### 1 **HAP benefits**

Due to data, resource, and methodology limitations, we were unable to estimate the
benefits associa ted with the 1,0 14 tons of hazardous air pollutants that would be reduced as a result of this rule. Available emissions data show that several different HAPs are emitted from stationary engines, either contained within the fuel burned or formed during the combustion process. The HAPs measured in emission tests conducted on diesel fired stationary RICE
include 1,3

- butadiene, acetaldehyde, acrolein, benzene, ethylbenzene, formaldehyde, n

- hexane, naphthalene, polycyclic aromatic hydrocarbons (PAHs) , polycycl ic organic matter, styrene, toluene, and xylene. Metallic HAPs from diesel fired stationary RICE that have been measured
include cadmium, chromium, lead, manganese, mercury, nickel, and selenium.

Although numerous HAPs may be emitted from RICE, a few H APs account for 80% of
the total mass of HAPs emissions from diesel stationary RICE. These HAPs are formaldehyde (25%), acetaldehyde (19%), PAH (18%), naphthalene (9%), and acrolein (9%).

Formaldehyde

Since 1987, EPA has classified formaldehyde as a pro bable human carcinogen based on evidence in humans and in rats, mice, hamsters, and monkeys. 1 

### EPA is currently reviewing recently published epidemiological data. For instance, research conducted by the National Cancer Institute (NCI) found an increased risk of nasopharyngeal cancer and lymphohematopoietic malignancies such as leukemia among workers exposed to formaldehyde. 2

, 3 

### In an analysis of the lymphohematopoietic cancer mor tality from an extended
follow

- up of these workers, NCI confirmed an association between lymphohematopoietic cancer risk and peak exposure s. 4 

### A recent National Institute of Occupational Safety and Health (NIOSH) study of garment workers also found increase d risk of death due to leukemia among workers exposed to formaldehyde. 5 Formatted: Highlight

1 U.S. EPA. 1987. Assessment of Health Risks to Garment Workers and Certain Home Residents from Exposure to

Formaldehyde, Office of Pesticides and Toxic Substances, April 1987. 

### Extended follow

- up of a cohort of British chemical workers

2 Hauptmann, M..; Lubin, J. H.; Stewart, P. A.; Hayes, R. B.; Blair, A. 2003. Mortality from lymphohematopoetic malignancies among workers in formaldehyde industries. Journal of the National Cancer Institute 95: 1615

- 1623.
3 Hauptmann, M..; Lubin, J. H.; Stewart, P. A.; Hayes, R. B.; Blair, A. 2004. Mortality from solid cancers among workers in formaldehyde industries. American Journal of Epidemiology 159: 1117

- 1130.
4 Beane Freeman, L. E.; Blair, A.; Lubin, J. H.; Stewart, P. A.; Hayes, R. B.; Hoover, R. N.; Hauptmann, M. 2009. Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries: The National Cancer Institute cohort. J. National Cancer Inst. 101: 751

- 761.
5 Pinkerton, L. E. 2004. Mortality among a cohort of garment workers exposed to formaldehyde: an update. Occup. Environ. Med. 61: 193

- 200. Comment [A1]: This is a list of 13 compounds. However just below, in highlight, 5 compounds are emphasized. What are the % mass releases of these other 8? It would make sense for EPA to list and discuss them in order of most to least. Its not clear that many of them are released . We note that the write up below discusses 5 compounds one of these i s not listed in highlight( POM) This is very confusing. We suggest a write up that includes the 5 in highlight. Unclear why the total list of 13 is provided without any
context.

### 2 did not find evidence of an increase in nasopharyngeal or lymphohematopoietic cancers, but a continuing statistically signif icant excess in lung cancers was reported. 6



### In the past 15 years there has been substantial research on the inhalation dosimetry for formaldehyde in rodents and primates by the CIIT Centers for Health Research (formerly the Chemical Industry Institute of Toxicology), with a focus on use of rodent da ta for refinement of the quantitative cancer dose

- response assessment. 7 , 8 , 9 

### CIIT’s risk assessment of formaldehyde incorporated mechanistic and dosimetric information on formaldehyde

. However, it should be
noted that recent Recent research published by EPA indicates that whe n two

- stage modeling assumptions are varied, resulting dose

- response estimates can vary by several orders of magnitude. 10 , 11 , 12 , 13 

### These findings are not supportive of interpreting the CIIT model results as providing a conservative (heal th protective) estimate o f human risk. 14 

### EPA research also
examined the contribution of the two

- stage modeling for formaldehyde towards characterizing the relative weights of key events in the mode

- of

- action of a carcinogen. For example, in one
part icular paper, the model

- based inference in the published CIIT study that formaldehyde’s direct mutagenic action is not relevant to the compound’s tumorigenicity was found not to hold under variations of modeling assumptions. 15

6 Coggon, D, EC Harris, J Poole, KT Palmer. 2003. Extended follow

- up of a cohort of British chemical workers exposed to formaldehyde. J National Cancer Inst. 95:1608

- 1615.

7 

### Conolly, RB, JS Kimbell, D Janszen, PM Schlosser, D Kalisak, J Preston, and FJ Miller. 2003. Biologically motivated computational modeling of formaldehyde carcinogenicity in the F344 rat. Tox Sci 75: 432

- 447.

8 

### Conolly, RB, JS Kimbell, D Janszen, PM Schl osser, D Kalisak, J Preston, and FJ Miller. 2004. Human respiratory tract cancer risks of inhaled formaldehyde: Dose

- response predictions derived from biologically

- motivated computational modeling of a combined rodent and human dataset. Tox Sci 82: 279

- 29 6.

9 

### Chemical Industry Institute of Toxicology (CIIT).1999. Formaldehyde: Hazard characterization and dose

- response assessment for carcinogenicity by the route of inhalation. CIIT, September 28, 1999. Research Triangle Park, NC.

10 U.S. EPA. Analysis of th e Sensitivity and Uncertainty in 2

- Stage Clonal Growth Models for Formaldehyde with

Relevance to Other Biologically

- Based Dose Response (BBDR) Models. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/R

- 08/103, 2008
11 Subramaniam, R; Chen, C; Crump, K; .et .al. (2008) Uncertainties in biologically

- based modeling of

formaldehyde

- induced cancer risk: identification of key issues. Risk Anal 28(4):907

- 923.
12 Subramaniam, R; Chen, C; Crump, K; .et .al. (2007). Uncertainties in the CIIT 2

- stage mode l for formaldehyde

induced nasal cancer in the F344 rat: a limited sensitivity analysis

- I. Risk Anal 27:1237
13 Crump, K; Chen, C; Fox, J; .et .al. (2008) Sensitivity analysis of biologically motivated model for formaldehyde

induced respiratory cancer in hu mans. Ann Occup Hyg 52:481

- 495.
14 Crump, K; Chen, C; Fox, J; .et .al. (2008) Sensitivity analysis of biologically motivated model for formaldehyde

induced respiratory cancer in humans. Ann Occup Hyg 52:481

- 495.
15 Subramaniam, R; Chen, C; Crump, K; .et .al. (2007). Uncertainties in the CIIT 2

- stage model for formaldehyde

induced nasal cancer in the F344 rat: a limited sensitivity analysis

- I. Risk Anal 27:1237 Comment [A2]: Edit made for tone. We note that all this information seems to get into a he said/she said type discussion which really seems inappropriate. EPA should simply say a new IRIS assessment will be forthcoming after review of all the science and not get into picking certain new studies to cite and certain new studies to dis

- credit. Comment [A3]: Unc lear exactly what this means. Do you mean protection of sensitive subpopulations? Preference would be to delete this as being an unnecessary interpretation but alternative approach would be to use a direct quote from the authors of the paper. Perhaps EPA s hould use these sentences from the paper: “However, the analysis presented herein shows that the Conolly et al. model is highly sensitive to uncertain model assumptions, and other reasonable assumptions are equally compatible with the data but lead to much higher risks. These risks can be considerably higher than what would be obtained using standard statistical modeling approaches ( USEPA, 2005 ). Thus, the formaldehyde human model cannot reasonably be used to narrow the range of low

- dose human risk over that predicted by the standard regulatory approach.” (in the discussion). The abstract has the following conclusion, but the context would need explaining for use here: “Thus, we conclude that estimates of human risk by Conolly et al. (2004) are extremely sensitive to modeling assumptions. This calls into question the basis for the Conolly et al. claim of de minimis human risk and suggests caution in using the model to derive h uman exposure standards for formaldehyde.” Comment [A4]: Need citation

### 3 Based on the developments of the last decade, i n 2004, the working group of the IARC concluded that formaldehyde is carcinogenic to humans (Group 1), on the basis of sufficient evidence in humans and sufficient evidence in experimental animals

- a higher c lassification than previous IARC evaluations

. After reviewing the currently available epidemiological evidence, the IARC (2006) characterized the human evidence for formaldehyde carcinogenicity as “sufficient,” based upon the data on nasopharyngeal can cers; the epidemiologic evidence on leukemia was characterized as “strong.” 16



### Formaldehyde exposure also causes a range of noncancer health effects, including irritation of the eyes (burning and watering of the eyes), nose and throa t. Effects from repeated

expos ure in humans include respiratory tract irritation, chronic bronchitis and nasal epithelial lesions such as metaplasia and loss of cilia. Animal studies suggest that formaldehyde may also cause airway inflammation

– including eosinophil infiltration into the airways. There are several studies that suggest that formaldehyde may increase the risk of asthma

– particularly in the

young. EPA is reviewing the recent work cited above from the NCI and NIOSH, as well as the analysis by the CIIT Centers for Health Research and other studies, as part of a reassessment of the human hazard and dose

- response associated with formaldehyde.

17 , 18



### Acetaldehyde is classified in EPA’s IRIS database as a probable human carcinogen,
based on nasal tumors in rats, and is considered toxic by the inhalation, oral, and intravenous

routes.

Acetaldehyde

19

16 International Agency for Research on Cancer (2006) Form aldehyde, 2

- Butoxyethanol and 1

- tert

- Butoxypropan

- 2

-

ol. Monographs Volume 88. World Health Organization, Lyon, France. 

### Acetaldehyde is reasonably anticipated to be a human carcinogen by the U.S. DHHS in
the 11 th 

### Report on Carcinogens and is classified as possibly carcinogenic to humans (Group 2B)

17 Agency for Toxic Substances and Disease Registry (ATSDR). 1999. Toxicological profile for Formaldehyde.

Atlanta, GA: U.S. Department o f Health and Human Services, Public Health Service. http://www.atsdr.cdc.gov/toxprofiles/tp111.html

18 WHO (2002) Concise International Chemical Assessment Document 40: Formaldehyde. Published under the

joint sponsorship of the United Nations Environment P rogramme, the International Labour Organization, and the World Health Organization, and produced within the framework of the Inter

- Organization Programme for the Sound Management of Chemicals. Geneva.
19 U.S. EPA (1988). Integrated Risk Information System File of Acetaldehyde. Research and Development,

National Center for Environmental Assessment, Washington, DC. This material is available electronically at http://www.epa.gov/iris/subst/0290.htm. Comment [A5]: Please provide IARC citation.

Comment [A6]: Please provide citation for all of the sentences in this paragraph..

### 4 by the IARC. 20 , 21



### The primary noncancer effects of exposure to acetaldehyde vapors include irritation of the eyes, skin, and respiratory tract. EPA is currently conducting a reassessment of cancer risk from inhalation exposure to acetaldehyde.

22 

### In shor t

- term (4 week) rat studies, degeneration of olfactory epithelium was observed at various concentration levels of acetaldehyde exposure. 23 , 24 

### Data from these studies were used by EPA to develop an inhalation reference concentration.
Some asthmatics have be en shown to be a sensitive subpopulation to decrements in functional expiratory volume (FEV1 test) and bronchoconstriction upon acetaldehyde inhalation. 25 

### The agency is currently conducting a reassessment of the health hazards from inhalation exposure to

a cetaldehyde.

POM is generally defined as a large class of organic compounds which have multiple benzene rings and a boiling point greater than 100 degrees Celsius. Many of the compounds included in the class of compounds known as POM are classified by EPA as probable human carcinogens based on animal data. One of these compounds, naphthalene, is discussed separately below. Polycyclic aromatic hydrocarbons (PAHs) are a subset of POM that contain only hydrogen and carbon atoms. A number of PAHs are known or suspected carcinogens

. EPA’s IRIS program has not evaluated the health effects of PAH’s, although ATSDR has conducted a
review of non

- cancer effects. Recent studies have found that maternal exposures to PAHs (a subclass of POM) in a population of pregnant women w ere associated with several adverse birth outcomes, including low birth weight and reduced length at birth, as well as impaired cognitive development at age three. Polycyclic Organic Matter (POM) Polyaromatic Hydrocarbons

26 , 27

20 U.S. Department of Health and Human Services National Toxi cology Program 11th Report on Carcinogens available at: http://ntp.niehs.nih.gov/go/16183. 

### EPA has not yet evaluated these recent studies

. PAHs can be

21 International Agency for Research on Cancer (IARC). 1999. Re

- evaluation of some organic chemicals, hydrazine, and hydrogen peroxide. IARC Monographs on the Evalua tion of Carcinogenic Risk of Chemical to Humans, Vol 71. Lyon, France.
22 U.S. EPA (1988). Integrated Risk Information System File of Acetaldehyde. This material is available electronically at http://www.epa.gov/iris/subst/0290.htm.
23 U.S. EPA. 2003. Inte grated Risk Information System File of Acrolein. Research and Development, National Center for Environmental Assessment, Washington, DC. This material is available electronically at http://www.epa.gov/iris/subst/0364.htm.
24 Appleman, L.M., R.A. Woutersen, and V.J. Feron. (1982). Inhalation toxicity of acetaldehyde in rats. I. Acute and subacute studies. Toxicology. 23: 293

- 297.
25 Myou, S.; Fujimura, M.; Nishi K.; Ohka, T.; and Matsuda, T. (1993) Aerosolized acetaldehyde induces histamine

- mediated bronchoc onstriction in asthmatics. Am. Rev. Respir.Dis.148(4 Pt 1): 940

- 943.
26 Perera, F.P.; Rauh, V.; Tsai, W

- Y.; et al. (2002) Effect of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population. Environ Health Perspect. 111: 201

- 205. Comment [A7]: This section should be replaced with a discussion that focuses on PAH’s only (like is done for n aphthalene)

Comment [A8]: Provide citation

— perhaps this is NTP?

### 5 harmful to your health un der some circumstances. Several of the PAHs, including benz[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, chrysene, dibenz[a,h]anthracene, and indeno[1,2,3

- c,d]pyrene, have caused tumors in laboratory anima ls when they breathed these substances in the air, when they ate them, or when they had long periods of skin contact with them. Studies of people show that individuals exposed by breathing or skin contact for long periods to mixtures that contain PAHs
and other compounds can also develop cancer. 28



### Naphthalene is found in small quantities in gasoline and diesel fuels. Naphthalene emissions have been measured in larger quantities in both gasoline and diesel exhaust compared with evaporative emissions from mobile sources, indicating it is primarily a product of
combustion. EPA , in 2004, released an external review draft of a reassessment of the inhalation carcinogenicity of naphthalene based on a number of recent animal carcinogenicity studie s. Naphthalene

29 

### The draft reassessment completed external peer review. 30 

### Based on external peer review comments received, additional analyses are being undertaken. This external review draft does not represent official agency opinion and was released solely for the purposes of external peer review and public comment. The National Toxicology Program listed naphthalene as "reasonably anticipated to be a human carcinogen" in 2004 on the basis of bioassays reporting clear evidence of carcinogenicity in rats and some evi dence of carcinogenicity in mice. 31 

### California EPA has released a new risk assessment for naphthalene, and the IARC has reevaluated naphthalene and re

- classified it as Group 2B: possibly carcinogenic to humans. 32

27 Perera, F.P.; Rauh, V.; Whyatt, R.M.; Tsai, W.Y.; Tang, D.; Diaz, D.; Hoepner, L.; Barr, D.; Tu, Y.H.; Camann, D.; Kinney, P. (2006) Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner

- city children. Environ Health Perspect 114: 1287

- 1292.
28 http://www.atsdr.cdc.gov/toxprofiles/phs69.html
29 U. S. EPA. 2004. Toxicological Review of Naphthalene (Reassessment of the Inhalation Cancer Risk), Environmental Protection Agency, I ntegrated Risk Information System, Research and Development, National Center for Environmental Assessment, Washington, DC. This material is available electronically at http://www.epa.gov/iris/subst/0436.htm.
30 Oak Ridge Institute for Science and Educatio n. (2004). External Peer Review for the IRIS Reassessment of the Inhalation Carcinogenicity of Naphthalene. August 2004. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=84403

31 

### National Toxicology Program (NTP). (2004). 11th Report on Carcinogens. Public Health Service, U.S. Department of Health and Human Services, Research Triangle Park, NC. Available from: http://ntp

- server.niehs.nih.gov.

32 

### International Agency for Research on Cancer (IARC). (2002). Monographs on the Evaluation of the Carcinog enic Risk of Chemicals for Humans. Vol. 82. Lyon, France.

### 6 Naphthalene also causes a number of chronic non

- cancer effects in animals, including abnormal cell changes and growth in respiratory and nasal tissues. 33



### EPA determined in 2003 that the human carcinogenic potential of acrolein could not be
determined because the available data were inade quate. No information was available on the carcinogenic effects of acrolein in humans and the animal data provided inadequate evidence of carcinogenicity. Acrolein

34 

### The IARC determined in 1995 that acrolein was not classifiable as to its carcinogenicity in humans

. 35



### Acrolein is extremely acrid and irritating to humans when inhaled, with acute exposure resulting in upper respiratory tract irritation, mucus hypersecretion and congestion. The intense irritancy of this carbonyl has been demonstrated , in 1957, during c ontrolled tests in human subjects, who suffer intolerable eye and nasal mucosal sensory reactions within minutes of

exposure. 36 

### These data and additional studies which are more recent and more reliable for determining safe exposure levels, regarding acute effects of human exposure to acrolein are
summarized in EPA’s 2003 IRIS Human Health Assessment for acrolein. 37 

### Evidence available from studies in humans indicate that levels as low as 0.09 ppm (0.21 mg/m 3 

### ) for five minutes may elicit subjective complaints of eye irritation with increasing concentrations leading to more extensive eye, nose and respiratory symptoms. 38 

### Lesions to the lungs and upper respiratory tract of rats, rabbits, and hamsters have been observed after subchronic exposure to acrolein. 39 

### Acute exposure effects in animal studies report bronchial hyper

- responsiveness. 40

33 U. S. EPA. 1998. Toxicological Review of Naphthalene, Environmental Protection Agency, Integrated Risk Information System, Research and Development, National Center for Environmental Assessment, Washington, DC. This material is available electronically at http://www.epa.gov/iris/subst/0436.htm 

### In a recent study, the

34 Integrated Risk Information System File of Acrolein. Research and Development, National Center for Environmental Assessment, Washington, DC. This mate rial is available at http://www.epa.gov/iris/subst/0364.htm

35 

### International Agency for Research on Cancer (IARC). 1995. Monographs on the evaluation of carcinogenic risk of chemicals to humans, Volume 63, Dry cleaning, some chlorinated solvents and other i ndustrial chemicals, World Health Organization, Lyon, France.

36 Sim VM, Pattle RE. Effect of possible smog irritants on human subjects JAMA165: 1980

- 2010, 1957.
37 U.S. EPA (U.S. Environmental Protection Agency). (2003) Toxicological review of acrolein in support of summary information on Integrated Risk Information System (IRIS) National Center for Environmental Assessment, Washington, DC. EPA/635/R

- 03/003. Available online at: http://www.epa.gov/nc ea/iris

. 38 Weber

- Tschopp, A; Fischer, T; Gierer, R; et al. (1977) Experimentelle reizwirkungen von Acrolein auf den Menschen. Int Arch Occup Environ Hlth 40(2):117

- 130. In German
39 Integrated Risk Information System File of Acrolein. Office of Research an d Development, National Center for Environmental Assessment, Washington, DC. This material is available at http://www.epa.gov/iris/subst/0364.htm
40 U.S. EPA (U.S. Environmental Protection Agency). (2003) Toxicological review of acrolein in support of summary information on Integrated Risk Information System (IRIS) National Center for Environmental Assessment, Washington, DC. EPA/635/R

- 03/003. Available online at: http://www.epa.gov/nc ea/iris

. Comment [A10]: Suggest deletion and replacing with the study in English upon which the IRIS RfC is based. This is more relevant

### 7 acute respiratory irritant effects of exposure to 1.1 ppm acrolein were more pronounced in mice with allergic airway disease by comparison to non

- dis eased mice which also showed decreases in respiratory rate. 41 

### Based on these animal data and demonstration of similar effects in humans (i.e., reduction in respiratory rate), EPA expects that indi viduals with compromised respiratory function (e.g., emphysema, asthma) are expected to b may be at e at increased risk of developing adverse responses to strong respiratory irritants such as acrolein.

In addition to the compounds describe d above, other compounds in gaseous hydrocarbon
and PM emissions from RICE engines would be affected by this rule . Information regarding the health effects of these compounds can be found in EPA’s IRIS database. Other Air Toxics

42



### The distance that these HAPs travel away f rom the emission source depends on several
factors. HAPs such as formaldehyde, acetaldehyde, PAHs, and acrolein are emitted as gases

. Regional photochemical model simulations have shown that gaseous HAPs like formaldehyde and acetaldehyde can be transpor ted hundreds of kilometers from their emissions source in distinct plumes (U.S. EPA, 2010b). Further, these emissions can contribute to regional airmasses with elevated concentrations of gaseous HAPs. These polluted airmasses can be transported
thousa nds of kilometers and affect locations well distant from the original emissions source. Some gaseous HAPs transform into particles in the atmosphere

. For HAPs emitted as particles, such as metals, the travel distance primarily depends on the size of t he particle and meteorological conditions, such as wind speed and precipitation. Fine particles can have an atmospheric half

- life of days to weeks and travel hundreds to thousands of kilometers, whereas ultrafine and coarse particles travel less than ten kilometers (U.S. EPA, 2009c).

**Carbon monoxide co**  **- benefits** 

Carbon monoxide (CO) exposure is associated with a variety of health effects. Without knowing the location of the emission reductions and the resulting ambient concentrations using
fine

- scale air quality modeling, we were unable to estimate the exposure to CO for nearby populations. Due to data limitations, we were unable to estimate the benefits associated with the 14,000 tons reductions in CO emissions that would occur as a result of this ru le

.

41 Morris JB, Symanowicz PT, Olsen JE, et al. 2003. Immediate sensory nerve

- mediated respiratory responses to irritants in healthy and allergic airway

- diseased mice. J Appl Physiol 94(4):1563

- 1571.
42 U.S. EPA Integrated Risk Information System (IRI S) database is available at: www.epa.gov/iris Comment [A11]: Caveat needed here as it is well known tha t animal models are not good surrogates for humans with emphysema or asthma thus this statement seems a bit odd and since no direct science supports it, need to be clear that this is an EPA inference.

Comment [A12]: What is this. If it is a TSD has it been peer reviewed? If not, please mention this and discuss plans for reviewing the modeling results. Because it is a TSD for a rule, does not automatically mean that it meets IQ standards and should be relied upon as sc ientifically correct in its conclusions. Peer review is important. Comment [A13]: Which ones? What percentile? What determines if this happens? Without knowing this then essentially we know nothing about how far a hap like formaldehyde or acetaldehyde will travel.

Comment [A14]: S ee comment above regarding peer review. This sentence seems very generic. If the bottom line is that we know nothing about how HAPs from RICE will travel, we should say that more clearly.