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EPA REGISTRATION DIVISION COMPANY 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 preparing the pesticide petition. In 

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

maintain the outline. Please do not change 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 time 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 - Remove
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B. Toxicological Profile Carbon dioxide, CAS No. 124-38-9, is a clear, colorless, 

odorless, noncombustible gas at standard 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 dioxide 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 plant 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 dioxide 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 balance, the liberation of oxygen to tissues 

and it is an end-product of carbohydrate 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 extinguisher, 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 insecticide 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 dioxide. The available toxicity studies on 

carbon dioxide have been conducted using the inhalation route of exposure. The 

inhalation route of exposure has been tested 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 dispersed 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 animals were exposed to 30% carbon dioxide 

environment for 2 hours followed by an exposure to 40% carbon dioxide then 

abruptly returned to normal air. Eleven dogs died within 10 minutes due to 

ventricular fibrillation, 4 survived with cardiac arrhythmias, and 2 survived with no 

adverse effects. 
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In a second study, rats were exposed to 50% carbon dioxide air and died within 6 

hours. Another group of rats were exposed to 25% carbon dioxide air and died 

within 36 hours. Deaths were caused by pulmonary injury. When 20% carbon 

dioxide was tested, cerebral depression occurred 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 column 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 extremities 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 animals initially showed a decrease in body 

weight but later returned to normal weight. In addition during the first three days 

of exposure, the animals had higher blood 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 both groups the decrease in weight was 

attributed to a reduced food intake. The rats 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. 
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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% concentration. 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 the 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 toxicity studies. Anesthetizing animals prior to 

euthanization via decapitation has long been 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 increased 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 Determination 
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 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 classified 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 foods is insignificant 

compared with the amount that the human body ingests daily. The Select 

Committee on GRAS substances have concluded 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 dioxide does not accumulate in treated 

raw agricultural commodities but rather diffuses into the atmosphere following 

application. Therefore, no residues of carbon dioxide are found in or on raw 

agricultural commodities. In both the RED and the TRED, EPA concluded the 

currently registered uses of carbon dioxide will not result in unreasonable 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 information 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 infants 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 products, and would be 

most appropriately addressed through the use of protective equipment, adequate 

ventilation, and labeling.”

F. International Tolerances

 NA - Remove