EXECUTIVE SUMMARY

Whitmire Micro

- Gen Research Laboratories, Inc., c/o Landis international, Inc. submitted a petition (0E7811) requ esting a tolerance exemption for carbon dioxide ( CAS Reg. No. 124

- 38

- 9). The petitioner requested an exemption from the requirement of a tolerance for residues of this chemical when used as an inert ingredient as a propellant in pre

- and post

- harvest appl ications under 40 CFR 180.910 and when applied to animals under 40 CFR 180.930 . EPA published the Notice of Filing for this petition in the Federal Register on December 22, 2010 (75 FR 80489). No comments were received in response to this notice.

Be cause carbon dioxide is the fourth most abundant gas in the Earth’s atmosphere and is a normal constituent of the atmosphere at about 0.03% (300 ppm), humans are continually exposed

to low levels daily. In addition, carbon dioxide can be found in a variety of foods and consumer products, including carbonated beverages, use in aerosol cans, and coffee packaging. It is a natural part of metabolism and is essential for plant and animal respiration. The U.S. Food and Drug Administration (FDA) has a ffirmed carbon dioxide as a Substance Generally Recognized as Safe (GRAS) and has approved its use as a direct food additive under (21 CFR 184.1240).

Carbon dioxide is used as an active ingredient in pesticide fumigants to control insects in

stored food and feed and currently has a tolerance exemption under 40 CFR 180.1049. It is currently approved for use as an inert ingredient propellant, buffering agent, etc., in pesticide products applied to non

- food sites such as wasp and ornamental flower sprays.

Carbon dioxide has been well studied and sufficient toxicity data and information are available from a variety of publicly available sources. In 1991, EPA published a Reregistration Eligibility Decision Document (RED) that included carbon dioxide. In addit ion, in April 2004, the EPA Office of Pesticide Programs’ Lower Risk Chemical Focus Group conducted a tolerance reassessment for carbon dioxide. The Report of Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision ( TRED) for Carbon Dioxide was issued in 2004. The Agency has searched and has not found any more recent information that would change the conclusions found in the RED and TRED. Therefore, these documents are being used here to evaluate the proposed exempti ons from the requirement of a tolerance for the use of carbon dioxide under 40 CFR 180.910 and 40 CFR 180.930. The following provides brief summaries of the toxicity findings discussed in the RED and TRED. Please refer to these documents for the full

desc ription. The RED and TRED are available on EPA’s website at http://www.epa.gov/pesticides/reregistration/status.htm

.

The toxicity database is sufficient for carbon dioxide. In terms of hazard, there are low concerns and no residual uncertainties regarding prenatal and/or postnatal toxicity. The toxicity studies showed that toxic effects of concern were observed only at high levels of carbon dioxide exposures including cardiac and deve lopmental effects. Nevertheless, these toxic effects are likely to be associated with the imbalance initiated by excess carbon dioxide upsetting the acid/base balance in the blood of the mother, as well as, the blood’s ability to transport oxygen to critic al tissues causing hypoxia in both mother and offspring. Therefore, these studies do not indicate an extra susceptibility in fetuses. For this reason, a safety factor analysis has not been used to assess risk and, therefore, the additional tenfold safety factor for the protection of infants and childrenwas reduced to 1X. As noted in the RED, “In moderate increases of carbon dioxide exposure, the

human body has rapid compensatory mechanisms to restore the normal balances through increased respiration to exhale it and restoration of normal acidity by the kidneys.” ( US EPA

, 1991).

The toxicology data for carbon dioxide are all derived from inhalation studies using high concentrations of carbon dioxide. Although these data show carbon dioxide does pose some hazard at concentrations well above normal atmospheric levels, these data have limited relevance to evaluating the safety of carbon dioxide residues in food. Because it is a gas, carbon dioxide would be expected to leave little or no residues on plant com modities, and, to the extent carbon dioxide is absorbed by the plant, it would likely be converted by the photosynthesis process into sugars and other organic compounds that are not of toxicological concern.

No residue data were submitted for carbon dioxi de; however, carbon dioxide is not expected to accumulate in treated raw agricultural commodities but rather diffuse into the atmosphere following application due to its physical and chemical properties. In the absence of reliable data regarding dietary ex posures to carbon dioxide, the Agency assessed dietary exposure using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCIDTM, Version 2.03). The model assumed that the inert ingredient is used on all

commodities and that residues will be present for every consumed commodity at the highest

tolerance level residue for all food forms (including meat, milk, poultry, and eggs), using default processing factors for dried commodities and assuming that 100% of all crops are “treated” with the inert ingredient. In addition, a default concentration of 100 ppb was assumed for the inert ingredient residues in drinking water. Considering the extremely conservative nature of this screening level model the Agency concluded that the estimated dietary (food and drinking water) exposures from carbon dioxide when used in pesticide formu lations are 10,000 fold less tha n the

amount of carbon dioxide naturally produc ed by the human body each day. As stated in the RED, “carbon dioxide is produced by the body’s metabolism and is always present in the body at about 6 percent concentration. An average adult human will produce more than 500 g of carbon dioxide daily under resting conditions, and will produce much more when active.”( US EPA

, 1991). Therefore the Agency concluded that the estimated dietary risk for carbon dioxide is not a concern.

In evaluating the potential for exposure from the use of carbon dioxide in residential pesticide products, dermal exposures of concern are not anticipated due to its dissipating nature. Inhalation is the primary route of exposure from carbon dioxide because of its high vapor pressure. In assessing the potential for increased risk to acute inhalation exposure fo rm indoor uses of carbon dioxide, when used as a propellant in residential pesticide products, EPA used its

conservative E

- FAST screening level model. The E

- FAST consumer aerosol paint can model scenario was used because potentially it resembles a typical use of a residential pesticide product using carbon dioxide as a propellant. This scenario estimates potential acute i nhalation exposure

over 20 minu tes of aerosol paint use in an enclosed utility room. The concentration of carbon dioxide in aerosol pain t products used in the E

- FAST model was 100%. The results of the

conservative E

- FAST modeling show a peak concentration potential of 4923 ppm (8860 mg/m 3 ).

Since the extre mely conservative E

- FAST model maximum levels of exposure are less tha n the

maximum permitted exposure limits established as safe by OSHA or NIOSH, the Agency concludes that inhalation exposures from the use of carbon dioxide as an inert ingredient in pesticide products are not a concern.EPA expects aggregate exposure to carbon dioxide to pose no appreciable risk to human

health given the natural occurrence of carbon dioxide in commonly

- consumed foods; its necessity

in the proper functioning of the human body; and its ubiquitous presence in the natural

environment. Furthermore , since t here are no concerns from dietary (food and drinking water) or residential exposures from the use of carbon dioxide as an inert ingredient as a propellant in pesticide product, no further aggregate assessments are necessary.

Environmental fate and ecolo gical effects of concern are not expected from the proposed use pattern of carbon dioxide as an inert ingredient in pesticide products.

Environmental Justice Statement

Potential areas of environmental justice concerns, to the extent possible, were consid ered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf

.

Taking into consideration all available information on carbon dioxide, it has been determined that there is a reasonable certainty that no harm to any population subgroup, including infants and children, will result from aggregate exposure to thi s chemical when used as an inert ingredient as a propellant in pre

- and post

- harvest applications under 40 CFR 180.910 and when applied to animals under 40 CFR 180.930, when considering dietary exposure and all other non

occupational sources of pesticide e xposure for which there is reliable information. Therefore, the exemption from the requirement of a tolerance for residues of carbon dioxide (CAS Reg. No. 124

- 38

- 9) when used as an inert ingredient as a propellant in pre

- and post

- harvest applications und er 40 CFR 180.910 and when applied to animals under 40 CFR 180.930, can be considered safe

under section 408 of the FFDCA.I

. BACKGROUND

In 1982, carbon dioxide was registered for use as an active ingredient (fumigant) to control

insects and mites in s tored grain. In 1980, EPA exempted carbon dioxide from tolerances in or on raw agricultural commodities (40 CFR 180.1049). In 1981, a food additive regulation was established for carbon dioxide for use after harvest in modified atmospheres for stored pro duct insect control on all processed agricultural commodities. (21 CFR 193.45) This exemption was redesignated in 1988 as 40 CFR 185.650. EPA consolidated these exemptions for carbon dioxide under 40 CFR 180.1049 in May, 2000. ( See 65 FR 33703 May 24, 200 0).

In 1991, EPA published a Reregistration Eligibility Decision Document (RED) that

included carbon dioxide. In addition, the Report of Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Carbon Di oxide

was issued in 2004. These documents are available on EPA’s website at http://www.epa.gov/pesticides/reregistration/status.htm

.

EPA has received a petition (#0E7811) from Whitmir e Micro

- Gen Research Laboratories, Inc., c/o Landis international, Inc. requesting a tolerance exemption for carbon dioxide ( CAS Reg.

No. 124

- 38

- 9). The petitioner requested an exemption from the requirement of a tolerance for

residues of this chemical whe n used as an inert ingredient as a propellant applied pre

- and post

harvest under 40 CFR 180.910 and applied to animals under 40 CFR 180.930. EPA published the Notice of Filing for this petition in the Federal Register on December 22, 2010 (75 FR 80489 ). No comments were received in response to this notice.

This document provides an assessment of carbon dioxide for the requested tolerance exemption, and is based on information and data submitted by the petitioner and on information

and data found i n a variety of publicly available sources including EPA’s Reregistration Eligibility

D Decision Document (RED, 1991); EPA’s Tolerance Reassessment Progress and Risk Management Decision for Carbon Dioxide (TRED, 2004), EPA’s Inventory of U.S. Greenhouse

Gas Emissions and Sinks 1990

- 2009 (EPA, 2011 ); and the National Library of Medicine’s, Hazardous Substances Data Base (HSDB, 2010).

In addition, a substantial amount of information and data are found in the public literature especially in reference to climate change such as the Intergovernmental Panel on Climate Change (IPCC) reports ( http://www.ipcc.ch/ ), as well as, EPA Factsheets f ound at http://www.epa.gov/climatechange/

.

II. Inert Ingredient Profile

A. Summary of Uses

Pesticide Uses

As an active ingredient, carbon dioxide is used indoors as a fumigant to control insects in

stored fo od and feed. It is also used as an ingredient in pesticide products such as wasp and hornet sprays, roach sprays, and ornamental plant sprays.Other Uses

C arbon dioxide is used for a wide variety of non

- pesticide applications. It is best known for

its use in the carbonation of beverages. It is also used in water softening, manufacturing of aspirin, as a propellant in aerosol cans and in the coffee packaging process. (TRED, 2004) In addition carbon dioxide is used in refrigeration, fire fighting, weld ing operations, rubber tumbling, mining operations, and oil well secondary recovery. (RED, 1991)

The U.S. Food and Drug Administration (FDA) permits a variety of uses of carbon dioxide including its use as a direct food additive in bottled water, sal ad dressing, mayonnaise, and use on medical devices (see 21 CFR for more information). FDA has also affirmed carbon dioxide as a substance Generally Recognized As Safe (GRAS) as a direct human food ingredient when used as a leavening agent, a processing ai d, and a propellant, aerating agent, and gas. (21 CFR 184.1240)

A. Physical Chemical Properties

Some of the physical and chemical characteristics of Carbon Dioxide, along with its structure and nomenclature, are found in Table 1.

Table 1. Physical and Chemical Properties of Carbon Dioxide

Parameter Value Reference

Structure (ChemIDPlus, 2011)

Molecular Formula C

- O2

CAS # 124

- 38

- 9

(NIOSH Pocket Guide, 20 10 ) Molecular Weight 44.0

Common Names Carbonic acid gas; Dry IceTable 1. Physical and Chemical Properties of Carbon Dioxide

Parameter Value Reference

Physical State Colorless Gas or colorless liquid; Solid form is utilized as dry ice

(HSDB , 2010) Melting Point (°C)

- 56.58 o C (triple point)

Boiling Point (°C)

- 78.5 o C/sublimation

Density Absolute Density: 0.1146 lb/cu ft at 25 deg C; (gas at 0 deg C) 1.976 g/L at 760 mm Hg

Vapor Pressure 4.83X10 +4 mmHg at 25 o C

Solubility in water (mL CO2/100 mL H2O at 760 mm Hg) 171 at 0 deg C; 88 at 20 deg C; 36 at 60 deg C

Henry's Law Constant 0.035 (mol.kg*bar) (NIST, 2008)

III. Hazard A ssessment

Carbon dioxide has been well studied and sufficient data covering major biological considerations are available from a variety of public sources. The primary sources of data for this assessment are the U.S. EPA’s Reregistration Eligibility Decision (RED) d ocument that included carbon dioxide which was completed in September of 1991; and the Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Carbon Dioxide issued by EPA in 2004. The Agency has searched and has not found any more recent information that would change the conclusions found in these documents. Therefore, these documents are being used here to evaluate the proposed exemption from the requirement of a

tolerance for use as an inert ingredient as a propellant applied pre

- and post

- harvest under 40 CFR 180.910 and applied to animals under 40 CFR 180.930. The following provides brief summaries of the toxicity findings discussed in the RED and TRED. Please refer to these documents for the full description. They are available on EPA’s website at http://www.epa.gov/pesticides/reregistration/status.htm

.

A. Toxicity

All the available acute studies evaluat ed in the RED used the inhalation route of administration. The acute inhalation toxicity studies showed that effects of concern only occurred at very high concentrations of carbon dioxide ( US EPA, 1991).

As noted in the RED, “Subchronic exposure of laboratory animal species to various

concentrations of carbon dioxide h as resulted in different effects. Guinea pigs exposed to 15 percent carbon dioxide for 7 days lost weight at first but later returned to normal weight. They also had higher blood corticosteroid s, lower adrenal epinephrine, decreased adrenal cholesterol, higher arterial free fatty acids, and decreased lymphocytes in the first 3 days of exposure” ( US

EPA , 1991)“Rats exposed to 10 percent carbon dioxide for 30 days had a weight loss of 14

- 27 percent ;

those exposed to 20

- 25 percent for 34 days had a 50 percent loss. The weight losses were attributed to the reduced food intake. The weight was regained when the rats returned to a normal atmosphere” ( US EPA , 1991)

“No effects were seen in male rhesus mon keys that spent 93 days in an atmosphere with 3 percent carbon dioxide”. ( US EPA , 1991)

In chronic toxicity studies, some adverse effects on sperm production were found when animals were given concentrated doses of carbon dioxide higher than the levels norm ally breathed in air. The RED noted that “when pregnant rats were exposed to 6 percent carbon dioxide for one full day, 23.4 percent of the offspring had cardiac abnormalities, and there was also an increased incidence of skeletal malformations (10.9 perc ent). Vertebral column malformations were reported in rabbits when the pregnant dams were exposed to 10

- 13 percent carbon dioxide. Pregnant guinea pigs exposed to 0.48 percent carbon dioxide for 10 minutes daily for 20 days had a high number of miscarria ges and flaccid paralysis of the hind limbs in the pups carried to term. Another group exposed to 0.42 percent carbon dioxide for 1 hour daily for 30 days had no miscarriages, but many of the offspring were microcosmic and many

of these had neuromuscular defects of the hind limbs.” ( US EPA , 1991) These toxic effects are likely to be associated with the imbalance initiated by excess carbon dioxide upsetting the acid/base balance in the blood of the mother, as well as, the blood’s ability to transport oxygen

t o critical tissues causing hypoxia in both mother and offspring. Therefore, these studies do not

indicate an extra susceptibility in fetuses.

The toxicology data for carbon dioxide are all derived from inhalation studies using high

concentrations of carbo n dioxide. Although these data show carbon dioxide does pose some hazard at concentrations well above normal atmospheric levels, these data have limited relevance to evaluating the safety of carbon dioxide residues in food. Because it is a gas,

carbon di oxide would be expected to leave little or no residues on plant commodities, and, to the extent carbon dioxide is absorbed by the plant, it would likely be converted by the photosynthesis process into sugars and other organic compounds that are not of toxi cological

concern.

B. Metabolism:

The RED reported that “carbon dioxide is produced by the body’s metabolism and is always present in the body at about 6 percent concentration. An average adult human will produce more than 500 g of carbon dioxide daily under resting conditions, and will produce much more when active.” ( US EPA , 1991) Additional carbon dioxide reduces the blood pH (acidifies the blood) which reduces hemoglobin’s affinity for oxygen. Therefore, the oxygen transport capacity of the blood is r educed. This is known as the Bohr Effect. (More information on the Bohr Effect can be found in the Textbook of Medical Physiology 10 th edition, Guyton and Hall, 2000). This, as noted in the RED, “stimulates breathing, which exhales the carbon

dioxide carri ed to the lungs from the cells by the blood

- stream. An increase in carbon dioxide concentration stimulates the heart rate, increases the blood pressure, increases adrenalin flow, and relaxes the vascular smooth muscles. In addition, carbon dioxide reacts with water in thebody to form carbonic acid, which dissociates to hydrogen ion and bicarbonate. An increase in

carbon dioxide in the body increases acidity, and then the kidneys act to restore normal acidity.” (RED, 1991)

IV. FQPA Safety Factor considerat ions

In general . Section 408(b)(2)(c) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the FQPA safety factor (SF). In applying th is provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA support the choice of a

different factor.

The toxicity database is sufficient for carbon dioxide. In terms of haza rd, there are low concerns and no residual uncertainties regarding prenatal and/or postnatal toxic ity. The toxicity

studies show that toxic effects of concern were observed only at high levels of carbon dioxide exposures including cardiac and developmental effects. Nevertheless, these toxic effects are likely to be associated with the imbalance initiated by excess carbon dioxide upsetting the acid/base balance in the blood of the mother, as well as, the blood’s ability to transport oxygen to critical

tissue s causing hypoxia in both mother and offspring. Therefore, these studies do not indicate an extra susceptibility in fetuses and there is no concern at this time for increased sensitivity to infants and children to carbon dioxide when used as an ingredient in pesticide formulations. For the same reason, a safety factor analysis has not been used to assess risk and, therefore, the additional tenfold safety factor for the protection of infants and children was reduced to 1X. As noted in the RED, “In moderat e increases of carbon dioxide exposure, the human body has rapid compensatory mechanisms to restore the normal balances through increased respiration to exhale it and restoration of normal acidity by the kidneys.” ( US EPA , 1991).

V. Aggregate Exposure

In examining aggregate exposure, the FFDCA section 408 directs EPA to consider available information concerning exposures from the pesticide residue in food and all other non

occupational exposures, including drinking water from ground water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses). For carbon dioxide, a qualitative assessment for all pathways of human exposure (food, drinking water, and residential) is appropriate given the lack of human health concerns associated with exposure to this chemical as an inert ingredient in pesticide formulations.

Because carbon dioxide is the fourth most abundant gas in the Earth’s atmosphere and is a normal constituent of the atmosphere at about 0 .03% (300 ppm), humans are continually exposed to low levels by both dermal and inhalation routes. Exposure to carbon dioxide occurs daily from using a variety of foods and consumer products, including carbonated beverages, use in aerosol cans, coffee pac kaging, etc. Carbon dioxide has been affirmed by FDA as a substance GenerallyRecognized as Safe (GRAS) and as an indirect food additive in such foods as salad dressings,

mayonnaise, and bottled water.

A. Dietary Exposure(From Food and Drinking Water):

In evaluating dietary exposure to carbon dioxide, EPA considered exposure under the proposed exemption from the requirement of a tolerance. EPA assessed dietary exposures from carbon dioxide in food and drinking water as follows:

No residue data were submitted for carbon dioxide; however, carbon dioxide is not expected to accumulate in treated raw agricultural commodities but rather diffuse into the atmosphere following application due to its physical and chemical properties. In th e absence of reliable data regarding dietary exposures to carbon dioxide, the Agency assessed dietary exposure using its highly conservative Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCIDTM, Version 2.03 )

. Thi s approach uses surrogate information to derive upper bound exposure estimates for the subject inert ingredient. Upper bound exposure estimates are based on the highest tolerance for a given commodity from a list of high

- use insecticides, herbicides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the absence of residue data is contained in the memorandum entitled “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drink ing Water) Dietary Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA

- HQ

OPP

- 2008

- 0738.

The Agency believes the assumptions used to estimate dietary exposures le d to an extremely conservative assessment of dietary risk due to a series of compounded conservatisms. For example, the model assumes that the inert ingredients are used on all commodities and that residues will be present for every consumed commodity at the highest tolerance level residue for all food forms (including meat, milk, poultry, and eggs), using default processing factors for dried

commodities and assuming that 100% of all crops are “treated” with the inert ingredient. In
addition, a default c oncentration of 100 ppb was assumed for the inert ingredient residues in drinking water. Accordingly, although sufficient information to quantify actual residue levels in food is not available, the compounding of these conservative assumptions will lead to a significant exaggeration of actual exposures. EPA does not believe that this approach underestimates exposure in the absence of residue data. Considering the extremely conservative nature of this screening level model the Agency concluded that the esti mated dietary (food and drinking water) exposures from carbon dioxide when used in pesticide formulations are 10,000 fold less than exposures that are naturally produced by the human body each day;. As stated in the RED, “carbon dioxide is produced by th e body’s metabolism and is always present in the body at about 6 percent concentration. An average adult human will produce more than 500 g of carbon dioxide daily under resting conditions, and will produce much more when active.”( US EPA , 1991).

Therefore th e Agency concluded that the estimated dietary risk for carbon dioxide is not a concern.B. N on
- D ietary E

xposure

.

The term “residential exposure” is used in this document to refer to non

- occupational, non

dietary exposure (e.g., textiles (clothi ng and diapers), carpets, swimming pools, and hard surface disinfection on walls, floors, tables).

Dermal Exposure . I n evaluating the potential for exposure from the use of carbon dioxide in residential pesticide products, dermal exposures of concern are not anticipated due to its physical and chemical properties and dissipating nature.

Inhalation Exposure

. Inhalation is the primary route of exposure from carbon dioxide because of its high vapor pressure. Because of the potential increased risk to acute inhalation exposure from indoor uses, EPA used its conservative E

- FAST screening level model to estimate the potenti al for inhalation exposures from indoor uses of carbon dioxide as a propellant in residential pesticide products. E

- Fast was developed by EPA’s Office of Pollution, Prevention and Toxics as a tool to

estimate concentrations of chemicals released from cons umer products. Modeled estimates of concentrations and doses are designed to significantly overestimate exposures for use in a screening level assessment. For carbon dioxide, E

- FAST’s aerosol paint scenario was selected because it potentially resembles a use of a residential pesticide product using carbon dioxide as a propellant. This scenario estimates potential acute inhalation exposure over 20 minutes of aerosol paint use in an enclosed utility room. The Agency considers an acute inhalation exposure t o be a single event occurring over a period of less than 24 hours. In this case, the E

- FAST model generated estimates of exposure are expected to be greater than what is reasonably anticipated

from the use of carbon dioxide as an inert ingredient in resid ential

- use pesticide products. The concentration of carbon dioxide in aerosol paint products used in the E

- FAST model was 100%.

The results of the conservative E

- FAST modeling show a peak concentration potential of 4923 ppm (8860 mg/m 3 ). (Model results a re provided in Appendix A).

EPA does not expect actual exposure from residential use of carbon dioxide as a propellant

as an inert ingredient in pesticide products to exceed these modeling estimates ( peak concentration potential of 4923 ppm (8860 mg/m 3 ) ) and expects that outdoor exposure concentrations would also

be lower. The Occupation Safety and Health Administration (OSHA) evaluated high levels of carbon dioxide in certain occupations settings and established a permissible exposure limit of 0.5% (or 5 ,000 ppm) for the maximum allowable concentration of carbon dioxide in air for eight hours

continuous exposure; and t he National Institute for Occupational Safety and Health (NIOSH) has recommended a maximum concentration to which operating personnel may b e exposed for a short period of time as 3.0% (or STEL of 30,000 ppm) fo r a 15 minute exposure interval (NIOSH, 2010). Since the extremely conservative E

- FAST model maximum levels of exposure are less than the limits established by OSHA or NIOSH, the Agenc y concludes that inhalation exposures from the use of carbon dioxide as an ingredient in pesticide products are not a concern.

C. Cumulative Exposure

Cumulative effects from substances with a common mechanism of toxicity

. Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revokea tolerance, the Agency consider “available information” concerning the cumulative effects of a

particular pesticide's residues and “other substances that have a common mechanism of toxicity.”

EPA has not found carbon dioxide to share a common mechanism of toxicity with any other substances, and the carbon dioxide do es not appear to produce a toxic metabolite produced by other substances. For the purp oses of this tolerance action, therefore, EPA has assumed that the carbon dioxide do not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative

.

VI

. Aggregate Risks and Détermination of Safety

EPA expects aggregate exposure to carbon dioxide to pose no appreciable risk given the natural occurrence of carbon dioxide in commonly

- consumed foods; its necessity to the proper functioning of the body; and its ubiquitous presence in the natural environment. Furthermore,

since there are no concerns from dietary (food and drinking water) or residential exposures from the use of carbon dioxide as an inert ingredient as a propellant in pesticide product, no further

aggregate assessments are necessary.

Taking into consideration all availab le information on carbon dioxide, EPA has determined that there is a reasonable certainty that no harm to any population subgroup will result from aggregate exposure to carbon dioxide under reasonable foreseeable circumstances. Therefore, the establishment of an exemption from tolerance f or residues of carbon dioxide (CAS Reg. No. 124

- 38

- 9) when used as an inert ingredient as a propellant in pesticide formulations applied pre

- and

post

- harvest under 40 CFR 180.910 and when applied to animals under 40 CFR 180.930 is safe

under FFDCA section 408.

VII

. Environmental Fate Ex posure

Carbon dioxide is a naturally occurring substance that’s physical and chemical properties

are well understood. The average person, through the natural process of breathing, produces approximately 1 kg of carbon dioxide per day. (EPA’s Climate Change website; http://www.epa.gov/climatechange/ ). It is one and one half times as dense as air and is very volatile with a vapor pressure of 4.83x10 +4 mm Hg at 25 o C (HSDB, 2010). It is typically found in air at concentrations of 0.03% and is the fourth most abundant gas in the Earth’s atmosphere. ( US

EPA , 1991)

. C arbon dioxide is a major component of the global carbon cycle by which it is exchanged in the atmosphere with oceans, land biotic, marine life and mineral reservoirs . (EPA,

20 11 )

When considering the use of carbon dioxide as an inert ingredient in pesticide products, the Agency concludes that it is unlikely that there would be any increase in measurable levels of carbon dioxide from the proposed pesticide uses that would add significantly to levels already present in the environment. Therefore, no environmental fate o r ecological effects of concern are expected from the use of carbon dioxide from the proposed use pattern as an inert ingredient inpesticide products. In addition, the environmental fate and ecological effects of carbon dioxide

when used as an active ingr edient was assessed in the Agency’s 1991Reregistraiton Eligibility document (RED). This document can be found at www.regulations.gov

.

X . Enviro n mental Justice

Potential areas of environmental justice concern s, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line wit h OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensi ve data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant . Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post application are evaluated.

Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

XI. Occupational Exposure

As stated in the RED, “Indoor use of carbon dioxide end

- use products as fumigants for postharvest treatment of raw and processed food commodities and cargo areas poses potential exposure risks for workers. Primary exposure hazards are associated with worker reentry into confined/enclosed spaces. Carbon dioxide gas may collect and be present in significantly higher concentrations in poorly ventilated depressions in grain bins, shafts, etc. and sites where

re circulation of air is minimal. Studies of workers exposed to high levels of carbon dioxide in other industries indicate that confirmatory air monitoring is essential in confined spaces. Even with ventilation systems present to purge areas of excess carbo n dioxide, some system design may be inadequate to reduce levels to the OSHA permissible exposure level (PEL of 10,000 ppm. Ventilation systems need to be periodically tested to determine system adequacy.” ( US EPA , 1991)

“Product labels must recommend air m onitoring while treated areas are being ventilated to reduce ambient levels of carbon dioxide. This monitoring will permit determination of post

application inhalation exposure levels at indoor use sites. During the following ventilation activities, sho rt

- term reentry of more than 15 minutes into treated areas may not occur prior to carbon dioxide levels falling below the OSHA short

- term exposure limit, STEL = 30,000 ppm, within the breathing zone for workers. Monitoring shall also be required for the l owest work areas within enclosed/confined spaces.” ( US EPA , 1991) Appropriate respiratory protection should beprovided during use, re

- entry, and emergencies as necessary.

XII. Human Studies

The RED c ited some human studies from the public literature to support the risk assessment; however, EPA does not rely solely on these studies for its risk assessment.

XIII. International limits (If any)

In making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international m aximum r esidue l imits (MRLs) established by the Codex Alimentarius Commission (Codex), as required by FFDCA section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and Agriculture Organization/World Health Organization food standards program, and it is recognized as an interna tional food safety

standards

- setting organization in trade agreements to which the United States is a party. EPA may establish a tolerance that is different from a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain the reasons for depar ting from the Codex level

.

The Codex has not established a MRL for carbon dioxide.XIV. REFERENCES

U.S. Environmental Protection Agency. Reregistration Eligibility Document (RED) Carbon and

Carbon Dioxide. 09/1991 http://www.epa.gov/oppsrrd1/reregistration/carbon_dioxide/

U.S. Environmental Protection Agency. Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Ri sk Management Decision (TRED) for Carbon Dioxide.

04/07/04 http://www.epa.gov/oppsrrd1/REDs/co2_tred.pdf

U.S. Environmental Protection Agency. RED Factsheet, Carbon Dioxide. 09/1991 http://www.epa.gov/oppsrrd1/REDs/factsheets/4019_co2fact.pdf

U.S. Environmental Protection Agency. Draft Inventory of U.S. Greenhouse Gas Emissions and

Sinks: 1990

- 2009. EPA 430

- R

- 11

- 005. 02/15/11 http://www.epa.gov/climatechange/emissions/usinventoryreport.html

U.S. Environmental Protection Agency. Climate Change. January 2011 http://www.epa.gov/climatechange/

U.S. Environmental Protection Agency. Office of Prevention, Pesticides & Toxic Substances;

Office of Pollution Prevention and Toxics. E

- FAST, Exposure, Fate Assessment Screening Tool. Last website update: March 2007. http://www.epa.gov/opptintr/exposure/pubs/efast.htm

National Institute of Standards and Technology. Carbon Dioxide. 2008. Retrieved on 01/18/11. http://webbook.nist.gov/cgi/cbook.cgi?ID=C124389&Mask=10

National Library of Medicine, National Institute of Health. Hazardous Substances Data Base (HSDB). April 2010. http: //www.toxnet.nlm.nih.gov

U.S. National Library of Medicine, National Institutes of Health. ChemID Plus. 2011 http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp

National Institute for Oc cupational Safety and Health (NIOSH). NIOSH Pocket Guide to Chemical

Hazards: Carbon dioxide. November 2010. Retrieved on 01/18/11 http://www.cdc.gov/niosh/npg/npgd0103.html

Guyton, Arthur and John H all. Textbook of Medical Physiology 10 th Edition . Philadelphia, PA: Saunders, 2000.

IPCC (2007) Climate Change 2007: The Physical Science Basis. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. S. Solomon , D. Qin, M. Manning, Z. Chen, M. Marquis, K.B. Averyt, M. Tignor and H.L. Miller (eds.). Cambridge University Press. Cambridge, United Kingdom 996 pp. ( http://www.ipcc.ch/APPENDIX A: E

- FAST Results for Carbon Dioxide 100% Latex Paint (Inhalation)

CEM Inputs ID Number: tmpcas

Product: unknown Chemical Name: carbon dioxide

Scenario: Aerosol Paint Population: Adult

Molecular Weight (g/mole): 44 Vapor Pressure (torr): 4.83e+04

Consumer Product Weight Fraction

- Central Tendency (unit less): 1 Consumer Product Weight Fraction

- High

- End (unit less): 1

Inhalation Inputs

Frequency of Use (chronic) (events/yr): 6 Exposure Duration (chronic) (years): 11

Frequency of Use (acute) (events/day): 1 Exposure Duration (acute) (days): 1

Mass of Product Used per Event

- Central Tendency (g): 227 Mass of Product Used per Event

- High

- End (g): 738

Inhalation Rate During Use (m 3 /hr): 1.1 Duration of Event

- Central Tendency (hours/event): 0.333

Inhalation Rate After Use (m 3 /hr): 0.55 Duration of Event

- High

- End (hours/event): 1

Zone 1 Volume (m 3 ): 20 Whole House Volume (m 3 ): 369

Air Exchange Rate (air exchanges/hr): 0.45 Body Weight (kg): 71.8

Portion of Aerosol in Air (unit less): 0.01

Activity Patterns

User: 1 1 1 1 1 1 1 2 3 5 5 4 2 4 6 7 4 2 2 7 4 4 4 1

Non

- User: 1 1 1 1 1 1 1 1 3 2 4 4 2 4 7 7 4 2 2 7 4 4 4 1

Hour:0 6 12 18

Start Time: 9 Room of Use: 5. Utility Room

Dermal Inputs

There are no Dermal inputs for this scenario.

Averaging Time (chronic) (days): 2.74e+04 Averaging time (acute) (days) : 1CEM Inhalation Exposure Estimates

ID Number: tmpcas

Scenario: Aerosol Paint Population: Adult

Exposure Duration (years) chronic: 11 Exposure Duration (days) acute: 1

Exposure Units Result AT (days)

Chronic Cancer

LADD pot (mg/kg

- day) 1.13e

- 01 2.74e+04

LADC pot (mg/m 3 ) 3.53e

- 01 2.74e+04

Acute

ADR pot (mg/kg

- day) 1.38e+02 1

Cp pot (mg/m 3 ) 8.86e+03 NA

LADD

- Lifetime Average Daily Dose(mg/kg

- day)

daddsdfsfsdfsdfsfd

sdfsadf LADC

- Lifetime Average Daily Concentration (mg/m 3 )

ADR

- Acute Dose Rate (mg/kg

- day) Cp

- Peak Concentration (mg/m 3 )

Note: 75 years = 2.738e+04 days pot

- potential dose

Note: The general Agency guidance for assessing short

- term, infrequent events (for most chemicals, an exposure of less than 24

hours that occurs no more frequently than monthly) is to treat such events as independent, acute exposures rather than as

c hronic exposure. (Methods for Exposure

- Response Analysis for Acute Inhalation Exposure to Chemicals (External
Review Draft). EPA/600/R

- 98/051. April 1998