### 8/2//2010

To: Docket

From: Elaine Manning, Sect or 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; Mi neral Wool Production; Pharmaceuticals Production; and Printing and Publishing Industry rulemaking issued on October 10, 2008. The updated Table 3.9-1 Summary of Emissi ons 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 Faci lities 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 notic ed incorrect coordina tes 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 cha nge 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 th e source category alone as shown in the attached Summary of Source Category Level Risk table, additional analysis was performed to access the “facility-w ide” risk. The results of the residual risk associated with all categories at the know n facilities (facility-wide) ar e 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 faci lity-specific emissions data for some of the source categories included in the facility-w ide 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 pr esented in the Source Category and Facility-wide Risk Results for Pharmaceuticals spreadsheet are based on emissions, as identified in the NATA, from all emissions s ources 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 f acility is minimal; the cancer MIR is 0.005 in a million and the maximum noncancer HI is zero for respirat ory/neurological and 0.00001 for liver. In contrast, there are other facilities wher e the source category impacts dominate the facility-wide risk. For example, one of the f acilities 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

HAP a 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

Benzene 6 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

HAP a 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 Categor y 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 27 a 

### 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 Maximu m 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 20 09. 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 ma ximum individual lifetime

### Table 3.9-2. Summary of Source Categor y Level Risks for Pharmaceuticals

Result HAP “Drivers”

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



### Table 3.9-3. Summary of Acute Refined Re sults for Pharmaceuticals Production

Facilities

Refined Results MAXIMUM ACUTE HAZARD QUOTIENTS ACUTE DOSE-RESPONSE VALUES

HAP Max. 1-hr.

Air Conc.

(mg/m 3 ) Based on

REL Based on

AEGL-1/

ERPG-1 Based on

AEGL-2/

ERPG-2 REL (mg/m 3 ) AEGL-1 (1-hr) (mg/m 3 ) ERPG-1 (mg/m 3 ) AEGL-2 (1-hr) (mg/m 3 ) ERPG-2 (mg/m 3 )

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 availabl e 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 va lues which are not in the table do not ca rry any potential for posing acute health risks, based on an analysis of cu rrently available emissions data.

Notes on Acute Dose-Response Values: REL – California EPA reference exposure level for no advers e effects. Most, but not all, RELs are for 1-hour exposures. AEGL – Acute exposure guideline levels represent em ergency 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 wh ich 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 eff ects 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 developi ng irreversible or other serious health e ffects or symptoms which could impair an individual’s ability to take protective action.Source Category and Facility-WideRisk Results for PharmaceuticalsFacilityID FacilityName City StateSourceCategoryMIR(in 1million)SourceCategoryResp_HISourceCategoryNeuro_HIFacilityWide MIR(in 1million)FacilityWideMAX_HIFacility-WideHI_TYPEPercentSourcerisk isofFacilityWideriskPHM_NEI46520ABBOTT HEALTHPRODS. INC. BARCELONETA PR 2 0 0 2 0.2 Respiratory HI 109%PHM_NEI46507SCHERING-PLOUGHPRODS. L.L.C.LAS PIEDRAS PR 0.09 0 0 0.08 0.0002 Liver HI 106%PHM_NEI43464ABBOTTLABORATORIESNORTHCHICAGOIL 0.5 0.002 0.0002 0.5 0.002 Respiratory HI 105%PHM_NEI7221MERCK &CO/CHEROKEE PLTRIVERSIDE PA 0.3 0.003 0.003 0.3 0.004 Whole body HI 104%PHM_NEI6379MERCK & CO., INC. -RAHWAY, NEWJERSEY RAHWAY NJ 0.8 0 0.00003 0.8 0.009 Whole body HI 103%PHM_NEI32109ELI LILLY ANDCOMPANY (LTC) INDIANAPOLIS IN 0.2 0.000 0.001 0.2 0.02 Respiratory HI 100%PHM_NEINJT$902SIEGFRIED (USA),INC. PENNSVILLE NJ 0.9 0.004 0.04 0.9 0.04NeurologicalHI 100%PHM_NEI34086TEVAPHARMACEUTICALSUSA INC-MEXICO MEXICO MO 0.04 0.0007 0.0001 0.04 0.0008 Respiratory HI 92%PHM_NEI38215BRISTOL-MYERSSQUIBB COMPANYDEWITT NY 0.07 0 0.000004 0.08 0.008 Whole body HI 90%PHM_NEI33914 Upjohn Co Kalamazoo MI 0.2 0.001 0.0004 0.3 0.3 Respiratory HI 84%PHM_NEI32342ELI LILLY &COMPANYTIPPECANOE LABSLAFAYETTE IN 0.4 0.01 0.0002 0.4 0.04 Respiratory HI 82%PHM_NEI46527BRISTOL-MYERSSQUIBB MFG. CO.2BARCELONETA PR 3 0.009 0.0006 4 0.1 Respiratory HI 77%PHM_NEI34261CLARIANT LIFESCIENCEMOLECULESCLARIANT LIFESCIESPRINGFIELD MO 2 0.002 0.002 3 0.003 Liver HI 73%PHM_NEIIN12844ELI LILLY &COMPANY-CLINTONLABS CLINTON IN 0.9 0.005 0.01 1 0.06 Respiratory HI 72%PHM_NEI12212CR-1, L.P. - DBACARGILLNUTRIPRODUCTS EDDYVILLE IA 0.06 0.00002 0 0.09 0.0001 Liver HI 69%PHM_NEIIL0918580 COGNIS CORP KANKAKEE IL 3 0.00008 0.00004 6 0.04DevelopmentalHI62%PHM_NEICO0025ROCHE COLORADOCORPBOULDER CO 0.2 0.002 0.0003 0.4 0.008 Liver HI 59%PHM_NEI46514Squibb ManufacturingIncHumacao PR 0.07 0.002 0 0.1 0.08 Respiratory HI 58%PHM_NEI6335 PFIZER INC GROTON CT 0.4 0.01 0.2 1 0.2NeurologicalHI32%PHM_NEI34769MALLINCKRODTINC.-MALLINCKRODTINC. ST. LOUIS MO 0.006 0 0.0001 1 0.1NeurologicalHI 0%PHM_NEIIN0710002SCHWARZ PHARMAMFG.,INC. SEYMOUR IN 0.0000 0.0000007 0.00000001 0.0009 0.000002 Liver HI 0%PHM_NEI41424 ALBEMARLE CORP ORANGEBURG SC 0.0006 0.00006 0.0002 5 0.1 Respiratory HI 0%PHM_NEI11906THE DOWCHEMICALCOMPANY U.S.A.,MIDLAND MIDLAND MI 0.005 0 0 40 0.8 Respiratory HI 0%PHM_NEI29397ABBOTTLABORATORIES ABBOTT PARK IL 0 0 0 0.6 0.004DevelopmentalHI 0%PHM_NEI7408 BISHOP FACILITY BISHOP TX 0 0.00009 0.00008 0.2 0.04 Respiratory HI 0%PHM_NEIILT$9807VIT EMONOGLYCERIDEPLANT DECATUR IL 0 0 0 0.0 0.006DevelopmentalHIPHM_NEI44597CHATTEMCHEMICALS, INC.CHATTANOOGA TN 0.003 0.0001 0.003 0.0 0.003NeurologicalHINotes:1. NATA results (facility-wide) are fromthe 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 2009Attachments: Appendix 1 Revised Emissions Inventory Support MemorandumAppendix 6 Detailed Risk Modeling ResultsAppendix 7 Acute Impacts Refined Analysis Figure