Source1:
Methylene chloride is a compound that is developed from natural elements such as methane gas or wood alcohol. In a liquid form, the solvent is colorless, easily evaporated, not easily burned and tends to have mildly sweet odor. Used as an industrial solvent and as a paint stripper, this compound may also be found in aerosol, pesticide and photographic film products. The methylene chloride found in the environment is a result of product release.
Biotransformation2:
Occurs in two locations-
Cell:
Occurs in the cytosolic fraction of the liver cell and results in carbon dioxide end product in addition to formaldehyde and formic as metabolic intermediates through the use of glutathione dependent enzymes. This pathway is generally indicating of carcinogenic activity.
Liver:
Through the P-450 mixed function oxidase pathway, carbon monoxide, carbon dioxide and chloride become an end product when methylene chloride is metabolized by microsomal oxidative dechlorination. The percentage of carbon monoxide produced is directly correlated with methylene chloride concentration. This pathway is primarily focused on detoxification.
Toxicokinetics3:
The primary route of methylene chloride exposure is through inhalation which absorbs at a rapid rate. As the concentration increases, the level of blood oxygen decreases which causes the cardiac output to increase in attempt to obtain more oxygen. Increased ventilation then leads to an increase of respiratory exposure and saturation may occur. Obesity plays a role in absorption and body fat has been proven to store methylene chloride, however, the compound tends to be eliminated fairly quickly once steady state is reached. Methylene chloride is distributed throughout the blood and is eliminate through urine after being metabolized in the liver.
Carcinogenicity1:
According to the DHHS, human carcinogen is anticipated in reference to significant evidence found in animal studies. . In addition, OSHA has concluded there is evidence of increased cancer risk for individuals working with methylene chloride and has declared the compound as a human carcinogen.
Mechanism of Action1,2:
Metabolized primarily in the liver where methylene chloride is transformed to carbon monoxide. As a result, carboxyhemoglobin levels increase while the ability to carry oxygen throughout the blood decreases. These levels have potential to diverge even more even hours after exposure.
Target Organs:
- Cardiovascular system
- Respiratory system
- Central nervous system
- Skin
Signs & Symptoms2:
Duration of exposure contributes to level of toxicity. Shorter durations appear to be less likely to cause permanent disabilities. Meanwhile, long term exposures have proven to produce liver toxicity in animal studies with indications of similar effects on humans.
Skin Contamination:
- Irritation
- Burns
Inhalation:
- Nausea
- Vomiting
- Light headedness
- Extremity numbness
- Fluctuating blood enzyme levels
- Difficulty breathing
- Bronchitis/pulmonary edema
- Unconsciousness
- Death
Genetic susceptibility1,3:
No structural abnormalities were observed. Behavioral alterations and mentally retarded development was found in animal studies. Methylene chloride has been proven to cross the placental barrier in both rats and humans, including breast milk. Depending on the concentration, this ingestion exposure could result in fatal poisoning.
Treatments:
Immediate removal from exposing environment
Oxygen treatment to decrease carboxyhemoglobin and increase oxygen levels
Liver function tests to identify potential hepatic toxicity
Biomarkers3:
Methylene chloride exposure may be confirmed through blood, breath or urine. Correlations have been observed between methylene chloride levels in urine and the respiratory tract. Carbon monoxide concentrations within the alveolar air is another indication of exposure, however, must be confirmed through another indication. Carboxylhemoglobin levels significantly increase during methylene chloride exposure and are dependent on duration.
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