Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reports from Japan and India and data submissions to the US EPA indicate that exposure to cholinesterase (ChE)-inhibiting organophosphorous insecticides (OP) can produce ocular toxicity, in particular long-lasting changes in retinal physiology and anatomy. We have examined the effects of a 1 year dietary exposure to the OP chlorpyrifos (CPF) on retinal structure and function. Adult male Long-Evans rats were fed CPF in their diet at the rate of 0, 1 (low), or 5 (high) mg/kg body weight/day. In addition, half of each feeding group received an oral (spike) dose of CPF in corn oil (45 mg/kg) or corn oil (VEH) alone every 2 months, resulting in six exposure groups: Control-VEH, Control-CPF, Low-VEH, Low-CPF, High-VEH, and High-CPF. Dark-adapted electroretinograms (ERG) were measured 3-5 months (n= 15-18/group) after the completion of dosing. There were no significant differences between dose or spike groups in a-wave, b-wave, or oscillatory potential amplitudes or implicit times. In addition, the time course of dark adaptation were measured in a subset of these rats (6-8/group) eight months after the completion of dosing by determining the flash intensity needed to elicit a 40 microV b-wave at selected intervals after bleaching 90% of the photopigment. Rats receiving the episodic oral spike of CPF showed a slowed recovery of dark-adapted sensitivity compared to rats receiving the corn oil VEH across chronic dosing conditions. No effects were seen on retinal morphology. This result suggests that episodic high dose exposures to CPF may result in altered retinal function. This effect, akin to effects seen in aging humans and humans exposed to other ChE-inhibiting compounds, may reflect alterations in the photoreceptors and retinal pigment epithelium (RPE) complex necessary for regenerating photopigment.
 ...
PMID:Repeated spike exposure to the insecticide chlorpyrifos interferes with the recovery of visual sensitivity in rats. 1624 59

Biomonitoring is a valuable tool for identifying exposures to chemicals that pose potential harm to human health. However, to date there has been little published on ways to evaluate the relative public health significance of biomonitoring data for different chemicals and even less on cumulative assessment of multiple chemicals. The objectives of our study are to develop a methodology for a health risk interpretation of biomonitoring data and to apply it using NHANES 1999-2002 body burden data fororganophosphorus (OP) pesticides. OP pesticides present a particularly challenging case given the nonspecificity of manymetabolites monitored through NHANES. We back-calculate OP pesticide exposures from urinary metabolite data and compare cumulative dose estimates with available toxicity information for a common mechanism of action (brain cholinesterase inhibition) using data from U.S. EPA. Our results suggest that approximately 40% of children in the United States may have had insufficient margins of exposure (MOEs) for neurological impacts from cumulative exposures to OP pesticides (MOE less than 1000). Limitations include uncertainty related to assumptions about likely precursor pesticide compounds of the urinary metabolites, sources of exposure, and intraindividual and temporal variability.
 ...
PMID:Evaluating cumulative organophosphorus pesticide body burden of children: a national case study. 1992 15

Fleas, ticks, and mites are a major problem in many areas of the country for pet owners, and one treatment option involves the use of dips that contain pesticides. In the present study, dogs were dipped with a commercial phosmet (Imidan(R)) flea dip using the recommended guidelines for four consecutive treatments to determine the residues available for transfer to humans from the fur of the dogs. Twenty-four dogs of various breeds and weights were dipped, and each animal's fur was sampled with cotton gloves by petting for 5 minutes in a 10'' x 4'' area along the upper back before dipping and at 4 hours, and 1, 3, 7, and 14 days after dipping. Over the 4 dippings the 4-hour samples had a geometric mean of 2653 mug, and the 1-, 3-, 7-, and 14- day samples had geometric means of 877, 316, 84, and 20 mug, respectively. The samples ranged (in mug) from 80 to 16,794 at 4 hours, 44 to 7028 at 1 day, 1 to 4897 at 3 days, 1 to 2691 at 7 days, and 0.3 to 835 at 14 days. The residues removed by the petting did increase with the subsequent dips, but this was probably due to handler experience. The increase is not attributed to accumulation since there was less than 2% of transferable residue on the dog at 14 days post application. There was no significant inhibition of the plasma cholinesterase in the dogs over the study, suggesting that there was either a very low level of dermal absorption of phosmet or there was rapid detoxication (supported by EPA R 825170-01-0).
 ...
PMID:Effects of topical phosmet on fur residue and cholinesterase activity of dogs. 2002 Oct 25

Chlorpyrifos was selected for EPA's Endocrine Disruptor Screening Program (EDSP) based on widespread use and potential for human and environmental exposures. The purpose of the program is to screen chemicals for their potential to interact with the estrogen, androgen, or thyroid pathways. A battery of 11 assays was completed for chlorpyrifos in accordance with test guidelines developed for EDSP Tier 1 screening. To determine potential endocrine activity, a weight-of-evidence (WoE) evaluation was completed for chlorpyrifos, which included the integration of EDSP assay results with data from regulatory guideline studies and the published literature. This WoE approach was based on the OECD conceptual framework for testing and assessment of potential endocrine-disrupting chemicals and consisted of a systematic evaluation of data, progressing from simple to complex across multiple levels of biological organization. The conclusion of the WoE evaluation is that chlorpyrifos demonstrates no potential to interact with the estrogen, androgen, or thyroid pathways at doses below the dose levels that inhibit cholinesterase. Therefore, regulatory exposure limits for chlorpyrifos, which are based on cholinesterase inhibition, are sufficient to protect against potential endocrine alterations. Based on the results of this WoE evaluation, there is no scientific justification for pursuing additional endocrine testing for chlorpyrifos.
...
PMID:Chlorpyrifos: weight of evidence evaluation of potential interaction with the estrogen, androgen, or thyroid pathways. 2352 72

Computational approaches have recently gained popularity in the field of read-across to automatically fill data-gaps for untested chemicals. Previously, we developed the generalized read-across (GenRA) tool, which utilizes in vitro bioactivity data in conjunction with chemical descriptor information to derive local validity domains to predict hazards observed in in vivo toxicity studies. Here, we modified GenRA to quantitatively predict point of departure (POD) values obtained from US EPA's Toxicity Reference Database (ToxRefDB) version 2.0. To evaluate GenRA predictions, we first aggregated oral Lowest Observed Adverse Effect Levels (LOAEL) for 1,014 chemicals by systemic, developmental, reproductive, and cholinesterase effects. The mean LOAEL values for each chemical were converted to log molar equivalents. Applying GenRA to all chemicals with a minimum Jaccard similarity threshold of 0.05 for Morgan fingerprints and a maximum of 10 nearest neighbors predicted systemic, developmental, reproductive, and cholinesterase inhibition min aggregated LOAEL values with R2 values of 0.23, 0.22, 0.14, and 0.43, respectively. However, when evaluating GenRA locally to clusters of structurally-similar chemicals (containing 2 to 362 chemicals), average R2 values for systemic, developmental, reproductive, and cholinesterase LOAEL predictions improved to 0.73, 0.66, 0.60 and 0.79, respectively. Our findings highlight the complexity of the chemical-toxicity landscape and the importance of identifying local domains where GenRA can be used most effectively for predicting PODs.
 ...
PMID:Quantitative prediction of repeat dose toxicity values using GenRA. 3155 May 20


<< Previous 1 2