Sprague-Dawley rats were subchronically exposed to n-hexane either by repetitive subcutaneous injections of increasing doses up to 2 g/kg or by continuous inhalation of 400 to 600 ppm (Schaumburg and Spencer 1976). Lewey F, Alpers B, Bellet S, Creskoff A, Drabkin D, Ehrich W, Frank J, Jonas L, McDonald R, Montgomery E, Reinhold J (1941). The following research needs have been identified: Occupational exposure to organic solvents can cause adverse health effects, and the potential for these solvent-induced effects may increase the risk of accidental injuries. Appendix A lists those chemicals and mixtures with NIOSH RELs, OSHA PELs, and ACGIH TLVs (ACGIH 1986). Correspondence between the two systems of nomenclature is not exact, but the categories produced by these two workshops do help clarify the chronic effects of solvents on the CNS. Criteria for a recommended standard: occupational exposure to toluene. Int Arch Occup Environ Health 51:365-369. WHO, Nordic Council of Ministers (1985). J Soc Occup Med 33:13-18. Cookies used to make website functionality more relevant to you. The control room should be maintained at a greater air pressure than that surrounding the process equipment so that air flows out of the room rather than into it. Inhalation and percutaneous absorption are the primary routes of solvent uptake into the peripheral blood, which begins within minutes of the onset of exposure (WHO 1985; Engstrom et al. Our intention is to provide anyone who needs it with ready access to the information in these documents; we welcome suggestions concerning their content, style, and distribution. However, NIOSH believes that the collective toxicologic and epidemiologic data on organic solvent neurotoxicity provide sufficient evidence to warrant concern about adverse health effects from occupational exposure to these chemicals. J Ind Hyg and Toxicol 23:415-436. Each PEL is determined as an 8-hr time-weighted average (TWA) concentration, and it is based on the 1968 threshold limit value TLV of the American Conference of Governmental Industrial Hygienists (ACGIH) (ACGIH 1968) for a specific organic solvent. Symptoms, which may appear immediately after exposure or be delayed, may include: Limb weakness or numbness Loss of memory, vision, and/or intellect Headache Cognitive and behavioral problems Sexual dysfunction Individuals with certain disorders may be especially vulnerable to neurotoxicants. Amsterdam, the Netherlands: Elsevier Publishing Company. Neurotoxins usually cause acute effects in vertebrates including rapid paralysis of the peripheral skeletal and respiratory muscles. CRC Crit Rev Toxicol 7:279-356. *** Baker and Seppalainen 1986. The ACGIH designation C indicates the concentration that should not be exceeded during any part of the working exposure.The ACGIH designation A2indicates an industrial substance suspected of having carcinogenic potential for humans. Determination of the reversibility of neurotoxic effects of solvent exposure. This result suggests an ethanol-mediated inhibition of microsomal xylene metabolism. Fifty-six workers were diagnosed as having occupational diseases caused by exposure to organic solvents (primarily halogenated and aromatic hydrocarbons and mixtures of paint solvents) for a mean duration of 9.1 years at concentrations reported to be generally below the Finnish threshold limit value (Lindstrom 1980). The exposed workers also showed a statistically significant decrease (p<0.05) in performance on the neuropsychologic tests of concentration ability/attention and abstraction functions (Type 2B) and a statistically significant correlation (p=0.045) between degree of exposure and neuropsychologic and neurologic test performance. Chronic exposure to CS2 at workplace concentrations of approximately 20 to 40 ppm produced psychomotor deficits and impaired intellectual function in viscose rayon workers compared with unexposed workers (Seppalainen and Haltia 1980; Hanninen 1971; Hanninen et al. Due to their high metabolic rate, neurons are at the greatest risk of damage caused by neurotoxins. [return to table] 9-259. Volume 2. Where closed systems cannot be used, local exhaust ventilation should be provided to direct vapors away from workers and to prevent the recirculation of contaminated exhaust air. 1980a) and in individuals who abusively inhaled the compound (Altenkirch et al. The studies that indicate the potential for organic solvents to induce toxic effects on the human nervous system are not without shortcomings. Cookies used to enable you to share pages and content that you find interesting on CDC.gov through third party social networking and other websites. NIOSH therefore recommends (1) that producers and users of organic solvents disseminate this information to their workers and customers, (2) that professional and trade associations and unions inform their members of the potential neurotoxic effects of working with organic solvents, and (3) that appropriate engineering controls, personal protective equipment, and worker education programs be used to reduce worker exposuresat least to the concentrations specified in existing Occupational Safety and Health Administration (OSHA) permissible exposure limits (PELs), or to NIOSH recommended exposure limits (RELs) or the American Conference of Governmental Industrial Hygienists (ACGIH) threshold values (TLVs) if they provide a greater degree of protection. Toxicants come from a variety of sources, but they tend to become . **ACGIH TWA recommendations are based on exposures of up to 8 hr per workday or 40 hr per workweek. These cookies may also be used for advertising purposes by these third parties. Med Lav 69:144-150. In contrast, 33 toluene-exposed workers who chronically ingested alcohol had significantly lower blood toluene concentrations (p<0.05) than did 13 workers from the same factory who seldom drank. Gamberale F (1976). A complete respiratory protection program should include (1) selection of respirators approved by the Mine Safety and Health Administration (MSHA) and NIOSH, (2) regular training of personnel, (3) fit testing, (4) periodic environmental monitoring, and (5) maintenance, inspection, and cleaning of equipment. Solvent elimination occurs through exhalation of the parent compound in expired air or through urinary or biliary excretion of water-soluble metabolites or of unchanged solvent. Epidemiologic research to establish the prevalence and incidence of neurologic disorders and to identify and validate quantitative tests for screening workers. Symptoms include: weakness in the extremities; tingling sensations or numbness; memory loss; loss of vision and/or intellect; uncontrollable obsessive and/or compulsive behaviors; delusions; headaches; cognitive and behavioral issues; and sexual dysfunction. Reproductive hazards recognized by NIOSH include 2-methoxyethanol and 2-ethoxyethanol (NIOSH 1983a), and methyl chloride (NIOSH 1984a). The frequency of abnormally slow nerve conduction velocities increased in a statistically significant manner (p<0.05) when the intermediate exposure group was compared with the high exposure group. Washington, DC: U.S. Government Printing Office, Office of the Federal Register. The examining physician should direct particular attention to the nervous, respiratory, reproductive, and cardiovascular systems, and to the skin, eyes, liver, blood, kidneys, and gastrointestinal tract, as these are the most likely targets for the adverse effects of organic solvents. Studies were conducted of automobile and industrial spray painters with long-term exposures to organic solvents at concentrations below the Swedish occupational exposure limit values and most NIOSH RELsor in the absence of RELs, OSHA PELs. [signature] Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publication No. Work Environ Health 11:86-93. Am J Ind Med 1:31-42. . A statistically significant decrease (p<0.05) in motor and sensory nerve conduction velocities was noted in the painters compared with an age-matched reference group of railroad engineers. These toxins bind the alpha-1 nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction, causing paralysis and asphyxia. Due to its harmful properties, this neurotoxin can damage the brain and cause other neurological issues. 1983). The side effects of Daxxify are also very similar to other neurotoxins currently on the market, which include headache, reaction at the injection site such as pain, swelling, itching, brushing, or . CIBs are prepared by the staff of the Division of Standards Development and Technology Transfer, NIOSH (Robert A. Taft Laboratories, 4676 Columbia Parkway, Cincinnati, Ohio 45226). The NIOSH Occupational Exposure Sampling Strategy Manual (Leidel et al. Lazar R, Ho S, Melen O, Daghestani A (1983). (1976). Correlation of reported neurotoxic effects with exposure data. Synthetic organic chemicals. 1980), which has been shown to have a greater neurotoxic potency than either parent compound (Krasavage et al. 356-373. Solvent encephalopathy. Spencer P, Couri D, Schaumburg H (1980a). System effectiveness should also be checked when there are any changes in production, process, or control that might result in increased exposure to airborne organic solvents. The effects of ethanol on blood toluene concentrations. Saving Lives, Protecting People, The National Institute for Occupational Safety and Health (NIOSH), National Institute for Occupational Safety and Health, Fatality Assessment and Control Evaluation Reports (FACE), Firefighter Fatality Investigation Reports, U.S. Department of Health & Human Services, Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode, Any supplied-air respirator that has a full facepiece and is operated in pressure-demand or other positive-pressure mode in combination with an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive-pressure mode, Any full-facepiece respirator (gas mask) with a suitable organic vapor canister, or any appropriate self-contained breathing apparatus of the escape-type. 83-119. These toxins have been linked to brain disorders, Peripheral Neuropathy and neurodegenerative diseases, such as Alzheimer's, Huntington's Chorea and Parkinson's disease. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, pp. These effects include disorders is characterized by reversible subjective symptoms (fatigability, irritability, and memory impairment), sustained changes in personality or mood (emotional instability and diminished impulse control and motivation), and impaired intellectual function (decreased concentration ability, memory, and learning ability). Waldron HA, Cherry N, Johnston JD (1983). The guidelines below are general in nature and should be adapted to specific work situations as required. Following absorption, organic solvents undergo biotransformation (which occurs primarily in the liver), or they accumulate in lipid-rich tissues such as those of the nervous system (WHO 1985; Bergman 1983). Cincinnati, OH: American Conference of Governmental Industrial Hygienists. Lead, plant product (drinking alcohol), atomic number 25 salt, gas (NO), neurolysin (e.g. 1978). A cross-sectional epidemiologic investigation on occupationally exposed industrial workers with special reference to the nervous system. Application and results of whole-body autoradiography in distribution studies of organic solvents. On the basis of the identified adverse health effects of solvent exposure, the National Institute for Occupational Safety and Health (NIOSH) recommends that employers use engineering controls, personal protective equipment and clothing, and worker education programs to reduce exposure to organic solventsat least to the concentrations specified in existing Occupational Safety and Health Administration (OSHA) permissible exposure limits (PELs), or to NIOSH recommended exposure limits (RELs) or the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (TLVs) if they provide a greater degree of protection. However, the chronic effects may be caused by metabolic activation of the parent compound, which results in more reactive intermediate metabolites (e.g., 2,5-hexanedione, a metabolite of n-hexane and methyl n-butyl ketone) that may alter nervous tissue structure. Thus special precautions are often necessary to prevent or limit worker exposure in these situations, and they frequently involve the use of personal protective equipment. 78-175. The Type 2 disorder has been divided into Type 2A (sustained personality or mood changes such as emotional instability and diminished impulse control and motivation) and Type 2B (impairment in intellectual function manifested by diminished concentration, memory, and learning capacity). 1981; Knox and Nelson 1966). Macroscopic manifestations of neurotoxin exposure can include widespread central nervous system damage such as intellectual disability, [5] persistent memory impairments, [16] epilepsy, and dementia. These surveys are necessary to determine the extent of worker exposure and to ensure that controls already in place are operational and effective. Neurophysiological and psychological picture of solvent poisoning. The relative neurotoxicity of methyl n-butyl ketone, n-hexane and their metabolites. In male and female Mongolian gerbils, 3 months of inhalation exposure to 60 ppm trichloroethylene followed by a 4-month recovery period produced increases in brain protein levels associated with brain damage (Haglid et al. An animal model of the mechanism of pathogenesis would lead to more accurate methods for predicting the neurotoxicity of organic solvents. PB-222-219/A06. The individual test profiles revealed that 14% of the exposed workers and none of the reference group workers had definite indications of brain dysfunction (toxic encephalopathy), as indicated by significant deviation (>l standard deviation) from expected values in two or more of the psychometric variables tested. Work Environ Health 9:131-139. EEG abnormalities persisted for 3 to 9 years in 42% of a group of patients diagnosed as having chronic solvent intoxication after occupational exposure (Seppalainen and Antti-Poika 1983). Current Intelligence Bulletin 43. Reproductive hazards recognized by NIOSH include 2- methoxyethanol, 2-ethoxyethanol, and methyl chloride. Eighty Swedish automobile and industrial spray painters experienced chronic exposures to mixtures of 19 organic solvents at breathing zone concentrations below the Swedish occupational exposure limit values and most NIOSH RELsor in the absence of a REL, below the OSHA PEL (Elofsson et al. Early neuronal alterations caused by experimental thinner inhalation in young rats. Respirator Selection Table for Solvents Identified by NIOSH as Potential Carcinogens, Table 3. Identification of the interactions or synergistic effects of solvent mixtures found in the workplace and the role of alcohol and other drugs in these interactions. Type 1 and 2 disorders are the most likely to be reported among solvent-exposed workers. Centers for Disease Control. A 27% increase in solvent uptake was noted in an inhalation study using 1,1,1-tri-chloroethane (Monster et al. Immediately dangerous to life or health. NIOSH (1984a). Salvini M, Binaschi S, Riva M (1971). NIOSH is also concerned about those organic solvents for which only neurotoxic effects have been reported. 1-39. In addition, the exposed workers had lower scores in all five tests for learning/memory and in the combined index for intellectual impairment, although none of these were statistically significant. Cassitto M, Bertazzi P, Camerino D, Bulgheroni C, Cirla A, Gilioli R, Graziano C, Tomasini M (1978). Psycho-physiological functions. Chloroethanes: review of toxicity. Psychologic testing also revealed statistically significant differences (p<0.05) between the exposed and reference groups in simple reaction time, manual dexterity, perceptual speed, and short-term memory. Seppalainen AM, Husman K, Martenson C (1978). Valciukas J, Lilis R, Singer R, Glickman L, Nicholson W (1985). Bruhn P, Arlien-Soborg P, Gyldensted C, Christensen E (1981). Workers should also be given access to relevant exposure and medical records (29 CFR 1910.20). 1971). The preexposure ingestion of ethanol caused statistically significant increases (p<0.05) in blood xylene concentrations compared with those produced by corresponding xylene exposures without ethanol. Persson L, Ronnback L, Haglid K (1976). Psychological tests as indicators of excessive exposure to carbon disulfide. Occupational exposure to neurotoxic monomers may take place at industries manufacturing, transporting and using chemical products and plastic products. -k-lj--kl. Effects of long-term exposure to solvents in the paint industry. n-Hexane and methyl n- butyl ketone. NIOSH (1984b). Testing of chemical classes and structural analogues to provide the ability to predict neurotoxicity. A syndrome occurring as a result of industrial exposure. Neurobehavioral performance tests of CNS function (i.e., Block Design and Embedded Figures) were administered to 55 shipyard painters, 95% of whom had more than 10 years of work experience that involved exposure to methyl isobutyl ketone, perchloroethylene, xylene, ethylene glycol, and mineral spirits. Table 2. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health. Spencer P., Schaumburg H, Sabri M, Veronesi B (1980b). 2,5-Hexanedione, a metabolic product of n-hexane (DiVincenzo et al. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publication No. Journalists reported the immediate impact of lives lost and homes and property destroyed, but more insidious dangers escaped notice. Chronic occupational exposure at concentrations above 100 ppm (Politis et al. 1978). Experimental and clinical neurotoxicology. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publication No. Gamberale F, Hultengren M (1974). The precise extent to which worker exposure to organic solvents increases the likelihood of accidents or illnesses remains to be determined, however. 1979). Evidence for peripheral neurotoxic effect of trichloroethylene. The effects of pesticides on the nervous system may be involved in their acute toxicity, as in case of most insecticides, or may contribute to chronic neurodegenerative disorders, most notably Parkinson's disease. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publication No. [return to table] NIOSH (1978b). Seppalainen AM (1985). Occupational Safety and Health Scand J Psychol 19:163-174. Scand J Work Environ Health 4:73-85. Abdel-Rahman M, Hetland L, Couri D (1976). 1982). Like n-hexane, MBK is also metabolized to 2,5-hexanedione (DiVincenzo et al. Research indicates that chronic exposure of animals to some organic solvents may cause irreversible CNS changes that are characteristic of brain damage. Chronic neurotoxicity in workers exposed to organic solvents over a period of months to years includes (1) peripheral neuropathies such as axonal degeneration seen in workers exposed to hexacarbon solvents (e.g., n-hexane, methyl n-butyl ketone), (2) Type 1 CNS symptoms such as fatigability irritability, and memory impairment, and (3) Type 2 mild toxic encephalopathy, including sustained personality or mood changes such as emotional instability, diminished impulse control and motivation, and impairment in intellectual function manifested by diminished concentration, memory, and learning capacity. 1978; Cassitto et al. Baltimore, MD: Williams and Wilkins, pp. United States International Trade Commission, USITC Publication 1745, pp. Neuropathol Neurobiol 2:209-216. A cross-sectional epidemiologic investigation on occupationally exposed car and industrial spray painters with special reference to the nervous system. New York, NY: American National Standards Institute. Maitotoxin is the most potent nonproteinaceous toxin known. concerning reversible and irreversible effects and direct versus indirect effects. Exposures at the STEL should not be longer than 15 min and should not be repeated more than four times per day. Kirk-Othmer encyclopedia of chemical technology. Solvents and the brain. [return to table] Monohalomethanes: methyl chloride, methyl bromide, methyl iodide. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health. Neurotoxicology 7:43-56. Riihimaki V, Pfaffli P (1978). Thank you for taking the time to confirm your preferences. Acute experimental exposures of human volunteers to one or several organic solvents have impaired psychomotor function as measured by reaction time, manual dexterity, coordination, or body balance. This state of affairs exists partly because most snake bites occur in areas where physicians, let alone neurologists, are . Criteria for a recommended standard: occupational exposure to trichloroethylene. In: Spencer P, Schaumburg H, eds. 1974). NIOSH considers the PELs, RELs, and TLVs for the specific organic solvents found in the workplace to be upper boundaries of exposure.
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