Tolerating Delay: How Much Toluene Is Too Much?
Just after I started at the United Auto Workers (UAW), a friend from graduate school who was working as an OSHA hygienist called me to ask whether the analytical method for toluene was any good. He’d been sampling (in a UAW-represented plant), standing well behind the worker, and had gotten a headache and was woozy from toluene vapors. He knew the worker’s exposure was much higher, but the result was well below the PEL. My friend’s reaction illustrates the force of an OEL: the idea that a PEL is a “safe” level was so ingrained that he first questioned the chemical analysis, instinctively ruling out the need for improved controls.

The sampling method for toluene was and is solid. What we need to examine—for toluene and other substances—is the “hierarchy of knowledge.”
The first level of the hierarchy of knowledge is the worker’s observation. The worker knows more about the job than anyone but rarely has the tools to generalize her experience, and will only notice symptoms with short latency. The next level is the practitioner’s experience: practitioners know about levels of exposure and evaluation criteria, and can generalize and communicate. Usually, the IH on the shop floor doesn’t have the authority to demand expensive controls in the face of PEL compliance.
Moving up the ladder, we have compilations of data into technical reports and standards (reports that support interventions). The next rung is peer-reviewed publications, usually from a limited range of situations, which are the raw material for authoritative risk assessments. Only peer-reviewed publications are considered in making authoritative recommendations such as those in criteria documents, EPA or ATSDR toxicological profiles, or proposed standards. Proposed rules go through the crucible of hearings and litigation, but sit at the very top of the hierarchy. Moving to risk communication, the risk assessment and management conclusions are simplified into fact sheets, the fact sheets go on the internet, and information is again simplified (or oversimplified) for popular consumption. EXPOSURE LIMITS So, forty-plus years ago, an observation showed the PEL for toluene didn’t protect, but exposures were permitted to continue. This invites us to ask what “we” know, and when did “we” know it?
OSHA’s web page for sampling for toluene provides information on exposure limits and what’s behind them. The OSHA PELs for toluene are 200 ppm, the NIOSH REL is 100 ppm, the ACGIH TLV is 20 ppm, and the Cal-OSHA PEL is 10 ppm—a twenty-fold range. Beyond this, the EPA reference concentration (RfC) is 5 mg/m3 (equivalent to 1.3 ppm), and the ATSDR minimal risk level (MRL) for chronic exposure is 0.08 ppm. (A draft toxicological profile proposes raising the MRL to 1.0 ppm. ATSDR doesn’t explain the reasons for raising the level.) The RfC and MRL can appropriately be adjusted upward to account for duration of exposure, and don’t have the legal force of an OSHA standard.
The OSHA page for toluene also lists target health effects. For the TLV, these include “female reproductive system damage and pregnancy loss, central nervous system impairment and visual impairment.” California also lists toluene as a developmental toxicant with a reference level of 7 mg/day.
When we say OSHA PELs are “out of date,” we can mean there’s new data since the 1968 TLV list, but also new ways of interpreting the data, then and now, both for toxic potential and toxic potency. The documentation for the TLVs published in 1972 repeats a TLV of 200 ppm based on a 1943 publication (among 13 references) although a 1970 reference noted increased reaction times at 200 ppm, an early application of neurobehavioral testing. Today the limit would be set below the LOAEL or NOAEL, based on uncertainty factors, but the ACGIH practice at the time was frequently to set the limit at the NOAEL or sometimes at the LOAEL.
The 2007 documentation for the TLVs states that by 1973, ACGIH had reduced the TLV to 100 ppm (too late for the initial PEL adoption) and by 1992 to 50 ppm. The NIOSH REL, based on a 1971 criteria document, was stuck at 100 ppm, consistent with the 1973 TLV, where it is today. The 1989 OSHA PEL update temporarily reduced the PEL to 100 ppm, but this was flushed in 1992 when an appeals court sided with industry and vacated the entire rule. Then, in 2007, the TLV was reduced to 20 ppm. The 2007 documentation, which lists 109 references, including both neurobehavioral and developmental endpoints, is a major improvement over the 1972 version and superior to the NIOSH 1971 criteria document, both in scientific support and in final recommendation. Nevertheless, the specific reasons for going from 50 ppm to 20 ppm are not explicit. Cal-OSHA established a PEL of 10 ppm in 2009, using a quantitative approach to setting limits for both developmental and neurobehavioral endpoints. RISK ASSESSMENT As practitioners, we are supposed to apply the reference concentrations but also think about the basis for those values. To what degree are controls to prevent neurobehavioral effects, especially impaired color vision, also necessary to prevent chronic solvent encephalopathy and developmental disabilities?
First, are symptoms of short-onset neurological impairment experienced at levels below 200 or 50 ppm? How are subjective responses—fatigue, headache, confusion—related to the neurobehavioral test battery? The battery was deployed to give a quantitative measure of these effects to go along with exposure measurements. My impression is that the battery doesn’t show effects at lower exposure levels where symptoms still persist, so it’s not being used much anymore. For a study comparing toluene to alcohol, toluene effects weren’t statistically significant until Michigan undergraduates were buzzed to the equivalent of four beers and tending to fall asleep.
Is prevention of chronic solvent exposures necessary to prevent solvent-associated adverse developmental outcomes?
Second, is impaired color vision a conveniently measured manifestation of general dysfunction of the central nervous system? This effect is observed for most classes of solvents and can be hypothesized to result from a common pathway (gamma amino butyric acid and related receptors). I think this supports a hypothesis of adverse effect on other CNS functions that are more difficult to measure.
Third, is prevention of solvent-induced CNS dysfunction necessary to prevent chronic disability associated with solvent exposure? Severe and disabling neurological conditions—dementia, Alzheimer’s, Parkinson’s—afflict a large number of people. It seems generally accepted that solvent abuse (“huffing”)—and toluene abuse specifically—is associated with severe impairment. The association of chronic, occupational-level exposure with such effects has dissenters, but there is certainly at least limited evidence. I’m not prepared to do a systematic review or meta–analysis here, but someone should.
Fourth, is prevention of chronic solvent exposures necessary to prevent solvent-associated adverse developmental outcomes? It seems generally accepted that toluene abuse during pregnancy results in adverse outcomes. Again, the association of chronic, occupational-level exposure with such effects has dissenters, but there is at least limited evidence, and someone should do a systematic review or meta-analysis.
Finally, a general observation: I see a rough road to getting an OSHA PEL at 10 ppm or below. Cal-OSHA has attempted a risk analysis that touches the bases but hasn’t faced the full force of big-league industry opposition and Office of Management and Budget procedural objections and demands for economic analysis. I believe the evidence supports prevalence of “material impairment to health or functional capacity” under current conditions.
For general approaches beyond toluene, we (the IH profession) have a moderately robust risk assessment scheme for carcinogens, including hazard identification (classification) and dose-response assessment (potency). For results like neurological impairments and developmental disabilities, we need an organized, governmental approach to hazard identification and potency assessment—not just for toluene but for many other agents.
FRANK MIRER, PhD, CIH, is a professor in the CUNY School of Public Health in New York.
He can be reached at (212) 396-7782 or
British Journal of Industrial Medicine: “Acute Behavioural Comparisons of Toluene and Ethanol in Human Subjects” (November 1991).
California Office of Environmental Health Hazard Assessment: Proposition 65 No Significant Risk Levels (NSRLs) for Carcinogens and Maximum Allowable Dose Levels (MADLs) for Chemicals Causing Reproductive Toxicity (PDF, August 2013).
OSHA: Toluene.