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Methanol (Non-Cancer)

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311 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.

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

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 exposure does not lead to accumulation of oxidative DNA damage in bone marrow and spleen of mice, rabbits or primates

Authors: Mccallum, GP; Siu, M; Ondovcik, SL; Sweeting, JN; Wells, PG (2011) Molecular Carcinogenesis 50:163-172. HERO ID: 755522

[Less] Genotoxicity tests indicate methanol (MeOH) is not mutagenic, but a rodent study has suggested carcinogenic . . . [More] Genotoxicity tests indicate methanol (MeOH) is not mutagenic, but a rodent study has suggested carcinogenic potential, which could result from free radical-initiated oxidative DNA damage. To investigate this possibility we treated male CD-1 mice, New Zealand white rabbits, and cynomolgus monkeys with MeOH (2.0 g/kg ip) and assessed tissue oxidative DNA damage 6 h post-dose, measured as 8-hydroxy-2'-deoxyguanosine (8-oxodG). We found no MeOH-dependent increases in 8-oxodG in bone marrow or spleen of any species. Chronic treatment of CD-1 mice with MeOH (2.0 g/kg ip) daily for 15 d also did not increase 8-oxodG levels in these organs. Further studies in the DNA repair deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice supported these findings. Fibroblasts from Ogg1 KO mice accumulated 8-oxodG following acute exposure to the renal carcinogen potassium bromate (KBrO(3) ; 2.0 mM) but did not accumulate 8-oxodG following exposure to 125 mM MeOH 6 h post-treatment. Ogg1 KO mice accumulated 8-oxodG in bone marrow and spleen with age but not following exposure to MeOH. In addition, free radical-mediated hydroxynonenal-histidine protein adducts were not enhanced by MeOH in primate bone marrow or spleen, or in rabbit bone marrow or mouse spleen, although modest increases were observed in rabbit spleen and mouse bone marrow. Taken together these observations suggest that MeOH exposure does not promote the accumulation of oxidative DNA damage in bone marrow and spleen, and it is unlikely that human environmental exposure to MeOH would lead to lymphomas via this mechanism.

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

Altered methanol embryopathies in embryo culture with mutant catalase-deficient mice and transgenic mice expressing human catalase

Authors: Miller, L; Wells, PG (2011) Toxicology and Applied Pharmacology 252:55-61. HERO ID: 759184

[Less] The mechanisms underlying the teratogenicity of methanol (MeOH) in rodents, unlike its acute toxicity . . . [More] The mechanisms underlying the teratogenicity of methanol (MeOH) in rodents, unlike its acute toxicity in humans, are unclear, but may involve reactive oxygen species (ROS). Embryonic catalase, although expressed at about 5% of maternal activity, may protect the embryo by detoxifying ROS. This hypothesis was investigated in whole embryo culture to remove confounding maternal factors, including metabolism of MeOH by maternal catalase. C57BL/6 (C57) mouse embryos expressing human catalase (hCat) or their wild-type (C57 WT) controls, and C3Ga.Cg-Catb/J acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug=GD 1), exposed for 24 h to 4 mg/ml MeOH or vehicle, and evaluated for functional and morphological changes. hCat and C57 WT vehicle-exposed embryos developed normally. MeOH was embryopathic in C57 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed and turning, whereas hCat embryos were protected. Vehicle-exposed aCat mouse embryos had lower yolk sac diameters compared to C3H WT controls, suggesting that endogenous ROS are embryopathic. MeOH was more embryopathic in aCat embryos than WT controls, with reduced anterior neuropore closure and head length only in catalase-deficient embryos. These data suggest that ROS may be involved in the embryopathic mechanism of methanol, and that embryonic catalase activity may be a determinant of teratological risk.

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

Species- and strain-dependent teratogenicity of methanol in rabbits and mice

Authors: Sweeting, JN; Siu, M; Wiley, MJ; Wells, PG (2011) Reproductive Toxicology 31:50-58. HERO ID: 755519

[Less] Estimates of human risk for developmental toxicity of methanol (MeOH) are based on studies in rodents, . . . [More] Estimates of human risk for developmental toxicity of methanol (MeOH) are based on studies in rodents, which unlike humans use catalase to metabolize MeOH. Rabbits, like humans, may largely use alcohol dehydrogenase (ADH), and more accurately than rodents reflect primate MeOH and formic acid (FA) pharmacokinetic profiles. Here we show that New Zealand white rabbits and one strain of mouse (C3H) are resistant to MeOH teratogenicity, whereas C57BL/6J mice are susceptible. Neither rabbits nor mice were susceptible to the acute MeOH toxicity observed in humans. The strain-dependent teratological susceptibility in mice could not be explained by differences in MeOH or FA disposition, nor could the resistance of rabbits, which exhibited more prolonged FA accumulation, suggesting that different mechanisms underlie MeOH teratogenesis and the FA-mediated acute toxicity in humans. It is not clear if the human risk for MeOH developmental toxicity can be accurately estimated using sensitive rodent strains.

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

Physiologically based pharmacokinetic modeling of fetal and neonatal manganese exposure in humans: Describing manganese homeostasis during development

Authors: Yoon, M; Schroeter, JD; Nong, A; Taylor, MD; Dorman, DC; Andersen, ME; Clewell, HJ III (2011) Toxicological Sciences 122:297-316. HERO ID: 787185

[Less] Concerns for potential vulnerability to manganese (Mn) neurotoxicity during fetal and neonatal development . . . [More] Concerns for potential vulnerability to manganese (Mn) neurotoxicity during fetal and neonatal development have been raised due to increased needs for Mn for normal growth, different sources of exposure to Mn, and pharmacokinetic differences between the young and adults. A physiologically based pharmacokinetic (PBPK) model for Mn during human gestation and lactation was developed to predict Mn in fetal and neonatal brain using a parallelogram approach based upon extrapolation across life stages in rats and cross-species extrapolation to humans. Based on the rodent modeling, key physiological processes controlling Mn kinetics during gestation and lactation were incorporated, including alterations in Mn uptake, excretion, tissue-specific distributions, and placental and lactational transfer of Mn. Parameters for Mn kinetics were estimated based on human Mn data for milk, placenta, and fetal/neonatal tissues, along with allometric scaling from the human adult model. The model was evaluated by comparison with published Mn levels in cord blood, milk, and infant blood. Maternal Mn homeostasis during pregnancy and lactation, placenta and milk Mn, and fetal/neonatal tissue Mn were simulated for normal dietary intake and with inhalation exposure to environmental Mn. Model predictions indicate similar or lower internal exposures to Mn in the brains of fetus/neonate compared with the adult at or above typical environmental air Mn concentrations. This PBPK approach can assess expected Mn tissue concentration during early life and compares contributions of different Mn sources, such as breast or cow milk, formula, food, drinking water, and inhalation, with tissue concentration.

Data/Software
Data/ Software

Benchmark Dose Software (BMDS)

Author: U.S. EPA (2011) HERO ID: 786603

[Less] EPA has released the Benchmark Dose Software (BMDS) Version 2.2, a tool which is used to facilitate . . . [More] EPA has released the Benchmark Dose Software (BMDS) Version 2.2, a tool which is used to facilitate the application of benchmark dose (BMD)1 methods to EPA hazardous pollutant risk assessments.

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

Analysis of manganese tracer kinetics and target tissue dosimetry in monkeys and humans with multi-route physiologically based pharmacokinetic models

Authors: Schroeter, JD; Nong, A; Yoon, M; Taylor, MD; Dorman, DC; Andersen, ME; Clewell, HJ III (2011) Toxicological Sciences 120:481-498. HERO ID: 711412

[Less] Manganese (Mn) is an essential nutrient with the capacity for toxicity from excessive exposure. Accumulation . . . [More] Manganese (Mn) is an essential nutrient with the capacity for toxicity from excessive exposure. Accumulation of Mn in the striatum, globus pallidus, and other midbrain regions is associated with neurotoxicity following high-dose Mn inhalation. Physiologically based pharmacokinetic (PBPK) models for ingested and inhaled Mn in rats and nonhuman primates were previously developed. The models contained saturable Mn tissue-binding capacities, preferential fluxes of Mn in specific tissues, and homeostatic control processes such as inducible biliary excretion of Mn. In this study, a nonhuman primate model was scaled to humans and was further extended to include iv, ip, and sc exposure routes so that past studies regarding radiolabeled carrier-free (54)MnCl(2) tracer kinetics could be evaluated. Simulation results accurately recapitulated the biphasic elimination behavior for all exposure routes. The PBPK models also provided consistent cross-species descriptions of Mn tracer kinetics across multiple exposure routes. These results indicate that PBPK models can accurately simulate the overall kinetic behavior of Mn and predict conditions where exposures will increase free Mn in various tissues throughout the body. Simulations with the human model indicate that globus pallidus Mn concentrations are unaffected by air concentrations < 10 μg/m(3) Mn. The use of this human Mn PBPK model can become a key component of future human health risk assessment of Mn, allowing the consideration of various exposure routes, natural tissue background levels, and homeostatic controls to explore exposure conditions that lead to increased target tissue levels resulting from Mn overexposure.

Technical Report
Technical Report

Review of the Environmental Protection Agency's draft IRIS assessment of formaldehyde

Author: NRC (2011) (1-194). Washington, DC: The National Academies Press. HERO ID: 710724

[Less] Formaldehyde is ubiquitous in indoor and outdoor air, and everyone is exposed to formaldehyde at some . . . [More] Formaldehyde is ubiquitous in indoor and outdoor air, and everyone is exposed to formaldehyde at some concentration daily. Formaldehyde is used to produce a wide array of products, particularly building materials; it is emitted from many sources, including power plants, cars, gas and wood stoves, and cigarettes; it is a natural product in come foods; and it is naturally present in the human body as a metabolic intermediate. Much research has been conducted on the health effects of exposure to formaldehyde, including effects on the upper airway, where formaldehyde is deposited when inhaled, and effects on tissues distant from the site of initial contact. The U.S. Environmental Protection Agency (EPA) released noncancer and cancer assessments of formaldehyde for its Intergated Risk Information System (IRIS) in 1990 and 1991, respectively. The agency began reassessing formaldehyde in 1998 and released a draft IRIS assessment in June 2010. Given the complexity of the issues and the knowledge that the assessment will be used as the basis of regulatory decisions, EPA asked the National Research Council (NRC) to conduct an independent scientific review of the draft IRIS assessment. In this report, the Committee to Review EPA's Draft IRIS Assessment of Formaldehyde first addresses some general issues associated with the draft IRIS assessment. The committee next focuses on questions concerning specific aspects of the draft assessment, including derivation of the reference concentrations and the cancer unit risk estimates for formaldehyde. The committee closes with recommendations for improving the IRIS assessment of formaldehyde and provides some general comments on the IRIS development process.