EPA ANTIMICROBIALS DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA ANTIMICROBIALS DIVISION CONTACT: VELMA NOBLE, 703-308-6233

EPA INERT INGREDIENTS ASSESSMENT BRANCH CONTACT: P.V. SHAH, 703-308-6341

The informative summary, which may be published in accordance with Section 2, is provided separately

in both hard and electronic copy in the current Notice of Filing template format.

The Environmental Protection Agency (EPA) has received a pesticide petition from The Clorox Company 

(“Clorox”), 1221 Broadway Oakland, CA 94612-1888 requesting, 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 180.940 to 

establish an exemption from the requirement of a tolerance for Saturated Aliphatic Acyclic Linear 

Primary Alcohols, Aldehydes and Acids when used as fragrances in formulations used on food-contact 

surfaces when applied/used in indoor residential settings at a maximum rate of 0.025%. EPA has

determined that the petition contains data and information regarding the elements set forth in section 408 

(d)(2) of the 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.

The low-molecular weight saturated aliphatic primary alcohols, aldehydes and acids are ubiquitous in 

nature and these compounds have been found in the vast majority of all fruits and vegetables and their 

associated fats and oils, animal tissue and fats and beverages. These compounds collectively have use as 

conventional, biochemical and antimicrobial pesticides in addition to being used as both flavoring and 

fragrance agents. In most cases, exposures from natural sources exceed those from use as a flavor 

compound or a fragrance component. Some group members (such as propionic acid) are endogenous and 

normal products of mammalian metabolism and all are readily and rapidly metabolized to innocuous 

products that are either excreted or incorporated into biomolecules. The Congener group members all 

pose low toxicity to mammals, are readily biodegradable, and have a safe history of use. Both the Joint 

FAO/WHO Expert Committee on Food Additives (JECFA) and the Flavor Extract Manufacturers’ 

Association (FEMA) have evaluated every member of the Congener group for use as a flavor compound. 

All Congener group members are listed in the regulations at either 21 CFR 172, 21 CFR 182 or 21 CFR 

184 governing Food Additives Permitted for Direct Addition to Food for Human Consumption, Generally 

Recognized as Safe (GRAS) or Direct Food Substances Affirmed as GRAS, respectively. Every 

Congener group member is on the EPA Fragrance Ingredient List (a list of inert fragrance ingredients 

approved for non-food use). At least one Congener group member (valeric acid) has been “reassessed” as 

an inert ingredient. 

A. Plant metabolism. Because Clorox is petitioning for an exemption from the requirement of a tolerance, 

plant metabolism data are not needed.

Analytical method. Because Clorox is petitioning for an exemption from the requirement of a tolerance, 

an enforcement analytical method is not needed.

Magnitude of residues. Because Clorox is petitioning for an exemption from the requirement of a 

tolerance, residue data are not needed; however, estimates of residue magnitude from use of indoor food 

contact sanitizing solutions are presented herein. Assuming a maximal concentration of 0.025% in a foodcontact sanitizing solution, a summary of these residues is as follows:

Child Resident Adult Resident

Dermal exposure/non- 0.68 μg/kg BW/day Dermal exposure/non- 0.33 μg/kg BW/day
dietary (see RES-2) dietary (during 

application)

(see RES-1)

Incidental 

ingestion/non-dietary

1.4 μg/kg BW/day

(see RES-3)

Oral ingestion/dietary 1 μg/kg BW/day

(see RES-4)

Oral ingestion/dietary 0.36 μg/kg BW/day

(see RES-4)

TOTAL 3.1 μg/kg BW/day TOTAL 0.69 μg/kg BW/day

B. Toxicological profile:

Linear aliphatic acyclic alcohols, aldehydes and carboxylic acids are absorbed through the gastrointestinal

tract and rapidly metabolized. Following absorption, alcohols are oxidized to their corresponding 

aldehyde, and aldehydes are oxidized to corresponding carboxylic acids via enzyme pathways with a high 

capacity (i.e. fatty acid and tricarboxylic acid cycles, which are a fundamental mechanism of cell 

biochemistry). Fatty acids are endogenous and essential dietary components. Short- and medium-chain 

fatty acids are converted rapidly to carbon dioxide and water in the mitochondria of liver and other 

tissues. Fatty acids taken up by tissues can be stored chiefly as triglycerides in adipose tissue or oxidized 

for energy via the above pathways. Some aliphatic acids undergo beta-oxidation to yield products that are 

then further metabolized by the fatty acid cycle. In general, the fatty acid pathway converts aliphatic 

alcohols and aldehydes to acetyl Coenzyme A units, which then enter the tricarboxylic acid cycle (i.e. 

citric acid cycle, or most commonly “Krebs cycle”). The Krebs cycle is a series of reactions through 

which aerobic organisms make energy from carbohydrates, fats and proteins. 

Acute toxicity. Linear aliphatic alcohols, aldehydes and carboxylic acids exhibit low acute toxicity. 

Available oral or gavage studies in rodents (mainly rats) indicate LD50 values ranging from 720 to in 

excess of 20,000 mg/kg BW. This is expected given the rapid and complete metabolism the 

Congener group members undergo in vivo. 

Genotoxicity. Available in vitro and in vivo genotoxicity studies for the saturated aliphatic acyclic linear 

primary alcohols, aldehydes, and carboxylic acids generally exhibited consistent negative results in 

the Ames assay, the unscheduled DNA synthesis test, and in vitro or in vivo mouse micronucleus test. 

However, genotoxic activity has been reported for some low molecular weight alcohols, carboxylic 

acids and aldehydes, including in the sister chromatid exchange (SCE) assay, the chromosomal 

aberration test and the forward mutation assays with mouse lymphoma and Chinese hamster lung 

cells. The positive results from the in vitro genotoxicity assays for aliphatic aldehydes is likely due to 

reactivity of the aldehyde functional group. 

Reproductive and developmental toxicity. There is no evidence to conclude that oral ingestion of the 

Congener group as fragrance ingredients would be associated with reproductive or developmental 

toxicity, particularly in the light of low acute and chronic toxicity, rapid metabolism and low and 

infrequent exposure. 

Subchronic and chronic toxicity. The alcohols and aldehydes display slightly greater relative toxicity 

than the acids (which overall is quite low for the entire Congener group), and this is to expected as 

these classes must be metabolized to acids prior to complete degradation to water and carbon dioxide. 

As seen with the acute toxicity data, the repeat-dose toxicity for the Congener group members is 

fairly consistent when route of exposure, species differences, etc. are taken into account.

The toxicity data for the aldehydes are largely derived from either Komsta et al. (1988) or Trubek 

(1958), which were all done on murine species where no effect was found at the highest dose for 

several chemicals and the resultant no-observed effect levels (NOELs) range from > 112 to > 166 

mg/kg BW/day. In one instance (acetaldehyde), a NOEL and a low-observed effect level (LOEL) of 

125 and 625, respectively, were reported based on rat forestomach irritation. Given that there is no 

analogous structure in humans, others have adjusted no-effect levels based on rat forestomach 

irritation for human equivalency. For nonanoic acid, a NOEL of 150 mg/kg BW/day based on 
forestomach irritation was adjusted to a human NOEL of 1,000. (See description below.) 

Furthermore, the High Production Volume Challenge submission for the C7-C9 aldehydes speculated 

that the NOEL for all the aldehydes in the category should likely be in excess of 300.

The toxicity data for the alcohols demonstrate similar toxic potential in dog and rabbit in addition to 

rodents that are of the same magnitude as the aldehydes. Available gavage studies indicate that this 

route of exposure results in lower NOELs (greater toxicity to experimental animal), although two of 

the three available gavage studies did not find effects at the highest dose (ranging from > 50 to > 

180). Available dietary studies cover rat, dog and rabbit and range from 695 to 1,000.

The best coverage of the three groups is found among the acids, with all but one study (rabbit) done 

in the rat and as a result, the data set is remarkably consistent. Again, exposure via gavage results in 

lower NOELs (ranging from 1,000 to 1,750 in three studies) than the dietary studies (ranging from 

1,000 to 10,000 in nine studies). One study (acetic acid) was via unspecified oral route and did not 

observe effects at the only reported dose (> 350 mg/kg BW/day).

Carcinogenicity. Overall, the Congener group poses low concern for carcinogenicity given several 

observations. First, the Congener group displays consistent negative findings in the Ames test, 

unscheduled DNA synthesis and both in vivo and in vitro mouse micronucleus tests. Second, the 

aliphatic aldehydes (for which there are several positive findings) are rapidly oxidized to acids that 

are metabolized via the citric acid cycle. Third, some members of the Congener group are 

endogenous and products of normal metabolism. Finally, exposures are infrequent and of low 

magnitude.

Endocrine effects. A review of information from public sources, including the World Health 

Organization, the Agency of Toxic Substances and Disease Registry, and the Environmental 

Protection Agency indicate that potential endocrine effects from exposure to members of the 

Congener group have not been studied. To the best of our knowledge, nothing in the available 

literature suggests that Congener group members are “endocrine disruptors” or mimic intrinsic 

hormonal activity. 

C. Aggregate Exposure

The exposure assessment consisted of two parts, a dietary and a non-dietary assessment. The dietary 

assessment included exposure to group constituents in food based on their use as flavoring additives and 

as naturally occurring substances. The dietary assessment also included potential oral exposure to group 

constituents when used as fragrances in antimicrobial pesticides because it was assumed end-use products 

would be used on both food and non-food contact surfaces, therefore, an estimate of the potential 

exposure to a fragrance ingredient in antimicrobial residue that could migrate to food was included.

The non-dietary assessment included potential exposures to group constituents when end-use products are 

used on either food or non-food contact surfaces. Based on review of the residential exposure 

assessments in recent Re-registration Eligibility Decision (RED) documents by EPA, it was concluded 

that dermal exposure to an adult resident applying a cleaning product to a surface, and a child exposed to 

this same surface post-application via dermal contact and incidental ingestion (i.e., hand-to-mouth 

contact), constitute the applicable scenarios and exposure routes with the greatest potential exposure. 

Dietary and non-dietary exposures, as presented previously, were aggregated for short-term durations 

(i.e., 1-30 days) for all exposures, using available NOELs from sub-chronic oral toxicity studies (a repeat 

exposure study of at least 21 days). This approach is consistent with the EPA Office of Pesticide 

Programs (OPP) principles for aggregate risk assessment as well as JECFA’s Procedure for Evaluating 

Flavor Ingredients. Oral NOELs were used to assess potential risk from dermal absorption by 

conservatively assuming 100% dermal absorption and the same potential health effect whether exposed 
via the oral or dermal route. Health risk was estimated using margin of exposure (MOE) as the hazard 

metric. Use of an MOE is particularly appropriate for chemicals whose underlying mechanism of toxicity 

involves a threshold process, where a NOEL is identified for a chemical, such as those identified for 

group constituents. 

1. Dietary exposure - food.

i. Acute. There are no acute dietary exposure concerns as the acute toxicity of the Congener 

group members is quite low and there is an extensive history of safe ingestion given virtually all 

the Congener group members are found naturally in foods and/or beverages. An acute dietary 

risk assessment is not required, as further evidenced by waiving dietary assessment requirements 

for all EPA pesticide actions taken on Congener group members to date (i.e. propionic acid, 

aliphatic alcohols, octanoic acid, nonanoic acid, and decanoic acid all were not considered dietary 

risks).

ii. Chronic indirect. Using a worst-case scenario, the exposure resulting from the use of 

Congener group members at the maximal concentration of 0.025% in a food-contact sanitizing 

solution would be 3.1 μg/kg BW/day for a 15-kg person (child) and 0.69 μg/kg BW/day for a 60-

kg person (adult) (0.59 μg/kg BW/day for a 70-kg adult). This is generally well below levels 

found in naturally occurring sources in the diet.

iii. Chronic direct. A typical adult ingests from < 1 to 39,700 μg/day of Congener group 

members via diet, all from naturally occurring sources in food and/or beverages. See Table 6 

for daily per capita intakes of individual Congener group members and refer to Section 6 for 

a description of methodology. Exposure to Congener group members in specific food items, 

such as the ingestion of acetic acid through foods containing vinegar or propionic acid 

through foods containing the preservative calcium propionate, can exceed daily intakes via 

uses of flavors or fragrances, yet have demonstrated a history of safe ingestion. 

2. Drinking water exposure

i. Acute. There are no acute dietary exposure concerns via drinking water as the acute

toxicity of the Congener group members is quite low and there is an extensive history of safe 

ingestion given virtually all the Congener group members are found naturally in 

foods and/or beverages. A drinking water assessment is not required, as further evidenced by 

waiving dietary assessment requirements for all EPA pesticide actions taken on Congener 

group members to date (i.e. propionic acid, aliphatic alcohols, octanoic acid, nonanoic 

acid, and decanoic acid all were not considered risks via this pathway).

ii. Chronic. There are no chronic dietary exposure concerns via drinking water as the acute 

toxicity of the Congener group members is quite low and there is an extensive history of safe 

ingestion given virtually all the Congener group members are found naturally in 

foods and/or beverages. A drinking water assessment is not required, as further evidenced by 

waiving dietary assessment requirements for all EPA pesticide actions taken on Congener 

group members to date (i.e. propionic acid, aliphatic alcohols, octanoic acid, 

nonanoic acid, and decanoic acid all were not considered risks via this pathway).

3. Nondietary exposure. Non-dietary exposure to an adult during application of a food contact 

sanitizing solution was estimated to be 0.33 μg/kg BW/day. Total non-dietary exposure to a child 

was determined from post-application contact with treated surfaces as well as incidental ingestion 

following hand-to-mouth contact. The former exposure was estimated to be 0.68 μg/kg BW/day and 

the latter 1.4 μg/kg BW/day, for a total non-dietary exposure estimate of 2.08 μg/kg BW/day for a 

child resident.

D. Cumulative Effects - No cumulative adverse effects are expected from long-term exposure to the 

members of the Saturated Aliphatic Acyclic Linear Primary Alcohols, Aldehydes and Acids Congener 

Group. Despite the fact that the members share common mechanisms of toxicity with one another, 

cumulative effects are not anticipated due to the low mammalian toxicity and very low levels of exposure. 
The common mechanisms of toxicity in this case (i.e. tricarboxylic acid cycle, or “Krebs cycle”) are wellstudied high-throughput pathways.

E. Safety Determination

A “worst case” exposure analysis was performed on the individual members of Saturated Aliphatic 

Acyclic Linear Primary Alcohols, Aldehydes and Acids to generate margin of exposure (MOE) values for 

both the US population (as estimated by an adult exposed dermally during the indoor application of a 

food contact sanitizing solution) and children (as estimated by indoor post-application dermal and 

incidental oral exposure to 3 year old). This analysis estimated the MOE via inert ingredients used as 

flavor or fragrance components of a food-contact sanitizing solution as well as by considering those 

compounds that contain structural features that permit no strong initial presumptions of safety or may 

suggest toxicological effects (Munro et al., 2008). The MOE calculation for an individual fragrance 

component is based on the combined or “aggregated” oral intake of the component from natural 

occurrence, use as a flavor compound and use as a fragrance in food-contact sanitizing solutions intended 

for use in indoor residential settings. Subchronic/chronic no effect levels (NOELs) were the primary 

toxicity metric used in the analysis and were obtained from mostly JECFA and supplemented by EPA, 

Organiziation for Economic Copperation and Development (OECD), etc. Potential dietary exposures to 

residues on food were estimated using the IDREAM model and non-dietary exposures were estimated and 

aggregated to determine total exposure from use of Congener group members in a pesticide formulation. 

Detailed methodology was previously submitted to the Agency and subsequently approved by EPA staff. 

Given the exposure methodology is intended to be protective of a 3-year old child, the findings of this 

conservative, assessment is protective of both general US population as well as infants and children.

1. U.S. population. This conservative screening-level risk analysis demonstrates acceptable (i.e. 

100 or greater) margins of exposure (MOEs) for the U.S. population even when considering total 

aggregate intake from potential exposures from natural occurrence, use as a flavor compound 

and, most importantly, dietary and non-dietary routes of exposure during and following 

application of a food-contact sanitizing solution used indoors.

2. Infants and children. The risk assessment used an exposure scenario protective of a three-yearold child resident exposed to Congener group members from both dietary and non-dietary 

sources, including post-application exposure to residue following indoor use as a food-contact 

surface sanitizer. This conservative screening-level risk analysis demonstrates acceptable (i.e. 100 

or greater) margins of exposure (MOEs) for infants and children.

F. International Tolerances - No Codex Alimentarius maximum residue levels have been established for 

any of the Saturated Aliphatic Acyclic Linear Primary Alcohols, Aldehydes and Acids Congener Group

members.