Document ID: EPA-HQ-OPPT-2011-0941-0204
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2018-07-23T04:00Z

Number/Name: S-17-0004: Oxazolidine, 3,3'-methylenebis[5-methyl- 

SUMMARY INFORMATION

Human Health Hazard: 
       Moderate absorption through the skin and good absorption through the lungs and GI tract.
       Concern for irritation to skin, eyes, lungs and mucous membranes.
   
Human Health Risk:
 Low risk for lung toxicity to workers exposed via inhalation. 
 Worker risks for irritation/corrosion from dermal exposure cannot be quantified, but may be mitigated by use of impervious gloves. 
 Low risks to the general population from drinking water exposure.

Test recommendation: 
 None

PART A  - S-17-0004
SAT Date: 2/14/17
Health Assessor: M. Naidu

Structure:  

 
  

 CASRN: 2058285-17-7
 Chemical Category: 
 Chemical Category Health Concerns: 
 Category Testing Strategy:
 
 PMN Health Rating: 2
 SAT Key Words: MUT, ONCO, IRR, SYSTEMIC
 Absorption:  The substance has moderate absorption through the skin and good absorption through the lungs and GI tract. In stomach acid, the PMN substance is expected to release three moles of formaldehyde per mole of PMN substance. 
 SAT Health Summary: As in stomach expected to release 3 moles of HCHO per mole of PMN, concerns exist for mutagenicity, oncogenicity and developmental toxicity.

 PMN Data: 
      No data
      Analog Data: (analog, structure, study summary, POD): P-03-0325 and S-07-0006
      P-03-0325: severe eye and skin irritant, positive in the mouse lymphoma assay, and has moderate acute toxicity (LD50 = 670 mg/kg) with possible signs of neurotoxicity and dermal LD50 1400 mg/kg. The NOAEL from 90-day oral tox study was 72 mg/kg with reduced creatinine and calcium and increased cholesterol at 180 mg/kg and increased phosphorus at 72 and 180 mg/kg. Based on release of formaldehyde, there is concern for mutagenicity, oncogenicity (at high doses), possible allergic responses and uncertain concern for developmental toxicity.
 Other Information: (structural alert or component of interest, basis, etc.). SDS says carbon monoxide carbon dioxide, (dense) black smoke, aldehydes and organic acids are decomposition products.
EPA's Office of Pesticide Programs assessed risk of formaldehyde for re-registration as an antimicrobial agent (attached). In that assessment OPP assessed inhalation risk using an inhalation NOAEC of 0.12 mg/m[3] (0.015 mg/kg-bw) from Horvath et al. 1988 [JAMA 259, no. 5: 701-707, 1988], who reported nasal and respiratory effects in 109 workers occupationally exposed to formaldehyde via inhalation.
      PMN MW = 186 g/mol therefore g HCHO = g PMN /186 * 30 * 3 = roughly one-half.
 Point of Departure Selected and Basis: (oral) 72 mg/Kg oral route for analog P-03-0325
 Inhalation POD: NOAEC = 0.015 mg/kg-bw/day based on formaldehyde released at point of contact
      
 Oral POD: NOAEL = 15 mg/kg/day for formaldehyde based on reduced body weight gain and histopathology 

 Inhalation IUR: 1.3E-5 per ug/m[3] = 1.3E-2 per mg/m[3] = 0.013 per mg/m[3] (EPA/IRIS) (Note: inhalation IUR not used assuming formaldehyde generated in stomach acid not respiratory tract.)

Exposure Routes of Interest: (Be extremely clear when excluding routes; consider potential future scenarios and if these routes can still be ruled out.
 _ x__Inhalation: [Rationale if excluded]
 _ x__Dermal: [Rationale if excluded]
 _ x__Ingestion: [Rationale if excluded]

PART B
Focus Date: 3/2/17
Focus Assessor: S. Oxendine
USES and EXPOSURES:  
Uses:  Anticorrosive agent/H2S scavenger in oilfield operations (50%)  Anticorrosive agent/H2S scavenger in hydraulic fluids (50%) SNUR Reference (P-03-0325): 40 CFR 721.10461
Worker Exposure: Imported Proc/Form: Solution, 2-5% in concentrate for hydraulic fluid. 

 USE 1:  Oilfield Anti-Corrosive (50% of PV)
 Inhalation: PDR = 5.3E-2 mg/day over 8 days/yr (worst case) 
 Dermal:  (Liquid; 100%) PDR= 2200 mg/day over 250 days/yr
 USE 2:  Hydraulic Fluid Anti-Corrosive (50% of PV)
 Inhalation: PDR = 3.5E-2 mg/day over 4 days/yr (worst case)
 Dermal:  (Liquid; 100%) PDR= 2200 mg/day over 250 days/yr
 SDS: 
Gen Eqpt: chemical resistant gloves (natural rubber, neoprene, nitrile) / safety goggles or safety glasses. If a splash hazard exists, splash goggles with a face shield may be needed/ local exhaust or process enclosure ventilation system. Use with adequate ventilation to ensure exposure levels are maintained below exposure limits
Respirator: Use NIOSH approved respirators if ventilation is inadequate to control vapors
Health Effects: Harmful if swallowed / Harmful in contact with skin/ Harmful if inhaled / Causes severe skin burns and eye damage

 General Population Exposure:  

Exposure Scenario[1]
                                     Water
                                   Landfill
                                   Stack Air
                                 Fugitive Air
Release activity(ies)[2]; exposure calculation(s)[3]
                                Drinking Water
                                Fish Ingestion
                                    7Q10[4]
                                    CC = 65
                               PDM Days Exceeded
                                     LADD
                                      ADR
                                 (24-hr conc.)
                                     LADD 
                                (Annual conc.)
                                     ADR 
                                 (24-hr conc.)
                                     LADD 
                                (Annual conc.)

                                      ADR
                                     LADD
                                      ADR
                                     LADD
                                       
                                       
                                       
                                       
                                       
                                       
                                       

                                   mg/kg/day
                                   mg/kg/day
                                   mg/kg/day
                                   mg/kg/day
                                     μg/l
                                    # Days
                                   mg/kg/day
                             mg/kg/day (ug/m[3])
                             mg/kg/day (ug/m[3])
                             mg/kg/day (ug/m[3])
                             mg/kg/day (ug/m[3])
USE1: Max ADR: max acute eco
                                   2.14E-02
                                      ---
                                   2.09E-03
                                      ---
                                   9.67E+02
                                      ---
                                      ---
                                      ---
                                      ---
                                      ---
                                      ---
USE1: PDM1
                                      ---
                                      ---
                                      ---
                                      ---
                                   1.68E+02
                                      143
                                      ---
                                      ---
                                      ---
                                      ---
                                      ---
USE1: Max LADD
                                      ---
                                   1.92E-04
                                      ---
                                   4.38E-06
                                      ---
                                      ---
                                   2.09E-05
                                      ---
                                      ---
                                      ---
                                      ---
USE2: Max ADR: max acute eco
                                   2.65E-02
                                      ---
                                   2.59E-03
                                      ---
                                   1.20E+03
                                      ---
                                      ---
                                      ---
                                      ---
                                      ---
                                      ---
USE2: PDM1
                                      ---
                                      ---
                                      ---
                                      ---
                                   3.99E+02
                                      168
                                      ---
                                      ---
                                      ---
                                      ---
                                      ---
USE2: Max LADD
                                      ---
                                   3.04E-04
                                      ---
                                   6.94E-06
                                      ---
                                      ---
                                   3.32E-04
                                      ---
                                      ---
                                      ---
                                      ---
[1] Exposure scenario titles consist of release activity followed by exposure calculation abbreviation.
2 Release activities are from engineering report's Manufacturing (Mfg), Processing (Proc) and Use release activity labels. Multiple release activities are combined in one exposure scenario if their releases occur at same location.
[3] Exposure calculations are Acute Dose Rate (ADR), Lifetime Average Daily Dose (LADD), and Probabilistic Dilution Model (PDM).  There may be one, two, or all three exposure calculations per exposure scenario. CC is the aquatic concentration of concern.
[4] This column displays concentration values for the 7Q10 streamflow, which is defined as the average daily streamflow of the seven consecutive days of lowest flow within a ten year period.
         

 Consumer Exposure:  Consumer exposure is not expected

RISK CALCULATIONS:
 Worker Calculations: Low risk concern - MOE = 141.5 (benchmark MOE = 100)
   
   
   
   

   General Population Calculations: Low risk concern - MOE = 1402 (benchmark MOE = 100)
Focus General Population and Consumer MOE Calculations 
MOE = (POD x Abs Rate) / ((PDR x Abs Rate) / BW)   Benchmark (acceptable) MOE >=100
Exposure Scenarios and Values[1]
                            POD= NOAEL (mg/kg/ day)
                                       
                          POD Route Absorption Adj[2]
                                       
                          Acute Dose Rate (mg/kg/bw)
                                       
                       Exposure Route Absorption Adj[2]
                                       
                       Margin of Exposure (POD/PMN Dose)
GENERAL POPULATION RISK
Highest Doses

 
Drinking Water [2.14E-02]
                                      15
                                       x
                                     100%
                                      /
                                    0.0107
                                       x
                                     100%
                                       =
                                     1402
1 General Population and Consumer ingestion Acute Dose Rates are from the Exposure Report and are generated using E-FAST which assumes a 100% absorption rate, and uses an average adult body weight of 80 kg.  Consumer ADRs are generated using the Consumer Exposure Module within the E-FAST CBI version called "NCEM2" model.
2 Absorption adjustments for Focus: Assume 100%.
3 Benchmark (Acceptable) MOEs are 100 for NOAEL-based assessment 
   
   Consumer Calculations: Consumer risks not calculated because exposures are not expected.