Publications by authors named "Barbara Neal"
Article Synopsis
- * Research indicated that toxaphene activated certain genes related to the constitutive androstane receptor (CAR) in the liver, specifically causing significant changes at higher doses, while minimal activation of the aryl hydrocarbon receptor (AhR) was observed.
- * Experiments with CAR knockout mice confirmed that the induction of CAR target genes was crucial in the process, suggesting that toxaphene's liver tumor promotion occurs through a nongenotoxic mechanism associated with cell proliferation and preneoplastic lesion expansion.
The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was evaluated in five in vitro screening assays to assess the potential for interaction with the androgen, estrogen and steroidogenesis pathways in the endocrine system. The assays were conducted to meet the requirements of the in vitro component of Tier 1 of the United States Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP), and included assays for estrogen receptor (ER) binding (rat uterine cytosol ER binding assay), ER-mediated transcriptional activation (HeLa-9903-ERα transactivation assay), androgen receptor (AR) binding (rat prostate cytosol AR binding assay), aromatase enzymatic activity inhibition (recombinant human CYP19 aromatase inhibition assay), and interference with steroidogenesis (H295R steroidogenesis assay). Results from these five assays demonstrated that 2,4-D does not have the potential to interact in vitro with the estrogen, androgen, or steroidogenesis pathways.
View Article and Find Full Text PDFRelevance weighting of tier 1 endocrine screening endpoints by rank order.
Birth Defects Res B Dev Reprod Toxicol
February 2014
Weight of evidence (WoE) approaches are recommended for interpreting various toxicological data, but few systematic and transparent procedures exist. A hypothesis-based WoE framework was recently published focusing on the U.S.
View Article and Find Full Text PDFLife-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96.
View Article and Find Full Text PDFArticle Synopsis
- A study on 2,4-Dichlorophenoxyacetic acid (2,4-D) in CD rats examined its potential toxicity across various areas, including systemic, reproductive, and developmental effects, using different dosage levels in the diet.
- The results indicated kidney damage, particularly in high-dose males and females, as the primary toxic effect, with some minor endocrine changes, but no significant reproductive or neurodevelopmental toxicity was observed.
- The established "No Observed Adverse Effect Level" for systemic toxicity was set at 300 ppm, which is significantly higher than what has been reported in human exposure studies.
2,4-Dichlorophenoxyacetic acid (2,4-D) was evaluated in both the Amphibian Metamorphosis Assay (AMA) and the Fish Short Term Reproduction Assay (FSTRA). In the AMA, tadpoles were exposed to mean measured 2,4-D concentrations of 0 (water control), 0.273, 3.
View Article and Find Full Text PDFAcetylcholinesterase inhibition dose-response modeling for chlorpyrifos and chlorpyrifos-oxon.
Regul Toxicol Pharmacol
June 2012
Article Synopsis
- This paper focuses on evaluating data related to cholinesterase inhibition caused by chlorpyrifos (CPF), particularly from a study by Marty et al. (2012) that included various tests on male and female rats.
- The analysis involves benchmark dose (BMD) estimates for acute and repeat doses to humans, indicating specific doses deemed safe, with findings suggesting no significant difference in response between genders or ages.
- The study concludes that brain cholinesterase inhibition is critical for assessing the risks associated with CPF exposure, implying that special safety measures for young populations are unnecessary based on the data reviewed.
Article Synopsis
- Risk assessments of acrylonitrile (AN) mainly concern its potential cancer risk and acute toxicity, with studies highlighting reproductive issues in workers, such as infertility and birth defects in China.
- An evaluation of existing studies found that while AN shows some toxicity, the evidence does not establish a direct cause-and-effect relationship suitable for risk assessment.
- Key findings indicate that NOAELs for AN are 10 mg/kg/day for oral exposure and 12 ppm for inhalation, with confidence in the inhalation studies suggesting that AN is unlikely to harm development or reproduction without significant maternal toxicity.
Risk assessment of toxaphene and its breakdown products: time for a change?
Crit Rev Toxicol
November 2008
Article Synopsis
- Technical toxaphene (TT), last used around 1982, has now mostly degraded into what is called weathered toxaphene, which consists of various chlorinated congeners primarily through dechlorination processes.
- The U.S. EPA assesses the risks of toxaphene based on toxicology studies conducted on the original technical version, without considering its environmental degradation.
- In contrast, the European Union models risks associated with weathered toxaphene by studying its effects through different degradation methods and using various animal models, suggesting a need for updated U.S. assessments.