Dose and Effect Thresholds for Early Key Events in a PPARα-Mediated Mode of Action.

Current strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor alpha (PPARα).

Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio).

Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish.

Developmental exposure to valproate and ethanol alters locomotor activity and retino-tectal projection area in zebrafish embryos.

Given the minimal developmental neurotoxicity data available for the large number of new and existing chemicals, there is a critical need for alternative methods to identify and prioritize chemicals for further testing. We outline a developmental neurotoxicity screening approach using zebrafish embryos. Embryos were exposed to nominal concentrations of either valproate or ethanol then examined for lethality, malformation, nervous system structure and locomotor activity.

Neurotensin analog NT77 induces regulated hypothermia in the rat.

The potential use of hypothermia as a therapeutic treatment for stroke and other pathological insults has prompted the search for drugs that can lower core temperature. Ideally, a drug is needed that reduces the set-point for control of core temperature (T(c)) and thereby induces a regulated reduction in T(c). To this end, a neurotensin analog (NT77) that crosses the blood brain barrier and induces hypothermia was assessed for its effects on the set-point for temperature regulation in the Sprague-Dawley rat by measuring behavioral and autonomic thermoregulatory responses.

Rat tail skin temperature monitored noninvasively by radiotelemetry: characterization by examination of vasomotor responses to thermomodulatory agents.

Introduction: Measurement of tail skin temperature (T(sk)) of the rat can provide important information on mechanisms pertaining to physiology, pharmacology, and toxicology. T(sk) is largely under control of peripheral vascular tone, which is also sensitive to most experimental manipulations such as handling and restraint. Hence, it is extremely difficult to acquire long-term measurements of T(sk) that are free of artifacts from experimental manipulation.

Dietary exposure to chlorpyrifos alters core temperature in the rat.

Administration of the organophosphate pesticide chlorpyrifos (CHP) to the male rat at a dose of 25-80 mg/kg (p.o.) results in hypothermia followed by a delayed fever lasting for several days.