To develop allopregnanolone as a therapeutic for Alzheimer's disease, we investigated multiple formulations and routes of administration in translationally relevant animal models of both sexes. Subcutaneous, topical (transdermal and intranasal), intramuscular, and intravenous allopregnanolone were bolus-administered. Pharmacokinetic analyses of intravenous allopregnanolone in rabbit and mouse i...

Hormesis has been defined as a dose-response relationship in which there is a stimulatory response at low doses, but an inhibitory response at high doses, resulting in a U- or inverted U-shaped dose response. To assess the proportion of studies satisfying criteria for evidence of hormesis, a database was created from published toxicological literature using rigorous a priori entry and evaluativ...

The impact of potentially toxic chemicals on wildlife is commonly assessed by comparing the intake of the contaminant with the "no observable effects level" (NOAEL) of intake. It is known, however, that there are considerable uncertainties inherent in this method. This study presents a Monte-Carlo based model to assess the degree of risk posed to birds (dunlin, Calidris alpina) from important e...

Toluene had been designated as a priority assessment chemical substance under the Japanese Chemical Substances Control Law (CSCL), and result of prioritization, detailed human health hazard was conducted Assessment II. We evaluated its general, reproductive, developmental toxicities, well genotoxicity carcinogenicity, based on information provided by domestic international risk organizations, f...

The threshold dose-response model is widely viewed as the most dominant model in toxicology. The present study was designed to test the validity of the threshold model by assessing the responses of doses below the toxicological NOAEL (no observed adverse effect level) in relationship to the control response (i.e., unexposed group). Nearly 1,800 doses below the NOAEL, from 664 dose-response rela...

stachys lavandulifolia is used as the herbal tea and its wide and potent medical effects have been reported for the extract in animal studies. this study aimed to find the safety profile of the extract to find the appropriate doses for further human studies. the aerial parts of the plant were air-dried and the hydroalcoholic extract was obtained and concentrated by percolation method with 140 m...

Iodomethane is a new pre-plant soil fumigant approved in the United States. Human exposure may occur via inhalation due to the high vapor pressure of iodomethane. A quantitative human health risk assessment was conducted for inhalation exposure. The critical effects of acute duration iodomethane exposure are: (1) fetal losses in rabbits, (2) lesions in rat nasal epithelium, and (3) transient ne...

In fish, selenium can bioaccumulate and cause adverse impacts. One of the fish species potentially at risk from selenium in the San Francisco Bay (California, USA) is the splittail (Pogonichthys macrolepidotus). Previous studies have derived a whole body NOAEL and LOAEL of 9.0 and 12.9 mg/kg-dw, respectively, for selenium in juveniles. However, the NOAEL/LOAEL approach leaves some uncertainty r...

Evaluations of studies for four well-known human developmental toxicants clearly suggest that a margin of exposure of 1/100th the NOAEL for the most sensitive animal species tested provides adequate safety for the human conceptus. The lowest reported human teratogenic exposures occurred at doses at least one log above the estimated "safe" or acceptable daily exposure based on the most sensitive...