OSHA did not formerly have an occupational exposure limit for the subtilisins; the ACGIH has established a ceiling limit of 0.06 µg/m3 for these substances. OSHA proposed a 0.06 µg/m3 ceiling for the subtilisins, and the final rule establishes this limit. NIOSH (Ex. 8-47, Table N1) agreed with the selection of this PEL. The subtilisins are proteolytic bacterial enzymes (produced by various Bacillus species) that are used primarily in laundry detergents but also in contact lens cleaners, film processing, and the food industry. They are considered a threat to occupational health because they cause immune-system-mediated bronchoconstriction and respiratory symptoms in addition to primary irritation of the skin and respiratory tract (ACGIH 1986/Ex. 1-3, p. 540; Pepys, Hargreave, Longbottom, and Faux 1969/Ex. 1-568).
A report by the California Department of Public Health (1969, as cited in ACGIH 1986/Ex. 1-3, p. 540) showed that several workers were hospitalized after exposure to subtilisins in a detergent formulation plant where the "safe limit" for subtilisins was set at 0.12 µg/m3. There is no information on whether this limit was exceeded in this episode or what other conditions prevailed. In addition to NIOSH's comment, OSHA received several other comments on the proposed limit for the subtilisins (Exs. 8-70, 3-684, 137, 164, and 98-13; Tr. p. 3-304; Tr. pp. 10-182 to 10-190). Most of these commenters were of the opinion that OSHA should not establish an exposure limit for the subtilisins because there is currently no method available to monitor workplace exposures to these substances. In addition, these commenters submitted information to the record on the subtilisins' health effects to supplement the data base relied on by OSHA in the proposed rule.
Typical of these comments was the submittal of Beth Concoby and Alice Caddow on behalf of Genencor, Inc., a manufacturer of subtilisins:
The Enzyme Technical Association (Exs. 8-70, 164, 137, and 98-13; Tr. pp. 10-182 to 10-190) specifically objected to the Agency's use of an early study on the subtilisins; OSHA has responded to this comment by carefully reviewing the recent toxicological literature on the subtilisins, including several new health studies submitted by these participants. These studies document the respiratory toxicity and sensitization potential of the subtilisins. For example, a study by Juniper and Roberts (1984, as cited in Exs. 8-70 and 3-684) reports that 3.7 percent of exposed workers experienced dose-related sensitization symptoms (enzyme asthma, or EA) on exposure to enzyme detergent powders. Symptoms included sweating, headache, pain in the chest, influenza-like symptoms, cough, breathlessness, and wheezing "sufficient at times to incapacitate the patient completely" (Juniper and Roberts 1984, p. 128, as cited in Exs. 8-70 and 3-684). This study also reports that the "prime initiating cause of episodes of EA in otherwise asymptomatic subjects was undoubtedly dust level 'peaks' rather than a low but continuous exposure" (Juniper and Roberts 1984, p. 131, as cited in Exs. 8-70 and 3-684).
In response to the objections of commenters (Exs. 8-70 and 3-684) that no sampling and analytical method exists for the subtilisins, OSHA notes that several such methods have been published (Fulwiler 1971; Fulwiler, Abbot, and Darcy 1972; Bruce, Dunn, Brotherton et al. 1976). The American Industrial Hygiene Association (Tr. p. 3-304) was in favor of keeping the subtilisins in this rulemaking and submitted a sampling and analytical method for these substances. Thus, OSHA finds that there is no issue of monitoring feasibility for this group of enzymes.
Another study in monkeys (Coate, Busey, Schoenfisch, and Newmann 1978, as cited in Exs. 8-70 and 3-684) reports the effects of exposing animals 6 hours/day, 5 days/week for 6 months to atmospheres containing synthetic detergent dust at 1, 10, or 100 mg/m3 together with enzyme dust at 0.001, 0.01, 0.1, or 1 mg/m3. Exposures to 10 or 100 mg/m3 detergent dust together with 0.01 or 1 mg/m3 enzyme dust produced gross signs of respiratory distress, pulmonary histopathological effects, and pulmonary function impairment (Coate et al. 1978, as cited in Exs. 8-70 and 3-684).
These studies and others (McMurrain 1970; Medical Research Council 1976; Zachariae, Hoegh-Thomsen, Witmeur, and Wide 1981; Thorne, Hillebrand, Magreni et al. 1986; Weill, Waggenspack, DeRouen, and Ziskind 1974, all as cited in Exs. 8-70 and 3-684) demonstrate convincingly the need for an exposure limit for the subtilisins. One study (Thorne, Hillebrand, Magreni et al. 1986, as cited in Exs. 8-70 and 3-684) reports that, in guinea pigs, the no-observed-effect level for pulmonary sensitization induced by exposure to the subtilisins for 15 minutes/day for 5 consecutive days was between 0.0083 and 0.041 mg/m3. Animals exposed on the same regimen at higher levels developed enzyme asthma (Thorne, Hillebrand, Magreni et al. 1986, as cited in Exs. 8-70 and 3-684). Recent evidence also demonstrates that the manufacturers of these enzymes have been able to control the dust exposures of their employees to levels "considerably lower than the proposed...TLV...recommendation 1/2 of a ceiling of 0.06 µg/m33/4" (McMurrain 1970, as cited in Ex. 3-684). These reductions in exposure have occurred as a result of a program of strict environmental controls and the adoption of a prilling process that encapsulates the enzymes to reduce enzyme-laden dust.
OSHA is establishing a ceiling limit of 0.06 µg/m3 for the subtilisins; the evidence described above indicates that a ceiling limit of 0.06 µg/m3 for the subtilisins is necessary to reduce the significant risks of respiratory sensitization, skin irritation, and respiratory effects among members of the exposed worker population; OSHA finds that all of these exposure-related health effects constitute material impairments of health. Recent studies (described above) show that this limit is being achieved at the present time. OSHA concludes that this limit will substantially reduce these significant risks.