OSHA's former permissible exposure limits for perchloroethylene (tetrachloroethylene) were 100 ppm as an 8-hour TWA, 200 ppm as a STEL not to be exceeded for more than five minutes in any three-hour period, and 300 ppm as a ceiling. On the basis of the chemical's narcotic effects in humans, the Agency proposed a revised PEL of 50 ppm TWA and a 15-minute STEL of 200 ppm for perchloroethylene; these are the limits recommended by the ACGIH (ACGIH 1986/Ex. 1-3, p. 464). NIOSH (Ex. 8-47, Table N6B) did not concur with the proposed limits and recommended that exposures be maintained at the lowest feasible limit and that this chemical be classified as a potential occupational carcinogen. OSHA has evaluated the health evidence for this substance and has determined that a further reduction in the PEL to 25 ppm as a TWA is warranted, and the Agency is establishing this limit in the final rule. Perchloroethylene is a clear, colorless, nonflammable liquid with an etheral odor.
Perchloroethylene is widely used as a solvent in the dry cleaning industry and in industrial degreasing operations. The narcotic effects associated with exposure to high levels of this chemical are well documented. A worker exposed to an estimated concentration of 1470 ppm perchloroethylene and Stoddard solvent for 3.5 hours lost consciousness (Stewart, Erley, Schaffer, and Gay 1961/Ex. 1-807). The most comprehensive studies of the effects of prolonged exposure to perchloroethylene vapors on human volunteers were conducted by Stewart and colleagues (Stewart, Hake, LeBrun et al. 1974/Ex. 1-970; Stewart, Hake, Wu et al. 1977/Ex. 1-971); these investigators concluded that prolonged exposure to 200 ppm results in early signs of CNS depression, while no response was elicited in men or women exposed repeatedly to 100 ppm for seven hours/day, except that performance on the Flanagan coordination test was significantly decreased in some exposed subjects (Stewart, Hake, Wu et al. 1977/Ex. 1-971, p. 28).
Based on these findings, the Agency concluded that its former PEL permitted workers to be exposed to a significant risk of CNS effects. In addition to examining the evidence for the chemical's narcotic effects, OSHA has reviewed a number of studies on the carcinogenicity of perchloroethylene. These investigations are summarized below.
In a 1977 gavage bioassay for carcinogenicity, perchloro-ethylene proved to be a liver carcinogen in mice but not in rats (NCI 1977c, as cited in ACGIH 1986/Ex. 1-3, p. 464). In 1986, the NTP conducted an inhalation bioassay of perchloroethylene (NTP 1986b/Ex. 8-31, Appendix 4), in which groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to perchloroethylene for six hours/day, five days/week, for two years. The exposure concentrations were 0, 200, or 400 ppm for rats and 0, 100, or 200 ppm for mice. Male and female rats exposed to either 200 or 400 ppm developed statistically significant increases in mononuclear cell leukemias. According to the NTP report (NTP 1986b/Ex. 8-31, Appendix 4), the increased incidences of leukemias were responsible for the early deaths observed in male and female rats exposed to perchloroethylene. At autopsy, most of the leukemias were determined to be in an advanced and probably fatal stage. Because of the effect of the leukemias on the early mortality of the exposed rats, a life-table analysis was used to test for the statistical significance of the findings; this analysis revealed that the increased incidence of leukemia was statistically significant in both low- and high-dose male rats and in low-dose female rats, and was marginally significant (p = 0.053) in high-dose female rats.
Male rats also developed a significant increase in renal tubular cell adenomas and carcinomas. Perchloroethylene induced a significantly increased incidence of hepatocellular carcinomas at both dose levels in mice of both sexes. The NTP Peer Review Panel concluded that there was "clear evidence of carcinogenicity of tetrachloroethylene" (perchloroethylene) in male rats and in male and female mice, and "some evidence" in female rats (Ex. 8-31, Appendix 4; Ex. 1-0000, p. 11).
In addition, a number of human studies were submitted to the rulemaking record that implicate perchloroethylene as a potential carcinogen (Ex. 8-31). Among these was a study by Brown and Kaplan (1987/Ex. 8-31, Appendix 6), which reported a statistically significant elevation in urinary tract cancer deaths among 1,690 dry cleaning workers exposed to perchloroethylene and other petroleum solvents. However, a subcohort of workers who used perchloroethylene as the primary solvent showed no increase in bladder cancer mortality. Brown and Kaplan concluded that "confounding exposure to petroleum solvents complicates any conclusions regarding the association between ...[perchloroethylene] and cancer of the urinary tract" (Brown and Kaplan 1987/Ex. 8-31, Appendix 6, p. 540).
Katz and Jowett (1981/Ex. 8-31, Appendix 9) studied the mortality pattern of 671 female dry cleaning workers for the period 1963 through 1977. Elevated incidences of cancers of the kidney and genitals were reported, along with a smaller excess of bladder and skin cancers and lymphosarcomas. The authors concluded that, although results obtained with the methodology used (proportionate mortality ratios) require careful interpretation, "this study raises the possibility that exposure to dry cleaning fluids may increase the risk of certain cancers" (Katz and Jowett 1981/Ex. 8-31, Appendix 9, p. 510). The dry cleaning fluids used by members of the cohort included carbon tetrachloride, trichloroethylene, and perchloroethylene.
Steinhagen et al. (1983/Ex. 8-31, Appendix 8) reported a significant excess of liver cancer among male workers in the laundry and dry cleaning industry in New Jersey. This study was a retrospective case-control study. The liver cancer cases were concentrated among individuals who processed clothes and were exposed to chemicals. The report did not identify the solvents in use (Steinhagen, Slade, Altman, and Bill 1983/Ex. 8-31, Appendix 8).
Duh and Asal (1984/Ex. 8-31, Appendix 7) examined the mortality experience of 440 dry cleaning workers in Oklahoma for the period 1975 through 1981. Elevated standardized mortality odds ratios (SMORs) were found for both lung cancer (SMOR = 1.7) and kidney cancer (SMOR = 3.8) (Duh and Asal 1984/Ex. 8-31, Appendix 7).
Eric Frumin of the Amalgamated Clothing and Textile Workers Union (ACTWU) submitted a quantitative risk assessment conducted by Dr. Dale Hattis of the Center for Technology Policy and Industrial Development at the Massachusetts Institute of Technology (Hattis 1986/Ex. 8-31, Appendix 11-A). This work was conducted in 1986 for the National Institute for Environmental Health Sciences. Dr. Hattis used a pharmacokinetic model that incorporated species-specific rates of formation for the metabolites of perchloroethylene. Using the rat leukemia and mouse liver tumor data from the NTP (1986b/Ex. 8-31, Appendix 4) bioassay, Dr. Hattis obtained a "best estimate" of the lifetime cancer risk (for workers exposed at the former 100-ppm OSHA limit for 45 years to perchloroethylene) of 45 deaths per 1,000 workers. The plausible upper limit at this level of exposure was 650 per 1,000 workers. The best-estimate lifetime risks associated with 45 years of exposure to 50 or 10 ppm of perchloroethylene were 27 and 6.4 deaths per 1,000 workers, respectively (the upper-confidence limits were 420 and 110 deaths per 1,000 workers, respectively). The ACTWU asserted that the studies reviewed above provide "overwhelming" evidence that perchloroethylene is a potential human carcinogen, and urged OSHA to establish a PEL lower than the proposed 50-ppm limit.
In its posthearing comments, the Halogenated Solvents Industry Alliance (HSIA) (Ex. 186) discussed several aspects of the data on perchloroethylene to support its contention that perchloroethylene should not be considered a probable human carcinogen. Specifically, the HSIA pointed out the following:
Brown and Kaplan (1987/Ex. 8-31, Appendix 6) found no increased evidence of cancer among a subcohort of workers exposed only to perchloroethylene and not to other dry cleaning solvents.
Both EPA and IARC have determined the human evidence on the carcinogenicity of perchloroethylene to be "inadequate."
The National Research Council of the National Academy of Sciences concluded that the results of the NCI gavage study (NCI 1977c) should be interpreted with caution because of the large doses administered, early mortality of the treated animals, and observed nephrotoxicity.
Regarding the NTP inhalation bioassay (NTP 1986b), the EPA Science Advisory Board (SAB) determined that the incidence of rat leukemia was not related to per-chloroethylene exposure, and that the development of male rat kidney tumors was brought about by a mechanism unique to male rats.
The EPA SAB stated that the mouse liver tumors observed in both the gavage (NCI 1977c) and inhalation (NTP 1986b) bioassays arose as a result of perchloroethylene-induced peroxisomal proliferation, a mechanism specific to rodents.
OSHA does not agree with the HSIA's interpretation of the meaning of the points raised by this group. First, the authors of the Brown and Kaplan (1987/Ex. 8-31, Appendix 6) study themselves pointed to the difficulty of establishing a definitive link between a particular solvent and an increased incidence of cancer in workers in the dry cleaning industry. For example, in the case of the group exposed to perchloro-ethylene only, the number of workers in the cohort was so small that even two or three exposure-related deaths in the perchloro-ethylene-only group would have caused a drastic swing in the SMR for bladder cancer in this subcohort. Thus, OSHA does not find that this study demonstrates the noncarcinogenicity of perchloroethylene.
As to the HSIA's second point, that neither the EPA nor IARC found the evidence for the carcinogenicity of perchloroethylene in humans adequate, OSHA notes that such evidence exists only for a handful of carcinogens (e.g., asbestos, benzene, vinyl chloride, arsenic), and that the overwhelming number of substances recognized as posing carcinogenic risks to workers have been determined to be carcinogenic on the basis of results in animals only. OSHA also believes that the regulation of many substances that have been designated as potential human carcinogens on the basis of clear evidence of their carcinogenicity in animals has undoubtedly contributed to the lack of evidence in humans by preventing overexposures to these substances in the workplace, and thus preventing cancer among these workers. Therefore, OSHA believes it appropriate and prudent to reduce workplace exposures to substances that have caused cancer in animals, especially when the animal studies are well-designed and carefully conducted bioassays.
The HSIA's third point, that the NCI gavage bioassay (NCI 1977c) has limitations, is irrelevant in the context of this discussion because OSHA is not relying on this bioassay to establish an appropriate limit for perchloroethylene.
The fourth point raised by the HSIA was that the Science Advisory Board of the EPA has questioned the relevance for human cancer risk of some of the tumors seen in the NTP (1986b/Ex. 8-31, Appendix 4) inhalation bioassay. OSHA believes that an explanation of the nature of the SAB's concern will demonstrate that an interpretation of the meaning of these data is a matter of professional judgment on which expert scientists themselves can differ. The SAB noted that there is some uncertainty regarding the significance of the leukemias observed in the perchloroethylene-exposed rats in the NTP (1986b/Ex. 8-31, Appendix 4) inhalation bioassay because the control rats in another NTP bioassay (NTP 1986c, the bioassay for methylene chloride) showed the same incidence of leukemias as the perchloroethylene-exposed rats (Ex. 186, pp. 6-7). However, OSHA points out that the independent peer review panel appointed by the NTP to evaluate the strength of the evidence for the carcinogenicity of perchloroethylene also considered the appropriateness of including the rat leukemia data when weighing the evidence for the carcinogenicity of perchloroethylene; the NTP panel concluded that the NTP (1986b/Ex. 8-31, Appendix 4) bioassay presented "clear evidence" of perchloro-ethylene's carcinogenicity in male rats (Ex. 8-31, Appendix 4, pp. 14-15). Thus, different scientists or groups of experts may interpret the same data differently; in this case, OSHA is not prepared to dismiss out-of-hand the leukemia data, given that leukemia contributed significantly to excess mortality in the perchloroethylene-exposed groups (NTP 1986b/Ex. 8-31, Appendix 4). The HSIA also questioned the relevance of the kidney tumors in male rats found in the NTP (1986b) bioassay. OSHA agrees with the SAB that these tumors may not be good predictors of human risk; however, the Hattis (1986/Ex. 8-31, Appendix 11-A) risk assessment did not use the rat kidney tumor data, and, in addition, OSHA is not relying on these findings to set the final rule's limit for perchloroethylene.
On the HSIA's fifth point, the significance of rat liver tumors as predictors of human cancer risk, OSHA notes that the SAB did not believe it appropriate to disregard the findings in the recent NTP (1986b/Ex. 8-31, Appendix 4) bioassay of perchloroethylene-dose-related increases in the incidence of liver tumors in mice. In a letter dated to EPA Administrator Lee Thomas in March 1988 (Ex. 186D), the SAB concluded:
Based on the expert opinion of the NTP Peer Review panel and the EPA SAB, OSHA finds that the NCI (1986b/Ex. 8-31, Appendix 4) inhalation bioassay rat leukemia and mouse liver tumor data, which form the basis for the perchloroethylene quantitative risk assessment performed by Dr. Hattis (1986/Ex. 8-31, Appendix 11-A), should be regarded at this time as being relevant to the determination of potential human cancer risk from exposure to perchloroethylene in the workplace. The use of the rat leukemia data for the risk assessment may, however, add additional uncertainty to the risk estimates.
When EPA's Science Advisory Board considered perchloro-ethylene in January of 1987 (Ex./186C), it designated this substance as a Category C substance (i.e., a possible human carcinogen). However, in a letter to EPA Administrator Lee Thomas in March of 1988 (Ex. 186D), the SAB concluded that the overall weight of evidence for perchloroethylene "lies on the continuum between categories B2 [probable human carcinogen] and C." The SAB also stated that the distinction between the B2 and C categories can be an arbitrary distinction on a continuum of weight of evidence.
OSHA agrees with the SAB that perchloroethylene is a substance that meets several of the criteria regarded by the SAB as meriting regulatory action. First, current exposures to perchloroethylene are high, often reaching the levels permitted by OSHA's existing PEL of 100 ppm. Second, several hundred thousand employees are regularly exposed to this widely used solvent. Third, the Hattis (1986/Ex. 8-31, Appendix 11-A) quantitative risk assessment suggests that a high cancer risk may be associated with exposure to perchloroethylene at OSHA's former or proposed PELs, indicating that exposures should be reduced to levels below the proposed 50-ppm level. Finally, the evidence for the carcinogenicity of perchloroethylene, which is briefly summarized below, is convincing.
The NTP (1986b/Ex. 8-31, Appendix 4) has concluded that perchloroethylene is carcinogenic by inhalation in both rats and mice. Based predominantly on the animal data, NIOSH has also concluded that perchloroethylene is a potential human carcinogen; NIOSH judged the evidence for perchloroethylene's carcinogenicity sufficient to warrant a separate 6(b) rulemaking (Ex. 8-47, Table N6B). In 1987, the International Agency for Research on Cancer (IARC) also classified perchloroethylene as a Category 2B carcinogen (i.e., a substance for which the evidence in animals is sufficient). The EPA's SAB has determined that perchloroethylene is a Category C carcinogen (i.e., a possible human carcinogen, and a carcinogen in animals). In addition, a number of human studies suggest elevated cancer risks, particularly of the kidney and bladder, among workers exposed to perchloroethylene and other solvents in dry cleaning facilities. Based on a review of all of the available evidence on perchloroethylene, including the testimony and briefs submitted by the parties, OSHA has determined that perchloroethylene is a potential human carcinogen that presents a significant risk of material health impairment to workers exposed to it in their places of work. This view was shared by several parties commenting in the record, including the Amalgamated Clothing and Textile Workers Union (Ex. 192), the AFL-CIO (Ex. 194), the American Public Health Association (Ex. 151), and NIOSH (Ex. 8-47).
The risk assessment conducted by Hattis (1986/Ex. 8-31, Appendix 11-A) estimates that there is an excess lifetime cancer mortality risk of 45 deaths per 1,000 workers exposed for 45 years to the current 100-ppm TWA PEL. Clearly, this high risk of mortality represents a significant risk. At the proposed level of 50 ppm, Dr. Hattis estimated the excess lifetime risk to be 27 deaths per 1,000 workers. OSHA concludes that this assessment and the underlying evidence clearly indicate that a further reduction in the PEL is necessary.
OSHA's analysis of the technological feasibility of reducing perchloroethylene exposures in affected industries, particularly in the dry cleaning industry, demonstrates that a PEL of 25 ppm is achievable using engineering and work practice controls; however, OSHA does not believe that information in the record at the present time demonstrates that it is feasible to reduce exposures to lower levels (see Section VII). In the dry cleaning industry, newer equipment, such as dry-to-dry dry cleaning machines, can achieve 25 ppm with engineering and work practice controls. This is true of smaller as well as larger operations.
The industry is gradually replacing older equipment with newer equipment, and a significant percentage of operations, including smaller operations, have installed such equipment. According to the industry, dry cleaning equipment is replaced at approximately 10-year intervals.
OSHA is providing a four-year phase-in period for the industry to come into compliance with the new levels through the use of engineering controls. Accordingly, OSHA believes that both smaller and larger dry cleaning operations can achieve the new 25-ppm TWA level in the ordinary course of the equipment replacement schedule. Consequently, the economic impact of the change to new equipment would not be great even for smaller operations.
In addition, use of older equipment in good condition results in employee exposure levels not much above the new 25-ppm PEL. Industry estimates indicate that levels of approximately 40 ppm can be attained. During the four-year interval noted in this regulation, reasonably priced retrofits for older equipment may be developed that can be used to achieve the 25-ppm PEL.
OSHA is, of course, sympathetic to the circumstances of small businesses. If, after three years following publication of this regulation, it appears that there will be significant economic impacts for small dry cleaning operations attempting to convert to new equipment or retrofit within the four years permitted by the standard, OSHA will consider extending the period for smaller dry cleaning operations to achieve compliance using engineering and work practice controls. If that situation develops, OSHA believes that a trade association petition bringing the facts to OSHA's attention would be appropriate. OSHA would, at that time, evaluate the available information and make a decision based on all the information obtainable.
OSHA is establishing in the final rule a revised 8-hour TWA PEL of 25 ppm for perchloroethylene. OSHA concludes that the revised limit will substantially reduce the significant risk of material impairment of health presented by exposure to this substance at the Agency's former PEL of 100 ppm.