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EPA REGISTRATION DIVISION CO MPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [P.V. Shah 703-308-1846]

INSTRUCTIONS: Please utilize this outline in p reparing the pesticide petition. In

cases where the outline element does not apply, please insert “NA-Remove” and

maintain the outline. Please do not chan ge the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green , i.e., “ [insert company name] ,” with the information specific to your action.

TEMPLATE:

Whitmire Micro-Gen Research Laboratories, Inc.

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from Whitmire Micro-Gen Research Laboratories, Inc., c/o Landis International, Inc. P.O. Box 5126 Valdosta, GA 31603-5126 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U. S.C. 346a(d), to amend 40 CFR part 180.

(Options (pick one))

1. by establishing a tolerance for residues of

2. to establish an exemption from the requirement of a tolerance for

Carbon Dioxide (CAS Reg. No. 124-38-9) under 40 CFR 180.910 and 40 CFR 180.930 when used as an inert ingredient as a propellant in pesticide formulations. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2 ) of FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this tim e or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry NA-Remove

1. Plant metabolism. NA - Remove

2. Analytical method. NA - Remove

3. Magnitude of residues. NA - Remove2

B. Toxicological Profile Carbon dioxide, CAS No. 124-38- 9, is a clear, colorless, odorless, noncombustible gas at standa rd temperature and pressure. Carbon Dioxide has a molecular formula of CO2, a molecular weight of 44.01 g/mole. Carbon dioxide in the solid state is known as dry ice and has a sublimation temperature of -78.5°C (-109.3°F). Carbon di oxide has no flash point, as it is noncombustible, and a vapor pressure of >1 atmosphere at 20°C. Carbon dioxide is miscible with hydrocarbons, most organic liquids and water (0.14g/100 g water). The Henry’s Law constant for carbon dioxide ranges from 0.031-0.045 mol/kg*bar

at 25°C.

Carbon dioxide is required for both plan t and animal life. This inert gas is ubiquitous in nature, produced by animal and human respiration, and is found in the atmosphere naturally at 0.03%. Carbon dioxide is the fourth most abundant gas in the atmosphere. Plants use carbon dioxi de as a key component in photosynthesis. Carbon dioxide also plays a key role in plant and animal metabolism. In humans,

carbon dioxide is involved in several vital functions, including regulation of respiration, the maintenance of acid-base bala nce, the liberation of oxygen to tissues and it is an end-product of carbohydra te and fat metabolism. The average adult produces more than 500 grams of carbon dioxide per day while resting.

Carbon dioxide is used in a plethora of applications including: carbonation of beverages, as a refrigerant, as a fire exti nguisher, for welding operations, mining,

and in the medical field as a coma-inducer or as a constituent of therapeutic oxygen.

Carbon dioxide is also used as an in secticide and has been exempted from a requirement of a tolerance under 40 CFR 180.1049 when used after harvest in modified atmospheres for stored insect control on food commodities. EPA established a food additive regulation for carbon dioxide in or on all processed agricultural commodities when used post-harvest under 40 CFR 185.650. In 21

CFR 184.124 carbon dioxide is classified as Generally Recognized as Safe (GRAS)

for use on food.

1. Acute toxicity. The EPA has determined there are a number of adequate acute toxicological studies on carbon di oxide. The available toxicity studies on carbon dioxide have been conducted using the inhalation route of exposure. The inhalation route of exposure has been test ed because under standard conditions of temperature and pressure carbon dioxide is a gas and other routes of administration are virtually impossible. When a product containing carbon dioxide is sprayed the amount in a formulation is immediately di spersed into the atmosphere. The amount dispersed in pesticide is not anticipated to increase the amount of carbon dioxide in the atmosphere to dangerous levels.

In a study conducted on dogs, the animal s were exposed to 30% carbon dioxide environment for 2 hours followed by an exposure to 40% carbon dioxide then abruptly returned to normal air. Elev en dogs died within 10 minutes due to ventricular fibrillation, 4 survived with ca rdiac arrhythmias, and 2 survived with no

adverse effects.3

In a second study, rats were exposed to 50% carbon dioxide air and died within 6 hours. Another group of rats were expose d to 25% carbon dioxide air and died within 36 hours. Deaths were caused by pulmonary injury. When 20% carbon dioxide was tested, cerebral depression occu rred and at 10%, no effects were seen.

In another experiment, rats were exposed to 20% carbon dioxide air for 2 hours followed by an increase in carbon dioxide up to 43%. The rats died anywhere

between 2.5 and 19.3 hours later and showed sever brain and spinal cord damage.

2. Genotoxicty. NA-Remove

3. Reproductive and developmental toxicity. On various animal species, harmful effects to sperm were detected when exposed to high carbon dioxide atmospheres. In one study, pregnant rats were exposed to 6% carbon dioxide for one full day. Of the offspring of said rats, 23.4% had cardiac abnormalities. There was also an increased incidence of skeletal malformations by 10.9%. When pregnant dams were exposed to 10-13% carbon dioxide, vertebral co lumn malformations were observed.

In another study, when pregnant guinea pigs were exposed to 0.48% carbon dioxide for 10 minutes per day for 20 days, there was a noticeable number of miscarriages and flaccid paralysis of the back extremit ies on the offspring that did survive. Another group of pregnant guinea pigs were instead exposed to 0.42% carbon dioxide for 1 hour per day for 30 days. No miscarriages were reported, but many of the offspring were microsomic and many had neuromuscular defects of the hind legs.

4. Subchronic toxicity. According to the Carbon and Carbon Dioxide Reregistration Eligibility Document (RED ), different concentrations of carbon dioxide have varying effects. In a study in which Guinea pigs were exposed to 15 percent carbon dioxide for 7 days, the anim als initially showed a decrease in body weight but later returned to normal weig ht. In addition during the first three days of exposure, the animals had higher bl ood corticosteroids, lower adrenal epinephrine, decreased adrenal cholesterol, higher arterial free fatty acids, and decreased lymphocytes. In a second study in which rats were exposed to 10 percent carbon dioxide for 30 days had a decreased body weights of 14-27 percent One group of rats was exposed to 20-25 percent carbon dioxide for 34 days showed a 50 percent decrease in body weight. In bo th groups the decrease in weight was

attributed to a reduced food intake. The ra ts increased body weight after a period of time at normal atmosphere. In a third study, male rhesus monkeys were exposed to a 3 percent carbon dioxide environment for 93 days and did not show any effects.

5. Chronic toxicity. Chronic poisoning from carbon dioxide under normal conditions is not likely.4

According to the RED, “Humans naturally have continual exposure to carbon dioxide without any indications of toxic effects from such ordinary exposures to carbon dioxide. Furthermore, since carbon dioxide is a normal constituent of the atmosphere at about 0.03 percent (300 ppm), there is continuous human exposure by inhalation and on the skin.”

6. Animal metabolism. Carbon dioxide is found naturally in the air making up 0.03% of the atmosphere and is the fourth most abundant gas in the atmosphere. Carbon dioxide is also produced by the human body during metabolism and is present in the body at around 6% concentr ation. Carbon dioxide is formed in the human body during metabolism and the average adult will produce upwards of about 500 grams per day. When introduced into the body at higher levels than normal, the carbon dioxide will react with the water in the body to form carbonic

acid. The carbonic acid then dissociates into bicarbonate and hydrogen ions. The kidneys then take over when it senses th e increase in acidity within the body, to restore the body’s natural acidity. Carbon dioxide is readily excreted by the body through the lungs, kidneys, intestines and skin.

7. Metabolite toxicology

. NA - Remove

8. Endocrine disruption

. Carbon dioxide has long been used to anesthetize animals prior to euthanizing them in toxici ty studies. Anesthetizing animals prior to euthanization via decapitation has long b een recognized as a humane alternative to decapitation alone. A study conducted by Reed et al , compared the levels of certain

hormones in rodents where carbon dioxide was used to asphyxiate the rodents prior

to euthanization versus no carbon dioxide . The study found the animals previously

anesthetized with carbon dioxide had in creased levels of plasma oxytocin, and arginine vasopressin.

C. Aggregate Exposure NA - Remove

1. Dietary exposure. NA - Remove

i. Food. NA - Remove

ii. Drinking water. NA - Remove

2. Non-dietary exposure

. NA - Remove

D. Cumulative Effects

NA - Remove

E. Safety Determination5

1. U.S. population. [Insert text.] Carbon dioxide is found naturally in the air making up 0.03% of the atmosphere and is the fourth most abundant gas in the atmosphere. Carbon dioxide is also classi fied as GRAS (Generally Recognized as Safe) for use on food according to 21 CFR 184.1240. There is extensive evidence supporting that the amount of carbon dioxide ingested daily in f oods is insignificant compared with the amount that the human body ingests daily. The Select

Committee on GRAS substances have conclude d that carbon dioxide poses no threat to the public when it is “used at levels that are now current or that might reasonably be expected in the future”.

The EPA thoroughly evaluated carbon dioxide in both 1991 (RED) and 2004 (TRED). In 1991, EPA determined carbon di oxide does not accumulate in treated raw agricultural commodities but rather di ffuses into the atmosphere following application. Therefore, no residues of carbon dioxide are found in or on raw agricultural commodities. In both th e RED and the TRED, EPA concluded the currently registered uses of carbon dioxide will not result in un reasonable effects to

the environment or human health.

2. Infants and children

. The Agency concluded there is also no concern for potential sensitivity to infants and children. An EPA memorandum dated April 1, 2004, states, “Based on the available informat ion on carbon dioxide, its expected use pattern, its safe history of use as a food additive, and its essential role in human metabolism and respiration, there is a reasonable certainty of no harm from exposure to carbon dioxide through its use in pesticides. Furthermore, there is no concern for potential sensitivity to infant s and children. As with all chemicals, carbon dioxide must be used safely according to good manufacturing or good agricultural practices. The Agency believes that exposure to levels of concern of carbon dioxide are unlikely as a result of its use in pesticide pr oducts, and would be most appropriately addressed through the use of protective equipment, adequate ventilation, and labeling.”

F. International Tolerances

NA - Remove