8/2//2010 

To: Docket 

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 for cancer 

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 the attached 

“Source Category and Facility Wide Risk Results for Pharmaceuticals” spreadsheet. The 

detailed risk modeling results for the facility-wide assessment is available in Appendix 6. 

We used the National Air Toxics Assessment (NATA) database for estimating facilitywide risks due to our lack of more recent facility-specific emissions data for some of the 

source categories included in the facility-wide 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 presented in the Source Category and 

Facility-wide Risk Results for Pharmaceuticals spreadsheet 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 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 

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 (REL) 

acetonitrile (AEGL-1) 

Number of Facilities With Potential for Acute 

Effects 4 N/A 

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. 
Source Category and Facility-Wide Risk Results for Pharmaceuticals 

FacilityID FacilityName City State 

Source 

Category 

MIR 

(in 1 

million)

Source 

Category

Resp_HI 

Source 

Category 

Neuro_HI 

FacilityWide MIR 

(in 1 

million)

FacilityWide 

MAX_HI

PHM_NEI46520 

ABBOTT HEALTH PRODS. INC. BARCELONETA PR 2 0 0 2 0.2 

PHM_NEI46507 

SCHERING-PLOUGH PRODS. L.L.C. LAS PIEDRAS PR 0.09 0 0 0.08 0.0002 L

PHM_NEI43464 

ABBOTT LABORATORIES 

NORTH CHICAGO IL 0.5 0.002 0.0002 0.5 0.002 

PHM_NEI7221 

MERCK & CO/CHEROKEE PLT RIVERSIDE PA 0.3 0.003 0.003 0.3 0.004 W

PHM_NEI6379 

MERCK & CO., INC. - RAHWAY, NEW JERSEY RAHWAY NJ 0.8 0 0.00003 0.8 0.009 W

PHM_NEI32109 

ELI LILLY AND COMPANY (LTC) INDIANAPOLIS IN 0.2 0.000 0.001 0.2 0.02 R

PHM_NEINJT$902 

SIEGFRIED (USA), INC. PENNSVILLE NJ 0.9 0.004 0.04 0.9 0.04 

NH

PHM_NEI34086 

TEVA PHARMACEUTICALS USA INC-MEXICO MEXICO MO 0.04 0.0007 0.0001 0.04 0.0008 

PHM_NEI38215 

BRISTOL-MYERS SQUIBB COMPANY DEWITT NY 0.07 0 0.000004 0.08 0.008 W

PHM_NEI33914 Upjohn Co Kalamazoo MI 0.2 0.001 0.0004 0.3 0.3 RPHM_NEI32342 

ELI LILLY & COMPANYTIPPECANOE LABS LAFAYETTE IN 0.4 0.01 0.0002 0.4 0.04 

PHM_NEI46527 

BRISTOL-MYERS SQUIBB MFG. CO.2 BARCELONETA PR 3 0.009 0.0006 4 0.1 R

PHM_NEI34261 

CLARIANT LIFE SCIENCE MOLECULESCLARIANT LIFE SCIE SPRINGFIELD MO 2 0.002 0.002 3 0.003 L

PHM_NEIIN12844 

ELI LILLY & COMPANY-CLINTON LABS CLINTON IN 0.9 0.005 0.01 1 0.06 
PHM_NEI12212 

CR-1, L.P. - DBA CARGILL NUTRIPRODUCTS EDDYVILLE IA 0.06 0.00002 0 0.09 0.0001 L

PHM_NEIIL0918580 COGNIS CORP KANKAKEE IL 3 0.00008 0.00004 6 0.04 

DH

PHM_NEICO0025 

ROCHE COLORADO CORP BOULDER CO 0.2 0.002 0.0003 0.4 0.008 L

PHM_NEI46514 

Squibb Manufacturing Inc Humacao PR 0.07 0.002 0 0.1 0.08 R

PHM_NEI6335 PFIZER INC GROTON CT 0.4 0.01 0.2 1 0.2 

NH

PHM_NEI34769 

MALLINCKRODT INC.-MALLINCKRODT INC. ST. LOUIS MO 0.006 0 0.0001 1 0.1 

NH

PHM_NEIIN0710002 

SCHWARZ PHARMA MFG.,INC. SEYMOUR IN 0.0000 0.0000007 0.00000001 0.0009 0.000002 L

PHM_NEI41424 ALBEMARLE CORP ORANGEBURG SC 0.0006 0.00006 0.0002 5 0.1 RPHM_NEI11906 

THE DOW CHEMICAL COMPANY U.S.A., MIDLAND MIDLAND MI 0.005 0 0 40 0.8 R

PHM_NEI29397 

ABBOTT LABORATORIES ABBOTT PARK IL 0 0 0 0.6 0.004 

DH

PHM_NEI7408 BISHOP FACILITY BISHOP TX 0 0.00009 0.00008 0.2 0.04 RPHM_NEIILT$9807 

VIT E MONOGLYCERIDE PLANT DECATUR IL 0 0 0 0.0 0.006 

DH

PHM_NEI44597 

CHATTEM CHEMICALS, INC. CHATTANOOGA TN 0.003 0.0001 0.003 0.0 0.003 

NH

Notes:  1. NATA results (facility-wide) are from the final 2005 NATA analysis, dated May 2010 and based on the 2005 NATA NEI. 

 RTR results (source category) are from RTR modeling conducted in April 2010 and based on 2002 (or earlier) data.

2. Facility closed down pharmaceutical operations in 2009 

Attachments: Appendix 1 Revised Emissions Inventory Support Memorandum  Appendix 6 Detailed Risk Modeling Results  Appendix 7 Acute Impacts Refined Analysis Figure