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Workplace Health & Safety Feb 2018Methylene chloride is an industrial solvent used in commercial paint strippers and degreasing agents. This chemical is widely used in consumer products, yet without...
Methylene chloride is an industrial solvent used in commercial paint strippers and degreasing agents. This chemical is widely used in consumer products, yet without appropriate protections, exposure may lead to death. Already banned in some countries, the Environmental Protection Agency (EPA) recently proposed limiting its use in the United States.
Topics: Humans; Methylene Chloride; Occupational Exposure; Solvents; United States
PubMed: 29053053
DOI: 10.1177/2165079917736319 -
Journal of Applied Toxicology : JAT 1995
Review
Topics: Animals; Carcinogens; Female; Humans; Male; Methylene Chloride; Nervous System; Reproduction; United States; United States Environmental Protection Agency
PubMed: 7594205
DOI: 10.1002/jat.2550150417 -
American Family Physician Apr 1993The effects of acute exposure to methylene chloride (dichloromethane) are due to its central nervous system depressant properties, which have resulted in fatalities.... (Review)
Review
The effects of acute exposure to methylene chloride (dichloromethane) are due to its central nervous system depressant properties, which have resulted in fatalities. Manifestations of acute exposure include mental confusion, fatigue, lethargy, headache and chest pain. Metabolic conversion of methylene chloride to carbon monoxide may place persons with preexisting coronary artery disease at increased risk. Sequelae following chronic exposure are unknown, but data suggest serious long-term effects. The Environmental Protection Agency considers methylene chloride to be a probable human carcinogen.
Topics: Aged; Environmental Exposure; Humans; Male; Methylene Chloride; Registries; United States
PubMed: 8465711
DOI: No ID Found -
The Journal of Emergency Medicine 1988The incidence of reported cases of toxicity resulting from methylene chloride exposure has increased within the last decade. A vast majority of these reports involve... (Review)
Review
The incidence of reported cases of toxicity resulting from methylene chloride exposure has increased within the last decade. A vast majority of these reports involve acute episodes, and the prevalence of domestic poisoning is relatively high. Diverse pathologic sequelae attributed to methylene chloride or its metabolites have been reported, although a distinct bias for central nervous system effects is evident. paradoxically, detoxification of methylene chloride via the mixed-function oxidase pathway is an inherently intoxicating event. Although the anomalous conversion of methylene chloride into carbon monoxide has increased the popular awareness of methylene chloride poisoning among medical personnel, lack of experience in diagnosis and treatment of methylene chloride poisoning is widespread. This review of 26 cases spanning 50 years reveals that the industrial and domestic use of methylene chloride is equally widespread. A compendium of the clinical experience with methylene chloride poisoning is presented.
Topics: Animals; Biotransformation; Gastrointestinal Diseases; Humans; Hydrocarbons, Chlorinated; Methylene Chloride; Mixed Function Oxygenases; Nervous System Diseases; Respiratory Tract Diseases
PubMed: 3049777
DOI: 10.1016/0736-4679(88)90330-7 -
JAMA Internal Medicine Jun 2021Methylene chloride is a halogenated organic solvent widely used in paint strippers, cleaners, adhesives, and sealants. Despite label warnings and occupational standards,...
IMPORTANCE
Methylene chloride is a halogenated organic solvent widely used in paint strippers, cleaners, adhesives, and sealants. Despite label warnings and occupational standards, methylene chloride-related fatalities continue to occur in the United States.
OBJECTIVE
To identify and analyze methylene chloride-related fatalities in the US.
DESIGN, SETTING, AND PARTICIPANTS
For this case series, we conducted systematic searches of sources, including PubMed and government databases, for unintentional fatalities in the US that were associated with exposure to methylene chloride or products containing methylene chloride between 1980 and 2018. We reviewed all available information, including inspection reports, autopsy reports, and medical records; data analyses were conducted from August 2018 to August 2020. Cases were categorized as those occurring in the home (consumer deaths) or at work (occupational deaths).
EXPOSURES
Methylene chloride or products containing methylene chloride.
MAIN OUTCOMES AND MEASURES
To determine characteristics of the methylene chloride-related fatalities, we recorded demographic information; the setting; circumstances, including information on safety measures used, if available; and products used. Where medical records were available, we recorded toxicology results and autopsy findings. We also obtained data about nonfatal methylene chloride cases from the American Association of Poison Control Centers.
RESULTS
From 1980 to 2018, 85 methylene chloride-related fatalities were identified in the US, including 74 (87%) in occupational settings; of those who died, 75 (94%) were men, and for the 70 cases with available information, the median (interquartile range) age of the decedents was 31 (24-46) years. Paint strippers were the most common products involved in methylene chloride-related fatalities (n = 60). The proportion of occupational fatalities related to paint stripping increased from 22 (55%) before 2000 to 30 (88%) after 2000. Similarly, occupational fatalities associated with bathtub or paint stripping in bathrooms increased from 2 (5%) before 2000 to 21 (62%) after 2000. From 1985 to 2017, the American Association of Poison Control Centers documented 37 201 nonfatal methylene chloride cases, with a decrease in the annual number of cases starting in the late 1990s.
CONCLUSIONS AND RELEVANCE
Results of this case series demonstrated that despite regulations to address the toxic effects of methylene chloride use for consumers and workers, there are continuing fatalities in the US, particularly in occupational settings. Prevention of fatalities associated with methylene chloride exposure should emphasize the use of safer substitutes, rather than hazard warnings or reliance on personal protective equipment.
Topics: Adult; Female; Humans; Male; Methylene Chloride; Middle Aged; Occupational Exposure; Poison Control Centers; Poisoning; United States; Young Adult
PubMed: 33871539
DOI: 10.1001/jamainternmed.2021.1063 -
Human & Experimental Toxicology Jan 1997B6C3F1 mice exposed to high dose levels of methylene chloride by inhalation for 2 years had an elevated incidence of liver and lung tumours. These tumours were not... (Review)
Review
B6C3F1 mice exposed to high dose levels of methylene chloride by inhalation for 2 years had an elevated incidence of liver and lung tumours. These tumours were not increased in rats or hamsters exposed under the same or similar conditions. This paper gives an overview of research conducted over the last 10 years into the mechanism of action of methylene chloride as a mouse carcinogen and into the relevance of the mouse data to humans exposed to this chemical. Data are presented on the comparative metabolism and pharmacokinetics of methylene chloride in mice, rats, hamsters and humans, on the toxicity of methylene chloride to the target organs in the mouse, and on the genotoxicity of methylene chloride in vitro and in vivo. The enzyme which activates methylene chloride to its carcinogenic form has been isolated, sequenced, and cloned, and its distribution studied within cells, organs and between species. Evidence has been obtained to show the methylene chloride caused cancer in mice as a result of interactions between metabolites of the glutathione S-transferase pathway and DNA. Damage to mouse lung Clara cells and increased cell division are believed to have influenced the development of the lung tumours. The species specificity was a direct consequence of the very high activity and specific cellular and nuclear localisation of a theta class glutathione S-transferase enzyme which was unique to the mouse. Consequently, DNA damage was not detectable in rats in vivo, or in hamster and human hepatocytes exposed to cytotoxic dose levels of methylene chloride in vitro. These results provide evidence that the mouse is unique in its response to methylene chloride and that it is an inappropriate model for human health assessment.
Topics: Administration, Inhalation; Animals; Carcinogenicity Tests; Cricetinae; Humans; Liver Neoplasms; Lung Neoplasms; Methylene Chloride; Mice; Mutagenicity Tests; Rats; Risk Assessment; Species Specificity
PubMed: 9023569
DOI: 10.1177/0960327197016001021 -
Cancer Causes & Control : CCC Dec 2013We searched MEDLINE and EMBASE for epidemiologic studies on occupational exposure to methylene chloride and risk of cancer. Estimates of study-specific odds ratios (ORs)... (Review)
Review
METHODS
We searched MEDLINE and EMBASE for epidemiologic studies on occupational exposure to methylene chloride and risk of cancer. Estimates of study-specific odds ratios (ORs) were calculated using inverse-variance-weighted fixed-effects models and random-effects models. Statistical tests for heterogeneity were applied.
RESULTS
We summarized data from five cohort studies and 13 case-control studies. The pooled OR for multiple myeloma was (OR 2.04; 95 % CI 1.31-3.17) in relation to occupational exposure to methylene chloride but not for non-Hodgkin's lymphoma, leukemia, breast, bronchus, trachea and lung, brain and other CNS, biliary passages and liver, prostate, pancreas, and rectum. Furthermore, we focused on specific outcomes for non-Hodgkin's lymphoma and multiple myeloma because of exposure misclassification. The pooling OR for non-Hodgkin's lymphoma and multiple myeloma was 1.42 (95 % CI 1.10-1.83) with moderate degree of heterogeneity among the studies (I (2) = 26.9 %, p = 0.205).
CONCLUSIONS
We found an excess risk of multiple myeloma. The non-Hodgkin's lymphoma and leukemia that have shown weak effects should be investigated further.
Topics: Humans; Meta-Analysis as Topic; Methylene Chloride; Neoplasms; Occupational Exposure; Risk Factors
PubMed: 24026192
DOI: 10.1007/s10552-013-0283-0 -
British Journal of Industrial Medicine Aug 1984
Topics: Accidents, Occupational; Burns, Chemical; Humans; Hydrocarbons, Chlorinated; Male; Methylene Chloride
PubMed: 6743591
DOI: 10.1136/oem.41.3.420 -
Toxicology Sep 1995The benefits of basing quantitative risk assessment on measures of 'internal dose', i.e. target organ exposures as estimated, for instance, by pharmacokinetic models,... (Review)
Review
The benefits of basing quantitative risk assessment on measures of 'internal dose', i.e. target organ exposures as estimated, for instance, by pharmacokinetic models, have been extensively discussed. Recasting risk assessment methods at the level of internal dose raises novel issues, however, some of which are explored by examining the 1987 revision by the US Environmental Protection Agency (EPA) of its cancer risk assessment for inhaled methylene chloride, which was based on the 1987 pharmacokinetic model results of Andersen and coworkers. The internal dose measure was the daily amount of methylene chloride metabolized by a glutathione-S-transferase pathway per 1 of target organ (liver and lung). Owing to high-dose saturation of a competing detoxification reaction, this metabolic activation is less-than-proportionally active at low exposure levels. For a given inhalation exposure, humans have relatively less metabolic activation than do mice, but this is shown to be a foreseeable consequence of their relatively lower breathing rate, a cross-species difference already accounted for in standard EPA methodology. Indeed, many species differences in the rates and tempos of physiological processes evince regular 'scaling' relationships across differently sized mammals. EPA's practice of scaling carcinogen doses by body surface area for cross-species extrapolation, often viewed as a correction for metabolic activation, is shown to be more reasonably regarded as an accommodation for the more general species variation in the pace of physiological processes underlying both pharmacokinetics and the carcinogenic response to internal doses. Under this view, the issue of cross-species dose scaling is not obviated by the use of pharmacokinetics.
Topics: Administration, Inhalation; Animals; Carcinogens; Dose-Response Relationship, Drug; Humans; Methylene Chloride; Mice; Models, Biological; Risk Assessment; Species Specificity
PubMed: 7482565
DOI: 10.1016/0300-483x(95)03039-i -
Journal of Occupational and... Jan 1997
Topics: Carbon Monoxide; Carboxyhemoglobin; Cardiovascular Diseases; Dose-Response Relationship, Drug; Environmental Exposure; Environmental Monitoring; Epidemiological Monitoring; Exercise Test; Humans; Male; Maximum Allowable Concentration; Methylene Chloride; Occupational Exposure; United States
PubMed: 9029426
DOI: 10.1097/00043764-199701000-00002