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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: PV 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.

BYK Additives Inc.

[IN-10781]

EPA has received a pesticide petition (IN-10781) from BYK Additives Inc., 1600 W. Hill 

Street, Louisville, KY 40210 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 to establish an exemption from the 

requirement of a tolerance for Quaternary ammonium compounds, benzylbis(hydrogenated tallow

alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with sepiolite (CAS #1574487-61-

8), when used as an inert suspending or structuring agent applied to growing crops under 40 CFR 180.920 

in pesticide formulations. The inert substance will be used as part of an inert mixture that is intended for 

use in pesticides. EPA has determined that the petition contains data or information regarding the elements 

set forth in section 408 (d)(2) of FDDCA; 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.

2. Analytical method. NA remove

3. Magnitude of residues. NA remove

B. Toxicological Profile

1. Acute toxicity. Acute oral and inhalation studies have been conducted in animals with many 

organoclay materials that are similar to Quaternary ammonium compounds, benzylbis(hydrogenated tallow

alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with sepiolite and give consistent 

results that classify these materials as Toxicity Category IV for these two endpoints. Oral LD50 values 

exceed 5000 mg/kg bw and inhalation LD50 values were consistently greater than 2 mg/L. An acute 

dermal toxicity study was conducted on stearalkonium bentonite; this substance was classified as Toxicity 

Category III for acute dermal toxicity based on the LD50 of >2000 mg/kg bw. Quaternary ammonium 

compounds, benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow 

alkyl)dimethylammonium salts with sepiolite is not expected to be irritating to the skin, based on results in 

other organoclays. Minimal eye irritation may occur in humans as a result of the physical nature of the clay 

particles, although moderate irritation has been reported in animals exposed to organoclays via the eye. 

Sensitization reactions were not observed in two structurally similar treated clays when tested in guinea 

pigs and humans.
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2. Genotoxicty. Treated clays similar to quaternary ammonium compounds, 

benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with 

sepiolite have been studied in a variety of bacterial and mammalian cell genotoxicity studies as well as in 

vivo genotoxicity studies. All of the genotoxicity studies on treated clays have been negative. These include 

an in vivo micronucleus assay and a modified mammalian bone marrow chromosome aberration assay. 

3. Reproductive and developmental toxicity. A one-generation reproductive toxicity study was 

carried out on the structurally similar substance, Quaternary ammonium compounds, 

benzylbis(hydrogenated tallow alkyl)methyl, salts with hectorite (CAS #121888-67-3) using OECD 

guideline 415. Female and male Sprague Dawley rats (24 sex/group) were dosed with 0, 50, 225, and 1000 

mg/kg bw during mating and through post natal day 21. The following endpoints were assessed: 

morbidity/mortality, clinical signs, body weight, food consumption, mating, gestation, number of live/dead 

offspring, litter body weight, litter clinical signs; food conversion ratio; mating performance and fertility; 

pre-coital interval; fertility indices (mating index and pregnancy index); gestation length; gestation and 

parturition index; lactation data including live birth index, viability indices; sex ratio; and offspring 

physical development and reflexology. A difference in mean litter body weights was not considered to be 

toxicologically important and there were no effects on other developmental endpoints. The study authors 

determined the NOAEL for systemic and reproductive/developmental effects to be the highest dose, 1000 

mg/kg bw/day.

In a 28-day toxicity study of stearalkonium bentonite, there were no histopathological findings in any 

reproductive organ including testis, epididymis, ovary, prostate, or uterus

4. Subchronic toxicity. Three 28-day OECD test guideline 407 studies (or close variations) were 

identified for three structurally similar treated clays. Study authors considered the highest dose (1000 

mg/kg bw/day) in each test to be the NOAEL. In the first study, rats receiving stearalkonium bentonite at 0, 

100, 316, or 1000 mg/kg bw/day showed no test substance-related effects after 28 days of dosing. A 

parallel high dose plus recovery group showed some differences from controls, but these were not seen in 

the high dose/non-recovery rats and therefore were not considered test substance -related. In the second 

study, a 1000 mg/kg/day dose of quaternary ammonium compounds, benzyl(hydrogenated tallow

alkyl)dimethyl, chlorides, compounds with bentonite for 28 days resulted in no mortalities, clinical signs of 

toxicity, effects on body weight or food consumption, or statistically significant findings for hematology or 

clinical chemistry in Charles River/CD rats. Changes in organ weights of treated animals were not 

considered toxicologically relevant. In the third study, quaternary ammonium compounds, 

benzylbis(hydrogenated tallow alkyl)methyl, salts with hectorite was dosed to Charles River/CD rats at 0 or 

1000 mg/kg bw/day. There were no mortalities, clinical signs of toxicity, changes in body weight gains, 

food consumption or hematological parameters. There were some differences from controls in clinical 

chemistry parameters and adrenal weights (males). None of the effects were considered toxicologically 

relevant based on their appearance in only one sex and their small deviation from control values, which 

were often still within the historical range of normal values. The authors considered the NOAEL to be 1000 

mg/kg bw/day.

5. Chronic toxicity. N/A Remove

6. Animal metabolism. A guideline study of the treated clay quaternary ammonium compounds, 

benzylalkyl (C14-C22) dimethyl, salts with bentonite (CAS #71011-24-0) showed that only a negligible 

concentration of treated clays is absorbed by orally dosed rats. After 48 hours, 0.16% and 0.95% of the 

administered dose remained in the carcass of rats dosed with 5 and 500 mg/kg bw, respectively.

Given that Quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, 

bis(hydrogenated tallow alkyl)dimethylammonium salts with sepiolite contains particles in the respirable 

size range, there is potential for accumulation following inhalation exposure of the raw material if it is still 

in dry particle form. Clearance from the lungs shows two phased clearance in which most of the fibers are 

cleared in the first phase. Fibers of sepiolite derived from Vallecas-Vicalvaro, Spain, such as those in the 

petitioned substance, have a total half-rate of clearance from the lungs of 89 days, with 95% of the fiber 

mass eliminated with a half-rate of 39 days.
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7. Metabolite toxicology. N/A Remove

8. Endocrine disruption. In the available toxicity studies on treated clays, there

was no evidence of endocrine disruptor effects.

C. Aggregate Exposure

1. Dietary exposure. The estimated dietary exposure to quaternary ammonium compounds, 

benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with 

sepiolite was determined using methods to estimate chronic dietary exposure for a generic inert ingredient. 

This assessment considers drinking water and crop-specific residues from pre-harvest applications of 

agricultural insecticides, herbicides and fungicides, assuming the highest established tolerance level residue 

for each commodity. The assessment assumes that the inert ingredient is used on all crops, and that 100% 

of all crops are treated with the inert. The inert ingredient is assumed to be present in all commodities 

treated with 57 of the most significant active ingredients at the maximum tolerance level as identified by 

the U.S. EPA for the default assessment. Chronic dietary exposure estimates were derived for the general 

US population and sub-groups of the population using the Dietary Exposure Evaluation Model, DEEMTM. 

The I-DEEM residue data set developed by EPA was used for the analysis. The inert ingredient is assumed 

to be in the formulation at a concentration of 50% for the default assessment, but this has been amended to 

account for the actual use level of Quaternary ammonium compounds, benzylbis(hydrogenated tallow

alkyl)methyl, bis(hydrogenated tallow alkyl) dimethylammonium salts with sepiolite in the end use 

product. The estimated chronic exposure for the total US population is 0.0076 mg/kg/day, about 0.076% of 

the chronic Population Adjusted Dose (cPAD). Children age 1 to 2 years old have the highest estimated 

exposure at 0.0282 mg/kg/day, about 0.282% of the cPAD. Both of these estimates give a margin of 

exposure that exceeds 1x104.

i. Food. There are no other known dietary sources of quaternary ammonium compounds, 

benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with 

sepiolite.

ii. Drinking water. Quaternary ammonium compounds, benzylbis(hydrogenated tallow

alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with sepiolite exposure via drinking 

water from use as an inert ingredient is not expected to be significant. Based on the physical chemical 

characteristics of the treated clays, the substance is expected to settle out in water. Exposure via drinking 

water was estimated in the DEEM dietary exposure assessment assuming a concentration of 100 ppb.

2. Non-dietary exposure. There are no known non-dietary sources of exposure to quaternary 

ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow

alkyl)dimethylammonium salts with sepiolite.

D. Cumulative Effects

Section 408(b)(2)(D) (9v) of the FFDCA requires that, when considering whether to establish, 

modify, or revoke a 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 made a common mechanism of toxicity finding as to quaternary ammonium 

compounds, benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow 

alkyl)dimethylammonium salts with sepiolite and other compounds. Quaternary ammonium compounds, 

benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with 

sepiolite does not appear to produce toxic metabolites in common with other substances. For the purpose of 

the tolerance exemption actions proposed, it is assumed that quaternary ammonium compounds, 

benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with 

sepiolite does not share a common mechanism of toxicity with other substances.
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E. Safety Determination

1. U.S. population. There is a reasonable certainty that no harm to humans will result from the use 

of quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated 

tallow alkyl)dimethylammonium salts with sepiolite as an inert ingredient in pesticide products. A NOAEL 

of 1000 mg/kg/day obtained in three 28-day toxicity tests and in a one-generation reproductive toxicity test 

was used as the point of departure for the chronic population adjusted dose (cPAD). Intraspecies and

interspecies uncertainty factors were combined for a total uncertainty factor of 100. The resulting cPAD is

10 mg/kg/day. For the total US population, the estimated chronic dietary exposure from food and drinking 

water for this treated clay, is less than 0.1% of the cPAD. This estimated exposure to quaternary 

ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, bis(hydrogenated tallow

alkyl)dimethylammonium salts with sepiolite is well below any level of potential concern

2. Infants and children. There is a reasonable certainty that no harm to infants and children will 

result from the use of quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, 

bis(hydrogenated tallow alkyl)dimethylammonium salts with sepiolite as an inert ingredient in pesticide 

products. A one-generation reproductive toxicity study in rats demonstrated no reproductive effects or 

effects on developmental endpoints. A cPAD of 10 mg/kg/day is protective of infants and children. The 

cPAD was derived for quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, 

bis(hydrogenated tallow alkyl)dimethylammonium salts with sepiolite based on the NOAEL of 1000 mg/kg

bw/day in the reproductive study as well as multiple subchronic studies. The estimated chronic dietary 

exposure from food and drinking water was highest (0.282% of cPAD) for children aged 1 to 2 years old. 

Estimated exposure of all infants to quaternary ammonium compounds, benzylbis(hydrogenated tallow

alkyl)methyl, bis(hydrogenated tallow alkyl)dimethylammonium salts with sepiolite was estimated to be

0.158% of the cPAD. These estimated exposures are well below any level of potential concern.

F. International Tolerances

N/A Remove