Recently I was invited to present at the 2016 International Neurotoxicology Conference on Manganese in New York. While I am, at best, a Sunday driver on manganese toxicity, my claimed expertise in the evolution of scientific knowledge and public health response—occupational exposure limits—justified my place on the program. There’s a simmering controversy, and litigation, over the association of manganese exposure in welding and Parkinson’s-like disease, which made it worth my while to take the subway across town to Mt. Sinai. My main interest was in manganese as a paradigm for evaluating OELs, and for how research evolves—and who evolves it.

Parkinson’s disease (PD) afflicts about 1 million Americans and about 1 in 100 people over 60, and may be underdiagnosed. PD, a movement disorder, also has a cognitive component, associated with degeneration of a brain structure that releases the neurotransmitter dopamine. Manganism, another disease associated with manganese exposures, presents with similar debilitative signs and symptoms but can be distinguished by specialists. Manganism has been reported since 1837 in mining, refining, and steelmaking, then in battery making, and now there is evidence of neurological effects from environmental exposures. The toxic potential of manganese has long been recognized, but the recognized toxic potency, as reflected in occupational exposure limits, has evolved over time. The OSHA PEL of 5 mg/m3, a ceiling value for manganese and compounds, was promulgated in 1971 based on the ACGIH Threshold Limit Values of 1968. The documentation for the TLVs from 1971 recommended a ceiling limit of 5 mg/m3 and included only13 references published from 1940 to 1969. My reading is that the numerical result was basically a lowest observed adverse effect level (LOAEL) from a 1943 study in a steel plant. The TLV was reduced to 1 mg/m3 in 1977. The NIOSH recommended exposure limit (REL) of 1 mg/m3 appears to have been derived from the TLV and then from testimony on the OSHA PEL update in 1989, although documentation for the REL and its actual promulgation date are not apparent. (The PEL update was flushed in 1992 when a Court of Appeals sided with industry.) In 2001, citing publications from 1937 to 1992, ACGIH adopted a TWA-TLV of 0.2 mg/m3 for manganese, elemental and inorganic compounds—a 25-fold reduction. The TLV was further reduced to 0.02 mg/m3 in 2013—250-fold less than the PEL—based on documentation with about 100 references through 2011.

Internationally, exposure limits vary from 0.02 mg/m3 respirable and 0.2 mg/m3 inhalable in Germany to 0.5 mg/m3 in the U.K. to 1 mg/m3 in Japan. Dates when these standards were promulgated are not readily available. The EPA IRIS reference concentration (RfC) of 5 x10-5 mg/m3 dates to 1995. The heavily documented and recent recommendation is the 2012 ATSDR minimal risk level (MRL) of 0.3 µg/m3 for chronic exposure. (Equating the RfC and MRL to 8-hour exposure limits requires taking into account duration of exposure.)