OSHA comments from the January 19, 1989 Final Rule on Air Contaminants Project extracted from 54FR2332 et. seq. This rule was remanded by the U.S. Circuit Court of Appeals and the limits are not currently in force.
CAS: 79-06-1; Chemical Formula: CH2=CHCONH2
The former OSHA 8-hour TWA permissible exposure limit for acrylamide was 0.3 mg/m3, with a skin notation, and the Agency proposed a revised PEL of 0.03 mg/m3, with a skin notation, for this substance, based on evidence of its carcinogenicity in animals. NIOSH (Ex. 8-47, Table N6A) concurs that these limits are appropriate for acrylamide. The ACGIH recommends a TLV of 0.03 mg/m3 for this substance (ACGIH 1986/Ex. 1-3, p. 12). The final rule promulgates an 8-hour TWA PEL of 0.03 mg/m3, with a skin notation, for acrylamide.
Acrylamide is a white solid and is widely used as a reactive monomer or intermediate in organic synthesis, and polyacrylamide is a polymer that is used in the manufacture of a host of products, including adhesives, mining chemicals, fibers, pharmaceuticals, animal feed, paper sizing, molded parts, textiles, and coagulant aids (American Cyanamid Company, Ex. 94; ACGIH 1986/Ex. 1-3, p. 12). Chronic exposure to acrylamide has been associated with neurotoxic effects in animals and humans; in cats, the no-effect dose level for neurotoxic effects ranges from 0.3 to 1.0 mg/kg/day (ACGIH 1986/Ex. 1-3, p. 12). Neuropathic effects caused by exposure to acrylamide are dose-related and have been seen in rats, cats, and monkeys. Observed effects in humans included muscular weakening, ataxia, incoordination, tremors, and hallucinations. Acrylamide can be absorbed through the skin in sufficient quantities to be systemically toxic; the dermal LDLo in rabbits is 1000 mg/kg (RTECS 1988).
Tests on the mutagenicity of acrylamide have produced conflicting results (ACGIH 1986/Ex. 1-3, p. 12). However, acrylamide is associated with reproductive effects; based on a drinking water study by Smith, Zenick, Preston et al. (1986/Ex. 1-1123), OSHA concluded that acrylamide causes dominant lethality in the male rat (53 FR 21191).
Two studies are available that demonstrate the carcinogenicity of acrylamide: Johnson, Gorzinsky, Bodner et al. (1986/Ex. 1-825) and Bull, Robinson, Laurie et al. (1984/Ex. 1-252). OSHA described both of these studies in the preamble to the proposed rule (53 FR 21191); they are briefly summarized here. In the Bull et al. (1984/Ex. 1-252) study, acrylamide was tested as a skin tumor initiator in female Sencar mice; 12-o-tetradecanoylphorbol-13-acetate (TPA) was used as a promoter. The authors administered six doses ranging from 0 to 50 mg/kg body weight over a two-week period. A dose-related increase in tumor incidence was observed for all routes of exposure tested, including topical, gastric intubation, and intraperitoneal injection. The same authors (Bull, Robinson, Laurie et al. 1986/Ex. 1-252) noted a dose-related increase in lung adenomas in A/J mice administered acrylamide either by gastric intubation or intraperitoneal injection.
The second study was performed by Johnson et al. (1986/Ex. 1-825) on male and female Fischer 344 rats given 0 to 2.0 mg/kg/day acrylamide in drinking water for a period of two years. During the last four months of this study, mortality from cancer was observed at a statistically significant rate in rats exposed at the highest dose level; in addition, tumor incidence increased in animals of both sexes in the highest dose group. In females, tumors of the mammary gland, central nervous system, thyroid gland, oral tissues, uterus, and clitoral gland were seen, while males developed tumors of the central nervous system, thyroid, adrenal gland, and scrotum (Johnson, Gorzinsky, Bodner et al. 1986/Ex. 1-825). Peripheral nerve degeneration was also seen in female rats exposed at the 2 mg/kg/day level (ACGIH 1986/Ex. 1-3, p. 13).
OSHA received comments on the proposed limit for acrylamide from NIOSH and from one other rulemaking participant. Linda Dulak, Toxicology Program Manager for the American Cyanamid Company, submitted a detailed critique of OSHA's discussion (53 FR 21191) of acrylamide's carcinogenicity (Ex. 94). According to Dr. Dulak: (1) the Johnson et al. (1986/Ex. 1-825) study described above is "inconclusive" with regard to acrylamide's carcinogenicity; (2) the Bull et al. (1984/Ex. 1-252) study demonstrates only that acrylamide is not a "complete" carcinogen; (3) OSHA has not demonstrated that the risk of exposure to acrylamide at the former PEL of 0.3 mg/m3 is significant; and (4) OSHA has not demonstrated that it is feasible, either technologically or economically, to achieve the proposed 0.03 mg/m3 limit (Ex. 94). The paragraphs below discuss each of these points in turn. Dr. Dulak believes that the results of the Johnson et al. (1986/Ex. 1-825) study should be regarded as "inconclusive" because (1) the presence of a viral infection in the animals of all dose groups "complicates the evaluation of the data"; (2) The highest dose administered was toxic to female rats; and (3) there were high background incidences of tumors among the controls (Ex. 94, p. 6). In addition, American Cyanamid states that the Bull et al. (1984/Ex. 1-252) study demonstrates only that acrylamide is not a complete carcinogen because animals administered acrylamide alone did not develop skin tumors (Ex. 94, p. 8). Dr. Dulak reported that American Cyanamid is currently conducting a second carcinogenicity study designed to clarify the questions that arose during the Johnson et al. (1986/Ex. 1-825) study, and preliminary review suggests that these results will differ significantly from those of the early study (Ex. 94, pp. 6-8). Dr. Dulak notes that the ACGIH is planning to review the expanded toxicological data base for acrylamide in the fall of 1988 and that the Food and Drug Administration and the Science Advisory Board of EPA are preparing to review the second American Cyanamid study when it becomes available (Exs. 3-961 and 8-76; Ex. 94, pp. 2-3). OSHA's response to Dr. Dulak's comments follows.
First, as regards the Bull et al. (1984/Ex. 1-252) study, prudent public-health policy dictates that all carcinogens, rather than only complete carcinogens, be regulated to levels that will provide worker protection. Second, OSHA notes that the authors of the Bull et al. (1984/Ex. 1-252) study are of the opinion that the potency of acrylamide as a tumor initiator is equal to that of ethyl carbamate, a widely recognized tumorigen (Klaasen, Amdur, and Doull 1986/Ex. 1-99, p. 123); in addition, these authors demonstrated that mice of a different strain (i.e., A/J mice) developed lung adenomas when given acrylamide by gastric intubation or intraperitoneal injection. Third, OSHA finds the Bull et al. (1984/Ex. 1-252) study, which showed a dose-related increase in skin tumors in one strain of mouse by three different routes of exposure and the development of lung tumors in another strain of mouse by two routes of administration, convincing evidence of acrylamide's carcinogenicity. OSHA looks forward to reviewing both the results of American Cyanamid's second study and the ACGIH TLV Committee's comments on acrylamide when these become available. However, the risk demonstrated by OSHA's risk assessment for acrylamide indicates that delaying regulatory action until additional research has been done would be inappropriate; further, it is the Agency's experience that research results are often not published for several years and that the deliberations of the ACGIH Committee are often time-consuming. OSHA finds it inappropriate to delay action when the best available evidence at present indicates a significant risk at the former PEL. Further, OSHA notes that the ACGIH was sufficiently persuaded of acrylamide's carcinogenicity by the findings of the Bull et al. (1984/Ex. 1-252) and Johnson et al. (1986/Ex. 1-825) studies to assign this substance an A2 (suspected human carcinogen) designation. The International Agency for Research on Cancer (IARC) was also convinced by the evidence presented in these studies; IARC judged that the evidence for the carcinogenicity of acrylamide in animals was sufficient (IARC 1986). However, in light of the ongoing research being conducted by American Cyanamid, OSHA will consider new evidence as it becomes available and will revise its limit if this action appears to be warranted.
In response to Dr. Dulak's third point (that, in American Cyanamid's view, OSHA has not demonstrated that risk at the former PEL of 0.3 mg/m3 is significant), OSHA points to the results of the Agency's quantitative risk assessment, which show that the maximum likelihood estimate of the risk at the former PEL of 0.3 mg/m3 is 10 cancer deaths per 1,000 workers exposed at that level over their working lifetimes (Table C15-2).
American Cyanamid believes that both the recent epidemiological findings of Sobel, Bond, Parsons, and Brenner (1986, as cited in Ex. 94) in a cohort mortality study of Dow Chemical Company acrylamide-exposed workers and additional results from a more recent mortality study (Collins et al. 1987/Ex. 3-961) of America Cyanamid's workers show that "acrylamide is not carcinogenic to people" (Ex. 94, pp. 9-10).
Dr. Dulak discussed the Collins et al. study (1987/ Ex. 3-961, Appendix V) at length in posthearing comment:
It was determined that the study was large enough to detect
the increased risk of cancer which OSHA has indicated would
occur at present exposure limits. These findings, therefore,
indicate that OSHA has overestimated the risk of cancer among
acrylamide workers at the present PEL (Ex. 94, p. 9).
OSHA does not agree that its quantitative risk assessment is inconsistent with the findings of the Collins et al. (1987) study. These investigators reported that the average cumulative exposures (defined as mg/m3-years, the product of airborne concentration and duration of exposure) for each of the four subcohort plants included in the study ranged from 0.07 to 1.54 mg/m3-years, with an overall average of 1.0 mg/m3-years. This cumulative exposure corresponds to a 45-year exposure to 0.02 mg/m3; at this level of exposure, OSHA's risk assessment shows that the excess lifetime cancer risk is less than one death per 1,000 workers. Thus, at the levels and durations of exposure experienced by the cohort studied by Collins et al. (1987), OSHA's risk assessment suggests that only one or two exposure-related excess cancer deaths would be expected among the 2,293 exposed employees; clearly, such a small excess cancer death rate, which represents an increase of only 3 percent over background rates for all neoplasms, would not have been detected by this study. OSHA finds that the results presented by Collins et al. (1987) are not inconsistent with the results of OSHA's quantitative risk assessment. OSHA therefore reaffirms in this final rule that it is appropriate to treat acrylamide as a potential occupational carcinogen.
In response to American Cyanamid's final point, which relates to the technological and economic feasibility of achieving the final rule's 0.03 mg/m3 8-hour TWA level, OSHA notes the following. First, with very few exceptions, the Agency's final Regulatory Impact Assessment (Section VII) has determined that the controls necessary to achieve compliance with the limits proposed in this rulemaking are both technologically and economically feasible. This is clearly the case for firms, such as American Cyanamid, in the Chemical Manufacturing sector, SIC 28. Second, the EPA (1986b) study submitted by American Cyanamid (Ex. 94), entitled Assessment of Airborne Exposure and Dermal Contact to Acrylamide During Chemical Grouting Operations, showed that most worker exposures were consistently below the 0.03 mg/m3 level at the present time. Third, a NIOSH study (Hills and Greife 1986, as cited in Ex. 94) of facilities engaged in acrylamide monomer manufacturing reported considerable variability in exposure levels between the four plants surveyed; the observed variability was due in part to differences in housekeeping practices, age and maintenance of equipment, and use of engineering controls and natural dilution ventilation. NIOSH recommended that both frequent washing of the production area and ventilation be used to reduce airborne exposures to acrylamide. OSHA believes that it is technologically feasible for affected facilities to achieve compliance with the level promulgated by this final rule (see the Technological Feasibility section of this preamble). The Agency is therefore setting a revised 8-hour TWA exposure limit of 0.03 mg/m3 for acrylamide, with a skin notation, based on the significant risk of cancer posed to workers exposed to this substance in the workplace. OSHA concludes that this effect represents a material impairment of health and functional capacity, and the Agency concludes that the 0.03 mg/m3 PEL will substantially reduce this significant occupational risk
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