Synergist - September 2010

bioassay and was rewarded by a rare acceptance. In retrospect, the UAW should also have petitioned for methoxyethanol and ethoxyethanol.

In 1993, OSHA proposed limits for methoxyethanol (0.1 ppm) and ethoxyethanol (0.5 ppm) and requested comments on a proposal to include BE in a standard for glycol ethers. The first two were identified as reproductive toxins in the laboratory and were leading candidates for the cause of known adverse reproductive outcomes among cleanroom workers in the semiconductor industry. BE also exerts adverse effects on reproductive health in the laboratory, but it was not studied in people and no limit was proposed. Hearings were held; the record was closed. Then, the first Bush administration departed. Nothing visible was done with the record during the Clinton administration. The proposal was withdrawn during the second Bush administration, which claimed there wasn’t enough exposure to glycol ethers to make it worthwhile.

Current exposure limits for BE are shown in Table 1.

Table 1. Exposure Limits for Butoxyethanol OSHA PEL

50 ppm NIOSH REL

5 ppm ACGIH TLV

20 ppm EPA RfC

0.3 ppm

ATSDR minimal risk levels (MRLs)

acute intermediate chronic

6 ppm

3 ppm

0.2 ppm

Carcinogen Classification and BE

In 2000, NTP reported that BE caused hemangiosarcoma (and some other tumors in male mice), forestomach tumors (by inhalation) in female mice, and adrenal tumors in female rats. The mouse studies were termed “some” evidence (i.e., positive studies), the female rats equivocal. You can read the full account at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr484.pdf. This report immediately spurred a series of studies funded by Syn-genta and the American Chemistry Council, among others, claiming to show that the hemangiosarcomas were secondary to busted red blood cells, and scoffing at forestomach tumors.

IARC considered BE in 2004 (published in 2006). The rule for sufficient evidence for carcinogenicity in laboratory studies is increased tumors in two or more species of animals or in two or more independent studies in one species. At the time, IARC did not consider the “positive” mouse studies in each gender independent, so the laboratory studies were “limited” and BE was “not classifiable.” Under the new rules published in 2006, the studies in two genders of mice would be considered independent, raising the laboratory evidence to “sufficient” and the classification to 2B.

INSIGHT | DEPARTMENT

You can read the full account at http://monographs.iarc.fr/ENG/ Monographs/vol88/mono88.pdf.

Reference Concentrations

The outliers in Table 1 are the EPA RfC and the ATSDR chronic MRL. Industrial hygienists should know how these health-based values are calculated.

An EPA reference calculation starts with a point of departure (POD), either a NOAEL or Benchmark Dose. The most important lesson is that the NOAEL is equivalent to a 10 percent (1 in 10) attack rate above background. This is pretty much the limit of direct observation of health effects in any study. Typically, EPA then divides the POD by uncertainty factors of tenfold for human variability, tenfold for extrapolation from laboratory to human, and tenfold if the effect was observed in less than a chronic study. Although a two-year bioassay is distinctly less than lifetime—it starts after pup hood, and ends with a terminal sacrifice with the majority of the test animals still alive—it’s considered a chronic study.

The RfC for BE is far from conservative. Starting with a POD of 16 mg/m3 for red cell pigment deposition in the liver, EPA applied an uncertainty factor of only 10, ignoring rat-to-human differences, leaving the RfC at 1.6 mg/m3, or 0.3 ppm. You can read the logic at www.epa.gov/iris/subst/0500.htm. To achieve mathematical equivalence with a PEL, we have to account for 20 m3 of air breathed for 365 days (community) with 10 m3 of air for 250 days breathed at work—approximately a threefold difference.

Lessons

We can draw at least two conclusions from the Gulf saga. First, it seems unlikely that picking up cold tar balls on a beach is more hazardous than laying down hot asphalt on a road (pretty much the same stuff as the tar balls). Yet, the beach cleanup workers are getting some training, a supervisor with HAZ-WOPER training, air monitoring, a registry for health studies, injury and illness records posted on the Internet, NIOSH review of first aid logs, PPE including respirators required for some jobs offshore, and a heat stress mitigation program including a work-rest regimen. The protections being provided (no matter how imperfectly) to the beach workers need to be provided to workers who are not on TV.

Second, it’s not enough to acknowledge that OSHA PELs are out of date. It’s not just new data that compels lower exposure limits. Modern understanding of a consistent approach to extrapolating from occupational health data to exposure limits aimed at acceptable risks was not applied for the 1968 TLVs, or the 1986 TLVs, or even later. It’s also unacceptable to ignore EPA’s reference concentrations, claiming these are aimed at protecting everybody, as if workers are immune at work to exposures endangering them at home.

FranklinMirer,PhD,CIH,isaprofessorintheEnvironmentalandOccupational HealthSciencesUrbanPublicHealthProgramatHunterCollegeSchoolofHealth Sciences in New York. He can be reached at (212) 481-7651 or fmirer@hunter.cuny.edu.