network model for the evolution of heterogeneous beliefs in an overlapping generation economy. Each agent gathers information from his contacts and forms an inflation forecast based on this information, using the belief generation procedures. When the actual inflation is realised, an agent is in a position to learn, i.e., adjust his own network strategy and belief. The learning is modelled as an evolving network process, i.e., a network of agents, with non-zero communication costs. Our simulation results suggest that the network economy as a whole acts efficiently in achieving convergence to the Pareto superior equilibrium, in which an agent’s perception of information is through communication and is subject to available resources. Copyright Springer Science + Business Media, Inc. 2005communication networks, heterogeneous agents,