9/8/2010 

To: Docket – ID No. EPA-HQ-OAR-2010-0600 

From: Elaine Manning, Sector Based Assessment Group 

Subject: Post Proposal Revisions for Pharmaceuticals Risk and Technology 

Assessment 

The attached minor revisions were made to the Pharmaceuticals source category 

risk assessment which was included in the proposal for the Group I Polymers and Resins; 

Marine Vessel Loading Operation; Mineral Wool Production; Pharmaceuticals 

Production; and Printing and Publishing Industry rulemaking issued on October 10, 2008. 

The updated Table 3.9-1 Summary of Emissions from the Pharmaceuticals Production 

Source Category, Table 3.9-2 Summary of Source Category Level Risk for 

Pharmaceuticals Production Facilities, and Table 3.9-3 Summary of Acute Refined 

Results for Pharmaceuticals Production Facilities reflecting the minor changes are 

attached. The most significant change from the October 10, 2008 proposal is the change 

in the maximum individual risk (MIR). During a review of facility source locations in 

the National Emissions Inventory (NEI) we noticed incorrect coordinates for a facility. 

Correction of the coordinates for this facility resulted in a change in the MIR from 10 to 

3. The attached Appendices 1, 6, and 7 provide the supporting information for the 

changes. 

We used a scaling factor of 25 percent to adjust for allowable emissions in the 

2008 proposal preamble. When the 25 percent scaling factor is applied to the updated 

MIR for this source category, the adjusted MIR could be as high as 4. Since the source 

category hazard index (HI) did not change from the 2008 proposal, the maximum 

adjusted HI for the source category is 0.3 as mentioned in the proposal preamble. 

In addition to the risk presented by the source category alone as shown in the 

attached Summary of Source Category Level Risk table, additional analysis was 

performed to access the “facility-wide” risk. The results of the residual risk associated 

with all categories at the known facilities (facility-wide) are presented in Appendix 6 

“Detailed Risk Modeling Results . We used the National Air Toxics Assessment 

(NATA) database for estimating facility-wide risks due to our lack of more recent 

facility-specific emissions data for some of the source categories included in the facilitywide analyses. Additionally, because we have not yet begun our thorough residual risk 

review for most source categories, we are unable at this time to estimate allowable 

facility-wide emissions. Thus, our facility-wide analysis is based solely on actual 

emissions. 
The facility-wide MIR and hazard HI available in Appendix 6 are based on 

emissions, as identified in the NATA, from all emissions sources at the identified 

facilities. The maximum facility-wide risks are estimated to be a cancer MIR of 40 in a 

million and a HI of 0.8, both of which occur at the same facility. The source category 

contribution to the facility-wide risk at this facility is minimal; the cancer MIR is 0.005 in 

a million and the maximum noncancer HI is zero for respiratory/neurological and 

0.00001 for liver. In contrast, there are other facilities where the source category 

impacts dominate the facility-wide risk. For example, one of the facilities with the 

highest source category cancer MIR (3 in a million) contributes 75% to its facility-wide 

cancer MIR of 4 in a million. 
Table 3.9-1 Summary of Emissions from the Pharmaceuticals Production Source Category 

Prioritized Inhalation Dose-Response Value 

Identified by OAQPS 

HAPa Emissions (tpy) 

Number of 

Facilities 

Reporting 

HAP (27 

facilities in 

data set) 

Unit Risk 

Estimate for 

Cancer? 

Reference 

Concentration 

for Noncancer? 

Health 

Benchmark 

Values for Acute 

Noncancer? 

PBHAP

? 

Methylene Chloride 388 19 Υ Υ Υ

Methanol 322 23 Υ Υ 

Acetonitrile 91 15 Υ Υ 

Toluene 90 18 Υ Υ 

Hexane 44 12 Υ Υ 

Ethylene Glycol 36 2 Υ 

Methyl Tert-Butyl Ether 31 8 Υ Υ Υ 

Hydrochloric Acid 11 11 Υ Υ 

N,N-Dimethylformamide 11 9 Υ Υ 

Ethylene Dichloride 3 3 Υ Υ Υ 

Xylenes (Mixture of o, m, 

and p Isomers) 5 8 Υ Υ 

Hydrogen Fluoride 5 2 Υ Υ 

Triethylamine 3 7 Υ Υ 

Methyl Chloride 3 3 Υ Υ 

Methyl Isobutyl Ketone 2 3 Υ 

Chloroform 2 5 Υ Υ 

Ethyl Benzene 1 6 Υ 

Glycol Ethers 1 4 Υ Υ 

Cyanide & Compounds 0.6 5 Υ 

Formaldehyde 0.6 7 Υ Υ Υ 

Hydrogen Cyanide 0.5 1 Υ Υ

Acetaldehyde 0.3 2 Υ Υ Υ 

Allyl Chloride 0.2 1 Υ Υ Υ 

Benzene6 0.2 5 Υ Υ Υ 

Chloroacetic Acid 0.1 1 Υ 

Lead & Compounds 0.1 3 Υ Υ

Manganese & Compounds 0.1 3 Υ 

Chlorobenzene 0.09 3 Υ Υ 

Phosgene 0.08 1 Υ Υ 

Cumene 0.06 1 Υ Υ 

1-Chloro-2,3-Epoxypropane 0.05 2 Υ Υ Υ 

Phenol 0.03 3 Υ Υ 

Acetophenone 0.02 2 

p-Dioxane 0.01 1 Υ Υ Υ 

Hydrazine 0.009 1 Υ Υ Υ 

Methyl Iodide 0.008 1 Υ 

Quinoline 0.008 1 
Table 3.9-1 Summary of Emissions from the Pharmaceuticals Production Source Category 

Prioritized Inhalation Dose-Response Value 

Identified by OAQPS 

HAPa Emissions (tpy) 

Number of 

Facilities 

Reporting 

HAP (27 

facilities in 

data set) 

Unit Risk 

Estimate for 

Cancer? 

Reference 

Concentration 

for Noncancer? 

Health 

Benchmark 

Values for Acute 

Noncancer? 

PBHAP

? 

PAH, total 0.005 3 Υ Υ

Phthalic Anhydride 0.004 1 Υ Υ 

Dimethyl Sulfate 0.002 1 Υ 

Cadmium & Compounds 0.0006 2 Υ Υ Υ

Ethylene Glycol Methyl 

Ether 0.0004 1 Υ Υ 

Mercury & Compounds 0.00003 1 Υ Υ Υ

Acetamide 0.000002 1 Υ

Acrolein 0.0000006 1 Υ Υ 

Naphthalene 0.00000004 1 Υ Υ 

Chromium (VI) 0.00000002 2 Υ Υ 

Nickel & Compounds 0.0000000003 1 Υ Υ Υ 

Chromium & Compounds 0.0000000002 1 Υ Υ 

Arsenic & Compounds 

(Inorganic Including 

Arsine) 0.00000000003 1 Υ Υ

Υ

 

Cobalt & Compounds 0.00000000001 1 Υ 

Selenium & Compounds 0.0000000000004 1 Υ 

Beryllium & Compounds 0.0000000000002 1 Υ Υ Υ 
Table 3.9-2. Summary of Source Category Level Risks for Pharmaceuticals 

Result HAP “Drivers” 

Facilities in Source Category 

Number of Major Source Facilities Estimated to 

be in Source Category 27 n/a 

Number of Facilities Identified in NEI and 

Modeled in post-NPRM Risk Assessment 27a

 n/a 

Cancer Risks 

Maximum Individual Lifetime Cancer Risk (in 1 

million) 3 ethylene dichloride 

Number of Facilities with Maximum Individual Lifetime Cancer Risk: 

 Greater than or equal to 100 in 1 million 0 n/a 

 Greater than or equal to 10 in 1 million 0 n/a 

 Greater than or equal to 1 in 1 million 4 ethylene dichloride, methylene 

chloride, hydrazine 

Chronic Noncancer Risks 

Maximum Neurological Hazard Index 0.2 manganese compounds 

Number of Facilities with Maximum Neurological Hazard Index: 

 Greater than 1 0 n/a 

Acute Noncancer Screening Results

Maximum Acute Hazard Quotient 

4 

2 

0.06 

methylene chloride (REL) 

acetonitrile (AEGL-1) 

acetonitrile (AEGL-2) 

Number of Facilities With Potential for Acute 

Effects 4 methylene chloride, methanol, chloroform, glycol ethers, acetonitrile 

Acute Noncancer Refined Results 

Maximum Acute Hazard Quotient 

2 

0.5 

chloroform/ glycol ethers(REL) 

acetonitrile (AEGL-1) 

Number of Facilities With Potential for Acute 

Effects 2 glycol ethers, chloroform 

Population Exposure 

Number of People Living Within 50 Kilometers 

of Facilities Modeled 36,000,000 n/a 

Number of People Exposed to Cancer Risk: 

 Greater than or equal to 100 in 1 million 0 n/a 

 Greater than or equal to 10 in 1 million 0 n/a 

 Greater than or equal to 1 in 1 million 2,000 n/a 

Number of People Exposed to Neurological Hazard Index: 

 Greater than 1 0 n/a 

Estimated Cancer Incidence (excess cancer cases 

per year) 0.0008 n/a 

Contribution of HAP to Cancer Incidence 

 methylene chloride 58% n/a 

 hydrazine 20% 

 ethylene dichloride 14% n/a 

Notes: 

a

 After the risk assessment was completed, it was learned that the Bristol Myers Squibb facility in Barceloneta, PR closed in 2009. Because the 

facility was operating at the time of the assessment, it remains in the data set at this time. It does not have the highest maximum individual lifetime 
Table 3.9-2. Summary of Source Category Level Risks for Pharmaceuticals 

Result HAP “Drivers” 

cancer risk estimate, the highest hazard index estimate, or the highest acute hazard quotient estimate. 

Table 3.9-3. Summary of Acute Refined Results for Pharmaceuticals Production 

Facilities 

Refined Results MAXIMUM ACUTE HAZARD 

QUOTIENTS ACUTE DOSE-RESPONSE VALUES 

HAP 

Max. 1-hr. 

Air Conc. 

(mg/m3

) 

Based on 

REL 

Based on 

AEGL-1/ 

ERPG-1 

Based on 

AEGL-2/ 

ERPG-2 

REL 

(mg/m3

) 

AEGL-1 

(1-hr) 

(mg/m3

) 

ERPG-1 

(mg/m3

) 

AEGL-2 

(1-hr) 

(mg/m3

) 

ERPG-2 

(mg/m3

) 

acetonitrile 10 n/a 0.5 0.02 22 540 

chloroform 0.3 2 n/a 0.001 0.15 310 310 

glycol ethers 0.2 2 n/a n/a 0.093 

methanol 25 1 0.1 0.001 28 690 690 2700 2700 

methylene chloride 18 1 0.08 0.001 14 690 690 1900 1900 

Notes on Refined Process: 

1) The screening was performed for all emitted HAP with available acute dose-response values. Only those pollutants whose 

screening HQs were greater than 1 for at least one acute threshold value are shown in the table. 

2) HAP with available acute dose-response values which are not in the table do not carry any potential for posing acute health 

risks, based on an analysis of currently available emissions data. 

Notes on Acute Dose-Response Values: 

 REL – California EPA reference exposure level for no adverse effects. Most, but not all, RELs are for 1-hour exposures. 

 AEGL – Acute exposure guideline levels represent emergency exposure (1-hour) limits for the general public. 

AEGL-1 is the exposure level above which it is predicted that the general population, including susceptible individuals, 

could experience effects that are notable discomfort, but which are transient and reversible upon cessation of exposure. 

AEGL-2 is the exposure level above which it is predicted that the general population, including susceptible individuals, 

could experience irreversible or other serious, long-lasting adverse health effects of an impaired ability to escape. 

 EPRG – Emergency Removal Program guidelines represent emergency exposure (1-hour) limits for the general public. 

ERPG-1 is the maximum level below which it is believed that nearly all individuals could be exposed for up to 1 hour 

without experiencing other than mild, transient adverse health effects. 

ERPG-2 is the maximum exposure below which it is believed that nearly all individuals could be exposed for up to 1 hour 

without experiencing or developing irreversible or other serious health effects or symptoms which could impair an 

individual’s ability to take protective action. 

Attachments: Appendix 1 Revised Emissions Inventory Support Memorandum 

 Appendix 6 Detailed Risk Modeling Results 

 Appendix 7 Acute Impacts Refined Analysis Figure