OSHA's previous Z-table limit for acetone was 1000 ppm as an 8-hour TWA. In the NPRM, the Agency proposed to lower this limit to 250 ppm as an 8-hour TWA. This proposed limit was derived from the NIOSH-recommended limit, which was based on a number of industrial and human volunteer studies reporting irritant and central nervous system effects resulting from exposure to acetone concentrations at levels below 1000 ppm; NIOSH (Ex. 8-47, Table N1) and the AFL-CIO (Ex. 194) concurred with the proposed limit. The ACGIH TLVs for acetone are 750 ppm as an 8-hour TWA and 1000 ppm as a 15-minute STEL. OSHA has carefully reviewed the scientific evidence and comments in the record and has determined that it is appropriate to revise the acetone PEL in the final rule to 750 ppm as an 8-hour TWA and to add a short- term limit of 1000 ppm. Acetone is a colorless, highly volatile, flammable liquid with an aromatic odor.
OSHA's proposed 250-ppm TWA limit for acetone was largely based on controlled human studies conducted by Nelson, Enge, Ross et al. (1943/Ex. 1-66) and Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191), as well as studies in workers conducted by Vigiliani and Zurlo (1955/Ex. 1-164) and Parmeggiani and Sassi (1954/Ex. 1-753). OSHA's reliance on these studies to establish a revised limit for acetone was criticized by Dr. William C. Thomas, Manager of Toxicology for the Hoechst Celanese Corporation, who testified on behalf of the Ketones Program Panel of the Chemical Manufacturers Association (CMA) (Ex. 8-54; Tr. 8/4/88, pp. 6-114 to 6-127; Exs. 149A, 149C). The National Marine Manufacturers Association (Ex. 181) agreed with Dr. Thomas' remarks. Summaries of each of these studies and of OSHA's response to Dr. Thomas' remarks follow.
In a controlled-exposure experiment, Nelson, Enge, Ross et al. (1943/Ex. 1-66) exposed an average of 10 human subjects (both male and female) to a variety of solvents, including acetone, for three to five minutes. Subjects were asked to judge the level of sensory irritation as absent, slightly irritating, or very irritating. Tests were conducted in a 1200-cubic-foot gas cabinet equipped with an anemostat to distribute the air uniformly. Acetone was reported to produce slight irritation on exposure to 300 ppm, but a concentration of 500 ppm produced a degree of eye, nose, and throat irritation that was still described by a majority of the subjects as "tolerable."
Dr. Thomas expressed five criticisms of the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study. These were: (1) the short duration of exposure used; (2) the study's failure to account for adaptation because "naive" subjects who had not had previous acetone exposure were used; (3) the authors' reliance on subjective responses rather than on objective medical examination; (4) the use of nominal (calculated) exposures rather than measured exposures; and (5) the introduction of potential bias because students who were involved in the experiment were used as test subjects (Tr. 8/4/88, pp. 6-114 to 6-117; Exs. 149A, 149C).
NIOSH addressed some of these issues in its criteria document for ketones (NIOSH 1978f, as cited in ACGIH 1986/Ex. 1-3, p. 6). In its analysis of the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study, NIOSH (1978f) concluded:
The concentrations of ketones in the exposure chamber were calculated (nominal) rather than measured analytically, so the true concentration may have been lower than reported.... [T]he use of experimenters as subjects was a possible source of bias, and the exposure periods of 3-5 minutes were not long enough to show if adaptation would occur.... The fact that exposure duration did not approach that of a normal workshift is a major limitation of...[this study]. However, the data are useful as a guide to the relative irritating properties of ketones and the concentrations at which these [properties] appear (NIOSH 1978f, p. 31).
Thus, despite these experimental limitations, NIOSH concluded that the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study was useful in identifying ketone concentrations that are irritating, and it relied on this study, at least in part, when recommending a 250-ppm TWA limit for acetone (NIOSH 1978f, as cited in ACGIH 1986/Ex. 1-3, p. 6).
The second paper discussed by Dr. Thomas is the report by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191). In this study, the authors exposed 25 healthy male subjects to 0, 100, 250, 500, or 1000 ppm acetone. Subjects were exposed for three hours in the morning and three hours in the afternoon, with a 45-minute period between exposures. Irritant responses were scored on a scale from 0 to 12, with a score of 12 representing severe irritation.
Most of the subjects exposed to 500 or 1000 ppm acetone reported irritation (scored between 4 and 5 in severity) during the first 90 minutes of exposure in the morning and the first 60 minutes of exposure in the afternoon. Subjects ceased to report irritation at the 90-minute mark during the afternoon exposure. A lesser degree of irritation was reported to occur among subjects exposed to 100 or 250 ppm acetone; however, this irritation subsided after the first 90 minutes of exposure in each of the two exposure periods. Subjects exposed to 250 ppm or higher reported feeling general weakness and a sense of tension even as long as 24 hours after exposure. Blood and urine samples taken during and after exposure showed increasing blood and urinary acetone levels among subjects exposed to 250 ppm or higher. Following the exposure period, these levels fell to normal values within about 25 to 35 hours after exposure was terminated. The authors also reported an increased leukocyte count in subjects exposed to 500 or 1000 ppm acetone; the increased white cell count persisted for about 24 hours after the cessation of exposure. The authors attributed this increased leukocyte count to acetone's irritant properties (Matsushita, Yoshimune, Inoue et al. 1969/Ex. 1-191).
Dr. Thomas criticized this study because it did not describe the methods used by its authors for measuring acetone exposures, and the blood acetone levels reported by Matsushita and colleagues (1969/Ex. 1-191) were about 2.5 times higher than those reported after similar exposures conducted by DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6). After a two-hour exposure to 500 ppm acetone, Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191) found a blood acetone level of 25 mg/L, compared to a level of 10 mg/L reported by DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6). Dr. Thomas suggested that the actual exposure levels employed by Matsushita and associates (1969/Ex. 1-191) may actually have been substantially higher than reported by these authors (Tr. 8/4/88, pp. 6-118 to 6-119; Exs. 149A, C).
OSHA has reviewed the report by DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6) and finds that the blood acetone results reported in this paper cannot be directly compared, as Dr. Thomas has done, with those reported by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191), for a number of reasons. First, the subjects studied by DiVincenzo, Yanno, and Astill fasted for eight hours prior to exposure; it is not clear that the subjects studied by Matsushita, Yoshimune, Inoue et al. fasted before they were exposed. Second, the blood acetone values reported by DiVincenzo, Yanno, and Astill were corrected for endogenous acetone (i.e., acetone levels that existed prior to exposure). The authors reported that endogenous acetone levels ranged from 0 to 10 mg/L of blood, or about as high as would occur after a two-hour exposure to 500 ppm of acetone. Whether Matsushita, Yoshimune, Inoue et al. corrected for endogenous blood acetone levels is uncertain; if they did not, their reported blood acetone levels may be as much as two times overstated. The third consideration is that the studies used different methods to measure blood acetone levels. Matsushita, Yoshimune, Inoue et al. used a colorimetric method, while DiVincenzo, Yanno, and Astill used a gas chromatographic approach. The use of different analytical methods by the two investigative groups complicates any comparison of their blood acetone results. Thus, OSHA does not agree that the results by DiVincenzo, Yanno, and Astill (1973, as cited by ACGIH 1986/Ex. 1-3, p. 6) demonstrate that the exposure levels used by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191) are necessarily understated. In addition to the two controlled-exposure studies discussed above, two industry studies were relied on by OSHA to support the reduction in the acetone PEL. One report by Parmeggiani and Sassi (1954/Ex. 1-759) indicated that six employees exposed to 307 to 918 ppm acetone in a rayon acetate plant experienced eye and throat irritation, dizziness, and inebriation. Five of the employees showed objective signs of pharyngeal irritation, four had lung irritation, and three had conjunctivitis. Although the authors attribute the observed CNS effects to excessive concomitant exposure to carbon disulfide, the irritant effects are more likely to have been the result of exposure to acetone, because carbon disulfide is not a primary irritant by vapor inhalation (Chemical Hazards of the Workplace, 2nd ed., Proctor, Hughes, and Fischman 1988, pp. 120-121). The other report, by Vigliani and Zurlo (1955/Ex. 1-164), found that acetone production workers exposed to 700 ppm acetone for three hours daily for 7 to 15 years experienced inflammation of the respiratory tract, stomach, and duodenum; giddiness; and loss of strength.
Dr. Thomas (Exs. 8-54, 149A, 149C; Tr. 8/4/88, pp. 6-114 to 6-127) criticized these two studies on the basis that the urinary acetone levels reported by Parmeggiani and Sassi (1954/Ex. 1-759) and by Vigliani and Zurlo (1955/Ex. 1-164) indicated that airborne exposures were much higher than the reported values. He stated that, based on these values, the employees observed in both of these studies were likely to have been exposed to acetone levels approximating 5000 ppm. OSHA is not convinced that the exposure levels reported in these two studies are understated. The studies by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191) and DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6) clearly demonstrate that blood and urinary acetone levels can increase with continued, daily exposure. Furthermore, in its criteria document, NIOSH (1978f, as cited in ACGIH 1986/Ex. 1-3, p. 6) cites a number of studies that demonstrate that skin absorption of acetone can result in elevated blood and urinary acetone levels. OSHA believes that the high urinary acetone levels reported in the workers studied by Parmeggiani and Sassi (1954/Ex. 1-759) and by Vigiliani and Zurlo (1955/Ex. 1-164) were most likely the result of an accumulated body burden of acetone brought about by long-term exposure and dermal absorption. Given these considerations, it does not appear appropriate to approximate airborne exposure levels on the basis of the urinary acetone levels reported in these two studies. To summarize, OSHA finds that the studies discussed above show that acetone is capable of producing sensory irritation at concentrations below 1000 ppm and that long-term exposure to acetone at levels below 1000 ppm can cause CNS disturbances. In addition, the ACGIH (1986/Ex. 1-3, p. 6) reports that chronic exposure to acetone causes respiratory irritation and headaches. Despite the methodological shortcomings of all of these studies, OSHA is impressed with the consistency of their findings. Both the Nelson, Enge, Ross et al. (1943/Ex. 1-66) and the Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-91) studies demonstrate that exposure to concentrations of acetone below 1000 ppm are associated with eye, nose, and throat irritation. Both industry studies (Parmeggiani and Sassi 1954/Ex. 1-759; Vigliani and Zurlo 1955/Ex. 1-164) report similar signs and symptoms of irritation and CNS disturbances in workers exposed to concentrations of acetone between 700 and 1000 ppm. OSHA is not persuaded by Dr. Thomas' arguments that exposure levels are understated in these reports; OSHA believes that the quantitative relationship between long-term exposure to acetone and urinary acetone levels is not sufficiently established to draw this conclusion. Therefore, OSHA concludes that the findings of these four studies are consistent in demonstrating the acute and long-term effects of acetone exposure at levels below 1000 ppm.
The Ketones Panel of the CMA (Tr. 8/4/88, pp. 6-100 to 6-113; Exs. 149A, 149B, and 179) also presented testimony by Dr. Robert Raleigh, Adjunct Professor of Medicine at the University of Rochester School of Medicine. Dr. Raleigh testified on a study he conducted among filter press operators who were exposed exclusively to acetone (Raleigh and McGee 1972, as cited in Ex. 8-54). In this study, 13 workers were asked about symptoms and were medically examined over a one-week period. Using grab bags, acetone samples were taken at random periods during each workshift. Subjective symptoms were recorded with each grab sample. Samples were analyzed by gas chromatography.
Over the period studied, TWA exposures to acetone varied from 950 to 1060 ppm. Of the 13 workers studied, nine (69 percent) reported eye irritation, five (38 percent) reported nasal irritation, and five (38 percent) reported throat irritation. Three (23 percent) employees reported experiencing lightheadedness. Some employees reported these symptoms more than once during the study period. There were four cases of eye irritation following short-term exposures to acetone concentrations below 1000 ppm. Eye irritation that was reported to be "strong" occurred following short-term exposures to approximately 1800 ppm. Physical examination revealed a few instances of redness of the nasal mucosa and slight infection of the mucosa of the nose and throat.
In his written testimony regarding this study, Dr. Raleigh concluded:
Dr. Raleigh also testified that the occurrence of transient dizziness was no cause for concern:
OSHA does not agree with Dr. Raleigh's interpretation of his study or with his view that dizziness, irritation and mild infections of the mucous membranes of the respiratory tract do not constitute material impairments of health. After reviewing the Raleigh and McGee report (1972, as cited in Ex. 8-54), OSHA notes that more than half the workers studied experienced sensory reactions from exposure to acetone at TWA levels equal to the former 1000-ppm OSHA limit. Furthermore, some of these reactions were characterized as "strong." OSHA believes that this study further demonstrates that the Agency's former 1000-ppm 8-hour TWA limit is insufficiently protective and does not prevent workers from experiencing these sensory effects. In addition, in contrast to Dr. Raleigh, OSHA characterizes transient dizziness in and of itself as an "adverse consequence." Dizziness connotes an effect on the central nervous system; in addition, dizziness is a serious safety hazard in the workplace. For the reasons stated earlier in this section, OSHA finds that such effects constitute material impairments of health. Thus, OSHA finds that the Raleigh and McGee study (1972, as cited in Ex. 8-54) is a recent, well-conducted study that provides additional support for the need to lower the former 1000-ppm TWA limit for acetone. Furthermore, OSHA finds the evidence that adverse effects can result from short-term exposures to levels of acetone at or near 750 ppm convincing; two controlled human studies (Nelson, Enge, Ross et al. 1943/Ex. 1-66; Matsushita, Yoshimune, Inoue et al. 1969/Ex. 1-191) reported sensory irritant effects upon short-term exposure to such levels of acetone, and two industry studies (Parmeggiani and Sassi 1954/Ex. 1-759; Vigliani and Zurlo 1955/Ex. 1-164) reported irritation and CNS effects among employees exposed to acetone levels ranging from 307 to 918 ppm in one instance and about 700 ppm in the other. In addition, two studies (Matsushita, Yoshimune, Inoue et al. 1969/Ex. 1-191; DiVincenzo, Yanno, and Astill 1973, as cited in ACGIH 1986/Ex. 1-3, p. 6) suggest that chronic exposure to acetone on a daily basis leads to the bioaccumulation of acetone. In light of the studies discussed above, OSHA concludes that it is necessary to reduce the limit for acetone to 750 ppm as an 8-hour TWA and 1000 ppm as a STEL to protect workers from the acute and chronic effects of acetone exposure. OSHA finds that the chemically induced sensory irritation associated with acute exposures to acetone can occur at levels only slightly above the 750-ppm level being established as an 8-hour TWA. In the absence of a STEL, the 750-ppm limit would permit excursions to levels as high as 12,000 ppm for brief periods. Such levels "depress the central nervous system, causing dizziness, weakness, and loss of consciousness" (Proctor, Hughes, and Fischman 1988, p. 49). An 8-hour TWA of 750 ppm is necessary to protect workers against the bioaccumulation of acetone, chronic irritation of the respiratory tract, and headaches associated with long-term acetone exposures. OSHA considers both the short-term sensory irritation associated with brief exposures to acetone and the increased blood and urinary accumulation and chronic respiratory irritation characteristic of long-term acetone exposures to be material impairments of health. Accordingly, OSHA is establishing in the final rule an 8-hour TWA PEL of 750 ppm and a STEL of 1000 ppm for acetone.