           PRESENTATION TO SACC PREPARATORY VIRTUAL MEETING ON DCM 
                               NOVEMBER 12, 2019
                                       
	
      
      Thank you for the opportunity to address the scope and clarity of the draft charge questions for the peer review of the draft TSCA Risk Evaluation of Methylene Chloride (Dichloromethane, or DCM).  I speak on behalf of the Halogenated Solvents Industry Alliance, or HSIA, which represents producers and users of DCM. These comments specifically address the charge questions and focus on how in the short term the Committee could assist EPA in addressing shortcomings of both the exposure and hazard elements of the draft Evaluation.  
      
Exposure (Charge Questions 4.1  -  4.6)
      EPA acknowledges that most of the exposure studies on which it relies were conducted in the 1980s, while recognizing that in 1997 the Occupational Safety and Health Administration (OSHA) adopted a standard under § 6(b)(5) of the Occupational Safety and Health Act lowering the permissible exposure limit (PEL) for DCM from 500 ppm to 25 ppm, and setting a short-term exposure limit, or STEL, of 125 ppm.  Employers generally keep concentrations of airborne DCM below a 12-1/2 ppm (8-hour TWA) action level to avoid triggering the standard's ancillary provisions.  How can EPA produce an assessment in 2019 that assumes workplace exposures are still at 1990s levels, when the current action level is only 2.5% of the earlier permissible exposure limit?  The 25 ppm PEL has been in effect for over 20 years.  
      In addition, EPA has adopted national emission standards, or NESHAPs, for most DCM applications, for which it relied on exposure assessments showing workplace concentrations below 25 ppm.  Indeed, some of these NESHAPs, such as the one for commercial paint stripping, require these operations to:
 Evaluate each application to ensure there is a need for paint stripping;
 Evaluate each application where a paint stripper containing DCM is used to ensure that there is no alternative paint stripping technology that can be used;
 Reduce exposure of all paint strippers containing DCM to the air;
 Optimize application conditions to reduce DCM evaporation; and
 Practice proper storage and disposal of paint strippers containing DCM (e.g., store stripper in closed, airtight containers).

Larger operations must:
   
       Develop and implement a written DCM minimization plan to minimize the use and emissions of DCM; and
       Maintain copies of annual usage of paint strippers containing DCM on site at all times.
      Most significantly for present purposes, covered businesses must maintain records of paint strippers containing DCM used for paint stripping operations sufficient to verify annual usage of paint strippers containing DCM. These records, and those maintained under other NESHAPs, are accessible to EPA.  At a minimum, the Committee should recommend that EPA review its own records for NESHAP-regulated sources to assess exposures in the post-§ 6(b)(5), post-NESHAPs era.
      
Hazard (Charge Questions 5.9 and 5.10 Chronic)
	Regarding potential cancer risk, HSIA applauds EPA's recognition that the highest quality data available  -  well-conducted worker cohort studies  -  show no overall increased cancer risk.  It is regrettable that the epidemiology is then ignored in favor of linear extrapolation from high-dose bioassays in mice.  It is most important that the Committee address the following charge questions:
 5.9.  Please comment on the appropriateness of using a linear low-dose extrapolation versus a non-linear or threshold approach, recognizing that methylene chloride is predominantly metabolized by cytochrome P450 2E1 to carbon monoxide at low concentrations (a high affinity, low capacity pathway) and by glutathione S-transferase T1-1 to two reactive intermediates (i.e., S-(chloromethyl)glutathione) and formaldehyde) at high concentrations (a low affinity, high capacity pathway).
         
 5.10. Please comment on the appropriateness of applying the PBPK model and assumptions within the model, specifically using the internal dose metric of daily mass of methylene chloride metabolized via the GST pathway as the basis for performing a linear low-dose extrapolation for quantifying potential cancer risks from chronic exposures to methylene chloride.

      We plan to provide comments in due course showing that mouse liver and lung tumors from methylene chloride exposure do not occur from events expected for genotoxic carcinogens, but from a non-genotoxic MOA that involves hypoxia from increased levels of carboxyhemoglobin and tissue carbon monoxide.  These data were published by Mel Andersen in 2017 using reactome ontologies and bioinformatic tools to evaluate and visualize the pattern of genomic responses in the liver and lung of female B6C3F1 mice following inhalation exposure to methylene chloride vapor from 100 to 4,000 ppm methylene chloride for 13 weeks (6 hours/day, 5 days/week).  A physiologically-based pharmacokinetic (PBPK) mouse model for methylene chloride, which includes both the conjugation and oxidation pathways, was modified to simulate the rates of methylene chloride oxidation to carbon monoxide (CO) in lung and liver and the time course of carboxyhemoglobin (HbCO) in blood.  The findings from Andersen et al. suggest that a non-linear or threshold approach should be considered to estimate cancer risk for methylene chloride.
         
         

         

