14
Methanol

Hector D. García, Ph.D.

Toxicology Group

Habitability and Environmental Factors Division

Johnson Space Center

National Aeronautics and Space Administration

Houston, Texas


Methanol (H3COH, CAS no. 67-56-1), the simplest alcohol, is a colorless, volatile, highly flammable liquid with a mild, characteristic, agreeable odor; it is completely miscible in water. One part per million (ppm) of methanol = 1.31 milligrams per cubic meter (mg/m3). An extremely wide range of odor threshold values for methanol vapor has been reported in the literature, from 5.5 mg/m3 (NLM 2007) to 26,840 mg/m3 (Ruth 1986).

In anticipation of longer-duration exploration missions, the purpose of this document is to establish a spacecraft maximum allowable concentration (SMAC) value for methanol for an extended exposure of 1,000 d and to revise the previous SMAC values based on recently available data.

OCCURRENCE AND USE

Methanol occurs naturally in humans and animals, in plants, including fresh fruits and vegetables, and in fermented products, including wine and other spirits (see Tables 14-1 and 14-2). It is produced from the distillation of wood or is synthesized catalytically from crude petroleum. It is used industrially in the manufacture of other chemicals and as a solvent. It is added to a variety of commercial and consumer products, including windshield washing solutions, deicing solutions, glass cleaners, duplicating fluids, solid canned fuels, paint thinners and removers, model airplane fuels, embalming fluids, lacquers, inks, and some formulations of gasohol motor fuel.

Methanol vapor concentrations in the atmosphere of the Shuttle and the International Space Station have rarely exceeded 1 mg/m3 and are generally less than 0.6 mg/m3.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 275
14 Methanol Hector D. García, Ph.D. Toxicology Group Habitability and Environmental Factors Division Johnson Space Center National Aeronautics and Space Administration Houston, Texas Methanol (H3COH, CAS no. 67-56-1), the simplest alcohol, is a colorless, volatile, highly flammable liquid with a mild, characteristic, agreeable odor; it is completely miscible in water. One part per million (ppm) of methanol = 1.31 milligrams per cubic meter (mg/m3). An extremely wide range of odor threshold values for methanol vapor has been reported in the literature, from 5.5 mg/m3 (NLM 2007) to 26,840 mg/m3 (Ruth 1986). In anticipation of longer-duration exploration missions, the purpose of this document is to establish a spacecraft maximum allowable concentration (SMAC) value for methanol for an extended exposure of 1,000 d and to revise the previous SMAC values based on recently available data. OCCURRENCE AND USE Methanol occurs naturally in humans and animals, in plants, including fresh fruits and vegetables, and in fermented products, including wine and other spirits (see Tables 14-1 and 14-2). It is produced from the distillation of wood or is synthesized catalytically from crude petroleum. It is used industrially in the manufacture of other chemicals and as a solvent. It is added to a variety of commercial and consumer products, including windshield washing solutions, deicing solutions, glass cleaners, duplicating fluids, solid canned fuels, paint thinners and removers, model airplane fuels, embalming fluids, lacquers, inks, and some formulations of gasohol motor fuel. Methanol vapor concentrations in the atmosphere of the Shuttle and the International Space Station have rarely exceeded 1 mg/m3 and are generally less than 0.6 mg/m3. 275

OCR for page 275
276 SMACs for Selected Airborne Contaminants TABLE 14-1 Methanol Concentrations in Foods and Beverages Source Concentration Fresh and canned fruit juices 1-43 mg/L (orange and grapefruit juices) 11-80 mg/L 12-640 mg/L (Average of 140 mg/L) Neutral spirits <1.5 g/L Beer 6-27 mg/L Wines 96-329 mg/L Distilled spirits 16-220 mg/L Bourbon 55 mg/L 50% grain alcohol 1 mg/L Brandies (United States, Canada, and Italy) 6,000-7,000 mg/L Beans 1.5-7.9 mg/kg Split peas 3.6 mg/kg Lentils 4.4 mg/kg Carbonated beverages ~56 mg/L Abbreviations: kg, kilogram; L, liter. Source: Data from NTP CERHR 2003. TABLE 14-2 Background Blood Methanol and Formate Concentrations in Humans mg of methanol/L, mg of formate /L, Subjects mean ± SD (range) mean ± SD (range) Twelve males on restricted diet 0.570 ± 0.305 3.8 ± 1.1 (no methanol-containing or methanol- (0.25-1.4) (2.2-6.6) producing foods) for 12 h Twenty-two adults on restricted diet 1.8 ± 2.6 11.2 ± 9.1 (no methanol-containing or methanol- (no range data) (no range data) producing foods) for 24 h Three males who ate a breakfast with no 1.82 ± 1.21 9.08 ± 1.26 aspartame-containing cereals and no juice (0.57-3.57) (7.31-10.57) Five males who ate a breakfast with no 1.93 ± 0.93 8.78 ± 1.82 aspartame-containing cereals and no juice (0.54-3.15) (5.36-10.83) (second experiment) Twelve adults who drank no alcohol 1.8 ± 0.7 No data for 24 h (no range data) Twelve adults who drank no alcohol 1.7 ±0.9 No data for 24 h (0.44.7) Thirty fasted adults <4 19.1 (no range data) (no range data) Twenty-four fasted infants <3.5 No data (no range data) Abbreviation: SD, standard deviation. Source: Data from NTP CERHR 2003.

OCR for page 275
277 Methanol SUMMARY OF ORIGINAL APPROACH SMAC values for methanol were previously published in volume 1 of this series, Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, for exposure durations of 1 h, 24 h, 7 d, 30 d, and 180 d (Wong 1994). These methanol SMACs were based on data in a report (Frederick et al. 1984) published by the National Institute for Occupational Safety and Health that described visual disturbances in 66 teacher aides exposed to methanol va- pors from “spirit” duplicating machines during a work week, with exposure du- rations in individual aides varying from 1 to 40 h/wk. The 1-h SMAC was calcu- lated by estimating a no-observed-adverse-effect level (NOAEL) from the 391- ppm average concentration at which visual effects were reported. This was done by multiplying 391 ppm by 0.1 (lowest-observed-adverse-effect level [LOAEL] to NOAEL factor) and again by (√66)/√100 as a “small n” factor to achieve a value of 32 ppm, rounded to 30 ppm. The calculations did not take into account the exposure duration beyond 7 d. To calculate a 24-h SMAC, Wong assumed that “unlike headaches, methanol’s ocular toxicity might not be entirely dependent on the blood concen- tration of formic acid and might not have a threshold” (Wong 1994, P. 162), but instead may depend on the total dose (concentration times duration). Therefore, he used Haber’s rule to reduce the 1-h SMAC by a factor of 8 h/24 h to a value of 11 ppm, rounded to 10 ppm. For the 7-, 30-, and 180-d SMACs, Wong ap- plied a “small n” factor, a 0.1 LOAEL-to-NOAEL factor, and a time factor of 40/168 to the 392 ppm LOAEL to extrapolate from a work week to a continuous 7-d exposure. He calculated an acceptable concentration of 7 ppm for 7 d, which he applied for exposure durations of 7, 30, and 180 d. CHANGES IN FUNDAMENTAL APPROACHES RECOMMENDED BY THE NATIONAL RESEARCH COUNCIL The original SMAC values for methanol, set in 1994 by King Lit Wong, were calculated using safety factors applied to a LOAEL. More recently, the National Research Council has recommended using a benchmark dose analysis for setting the point of departure and ten Berge’s generalization (CN × T = K) of Haber’s rule for extrapolating ACs based on short-duration studies to longer durations (when data permit). Although Wong applied a “small n” factor to a reported LOAEL to estimate a NOAEL, NASA and the National Research Council have since recommended (James and Gardner 1996) the use of a “small n” factor only when the data include an apparent NOAEL. NEW DATA SINCE 1994 Table 14-3 is a compilation of data from a selected list of currently avail- able studies (published up through and since 1994) on methanol toxicity. Since

OCR for page 275
TABLE 14-3 Toxicity Summary 278 Concentration/dose and Exposure Species and chemical form, route duration strain Effects Reference Acute and short-term exposure (≤10 d) Unknown high dose Single bolus Humans Severe metabolic acidosis, optic McMartin et al. 1980 (n = 2) disc edema, death in 1 of 2. Unknown high dose Single bolus Humans Severe metabolic acidosis, optic Hayreh et al. 1977, 1980 (n = 2) disc edema, blindness. Unknown high dose Single bolus Humans Severe metabolic acidosis, optic Jacobsen and McMartin (n = 2) disc edema, blindness. 1986 800 ppm 0.5, 1, 2, 8 h Humans MeOH concentration in breath, Batterman et al. 1998 (n = 4, 4, 4, 15) blood, and urine measured. No toxicity reported. 200 ppm 6h Humans No toxicity reported. Mean blood Lee et al. 1992 (n = 6) MeOH concentration increased from 1.8 µg/mL background to 7.0 µg/mL at rest or 8.1 µg/mL with light exercise. No increase in blood formate concentration at rest or exercising. 100 ppm 2h Humans No toxicity reported. Mean blood Ernstgard et al. 2005 (n = 8) MeOH concentration increased from 20 to 116 µM. 200 ppm 2h Humans No toxicity reported. Mean blood Ernstgard et al. 2005 (n = 8) MeOH concentration increased from 20 to 244 µM.

OCR for page 275
192 ppm 75 min Humans No significant effects on tests of Cook et al. 1991 (n = 12) sensory, behavioral, and reasoning performance. 200 ppm 4h Humans No significant effects on Chuwers et al. 1995 (n = 26) neurobehavioral performance. Serum MeOH concentration increased but serum formate concentration did not. 200 ppm 4h Humans No significant effects on D’Alessandro et al. 1994 (n = 26) neurobehavioral performance. Serum MeOH concentration increased, but serum formate concentration did not. 200 ppm 4h Humans Serum MeOH increased from 0.9 Osterloh et al. 1996 (n = 22) to 6.5 µg/mL. No toxicity reported. Subchronic exposure (11–100 d) 365- to 3,080-ppm vapors 1-40 h/wk Teacher aides, Dose-dependent incidence of Frederick et al. 1984 female blurred vision, headache, dizziness, and nausea. Chronic exposure (≥100 d) 32.7 mg of methanol/dose (as 3 doses/d, Human NOAEL for standard lab tests or Leon et al. 1989 metabolite of 900 mg of 7 d/wk, 6 mo (n = 53) symptoms experienced. aspartame/d) Abbreviations: MeOH, methanol; µM, micromolar. 279

OCR for page 275
280 SMACs for Selected Airborne Contaminants 1994, published studies on methanol have examined the metabolic, toxicoki- netic, histopathologic, neurobehavioral, and ocular effects of methanol in hu- mans and other animals after short-term inhalation of vapors or by other routes of exposure and the kinetics of elimination of methanol or formate from blood and urine (D’Alessandro et al. 1994, Chuwers et al. 1995, Osterloh et al. 1996, Batterman et al. 1998, Ernstgard et al. 2005). The results of these studies rein- force and expand upon the findings reported before 1994 but do not support Wong’s assumption that the ocular toxicity of methanol might not have a threshold. Studies and case reports before 1994 show that ocular effects are associ- ated only with blood formate concentrations in excess of 5 to 10 millimolar (225-450 mg/liter [L]) and are observed only after a latent, symptom-free period of about a day (6-30 h). Presumably, during this latent period, methanol is me- tabolized to formaldehyde, formate, and carbon dioxide (CO2) until the body’s stores of tetrahydrofolate are depleted and increasing blood formate concentra- tions lead to anoxia in the retinal cells, due to their relatively low concentrations of mitochondrial cytochrome oxidase (Nicholls 1975; Martin-Amat et al. 1977, 1978; Kavet and Nauss 1990). In the initial stages, developing ocular toxicity can be reversed, consistent with a mechanism involving the reversible inhibition of cytochrome c oxidase by formate and the need for prolonged retinal cell hy- poxia to gradually produce symptoms of impaired vision (Nicholls 1975). An- oxia leads to swelling of the retinal ganglion cells and progressive loss of vision if not reversed within about 24 h of the initiation of methanol intoxication. The delays seen in development of ocular toxicity in humans who ingest significant quantities of methanol can be attributed to two factors: the time necessary to deplete the body’s stores of tetrahydrofolate so that formate metabolism to CO2 is greatly decreased and formate begins to accumulate to concentrations that inhibit mitochondrial cytochrome oxidase in the retinal ganglia, and the time needed for the axonal swelling caused by the inhibition of cytochrome oxidase to reach a point at which vision is affected. Studies of controlled inhalation exposure of humans to methanol vapors, most of which have been published since 1994, describe only brief durations and relatively low concentrations—for example, 12 volunteers for 75 min at 192 ppm (Cook et al. 1991), 8 volunteers for 2 h at 100 and 200 ppm (Ernstgard et al. 2005), 22-26 volunteers for 4 h at 200 ppm (D’Alessandro et al. 1994, Chu- wers et al. 1995, Osterloh et al. 1996), 6 volunteers for 6 h at 200 ppm (Lee et al. 1992), and 15 volunteers for up to 8 h at 800 ppm (Batterman et al. 1998). For all of these studies, the doses and exposure durations are insufficient for ocular effects to be manifested. Although increases were observed in the con- centration of methanol in blood and urine, the formate concentrations in blood and urine increased only negligibly compared with background levels. Similar results were reported in monkeys, whose metabolism of methanol is believed to be similar to that of humans, with no increase in blood formate concentrations above background for 6-h exposures to methanol of up to 2,000 ppm (Medinsky and Dorman 1995). Similarly, in both normal and folate-

OCR for page 275
281 Methanol deficient monkeys exposed for 2 h to up to 900 ppm of [14C]methanol, [14C]methanol-derived formate concentrations in the blood remained below background formate concentrations (Medinsky et al. 1997). Unfortunately, none of the published studies, either in humans or in primates, reports continuous exposures of sufficient duration to provide confidence that steady state had been achieved, particularly in the blood concentration of formate. It is not known whether longer exposures at the tested concentrations could have led to deple- tion of the stores of tetrahydrofolate, resulting in saturation of formate metabo- lism and increasing blood and tissue concentrations of formate. A biologically based dynamic model of the disposition of methanol in humans and animals, based on and validated against published studies on methanol exposures in humans and animals, predicted that near steady-state concentrations of methanol in blood would be reached within 20 h after the start of a continuous inhalation exposure (Bouchard et al. 2001). This model implies that steady-state concentrations of methanol in blood had not been reached in any of the published studies in human volunteers. At the end of a hypothetical 5- d exposure to 200 ppm of methanol, Bouchard’s model predicted that the blood methanol concentration in humans would be 0.55 mg/deciliter (dL) (a >5-fold increase over mean background values), but that the methanol-derived increase in formate concentration in the blood would be only 0.016 mg/dL, which is small compared with the background value of 0.49 mg/dL in unexposed subjects but is in accord with experimental data from methanol exposures in primates and humans. Because there are no published studies of controlled exposures in humans involving the dose range at which formate metabolism to CO2 becomes saturated and blood formate concentrations begin to increase, the model did not include a saturation term for formate metabolism, and its usefulness is limited to situations in which tetrahydrofolate is not limiting. The amount of tetrahydrofolate in tis- sues is known to vary considerably among individuals and depends on their nu- tritional status. A healthy individual has 500-20,000 micrograms (µg) of folate in body stores. Humans need to absorb 50-100 µg of folate per day to replenish the daily degradation and loss through urine and bile. Otherwise, signs and symptoms of deficiency can manifest after 4 months (Gentili et al. 2007). Data from the National Health and Nutrition Examination Survey 1999-2000 (Pfeiffer et al. 2005) indicate that the prevalence of low serum folate concentrations (<6.8 nmol/L = <3 µg/L) in the U.S. population decreased from 16% before to 0.5% after the U.S. began requiring folic acid fortification of cereal-grain products in November 1998. U.S. astronauts on missions to the International Space Station lasting 128-195 d were found to have 20% lower folate concentrations in red blood cells at landing than before launch (Johlin et al. 1989). The folate concen- tration in red blood cells of many astronauts after landing approached the lower limit of the normal range. It is not known whether this decrease in folate would level off or continue to decrease with even longer missions (Johlin et al. 1989), but the reduction is believed to be due to inadequate food intake while in orbit.

OCR for page 275
282 SMACs for Selected Airborne Contaminants Simulations using Bouchard’s model suggest that an 8-h inhalation expo- sure to 500-2,000 ppm of methanol without physical exercise would be required just for the methanol-derived increase in formate concentration in the blood to equal the levels normally seen as backgrounds in humans (thus, presumably doubling the blood concentration of formate) (Bouchard et al. 2001). Note, how- ever, that, according to the model, a steady-state concentration of methanol in the blood would not have been achieved after 8 h of exposure (Bouchard et al. 2001). Note also that data from Lee et al. suggest that, although the amount of methanol volunteers inhaled during light exercise is 1.8 times the amount in- haled at rest, the concentration of methanol in the blood is only slightly, but not significantly, increased by light exercise (8.1 µg/mL compared with 7.0 µg/mL at rest and 1.8 µg/mL pre-exposure), and no increase in blood formate concen- tration was observed after a 6-h exposure to 200 ppm of methanol either at rest or during exercise (Lee et al. 1992). NEW RISK ASSESSMENT APPROACHES Neither the data available when the original SMACs were set in 1994 nor the data available since then include suitable dose-response data amenable to analysis using benchmark dose or ten Berge methodology. The published data on which the original SMACs were based did not include the raw data for indi- vidual subjects. RATIONALE FOR THE 1,000-D SMAC AND FOR REVISED 1-H, 24-H, 7-D, 30-D, AND 180-D SMACS Table 14-4 lists standards developed by government and nongovernmental agencies for methanol vapors. Table 14-5 lists the SMAC values for methanol whose derivation is described below. D’Allesandro and colleagues (D’Alessandro et al. 1994, Chuwers et al. 1995) reported no significant neurobehavioral effects in 26 volunteers exposed for 4 h to 200 ppm of methanol, whose peak serum methanol concentrations were 6.5 mg/L. A similar lack of effects was reported for 200-ppm exposures in 22 subjects exposed for 4 h (Osterloh et al. 1996), 12 subjects exposed for 75 min (Cook et al. 1991), 8 subjects exposed for 2 h (Ernstgard et al. 2005), and 6 subjects exposed for 6 h (Lee et al. 1992). Because no adverse effects were reported, the data could not be subjected to a benchmark dose analysis or to a ten Berge analysis. Therefore, the 1-h SMAC can be set equal to the NOAEL of 200 ppm reported in the studies cited above. 1-h SMAC = 200 ppm

OCR for page 275
283 Methanol TABLE 14-4 Air Standards for Methanol Vapors Set by Other Organizations Organization, Standard Amount Reference NIOSH NIOSH 2005 6,000 ppm (7,860 mg/m3) IDLH 200 ppm (260 mg/m3) REL TWA 250 ppm (325 mg/m3) ST, skin OSHA NIOSH 2005 200 ppm (260 mg/m3) PEL TWA ACGIH ACGIH 1997 200 ppm (260 mg/m3) TLV TWA, skin 250 ppm (325 mg/m3) TLV STEL, skin Abbreviations: ACGIH, American Conference of Governmental Industrial Hygienists; IDLH, immediately dangerous to life and health; NIOSH, National Institute for Occupa- tional Safety and Health; OSHA, Occupational Safety and Health Administration; PEL, permissible exposure limit; REL, recommended exposure limits; ST, short-term exposure limit (15 min); STEL, short-term exposure limit; TLV®, threshold limit value; TWA, time- weighted average. TABLE 14-5 SMACs for Methanol Vapors mg/m3 Duration ppm Target toxicity 1h 200 260 Ocular effects 24 h 70 90 Ocular effects 7d 70 90 Ocular effects 30 d 70 90 Ocular effects 180 d 70 90 Ocular effects 1,000 d 23 30 Ocular effects The mathematical model developed by Bouchard predicts that about 20 h of continuous inhalation exposure is needed for blood methanol concentrations to achieve near steady state at an atmospheric concentration of 200 ppm of methanol (Bouchard et al. 2001). The model predicts that 5 d of continuous ex- posure to methanol at 200 ppm would result in blood formate concentrations in humans of 0.16 mg/L, a value well below experimental mean background con- centrations in unexposed subjects (4.9-10.3 mg/L) reported by various authors. The finding that blood methanol concentrations should be near steady state but formate concentrations remain near background after the first 20 h implies that continuous exposure to methanol vapors at 200 ppm could be maintained indefi- nitely without risk of formate toxicity. The model explicitly assumes, however, that folate has not been depleted, because no saturation of formate metabolism was apparent in the experimental data used to validate the model. It is unknown, however, whether tetrahydrofolate concentrations would continue to decrease at exposure durations >20 h. Because 200 ppm of methanol differs by only about a

OCR for page 275
284 SMACs for Selected Airborne Contaminants factor of 2 from the 390-ppm average concentration reported to cause visual disturbances in teacher’s aides who worked with spirit duplicating machines (Frederick et al. 1984), and because Bouchard’s model has not been validated for exposure durations beyond 8 h, a safety factor for uncertainty should be ap- plied to the 200-ppm NOAEL for exposure durations exceeding 8 h. Given that formate’s visual toxicity is known to be a threshold response (Nicholls 1975; Martin-Amat et al. 1977, 1978; Kavet and Nauss 1990), a factor of 3 was ap- plied. Thus, 24-h, 7-d, 30-d, and 180-d SMACs = 200 ppm (NOAEL) ÷ 3 (safety factor) = 66.7 ppm, rounded to 70 ppm For setting a SMAC for a 1,000-d exposure, an additional factor of 3 was applied because of the potential for folate deficiency to develop in crewmembers on long-duration missions based on their tendency not to eat all the balanced diet provided to them. Thus, 1,000-d SMAC = 70 ppm (24-h, 7-, 30- , and 180-d SMACs) ÷ 3 (safety factor) = 23.3 ppm, rounded to 23 ppm The calculated SMAC values are summarized in Table 14-6. SPACEFLIGHT EFFECTS None of the reported adverse effects of methanol exposures is known to be affected by spaceflight, but the 1.7% to 12% reduction in total body water asso- ciated with prolonged microgravity would proportionately increase the blood concentration of methanol inhaled. However, the clinical ramifications of such a small effect on the toxicity of methanol would be expected to be negligible. Crews on long-duration missions have been found to have reduced folate con- centrations in blood cells compared with their preflight concentrations. If folate concentrations were to continue to decrease on longer missions, they could be- come low enough to limit the metabolism of formate derived from methanol, thereby increasing the toxicity of methanol. RECOMMENDATIONS FOR ADDITIONAL RESEARCH There are no published studies that elucidate the rate (mg/h) of continuous methanol vapor inhalation at which formate metabolism to CO2 begins to be- come saturated and blood formate concentrations begin to increase. After oral ingestion of liquid methanol, numerous case reports describe symptom-free la- tent periods of 6-30 h before vision impairment is manifested. To confidently predict a vapor concentration of methanol that would not cause ocular toxicity

OCR for page 275
TABLE 14-6 Acceptable Concentrations for Methanol (ppm) Uncertainty factor Acceptable concentration, ppm Folate Species and defi- Space- Effect Exposure data reference NOAEL Species Time flight ciency 1h 24 h 7d 30 d 180 d 1,000 d Visual 200 ppm, Human 1 1 1 1 1 200 – – – – – disturbance 75 min-6 h = Cook et al. 1991, NOAEL D’Alessandro et al. 1994, Chuwers et al. 1995, Ernstgard et al. 2005, Lee et al. 1992, Osterloh et al. 1996 Visual 200 ppm, 5 d Human 3 1 1 1 1 – 70 70 70 70 – disturbance (modeled) = Bouchard et al. NOAEL 2001 Visual 200 ppm, 5 d Human 3 1 1 1 3 – – – – – 23 disturbance (modeled) = Bouchard et al. NOAEL 2001 SMACs 200 70 70 70 70 23 Abbreviations: –, not calculated. 285

OCR for page 275
286 SMACs for Selected Airborne Contaminants during chronic exposures, data are needed from continuous exposures at a range of concentrations of animals or humans in both folate-deficient and folate- replete states to a range of concentrations of methanol vapors for least 1 d and preferably for several days. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 1997. 1997 TLVs and BEIs-Threshold Limit Values for Chemical Substances and Physical Agents; Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. Batterman, S.A., A. Franzblau, J.B. D’Arcy, N.E. Sargent, K.B. Gross, and R.M. Schreck. 1998. Breath, urine, and blood measurements as biological exposure indi- ces of short-term inhalation exposure to methanol. Int. Arch. Occup. Environ. Health 71(5):325-335. Bouchard, M., R.C. Brunet, P.O. Droz, and G. Carrier. 2001. A biologically based dy- namic model for predicting the disposition of methanol and its metabolites in ani- mals and humans. Toxicol. Sci. 64(2):169-184. Chuwers, P., J. Osterloh, T. Kelly, A. D’Alessandro, P. Quinlan, and C. Becker. 1995. Neurobehavioral effects of low-level methanol vapor exposure in healthy human volunteers. Environ. Res. 71(2):141-150. Cook, M.R., F.J. Bergman, H.D. Cohen, M.M. Gerkovich, C. Graham, R.K. Harris, and L.G. Siemann. 1991. Effects of Methanol Vapor on Human Neurobehavioral Measures. Research Report No. 42. Boston, MA: Health Effects Institute. D’Alessandro, A., J.D. Osterloh, P. Chuwers, P.J. Quinlan, T.J. Kelly, and C.E. Becker. 1994. Formate in serum and urine after controlled methanol exposure at the threshold limit value. Environ. Health Perspect. 102(2):178-181. Ernstgard, L., E. Shibata, and G. Johanson. 2005. Uptake and disposition of inhaled methanol vapor in humans. Toxicol. Sci. 88(1):30-38. Frederick, L.J., P.A. Schulte, and A. Apol. 1984. Investigation and control of occupa- tional hazards associated with the use of spirit duplicators. Am. Ind. Hyg. Assoc. J. 45(1):51-55. Gentili, A., M. Vohra, V. Subir, D. Chen, and W. Siddiqi. 2007. Folic acid deficiency. eMedicine Topic 802 [online]. Available: http://www.emedicine.com/med/ topic802.htm [accessed Jan. 16, 2008]. Hayreh, M.S., S.S. Hayreh, G.L. Baumbach, P. Cancilla, G. Martin-Amat, T.R. Tephly, K.E. McMartin, and A.B. Makar. 1977. Methyl alcohol poisoning. III. Ocular tox- icity. Arch. Ophthalmol. 95(10):1851-1858. Hayreh, M.S., S.S. Hayreh, G. Baumbach, P. Cancilla, G. Martin-Amat, and T.R. Tephly. 1980. Ocular toxicity of methanol: An experimental study. Pp. 35-53 in Neurotox- icity of the Visual System, W. Merrigan, and B. Weiss, eds. New York: Lippin- cott-Raven. Jacobsen, D., and K.E. McMartin. 1986. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med. Toxicol. 1(5):309-334. James, J.T., and D.E. Gardner. 1996. Exposure limits for airborne contaminants in space- craft atmospheres. Appl. Occup. Environ. Hyg. 11(12):1424 -1432.

OCR for page 275
287 Methanol Johlin, F.C., E. Swain, C. Smith, and T.R. Tephly. 1989. Studies on the mechanism of methanol poisoning: Purification and comparison of rat and human liver 10- formyltetrahydrofolate dehydrogenase. Mol. Pharmacol. 35(6):745-750. Kavet, R., and K.M. Nauss. 1990. The toxicity of inhaled methanol vapors. Crit. Rev. Toxicol. 21(1):21-50. Lee, E.W., T.S. Terzo, J.B. D’Arcy, K.B. Gross, and R.M. Schreck. 1992. Lack of blood formate accumulation in humans following exposure to methanol vapor at the cur- rent permissible exposure limit of 200 ppm. Am. Ind. Hyg. Assoc. J. 53(2):99-104. Leon, A.S., D.B. Hunninghake, C. Bell, D.K. Rassin, and T.R. Tephly. 1989. Safety of long-term large doses of aspartame. Arch. Intern. Med. 149(10):2318-2324. Martin-Amat, G., T.R. Tephly, K.E. McMartin, A.B. Makar, M.S. Hayreh, S.S. Hayreh, G. Baumbach, and P. Cancilla. 1977. Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus mon- key. Arch. Ophthalmol. 95(10):1847-1850. Martin-Amat, G., K.E. McMartin, S.S. Hayreh, M.S. Hayreh, and T.R. Tephly. 1978. Methanol poisoning: Ocular toxicity produced by formate. Toxicol. Appl. Pharma- col. 45(1):201-208. McMartin, K.E., J.J. Ambre, and T.R. Tephly. 1980. Methanol poisoning in human sub- jects. Role for formic acid accumulation in the metabolic acidosis. Am. J. Med. 68(3):414-418. Medinsky, M.A., and D.C. Dorman. 1995. Recent developments in methanol toxicity. Toxicol. Lett. 82-83:707-711. Medinsky, M.A., D.C. Dorman, J.A. Bond, O.R. Moss, D.B. Janszen, and J.I. Everitt. 1997. Phamacokinetics of Methanol and Formate in Female Cynomolgus Monkeys Exposed to Methanol Vapors. Research Report No. 77. Boston, MA: Health Ef- fects Institute. Nicholls, P. 1975. Formate as an inhibitor of cytochrome c oxidase. Biochem. Biophys. Res. Commun. 67(2):610-616. NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) No. 2005-151. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Cincinnati, OH. NLM (U.S. National Library of Medicine). 2007. Methyl Alcohol. Haz-Map Occupa- tional Exposure to Hazardous Agents. U.S. National Library of Medicine, Be- thesda, MD [online]. Available: http://hazmap.nlm.nih.gov/cgi-bin/hazmap_ generic?tbl=TblAgents&id=13 [accessed Nov. 15, 2007] NTP-CERHR (National Toxicology Program-Center for the Evaluation of Risks to Hu- man Reproduction). 2003. NTP-CERHR Monograph on the Potential Human Re- productive and Developmental Effects of Methanol. NIH Publication No. 03-4478. U.S. Department of Health and Human Services, National Toxicology Program- Center for the Evaluation of Risks to Human Reproduction. September 2003 [online]. Available: http://cerhr.niehs.nih.gov/chemicals/methanol/Methanol_ Monograph.pdf [accessed Jan. 17, 2008]. Osterloh, J.D., A. D’Alessandro, P. Chuwers, H. Mogadeddi, and T.J. Kelly. 1996. Serum concentrations of methanol after inhalation at 200 ppm. J. Occup. Environ. Med. 38(6):571-576. Pfeiffer, C.M., S.P. Caudill, E.W. Gunter, J. Osterloh, and E.J. Sampson. 2005. Bio- chemical indicators of B vitamin status in the U.S. population after folic acid forti- fication: Results from the National Health and Nutrition Examination Survey 1999-2000. Am. J. Clin. Nutr. 82(2):442-450.

OCR for page 275
288 SMACs for Selected Airborne Contaminants Ruth, J.H. 1986. Odor thresholds and irritation levels of several chemical substances: A review. Am. Ind. Hyg. Assoc. J. 47(3):A142-A151. Wong, K.L. 1994. Methanol. 149-167 in Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Vol. 1. Washington, DC: National Academy Press.