i

EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION 

COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN 

THE FEDERAL REGISTER 

EPA Biopesticides and Pollution Prevention Division contact: [insert name and 

telephone number with area code] 

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.

SUBMISSION: E-mail the completed template to: hollis.linda@epa.gov.

TEMPLATE: 

[D-I-1-4, Inc. a division of 1,4Group, Inc.]

[Insert petition number]

 EPA has received a pesticide petition ([insert petition number]) from [D-I-1-4, 

Inc. a division of 1,4Group, Inc.], [P.O. Box 680, Meridian, ID 83680] 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 amendment of an existing 

tolerance exemption for the biochemical pesticide [1,4-Dimethylnaphthalene (1,4-

DMN)].

 

Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, [D-I-1-4, Inc. a division of 

1,4Group, Inc.] has submitted the following summary of information, data, and 

arguments in support of their pesticide petition. This summary was prepared by [D-I-1-4, 

Inc. a division of 1,4Group, Inc.] and EPA has not fully evaluated the merits of the 

pesticide petition. The summary may have been edited by EPA if the terminology used 

was unclear, the summary contained extraneous material, or the summary unintentionally 

made the reader conclude that the findings reflected EPA’s position and not the position 

of the petitioner. 

I. [D-I-1-4, Inc. a division of 1,4Group, Inc.] Petition Summary

 [Insert petition number]

A. Product Name and Proposed Use Practices
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[Application as a plant growth regulator to inhibit sprouting of potatoes and other 

sprouting root, tuber and bulb crops during storage and shipping. 1,4-DMN is applied at 

low levels (2.5 ppm) during the storage season or during shipping to inhibit sprouting. 

Application of the product will not increase levels of 1,4-DMN above levels normally 

found in potatoes and other sprouting crops.]

B. Product Identity/Chemistry 

 1. Identity of the pesticide and corresponding residues. [1,4-Dimethylnaphthalene 

(1,4-DMN; DMN); OPP Chemical Code: 55802; CAS No. 571-58-4. 

 1,4-DMN is a plant growth regulator belonging to the chemical family of alkylsubstituted naphthalenes. 1,4-DMN occurs in potatoes and other sprouting crops, where 

it naturally inhibits sprouting. As a pesticide active ingredient, it is used as a plant 

growth regulator to inhibit sprouting of potatoes and other sprouting root, tuber and bulb 

crops during storage and shipping. 1,4-DMN is highly volatile and has a low solubility 

in water, and is expected to degrade rapidly in the environment. 

 1,4-DMN was first registered with EPA in 1994 and a tolerance exemption 

established at 40 CFR 180.1142 in February 1995. 

 With this petition the registrant requests the current tolerance exemption be 

amended to read: 

 “180.1142 - 1,4-Dimethylnaphthalene exemption from the requirement of a 

tolerance. An exemption from the requirement of a tolerance is established for residues 

of the plant growth regulator 1,4-Dimethylnaphthalene when applied post-harvest to 

potatoes and other sprouting root, tuber and bulb crops in accordance with good 

agricultural practices.”]

 2. Magnitude of residues at the time of harvest and method used to determine the 

residue. [N/A] 

 3. A statement of why an analytical method of detecting and measuring the levels 

of the pesticide residue are not needed. [An analytical method for residues is not 

applicable. It is expected that, when used as proposed, 1,4-Dimethylnaphthalene would 

not result in residues that are of toxicological concern.]

C. Mammalian Toxicological Profile

[Data on file in support of the current exemption at 40 CFR 180.1142 and 

reviewed in that final rule include: 

- Acute Oral Toxicity study (rat); LD50 of 2,730 mg/kg (MRID No. 430825-10). 

- Acute Dermal Toxicity study (rabbit); LD50 >2,000 mg/kg ( MRID No. 430825-

11). 
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- Acute Inhalation Toxicity study (rat); LC50 >4.16 mg/L (MRID No. 430825-12). 

- Primary Eye Irritation study (rabbit); moderate irritant (MRID No. 430825-13). 

- Primary Dermal Irritation study (rabbit); moderate irritant (MRID No. 430825-

14). 

- Dermal Sensitization study (guinea pig); not a sensitizer (MRID No. 430825-15). 

- Mutagenicity, Ames Test; negative (MRID No. 430825-16). 

- Mutagenicity, in vitro test for unscheduled DNA synthesis; negative (MRID No. 

430825-17). 

- Mutagenicity, in vivo micronucleus assay; negative (MRID No. 430825-18). 

EPA determined that 1,4-DMN is of low acute toxicity by the oral, dermal and inhalation 

routes. It is slightly irritating to eyes and mildly irritating to skin, and is not a skin 

sensitizer. 

Other data on file at the Agency include: 

- Subchronic 90-Day Oral Toxicity study (rat). 1,4-DMN was administered to 

groups of 10 male and 10 female Sprague-Dawley rats for 90 days, in the diet, at 

concentrations of 0, 500, 2500, or 10,000 ppm. An additional 10 rats/sex were 

included in the control and high-dose groups and were held for an additional 28 

days to evaluate the recovery potential from 1,4-DMN-induced effects. In 

addition to standard evaluations (such as body weights, clinical pathology, organ 

weights and histopathology), each rat was used to evaluate for potential 

neurotoxic effects of 1,4-DMN in a functional observational battery and an 

automated motor activity assessment, both performed during the 11th week of 

treatment. 

 Average daily intake of 1,4-DMN was 36, 174, and 713 mg/kg/day for animals in 

the low, mid and high dose groups, respectively. No treatment-related deaths 

occurred during the study. Treatment-related clinical signs were noted mostly in 

high-dose males and consisted primarily of discolored inguinal fur. No treatmentrelated differences were detected in the functional observational battery or motor 

activity assessments, indicating ,1,4-DMN does not express neurotoxic activity. 

Food consumption was significantly decreased in the high-dose group, which 

resulted in reduced body weights. Clinical pathology profiles did not reveal any 

biologically-relevant alterations. Select organ and organ-to-body or organ-to-brain 

weight ratios in the high and mid-dose groups were significantly different from 

controls, in most instances due to reduced body weights. Liver weight was 

increased in some mid and high dose females but there was no histopathological 

correlate. Histopathological findings indicated that the kidney was the target 

organ for 1,4-DMN. Chronic progressive nephropathy (CPN), basophilic tubules 

and mononuclear cell infiltration were observed. CPN was predominately noted in 

the high-dose males, and the precursory basophilic tubules and mononuclear cells 

were seen in the 161 mg/kg/day males. The incidence of kidney effects was 

greater in males than females. After the recovery period, the kidney effects 

persisted in 6 of 10 high-dose males. 
4

 The NOAEL for 1,4-DMN in rats is 32 mg/kg/day (500 ppm), based on the effect 

in the kidney of male animals at the next higher dose level, 2500 ppm (161 

mg/kg/day) (MRID No. 463168-06). 

New data submitted in support of this petition to amend the tolerance include: 

- Dermal Sensitization (Local Lymph Node Assay). To determine whether 1,4-

DMN causes contact hypersensitivity, three groups of female mice received either 

25, 50, or 100% solutions of the test substance applied to the dorsal surface of 

both ears daily for three consecutive days. Another group was similarly treated 

with the vehicle, an acetone olive oil mixture. Three days after the last 

application of 1,4-DMN, the animals received tritiated methyl thymidine after 

which the lymph nodes were removed from each animal. DNA was collected 

from the lymph node cells and the amount of tritiated methyl thymidine 

incorporated into the DNA was measured. The amount of radioactivity present in 

the DNA was equated to a Stimulation Index (SI). If the SI is greater than or 

equal to 3.0, the substance may cause skin sensitization. The SI values calculated 

for the 25, 50, and 100% 1,4-DMN were 2.1, 2.4, and 2.8, respectively, indicating 

that 1,4-DMN does not cause contact hypersensitivity. 

- Prenatal Developmental Toxicity study (rat). A developmental toxicity study 

was conducted in which 1,4-DMN was evaluated for teratogenic activity. In this 

study, 1,4-DMN was administered daily by oral gavage at dose levels of 0, 25, 80, 

or 250 mg/kg/day to groups of 23 timed-mated female rabbits. Treatment was 

from gestation day 6 through gestation day 28, a period that covers implantation, 

organogenesis, and histogenesis. The pregnant rabbits were sacrificed on 

gestation day 29. Fetuses obtained from the pregnant animals underwent visceral 

and skeletal examinations, while half of the fetuses underwent cephalic 

examinations. No treatment-related clinical signs were observed during the 

study. Mean food consumption was significantly reduced in the high dose group 

which resulted in reductions in body weight gains. There was no treatmentrelated differences in litter viability, number of implants, number resorptions, and 

the number of male, female, and total fetuses. No structural alterations were seen 

during the fetal examinations, indicating that 1,4-DMN did not induce fetal 

malformations. Thus, the NOEL for maternal toxicity was 80 mg/kg/day, while 

the NOEL for developmental toxicity was 250 mg/kg/day. 

- Measurement of Unscheduled DNA Synthesis in Rat Liver using an In 

Vivo/In Vitro Procedure. 1,4-DMN was evaluated in an in vivo unscheduled 

DNA synthesis (UDS) test at two dose levels. The choice of dose levels was 

based on the results of a range-finding study. 1,4-DMN was prepared in corn oil 

and administered to rats via oral gavage. Clinical signs and mortality were 

observed in the rangefinder at 1400 and 2000 mg/kg Therefore, 1000 mg/kg was 

considered the maximum tolerated dose (MTD) and was administered as the high 

dose in the definitive study. The second dose was 500 mg/kg. Separate groups of 
5

four rats each received either the vehicle control or the two positive controls, 2-

acetamidofluorene or dimethylnitrosamine. Livers were collected 2-4 hours or 

12-14 hours after dosing, and were dissociated with collagenase. The resulting 

hepatocytes were exposed to [3

H] thymidine. Incorporation of the radiolabeled 

thymidine into DNA was evaluated by autoradiography and grain counting. 

 Negative (vehicle) control animals gave a group mean net nuclear grain (NNG) 

value of 0.6 or less with no cells in repair. Group mean NNG values were 

increased by treatment with 2-acetamidofluorene and dimethylnitrosamine to 

more than 2.3 with at least 13.7 percent of the cells in repair. The vehicle control 

NNG value was consistent with both published and historical control data, and the 

system was shown to be sensitive to two known DNA damaging agents that 

require metabolism for their mutagenic activity. Since treatment with 500 or 

1000 mg/kg 1,4-DMN did not produce a group mean NNG value greater than 0.6 

and since none of the 1,4-DMN treated cells were found in repair, the test 

substance did not induce unscheduled DNA synthesis. Therefore, the results 

indicate that 1,4-DMN does not have mutagenic activity. 

- In vitro Percutaneous Absorption of 1,4-Dimethylnaphthalene Through 

Human Skin Membranes. The percutaneous absorption of 14C-1,4-

dimethylnaphthalene (1,4-DMN) was determined using human skin samples. The 

samples were derived from the abdomen and/or breast of six different skin donors 

directly after surgery. Subcutaneous fat was removed from the skin and the 

samples were stored at -18oC until use. After thawing, the skin was dermatomed 

to a thickness of approximately 400 μm. The skin membranes were placed in 9 

mm flow-through automated diffusion cells and were maintained at 32 ± 1oC. 

Prior to initiating the study, the integrity of the skin membranes was confirmed 

using tritiated water. Exposure duration was 8 hours, with 16 hours post-exposure 

time. The dose level, 12 μg/cm2

, was based on a worst case estimate of the potatoto-skin transfer of l,4-DMN residues during manual handling of treated potatoes. 

The donor compartment was covered with a charcoal filter to capture volatile 

radioactivity. 

 Receptor fluid samples were collected at 1 hour, 2 hours and at 2-hour intervals 

until 24 hours after application. After an exposure period of 8 hours, the 

unabsorbed test substance was removed from the application site using a mild 

soap solution (3 percent Teepol in water) and cotton swabs. At 24 hours after 

application, the diffusion cells were dismantled. Receptor and donor 

compartments were washed twice with 1.0 ml ethanol. Each skin membrane was 

tape stripped 15 times or until the epidermis was ruptured using Stripping Discs 

(CuDerm Corporation). Skin membranes were digested in a 1.5 M KOH solution 

with 20 percent ethanol for approximately 24 hours. Radioactivity was 

determined by liquid scintillation chromatography in receptor fluid, skin 

membranes, tape strips, skin wash, donor and receptor compartment, and in 

charcoal filter. 
6

 The recovery of 14C-1,4-DMN in one of the six replicates was low. Therefore, the 

results from five replicates were used to calculate the mean values. The mean 

recovery in these 5 replicates was 87.4  16.1 percent. The mean absorption of 

14C-1,4-DMN into the receptor fluid after 24 hours was 0.22 μg/cm2

, representing 

1.83% of the applied dose. The dermal absorption of 1,4-DMN in human skin was 

determined to be 2.5% of the applied dose, which includes the amount of 

radiolabel measured in the receptor compartment wash and the amount of 

radiolabel retained in the skin. 

- Reproductive Toxicity study, one-generation (rat). In an extended onegeneration reproductive toxicity study, 1,4-DMN was administered daily to 

Sprague-Dawley rats via their diet at doses of 0, 500, 2000, or 7500 

ppm. Parental animals were fed the diets for two weeks prior to mating, during 

the two-week mating period, and for the females, through gestation, lactation, and 

until necropsy. Body weight, body weight gain, food consumption, clinical signs 

of toxicity, incidence of morbidity and mortality, hematology, clinical chemistry, 

reproductive performance, and many offspring parameters were measured and 

recorded. In addition, sperm count, morphology, and motility was 

assessed. Immunologic endpoints measured include the T-cell dependent 

antibody response assay, splenic lymphocyte subpopulation analysis, and 

examination of thymus and spleen. Offspring continued to be exposed to 1,4-

DMN via lactation and diet. Some were culled while others were chosen for 

additional evaluations. Fetal developmental endpoints measured include 

anogenital distance, vaginal patency, and preputial separation. Diagnostic 

pathology was performed on many organs and tissues. 

 

 There were no treatment-related deaths or clinical signs of toxicity. Mean food 

consumption in the high dose animals was significantly reduced, most probably 

due to palatability of the 1,4-DMN in the diet. This resulted in reductions in body 

weights and body weight gains in the high dose group. Treatment with 1,4-DMN 

did not adversely affect reproductive performance, litter viability, or offspring 

survival. There was no evidence of immunotoxicity. While treatment with 1,4-

DMN caused an increase in liver weights in the high dose animals, there were no 

histological changes in the liver that suggested heptotoxicity. Thus, the increase 

in liver weights was determined to be an adaptive response such as enzyme 

induction. The NOAEL for reproductive toxicity in rats was shown to be 7500 

ppm. 

 

- Combined Chronic Toxicity / Carcinogenicity study (rat). D-I-1-4, Inc. 

conducted a combined chronic toxicity/carcinogenicity study in which SpragueDawley rats received daily oral doses of 1,4-DMN in their diets at 0, 150, 500, or 

3750 ppm, equivalent to 0, 10, 33, or 250 mg/kg/day. Animals assigned to the 

chronic toxicity phase received the test substance for 52 weeks while the animals 

in the carcinogenicity phase received 1,4-DMN for up to 104 weeks. Ingestion of 

the high dose of 250 mg/kg/day resulted in decreased food consumption with 

concurrent decreases in body weight and body weight gain. There were no 
7

treatment-related mortalities and no treatment-related effects on 

hematology, urinalysis, organ weights, or gross pathology. High dose male rats 

showed minimal to moderate histologic changes in the kidney, as did the high 

dose and mid dose females. Thus the NOEL for chronic toxicity was shown to be 

33 mg/kg/day for males and 10 mg/kg/day for females. Neoplasms found in this 

study were typical of those observed in aging rats. There was no treatmentrelated increase in the incidence of any type of neoplasm. Therefore, the 

administration of 1,4-DMN to male and female Sprague-Dawley rats did not 

cause carcinogenicity. The study was conducted in compliance with EPA 

Guideline 870.4300 and OECD Guideline 453.] 

D. Aggregate Exposure

 1. Dietary exposure. 

 i. Food. [Dietary exposure from use of 1,4-DMN, as proposed, is minimal. 

The intended use of 1,4-DMN is indoor application to post-harvest crops 

and it is applied at very low rates below naturally occurring levels. 1,4-

DMN is not considered persistent based on its characteristics, properties or 

known degradation pathways. 

 Acute toxicity studies have shown that 1,4-DMN is not toxic during acute, 

subchronic and chronic studies. Further, 1,4-DMN is not mutagenic as 

demonstrated in multiple studies. The results of toxicity testing and the 

lack of anticipated residues on treated commodities show there is no risk 

to human health from 1,4-DMN. Dietary exposures would not be 

expected to pose any quantifiable risk due to a lack of residues of 

toxicological concern. ]

 ii. Drinking water. [Similarly, exposure to humans from residues of 1,4-

DMN in consumed drinking water would be unlikely. Potential exposure 

to surface water would be negligible and exposure to drinking water (well 

or ground water) would be impossible to measure. The intended use of 

1,4-DMN is indoor application to post-harvest crops. The ingredient is 

not applied directly to water. 

 Acute toxicity studies have shown that 1,4-DMN is not toxic during acute, 

subchronic and chronic studies. Further, 1,4-DMN is not mutagenic as 

demonstrated in multiple studies. The results of toxicity testing and the 

lack of residues on treated commodities show there is no risk to human 

health from 1,4-DMN. Drinking water exposures would not be expected to 

pose any quantifiable risk due to a lack of residues of toxicological 

concern.]

 2. Non-dietary exposure. [The potential for non-dietary exposure to the general 

population, including infants and children, is unlikely as the proposed use sites are 

indoor and agricultural. The intended use of 1,4-DMN is application to post-
8

harvest crops. 1,4-DMN is not considered persistent based on its characteristics, 

properties or known degradation pathways. 

 Acute toxicity studies have shown that 1,4-DMN is not toxic during acute, 

subchronic and chronic studies. Further, 1,4-DMN is not mutagenic as 

demonstrated in multiple studies. The results of toxicity testing and the lack of 

residues on treated commodities show there is no risk to human health from 1,4-

DMN. Non-dietary exposures would not be expected to pose any quantifiable risk 

due to a lack of residues of toxicological concern.]

E. Cumulative Effects

 [It is not expected that, when used as proposed, 1,4-DMN would result in residues 

that are of toxicological concern. The intended use of 1,4-DMN is application to post 

harvest crops. 1,4-DMN is not considered persistent based on its characteristics, 

properties or known degradation pathways. 

Acute toxicity studies have shown that 1,4-DMN is not toxic during acute, subchronic 

and chronic studies. Further, 1,4-DMN is not mutagenic as demonstrated in multiple 

studies. The results of toxicity testing and the lack of residues on treated commodities 

show there is no risk to human health from 1,4-DMN.] 

F. Safety Determination

 1. U.S. population. [The results of toxicity testing and the lack of residues on 

treated commodities show there is no risk to human health from 1,4-DMN. The 

intended use of 1,4-DMN is application to post-harvest crops. There is a 

reasonable certainty of no harm to the general US population from exposure to 

this active ingredient.] 

 2. Infants and children. [As mentioned above, it is not expected that, when used 

as proposed, 1,4-DMN would result in residues that are of toxicological concern. 

There is a reasonable certainty of no harm for infants and children from exposure 

to 1,4-DMN from the proposed uses. ] 

G. Effects on the Immune and Endocrine Systems 

[To date there is no evidence to suggest that 1,4-DMN functions in a manner 

similar to any known hormone, or that it acts as an endocrine disrupter.] 

H. Existing Tolerances

[There is current a tolerance exemption established, as follows: 
9

 “40 CFR 180.1142. An exemption from the requirement of a tolerance is 

established for residues of the plant growth regulator 1,4-DMN when applied 

post-harvest to potatoes in accordance with good agricultural practices.” 

(February 8, 1995)] 

I. International Tolerances

[A Codex Alimentarium Commission Maximum Residue Level (MRL) is not 

required for 1,4-Dimethylnaphthalene.]