i

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.

[Loveland Products, Inc.]

[IN-10704]

EPA has received a pesticide petition (IN-10704) from Loveland Products, Inc., 

3005 Rocky Mountain Avenue, Loveland, CO 80538 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 to amend the exemption from the requirement of a tolerance for

[Phenol, 2-(2H-Benzotriazol-2-yl)-6-dodecyl-4-methyl- (CAS No. 23328-53-2)]

as an inert ingredient (UV stabilizer) not to exceed 10% w/w in pesticide 

formulations under 40 CFR §180.920 (pre-harvest uses). The petition proposes to 

amend the exemption from the requirement of a tolerance for residues of Phenol, 2-

(2H-Benzotriazol-2-yl)-6-dodecyl-4-methyl- in or on [all] raw agricultural 

commodities. CAS Reg. No. 23328-53-2 is approved as an inert ingredient (UV 

stabilizer) for use at no more than 0.6% in insecticide formulations applied to 

adzuki beans, canola, chickpeas, cotton, faba beans, field peas, lentils, linola, linseed, 

lucerne, lupins, mung beans, navy beans, pigeon peas, safflower, sunflower, and 

vetch (40 CFR 180.920). 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

1. Plant metabolism. [Not applicable. Remove based on the fact that this 

information is not required for the establishment of a tolerance exemption.]

2. Analytical method. [Not applicable. The petition proposes to amend the 

exemption from the requirement of a tolerance and no analytical method is required 

for establishing or amending a tolerance exemption.]
2

3. Magnitude of residues. [Not applicable. Remove based on the fact that this 

information is not required for the establishment of a tolerance exemption.]

B. Toxicological Profile

[In addition to data on phenol, 2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methyl- (CAS 

Reg. No. 23328-53-2; Tinuvin® 571), toxicity data are available on five surrogates: 

drometrizole (Tinuvin® P), octrizole (UV 329), Tinuvin® 328, Tinuvin® 234, and 2-

(2’-hydroxy-3,5;-di-tert-butylphenyl benzotriazole (HDBB; UV-320). The five 

surrogates have an identical molecular base, a benzotriazole moiety plus a mono- or 

di-substituted phenol. Therefore, data on these five surrogates is used to the 

support the toxicity database for CAS Reg. No. 23328-53-2. 

EPA previously considered data for CAS Reg. No. 23328-53-2 and structurallyrelated surrogate chemicals (Petition Nos. 8E7362 and 8E7363) and the data 

considered in those petitions, publicly available data not considered in previous risk 

assessments, and new data for CAS Reg. No. 23328-53-2 are summarized below. . 

Based on discussions with the Agency and on EPA’s previous risk assessment that 

retained the 10X FQPA safety factor due to an incomplete database (lack of a 

reproduction study), Loveland Products Inc. conducted an extended one-generation 

rat reproduction study with CAS 23328-53-2. That report is submitted with this 

petition. These data in addition to other available data not considered previously 

should allow the Agency to remove the 10X FQPA safety factor.]

1. Acute toxicity. [Acute toxicity studies on CAS Reg. No. 23328-53-2 are not 

available; however, studies are available on drometrizole, octrizole, Tinuvin 328 and 

Tinuvin 234. The acute oral toxicity of drometrizole, octrizole, Tinuvin 328 and 

Tinuvin 234 is low with LD50s ranging from <1000 mg/kg (octrizole) to >10000 

mg/kg (drometrizole). The acute dermal LD50 of Tinuvin 234 is >2000 mg/kg. The 

acute inhalation LC50 of drometrizole is >1420 mg/m3or 1.42 mg/L. Drometrizole is 

minimally irritating to the rabbit eye and was not irritating to rabbit skin. 

Drometrizole was tested in a maximization test in guinea pigs (positive), a human 

patch test (negative) and a LLNA assay (negative).]

2. Genotoxicty. [Genotoxicity studies are not available on CAS Reg. No. 

23328-53-2; however, studies are available on drometrizole, octrizole, Tinuvin 328 

and Tinuvin 234. Drometrizole was tested in a dominant lethal assay in mice, a 

somatic mutation assay in Chinese hamsters (in vivo), a chromosomal aberration 

assay in Chinese hamsters (in vivo), in two Ames Salmonella assays and a UDS assay 

in primary rat hepatocytes. Drometrizole was negative in all of the assays except for 

the UDS assay. Octrizole was tested in an Ames Salmonella assay in which it was 

negative. Tinuvin 328 was tested in two Ames Salmonella assays and was negative 

in both assays. Tinuvin 234 was tested in a nucleus anomaly assay (in vivo), a sister 

chromatid exchange assay (in vivo), an Ames Salmonella assay and an UDS assay in 

primary rat hepatocytes. The results of all assays were negative. A weight of the 

evidence on the results of the genotoxicity studies conducted on phenol benzotriazole 

would indicate that they have no genotoxic potential.]
3

3. Reproductive and developmental toxicity. [An extended one-generation rat 

reproduction study is available on CAS Reg. No. 23328-53-2 and a combined 

repeated dose toxicity reproduction/developmental toxicity screening test is 

available on drometrizole. In the CAS Reg. No. 23328-53-2 study, the NOAEL for 

parental and reproductive toxicity was 10,000 ppm (500 mg/kg/d). The NOEL for 

offspring toxicity was considered to be 2500 ppm based on effects on body 

temperature in PND 4 pups and on TSH levels in PND 22 female pups and the 

NOAEL was considered to be 5,000 ppm (250 mg/kg/d) based on the decreased body 

weight and body weight gain observed in pups at 10000 ppm from PND 4 to 21. 

After weaning, body weights were comparable to control body weights. In the 

drometrizole study, the reproductive/developmental toxicity NOAEL was the

highest dose tested, 300 mg/kg/day. The NOEL in males was considered to be <30 

mg/kg/day based on increased relative liver weights observed in all dose groups and 

30 mg/kg/day based on effects on liver and kidney weights and kidney 

histopathology. The NOAEL was concluded to be 300 mg/kg/day for males and 30 

mg/kg/day in females based on kidney lesions. 

Developmental toxicity studies are not available on CAS 23328-53-2; however, 

studies are available on drometrizole (mouse and rat) and Tinuvin 234 (rat). In the 

rat and mouse studies on drometrizole, the NOAEL for maternal and developmental 

toxicity was considered to 1000 mg/kg/day, the limit dose for studies of this type. 

For the Tinuvin 234 study, the maternal NOAEL was considered to be 3000 

mg/kg/day and the developmental NOAEL was considered to be 300 mg/kg/day 

based on the findings at 1000 mg/kg/day.]

4. Subchronic toxicity. [Subchronic toxicity studies are not available on CAS 

Reg. No. 23328-53-2; however, 28-day and/or 90-day rat studies are available on 

drometrizole, octrizole, Tinuvin 328, Tinuvin 234 and HDBB and 90-day dog studies 

are available on drometrizole and Tinuvin 328. The liver and kidney were the 

primary target organs in these studies. The NOAEL in a 90-day dietary rata study 

on drometrizole was considered to be the low dose (0.2% in diet) based on the effects 

on body weights, hematology parameters and kidney histopathology observed at the 

mid and high dose. The NOAEL in a 30-day dietary rat study on octrizole was 

considered to be 5.658 mg/kg/day, the highest dose tested. Based on the results from 

a 90-day dietary rat study on Tinuvin 238, the NOAEL was considered to be < 100 

ppm and the NOAEL was considered to be 100 ppm (approximately 20 mg/kg/day) 

based on increased liver weights and microscopic findings in the liver. In a 90-day 

dietary rat study on Tinuvin 234, the NOAEL was considered to be 50 ppm or 

approximately 2.5 mg/kg/day, based upon findings in the liver (increased liver 

weights and microscopic findings) at 300 ppm (approximately 15 mg/kg/day). 

Seventeen-day, 28-day and 90-day gavage studies on HDBB were conducted in rats. 

The 17-day study was conducted using PND 4 to PND 21 rat pups. The NOAEL 

was 2.5 mg/kg/day in male and female pups based on liver pathology observed at 

12.5 mg/kg/day. The 28-day and 90-day studies were conducted in adult rats. The 

NOAEL in the 28-day study was determined to be <0.5 mg/kg/day in males and 2.5 

mg/kg/day in females based on the increased A/G ratio observed in males at all dose 

levels and effects on liver weights and liver histopathology in in females observed at 
4

12.5 mg/kg/day. The NOAEL in the 90-day study was 0.1 mg/kg/day in males and 

2.5 mg/kg/day in females based on hematology and clinical chemistry findings, 

increased liver weights and liver pathology observed in males at 0.5 mg/kg/day and 

in females at 12.5 mg/kg/day. In the 90-day non-rodent drometrizole, the NOAEL 

was considered to be 1000 ppm or 31.75 mg/kg/day in males and 34.6 mg/kg/day in 

females based on increased levels of alanine aminotransferase at 3000 ppm and 

above. For Tinuvin 328 90-dog study, the NOAEL was considered to be 30 

mg/kg/day based on body weight effects and histopathology (primarily in the liver) 

observed at 60 mg/kg/day.]

5. Neurotoxicity: [No neurotoxicity studies were available on CAS Reg. No. 

23328-53-2 or its surrogates; however, no indications of neurotoxicity were observed 

in any of the repeated dose studies summarized above. In addition, some FOB 

parameters and motor activity was evaluated in the extended one-generation rat 

reproduction study with CAS Reg. No. 23328-53-2 and no effects were observed up 

to a dose of 10000 ppm (~500 mg/kg/day). Body temperature was reduced in PND 4 

pups, but not PND 0 pups in the absence of any other indications of neurotoxicity. 

Since the effect occurred in conjunction with other toxicity in the pups (reduced 

body weight and body weight gain), it was attributed to general toxicity.]

6. Chronic toxicity. [A chronic toxicity study is not available on CAS Reg. No. 

23328-53-2; however, a study (gavage) is available on HDBB in rats. In this study, 

the NOAEL was 0.1 mg/kg/day in males and 2.5 mg/kg/day in females based on 

hematology and clinical chemistry findings, increased liver weights and liver 

pathology observed in males at 0.5 mg/kg/day and of hematology findings, increased 

liver weights and liver pathology in females at 12.5 mg/kg/day. The study authors 

concluded from the results of a second study that castration reduced but did not 

abolish the gender differences in susceptibility of male and female rats to the effects 

of HDBB. A carcinogenicity study on CAS Reg. No. 23328-53-2 is not available; 

however, a study in mice is available on drometrizole. The NOAEL in this study 

was greater than 64 mg/kg/day in male mice and 62 mg/kg/day in female mice. 

Drometrizole was not carcinogenic to mice under the conditions of this study.

7. Animal metabolism. [A metabolism study is not available on CAS Reg. No. 

23328-53-2; however, a study in male rats is available on drometrizole. 

Drometrizole was mainly excreted in the urine and was completely eliminated by 

168 hours after administration. Residual radioactivity was found in the liver, blood, 

kidney and aorta.]

8. Metabolite toxicology. [No studies are available on the toxicity of CAS 

23328-53-2 or its surrogates.]

9. Endocrine disruption. [No studies on the potential endocrine disruption 

potential of CAS Reg. No. 23328-53-2 have been conducted. However, estrogen 

receptor competitive binding assays are available on drometrizole, Tinuvin 328 and 

HDBB and yeast two-hybrid estrogen assays (which tested for agonist and 

antagonist activity) have been conducted on drometrizole, Tinuvin 328, Tinuvin 234 
5

and HDBB. The results of these assays indicate that these compounds have no 

estrogen agonist or antagonist activity.]

C. Aggregate Exposure

1. Dietary exposure. [Concentrations of CAS Reg. No. will be 10% in pesticide 

formulations applied to growing crops. As a result, humans may be exposed to very 

low residue levels through the diet from food and water. The lowest NOAEL of 250 

mg/kg/day (extended one-generation rat reproduction study) is selected for risk 

characterization of chronic dietary exposures to CAS Reg. No 23328-53-2. Although 

the NOAEL in this study was lower in pups than adults, the pup body weight effects 

were observed only during lactation when dietary intake for offspring is the highest; 

therefore, an additional FQPA safety factor is not considered necessary. Assuming 

standard 100X uncertainty factors for inter- and intra-species variability and an 

FQPA safety factor of 1X, the reference dose for chronic dietary exposures of CAS 

Reg. No. 23328-53-2, cRfD, is 2.5 mg/kg/day.]

i. Food. [Using I-DEEM, the estimated chronic dietary exposure estimates for 

a generic inert ingredient that is assumed to constitute up to 50% of a formulated 

pesticide product are presented Table 1. Chronic dietary exposures based on 

default residues on all foods range from 0.142 mg/kg/day for Youth 13-19 years old 

to 0.621 mg/kg/day for children aged 1-2 years old. CAS Reg. No. 23328-53-2 is 

proposed to be used at no more than 10% in pesticide formulations so the dietary 

exposures are lower ranging from 0.0288 mg/kg/day for Youth 13-19 years old to 

0.125 mg/kg/day for children aged 1-2 years old.]

ii. Drinking water. [Chronic dietary exposures based on default residues on all 

foods and drinking water at 100 ppb range from 0.144 mg/kg/day for Youth 13-19 

years old to 0.624 mg/kg/day for children aged 1-2 years old (Table 1). CAS Reg. 

No. 23328-53-2 is proposed to be used at no more than 10% in pesticide 

formulations so the chronic dietary (food + water) exposure ranges from 0.0303

mg/kg/day for Youth 13-19 years old to 0.128 mg/kg/day for children aged 1-2 years 

old.

Table 1. Chronic Dietary Exposure Using I-DEEM

Population 

Subgroup 

Chronic Dietary Exposure

(50% Cap) (mg/kg/d)

% cRfD

(cRfD = 2.5 mg/kg/d)

(50% Cap)

% cRfD

(cRfD = 2.5 

mg/kg/d)

(10% Cap)

Food Only Food Only Food + Drinking 

Water at 100 ppb

Food + Drinking 

Water at 100 ppb

Food + Drinking 

Water at 100 ppb

U.S. Population 0.1894 0.1915 7.66 1.62

All infants (<1 year) 0.3902 0.3971 15.88 3.45

Children 1-2 yrs 0.6209 0.624 24.96 5.12

Children 3-5 yrs 0.459 0.4619 18.48 3.81

Children 6-12 yrs 0.2533 0.2553 10.21 2.12

Youth 13-19 yrs 0.1426 0.1441 5.76 1.21

Adults 20-49 yrs 0.1424 0.1444 5.78 1.24

Adults 50+ yrs 0.15 0.1521 6.08 1.30
6

Females 13-49 yrs 0.1434 0.1454 5.82 1.24

]

2. Non-dietary exposure. [There are no proposed uses for CAS Reg. No. 23328-

53-2 that would result in residential exposures to the U.S. population. Workers may 

experience dermal exposure during application of pesticide formulations if personal 

protective clothing is not worn. Concentrations of CAS Reg. No. 23328-53-2 are less 

than 10% in the formulation and dermal exposure will be limited by the irritation 

potential of the formulation. Thus, a safety finding for CAS Reg. No. 23328-53-2 

can be concluded for non-dietary exposures.]

D. Cumulative Effects

[It has not been determined that CAS Reg. No. 23328-53-2 has a common 

mechanism of toxicity with other substances.]

E. Safety Determination

1. U.S. population. [A dietary exposure assessment using current EPA inert 

screening level methodology (I-DEEM) was conducted. Based on the conservative IDEEM dietary exposure estimates, there is a reasonable certainty that no harm will 

result to the US population from the aggregate exposure to CAS Reg. No. 23328-53-

2 used at 10% w/w in pesticide formulations. The chronic dietary exposure is 

estimated to be 0.1915 mg/kg/day (1.62% cPAD) for the general U.S. population.]

2. Infants and children. [FFDCA section 408 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 pre- and post-natal toxicity and the completeness of 

the data base and exposure, unless EPA determines that a different margin of 

exposure (safety) will be safe for infants and children. Based on the available 

information discussed herein, Loveland Products Inc. believes that the FQPA safety 

factor should be reduced to 1X for the reasons described below. The cRfD is 

therefore equivalent to the chronic population adjusted dose (cPAD).

 The use of CAS Reg. No. 23328-53-2 at 10% w/w in pesticide formulations 

resulted in I-DEEM estimated chronic dietary exposures to children 1-2 

years of age, the potentially most exposed population, of 0.624 mg/kg/d 

(5.12% cPAD).

 There is a scientifically sound mammalian toxicity database for CAS Reg. 

No. 23328-53-2 and structurally related surrogate compounds that includes 

acute, subchronic, developmental, reproductive, and genotoxicity data. The 

data did not indicate developmental, reproductive, or neurological endpoints 

or genotoxic effects.

 There was also no consistent evidence of effects on the nervous system in the 

acute, repeated-dose oral toxicity or reproduction studies.

 CAS Reg. No. 23328-53-2 does not belong to a class of chemicals known or 
7

suspected of having adverse effects on the estrogen receptor or endocrine 

system.]

F. International Tolerances

[There are no known CODEX or international tolerances or tolerance 

exemptions established for CAS Reg. No. 23328-53-2.]