EPA’s final toxicological review of the noncancer effects of methanol on human health disappointed the Methanol Institute (MI) and also prompted a letter of disapproval from Senator David Vitter (R-LA), ranking member of the Senate Environment and Public Works Committee.  According to the MI and Vitter, the oral and inhalation reference doses included in the review are unnecessarily conservative and below the normal background levels of methanol to which people are exposed through diet.

IRIS

The toxicological review of methanol is intended to support the Agency Integrated Risk Information System (IRIS), a program in which the EPA evaluates information on health effects that may result from exposure to environmental contaminants. EPA’s regulatory activities are heavily influenced by information in IRIS. 

But the Agency’s approach to IRIS toxicological reviews came under attack in recent years, particularly regarding its assessment of several high-profile chemicals, including hexavalent chromium and formaldehyde. 

The concerns led to a National Research Council (NRC) review of the IRIS program.  The findings were not complimentary.  Among other things, the NRC found an EPA pattern through a number of IRIS reviews of not following a consistent underlying conceptual framework and not providing sufficient documentation on methods and criteria for identifying evidence from epidemiologic and experimental studies.   In 2011, Congress included language in the 2012 Consolidated Appropriations Act, directing the EPA to incorporate NRC’s recommendations to improve the IRIS program.

Congress’s interest in IRIS is understandable given how IRIS reviews can result in regulatory actions that can restrict the use of chemicals that play a key role in the economy.  Methanol is a high production volume chemical with many commercial uses and is a basic building block for numerous chemicals.  Many methanol derivatives are used in the construction, housing, and automotive industries. Consumer products that contain methanol include varnishes, shellacs, paints, windshield washer fluid, antifreeze, adhesives, and deicers.

Reference dose and concentration

According to EPA’s review, laboratory animals exposed to methanol developed several abnormalities, including skeleton malformations and reduced brain weight.  After making animal-to-human extrapolations, the Agency arrived at two reference numbers for methanol; that is, estimates of the daily exposure to methanol that can occur and not result in a deleterious effect for the human population, including sensitive subgroups, over a lifetime. 

• For ingestion, the review identified a reference dose (RfD) of 2 mg/kg body weight (bw)-day. 
• For inhalation, the review identified a reference concentration (RfC) of 20 mg/m3. 

Both the RfC and RfD were considerably higher than those included in a 2011 draft, wherein the EPA proposed an RfD of 0.4 mg/kg bw-day and an RfC of 2 mg/m3. 

Background levels

But the change appeased neither Vitter nor the MI.

  “The assessment employs dubious rhetorical arguments such as referring to ‘unquantifiable effects of uncertain adversity’ to justify its rejection of suggested higher ‘safe’ exposure levels,” writes Vitter.  “Further, the assessment fails to address a fundamental criticism that external exposures at the oral reference dose and inhalation reference concentration result in methanol levels in humans that are well within normal background levels from dietary exposures.”  

The MI expressed the same concern and added that the EPA used “overly conservative ‘uncertainty factors’ that effectively double-counted deficiencies in the literature.”

EPA’s September 2013 toxicological review of methanol

Senator Vitter’s letter

MI’s comment