Assessment of the developmental risks resulting from occupational exposure to select glycol ethers within the...

This risk assessment evaluates the potential human hazards of adverse developmental effects posed by exposure to 2-ethoxyethanol (2-EE), 2-ethoxyethanol acetate (2-EEA), 2-methoxyethanol (2-ME), and 2-methoxyethanol acetate (2-MEA) as they are currently used in semiconductor manufacturing. These glycol ethers are contained in positive photoresists used in the wafer fabrication process. The available data on the developmental toxicology of these glycol ethers indicates that each can selectively affect the offspring of pregnant animals that have been exposed to relatively low vapor concentrations. For these chemicals, the ratio of the lowest dose which adversely affected the pregnant animals (A) and the lowest dose which produced developmental effects in offspring (D), e.g., A/D ranged from 1-5. Approximately 400 workplace air samples of 4-8 h duration, both personal and area, from seven different companies were used to assess the degree of inhalation exposure during the manufacture of wafers. The geometric mean results obtained during personal sampling of workplace air for 2-EE, 2-EEA, 2-ME, and 2-MEA were 0.36, 0.02, 0.10, and 0.01 ppm, respectively. These levels are 14- to 500-fold lower than the applicable threshold limit value (TLV) currently recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). Specifically, the margins of safety between the typical occupational exposure and the TLV for 2-ME, 2-EE, 2-MEA, and 2-EEA are 50, 14, 500, and 250, respectively. The TLVs for these chemicals were set at levels considered sufficiently low to protect workers and their offspring from adverse effects and are about 2- to 10-fold lower than the various no-observed-effect levels (NOELs) obtained in animal tests. Based on more recent data, lower TLVs are indicated. The safety-factor approach, rather than mathematical models developed for estimating cancer risks, was used in this analysis. Historical data have shown that the application of safety factors of 10-100 to the NOEL, as determined in Segment II developmental toxicology tests in animals, should be adequate to protect humans. In its risk assessment guidelines, the U.S. Environmental Protection Agency (EPA) selected the uncertainty-factor approach as the most reasonable one for evaluating the hazards of developmental toxicants. This assessment indicates that the airborne concentrations of these glycol ethers in the semiconductor industry are, in general, sufficiently low to protect employees against their adverse developmental and reproductive effects as well as any other toxic effects as long as dermal exposure is minimal.