['Toxic and Hazardous Substances - OSHA']
['Toxic and Hazardous Substances - OSHA']
09/12/2024
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I. Primary Route of Entry
Inhalation.
II. Toxicology
Methylene Chloride (MC) is primarily an inhalation hazard. The principal acute hazardous effects are the depressant action on the central nervous system, possible cardiac toxicity and possible liver toxicity. The range of CNS effects are from decreased eye/hand coordination and decreased performance in vigilance tasks to narcosis and even death of individuals exposed at very high doses. Cardiac toxicity is due to the metabolism of MC to carbon monoxide, and the effects of carbon monoxide on heart tissue. Carbon monoxide displaces oxygen in the blood, decreases the oxygen available to heart tissue, increasing the risk of damage to the heart, which may result in heart attacks in susceptible individuals. Susceptible individuals include persons with heart disease and those with risk factors for heart disease.
Elevated liver enzymes and irritation to the respiratory passages and eyes have also been reported for both humans and experimental animals exposed to MC vapors.
MC is metabolized to carbon monoxide and carbon dioxide via two separate pathways. Through the first pathway, MC is metabolized to carbon monoxide as an end-product via the P-450 mixed function oxidase pathway located in the microsomal fraction of the cell. This biotransformation of MC to carbon monoxide occurs through the process of microsomal oxidative dechlorination which takes place primarily in the liver. The amount of conversion to carbon monoxide is significant as measured by the concentration of carboxyhemoglobin, up to 12 percent measured in the blood following occupational exposure of up to 610 ppm. Through the second pathway, MC is metabolized to carbon dioxide as an end product (with formaldehyde and formic acid as metabolic intermediates) via the glutathione dependent enzyme found in the cytosolic fraction of the liver cell. Metabolites along this pathway are believed to be associated with the carcinogenic activity of MC.
MC has been tested for carcinogenicity in several laboratory rodents. These rodent studies indicate that there is clear evidence that MC is carcinogenic to male and female mice and female rats. Based on epidemiologic studies, OSHA has concluded that there is suggestive evidence of increased cancer risk in MC-related worker populations. The epidemiological evidence is consistent with the finding of excess cancer in the experimental animal studies. NIOSH regards MC as a potential occupational carcinogen and the International Agency for Research Cancer (IARC) classifies MC as an animal carcinogen. OSHA considers MC as a suspected human carcinogen.
III. Medical Signs and Symptoms of Acute Exposure
Skin exposure to liquid MC may cause irritation or skin burns. Liquid MC can also be irritating to the eyes. MC is also absorbed through the skin and may contribute to the MC exposure by inhalation.
At high concentrations in air, MC may cause nausea, vomiting, light-headedness, numbness of the extremities, changes in blood enzyme levels, and breathing problems, leading to bronchitis and pulmonary edema, unconsciousness and even death.
At lower concentrations in air, MC may cause irritation to the skin, eye, and respiratory tract and occasionally headache and nausea. Perhaps the greatest problem from exposure to low concentrations of MC is the CNS effects on coordination and alertness that may cause unsafe operations of machinery and equipment, leading to self-injury or accidents.
Low levels and short duration exposures do not seem to produce permanent disability, but chronic exposures to MC have been demonstrated to produce liver toxicity in animals, and therefore, the evidence is suggestive for liver toxicity in humans after chronic exposure.
Chronic exposure to MC may also cause cancer.
IV. Surveillance and Preventive Considerations
As discussed in sections II and III of this appendix, MC is classified as a suspect or potential human carcinogen. It is a central nervous system (CNS) depressant and a skin, eye and respiratory tract irritant. At extremely high concentrations, MC has caused liver damage in animals. MC principally affects the CNS, where it acts as a narcotic. The observation of the symptoms characteristic of CNS depression, along with a physical examination, provides the best detection of early neurological disorders. Since exposure to MC also increases the carboxyhemoglobin level in the blood, ambient carbon monoxide levels would have an additive effect on that carboxyhemoglobin level. Based on such information, a periodic post-shift carboxyhemoglobin test as an index of the presence of carbon monoxide in the blood is recommended, but not required, for medical surveillance.
Based on the animal evidence and three epidemiologic studies previously mentioned, OSHA concludes that MC is a suspect human carcinogen. The medical surveillance program is designed to observe exposed workers on a regular basis. While the medical surveillance program cannot detect MC-induced cancer at a preneoplastic stage, OSHA anticipates that, as in the past, early detection and treatments of cancers leading to enhanced survival rates will continue to evolve.
A. Medical and Occupational History
The medical and occupational work history plays an important role in the initial evaluation of workers exposed to MC. It is therefore extremely important for the examining physician or other licensed health care professional to evaluate the MC-exposed worker carefully and completely and to focus the examination on MC's potentially associated health hazards. The medical evaluation must include an annual detailed work and medical history with special emphasis on cardiac history and neurological symptoms.
An important goal of the medical history is to elicit information from the worker regarding potential signs or symptoms associated with increased levels of carboxyhemoglobin due to the presence of carbon monoxide in the blood. Physicians or other licensed health care professionals should ensure that the smoking history of all MC exposed employees is known. Exposure to MC may cause a significant increase in carboxyhemoglobin level in all exposed persons. However, smokers as well as workers with anemia or heart disease and those concurrently exposed to carbon monoxide are at especially high risk of toxic effects because of an already reduced oxygen carrying capacity of the blood.
A comprehensive or interim medical and work history should also include occurrence of headache, dizziness, fatigue, chest pain, shortness of breath, pain in the limbs, and irritation of the skin and eyes.
In addition, it is important for the physician or other licensed health care professional to become familiar with the operating conditions in which exposure to MC is likely to occur. The physician or other licensed health care professional also must become familiar with the signs and symptoms that may indicate that a worker is receiving otherwise unrecognized and exceptionally high exposure levels of MC.
An example of a medical and work history that would satisfy the requirement for a comprehensive or interim work history is represented by the following:
The following is a list of recommended questions and issues for the self-administered questionnaire for methylene chloride exposure.
[84 FR 21544, May 14, 2019]
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