An analysis of exposure rate effects for benzene using a physiologically based pharmacokinetic model.

A new physiological pharmacokinetic model was used to explore the effect of exposure rate on the rate of formation of several crucial metabolites of benzene. Metabolite formation was compared following exposure to benzene over the course of an 8-hr workday and following a single exposure for 15 min. These exposures were based on the permissible exposure limit and short-term exposure limit of the benzene standard set by the Occupational Safety and Health Administration. The model was parametrized using in vitro and in vivo experimental data on benzene toxicokinetics and metabolism. Ranges, rather than fixed values, were assigned to the parameters. Model predictions show that the amounts of hydroquinone, catechol, and muconaldehyde formed in the body following a peak exposure to 32 ppm of benzene over 15 min are on average 20% higher than those formed following an equivalent dose of 1 ppm over an 8-hr period. The health consequences of these findings and the implications for policy concerning short-term exposure limits are discussed.

The role of threshold limit values in U.S. air pollution policy.

This paper analyzes the role of threshold limit values (TLVs) in national air pollution policy during the 1980s, a period in which the Environmental Protection Agency (EPA) sought to delegate to individual states the authority to evaluate and regulate airborne toxic substances. We focus on 20 carcinogens and 11 substances with non-genotoxic health effects that were regulated by local air toxics programs using TLVs. Data from EPA's National Air Toxics Information Clearinghouse indicate that maximum TLV-based Ambient Air Level guidelines (AALs) frequently exceed minimum TLV-based AALs by a factor of greater than 1,000. Cancer potency data from EPA's Integrated Risk Information System suggest significant risks remain at TLV-based AALs. Cancer risks at the median TLV-based AAL exceed 1,000 cases per million exposed persons for cadmium (1,040), nickel and its compounds (1,420), propylene oxide (1,550), coke oven emissions (1,860), benzene (2,500), arsenic and its compounds (7,300), N-nitrosodimethylamine (21,000), asbestos (21,500), and ethylene dibromide (55,000). We also summarize published studies that report non-genotoxic health effects in workers exposed at levels near the TLV for 11 substances whose AALs were based on TLVs. Contrary to the assumption frequently made by state air toxics program, TLVs cannot be taken to represent no observed effect levels (NOELs) for regulatory purposes.

Technological, economic, and political feasibility in OSHA's Air Contaminants Standard.

In 1989, after almost two decades of substance-by-substance standard setting, the Occupational Safety and Health Administration (OSHA) promulgated its Air Contaminants Standard, imposing new exposure limits for 376 toxic substances encountered in U.S. industry. In marked contrast to earlier regulations, the Air Contaminants Standard has generated relatively little industry opposition. This paper analyzes the standard in the context of the twenty-year debate over the appropriate role for technological feasibility and economic compliance costs in occupational health policy. The political feasibility of the new standard is traced to OSHA's abandonment of "technology forcing" in favor of reliance on "off-the-shelf" technologies already in use in major firms. While important as an embodiment of OSHA's new "generic" approach to regulation, the Air Contaminants Standard cannot serve as a model for future occupational health policy, due to its reliance on informal, closed-door mechanisms for establishing regulatory priorities and permissible exposure limits.

Implications of OSHA's reliance on TLVs in developing the air contaminants standard.

This paper evaluates the decision by the Occupational Safety and Health Administration (OSHA) to base its Air Contaminants Standard on the threshold limit values (TLVs) of the American Conference of Governmental Industrial Hygienists. Contrary to the claim made by OSHA in promulgating the standard, the TLV list was not the sole available basis for a generic standard covering toxic air contaminants. The National Institute for Occupational Safety and Health (NIOSH) presented data indicating that the TLVs were insufficiently protective for 98 substances. NIOSH Recommended Exposure Limits (RELs) were available for 59 of these substances. The ratio of PEL to REL ranged up to 1,000, with a median of 2.5 and a mean of 71.4. OSHA excluded 42 substances from the standard altogether despite the availability of NIOSH RELs, solely because no TLV had been established.

Regulation of occupational carcinogens under OSHA's Air Contaminants Standard.

We compare the information used by the Occupational Safety and Health Administration (OSHA) to regulate carcinogens under its 1989 Air Contaminants Standard to publicly available information on substances with potential carcinogenic activity. Carcinogenicity evaluations were obtained from the National Institute for Occupational Safety and Health (NIOSH), the American Conference of Governmental Industrial Hygienists (ACGIH), the National Toxicology Program (NTP), the Environmental Protection Agency (EPA), and the International Agency for Research on Cancer (IARC). We focus on three sets of substances: those which were regulated as carcinogens by OSHA in the Standard, those which were included in the Standard but whose exposure limits are based on noncarcinogenic effects, and those substances designated as potential carcinogens by NIOSH, ACGIH, and/or NTP but which were excluded from the Standard. The data indicate that OSHA relied almost exclusively upon the recommendations of the nongovernmental ACGIH to the exclusion of IARC and the three governmental bodies. Given their statutory authority to evaluate chemical carcinogenicity for regulatory agencies such as OSHA, the exclusion of NIOSH and NTP is particularly striking.