Health & Environmental Research Online (HERO)


Methanol (Non-Cancer)

Show Project Details Hide Project Details
343 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Methanol teratogenicity in mutant mice with deficient catalase activity and transgenic mice expressing human catalase

Authors: Siu, MT; Wiley, MJ; Wells, PG (2013) Reproductive Toxicology 36:33-39. HERO ID: 1508481

[Less] The role of catalase in methanol (MeOH) teratogenesis is unclear. In rodents it both detoxifies reactive . . . [More] The role of catalase in methanol (MeOH) teratogenesis is unclear. In rodents it both detoxifies reactive oxygen species (ROS) and metabolizes MeOH and its formic acid (FA) metabolite. We treated pregnant mice expressing either high (hCat) or low catalase activity (aCat), or their wild-type (WT) controls, with either MeOH (4g/kg ip) or saline. hCat mice and WTs were similarly susceptible to MeOH-initiated ophthalmic abnormalities and cleft palates. aCat and WT mice appeared resistant, precluding assessment of the developmental impact of catalase deficiency. Catalase activity was respectively increased at least 1.5-fold, and decreased by at least 35%, in hCat and aCat embryos and maternal livers. MeOH and FA pharmacokinetic profiles were similar among hCat, aCat and WT strains. Although the hCat results imply no ROS involvement, embryo culture studies suggest this may be confounded by maternal factors and/or a requirement for higher catalase activity in the hCat mice.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Application of an updated physiologically based pharmacokinetic model for chloroform to evaluate CYP2E1-mediated renal toxicity in rats and mice

Authors: Sasso, AF; Schlosser, PM; Kedderis, GL; Genter, MB; Snawder, JE; Li, Z; Rieth, S; Lipscomb, JC (2013) Toxicological Sciences 131:360-374. HERO ID: 1936108

[Less] Physiologically based pharmacokinetic (PBPK) models are tools for interpreting toxicological data and . . . [More] Physiologically based pharmacokinetic (PBPK) models are tools for interpreting toxicological data and extrapolating observations across species and route of exposure. Chloroform (CHCl(3)) is a chemical for which there are PBPK models available in different species and multiple sites of toxicity. Because chloroform induces toxic effects in the liver and kidneys via production of reactive metabolites, proper characterization of metabolism in these tissues is essential for risk assessment. Although hepatic metabolism of chloroform is adequately described by these models, there is higher uncertainty for renal metabolism due to a lack of species-specific data and direct measurements of renal metabolism. Furthermore, models typically fail to account for regional differences in metabolic capacity within the kidney. Mischaracterization of renal metabolism may have a negligible effect on systemic chloroform levels, but it is anticipated to have a significant impact on the estimated site-specific production of reactive metabolites. In this article, rate parameters for chloroform metabolism in the kidney are revised for rats, mice, and humans. New in vitro data were collected in mice and humans for this purpose and are presented here. The revised PBPK model is used to interpret data of chloroform-induced kidney toxicity in rats and mice exposed via inhalation and drinking water. Benchmark dose (BMD) modeling is used to characterize the dose-response relationship of kidney toxicity markers as a function of PBPK-derived internal kidney dose. Applying the PBPK model, it was also possible to characterize the dose response for a recent data set of rats exposed via multiple routes simultaneously. Consistent BMD modeling results were observed regardless of species or route of exposure.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats

Authors: Iyyaswamy, A; Rathinasamy, S (2012) Journal of Biosciences 37:679-688. HERO ID: 1446666

[Less] This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative . . . [More] This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

Technical Report
Technical Report

Proposition 65: Interpretive guideline no. 2012-01: Consumption of methanol resulting from pectin that occurs naturally in fruits and vegetables

Author: CalEPA (2012) HERO ID: 1015423


Data/Software
Data/ Software

Methanol PBPK Model

Author: U.S. EPA (2012) HERO ID: 1050301

Abstract: PBPK Data Files with Code for Human, Rat, Mouse, and Monkey Models

Technical Report
Technical Report

Summary health statistics for U.S. adults: National Health Interview Survey, 2011

Authors: Schiller, JS; Lucas, JW; Peregoy, JA (2012) (Vital and Health Statistics: Series 10, No. 256). Hyattsville, MD: National Center for Health Statistics. HERO ID: 1774667

[Less] Objectives-This report presents health statistics from the 2011 National Health Interview Survey (NHIS) . . . [More] Objectives-This report presents health statistics from the 2011 National Health Interview Survey (NHIS) for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, education, family income, poverty status, health insurance coverage, marital status, and place and region of residence. Estimates (frequencies and percentages) are presented for selected chronic conditions and mental health characteristics, functional limitations, health status, health behaviors, health care access and utilization, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age-adjusted and unadjusted versions. Data Source-NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2011, data were collected on 33,014 adults in the Sample Adult questionnaire. The conditional response rate was 81.6%, and the final response rate was 66.3%. The health information for adults in this report was obtained from one randomly selected adult per family. In very rare instances where the sample adult was not able to respond for himself or herself, a proxy was used. Highlights-In 2011, 61% of adults aged 18 and over had excellent or very good health. Eleven percent of adults had been told by a doctor or other health professional that they had heart disease, 24% had been told on two or more visits that they had hypertension, 9% had been told that they had diabetes, and 22% had been told that they had some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Nineteen percent of adults were current smokers, and 21% were former smokers. Based on estimates of body mass index, 34% of adults were overweight and 28% were obese.

Technical Report
Technical Report

Benchmark dose technical guidance

Author: U.S. EPA (2012) (EPA/100/R-12/001). Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum. HERO ID: 1239433


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Formation of hydroxymethyl DNA adducts in rats orally exposed to stable isotope labeled methanol

Authors: Lu, K; Gul, H; Upton, PB; Moeller, BC; Swenberg, JA (2012) Toxicological Sciences 126:28-38. HERO ID: 1039241

[Less] Methanol is a large volume industrial chemical and widely used solvent and fuel additive. Methanol's . . . [More] Methanol is a large volume industrial chemical and widely used solvent and fuel additive. Methanol's well known toxicity and use in a wide spectrum of applications has raised long-standing environmental issues over its safety, including its carcinogenicity. Methanol has not been listed as a carcinogen by any regulatory agency; however, there are debates about its carcinogenic potential. Formaldehyde, a metabolite of methanol, has been proposed to be responsible for the carcinogenesis of methanol. Formaldehyde is a known carcinogen and actively targets DNA and protein, causing diverse DNA and protein damage. However, formaldehyde-induced DNA adducts arising from the metabolism of methanol have not been reported previously, largely due to the absence of suitable DNA biomarkers and the inability to differentiate what was due to methanol compared with the substantial background of endogenous formaldehyde. Recently, we developed a unique approach combining highly sensitive liquid chromatography-mass spectrometry methods and exposure to stable isotope labeled chemicals to simultaneously quantify formaldehyde-specific endogenous and exogenous DNA adducts. In this study, rats were exposed daily to 500 or 2000 mg/kg [(13)CD(4)]-methanol by gavage for 5 days. Our data demonstrate that labeled formaldehyde arising from [(13)CD(4)]-methanol induced hydroxymethyl DNA adducts in multiple tissues in a dose-dependent manner. The results also demonstrated that the number of exogenous DNA adducts was lower than the number of endogenous hydroxymethyl DNA adducts in all tissues of rats administered 500 mg/kg per day for 5 days, a lethal dose to humans, even after incorporating an average factor of 4 for reduced metabolism due to isotope effects of deuterium-labeled methanol into account.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Oxidation of methanol, ethylene glycol, and isopropanol with human alcohol dehydrogenases and the inhibition by ethanol and 4-methylpyrazole

Authors: Lee, SL; Shih, HT; Chi, YC; Li, YP; Yin, SJ (2011) Chemico-Biological Interactions 191:26-31. HERO ID: 1054544

[Less] Human alcohol dehydrogenases (ADHs) include multiple isozymes with broad substrate specificity and ethnic . . . [More] Human alcohol dehydrogenases (ADHs) include multiple isozymes with broad substrate specificity and ethnic distinct allozymes. ADH catalyzes the rate-limiting step in metabolism of various primary and secondary aliphatic alcohols. The oxidation of common toxic alcohols, that is, methanol, ethylene glycol, and isopropanol by the human ADHs remains poorly understood. Kinetic studies were performed in 0.1M sodium phosphate buffer, at pH 7.5 and 25°C, containing 0.5 mM NAD(+) and varied concentrations of substrate. K(M) values for ethanol with recombinant human class I ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, and ADH1C2, and class II ADH2 and class IV ADH4 were determined to be in the range of 0.12-57 mM, for methanol to be 2.0-3500 mM, for ethylene glycol to be 4.3-2600mM, and for isopropanol to be 0.73-3400 mM. ADH1B3 appeared to be inactive toward ethylene glycol, and ADH2 and ADH4, inactive with methanol. The variations for V(max) for the toxic alcohols were much less than that of the K(M) across the ADH family. 4-Methylpyrazole (4MP) was a competitive inhibitor with respect to ethanol for ADH1A, ADH1B1, ADH1B2, ADH1C1 and ADH1C2, and a noncompetitive inhibitor for ADH1B3, ADH2 and ADH4, with the slope inhibition constants (K(is)) for the whole family being 0.062-960 μM and the intercept inhibition constants (K(ii)), 33-3000 μM. Computer simulation studies using inhibition equations in the presence of alternate substrate ethanol and of dead-end inhibitor 4MP with the determined corresponding kinetic parameters for ADH family, indicate that the oxidation of the toxic alcohols up to 50mM are largely inhibited by 20 mM ethanol or by 50 μM 4MP with some exceptions. The above findings provide an enzymological basis for clinical treatment of methanol and ethylene glycol poisoning by 4MP or ethanol with pharmacogenetic perspectives.

Technical Report
Technical Report

COT Statement on the effects of chronic dietary exposure to methanol

Author: COT (2011) HERO ID: 1712686

[Less] Methanol has characteristic toxic effects at high doses. However, methanol also occurs in the diet in . . . [More] Methanol has characteristic toxic effects at high doses. However, methanol also occurs in the diet in fruit and vegetables and from the breakdown of the artificial sweetener aspartame as well as being produced naturally within the body. The COT was asked to consider the potential effects of low level, chronic exposure to methanol.

A revised version of this statement was published on 1 August 2011 correcting a factual error in the reporting of study by Lindinger et al., (1997).