EXECUTIVE SUMMARY 

Dimethoxane is registered for use as a preservative for industrial adhesives, paints, 

emulsions, coatings, and specialty industrial products which include pigment slurries, dyestuffs, 

inks, thickeners, gums and lignosulfonate. Dimethoxane is also registered for use in textile 

chemicals and finishes, leather processing liquors and distillation fuels. There is currently one 

product registered. 

The RED for Dimethoxane was completed in 1996 and all of the above uses were found to be 

eligible for registration provided that the labels were modified to include precautionary language 

regarding skin sensitization and a label statement about the use of dimethoxane in food contact 

adhesives and coatings. In 2009, the registrant requested a label amendment to include 

preservation of household, industrial and institutional water based products. The human health 

aspects of this request were evaluated in D356732 (EPA, 2009) and it was determined that a 90 

day inhalation study and a dermal sensitization study would be needed to support these uses. 

 

Dimethoxane has a fairly high vapor pressure of 0.111 mm Hg @ 25 C and it rapidly hydrolyzes 

to acetaldehyde. Based upon the use patterns, physical/chemical properties and hazard data, the 

following exposures will need to be assessed: 

• Occupational dermal and inhalation exposure to dimethoxane and inhalation exposure to 

acetaldehyde during the open pour application of dimethoxane during paint preservation. 

• Occupational and residential dermal and inhalation exposure to dimethoxane and 

inhalation exposure to acetaldehyde during the use of dimethoxane treated paints. 

• Residential dermal and incidental oral exposures to textiles treated with textile chemicals 

and finishes that have been preserved with dimethoxane. 

• Residential dermal and incidental oral exposures to leather products treated with 

processing liquors that have been preserved with dimethoxane. 

To assess the above exposures, the following toxicological and exposure data will be needed: 

• Dermal sensitization threshold quantification study to quantify the dermal sensitization 

potential in humans

• 90 Day inhalation toxicity study in rats 

• Indoor exposure studies (dermal and inhalation) during material preservation, and indoor 

painting. 

• Leaching studies on textiles treated with dimethoxane preserved textile chemicals and 

finishes.

• Leaching studies on leather products treated with dimethoxane preserved leather liquors.

• Product use information

Page 2 of 22 
1.0 BACKGROUND 

1.1 Chemical Identity 

The chemical identity of dimethoxane listed in Table 1. 

Table 1 - Chemical Identity of Dimethoxane 

Chemical Name 2,6-dimethyl-m-dioxane-4-ol acetate 

Common Name Dimethoxane 

PC Code 001001 

CAS Registry Number 828-00-2 

Case No. 3064 

Empirical Formula C8O4H14

Structure 

1.2 Chemical and Physical Properties 

The physical and chemical properties of dimethoxane that are relevant for human health risk 

assessment are listed in Table 2. It should be noted that dimethoxane has a relatively high vapor 

pressure of 0.111 mm Hg at 23 C. 

Table 2 - Physical and Chemical Properties of Dimethoxane

Property Value Reference 

Molecular Weight 174.2 

Physical State Liquid EPA, 1996 

Density 1.060 – 1.075 @ 25 C EPA, 1996 

Solubility >2 gm/ml @ 25 C in methanol, hexane and 

water 

EPA, 1996 

Octanol/Water Partition Coefficient N/A - Hydrolyzes in water 

Vapor Pressure 0.111 mm Hg @ 23 C MRID 416782-05 

Henry’s Law Constant 1.24 x 10-7 atm-m3/mole @ 25 C Estimated using EPI Suite 

Page 3 of 22 
2.0 USE INFORMATION 

2.1 Formulation Types and Percent Active Ingredient

According to OPPIN, as of 9/7/2010, there is one end use product, Bioban DXN (464-682, 

approved 4/21/2010) that contains dimethoxane (87.0%) as the active ingredient (ai). This 

product is formulated as a liquid. 

2.2 Summary of Registered Uses 

According to product information (Dow Chemical, 2002), Bioban DXN is a biocide for the 

protection of water based industrial products, processes and systems against microbial growth 

and spoilage. Upon addition to aqueous systems, Bioban DXN undergoes hydrolysis to its 

microbiological active components acetaldehyde, aldol and acetic acid. It functions over a wide 

Ph range of 3 to 8 and it is not effective in systems with a Ph over 9. 

Dimethoxane is registered for use as a preservative for industrial adhesives, paints, 

emulsions, coatings, and specialty industrial products which include pigment slurries, dyestuffs, 

inks, thickeners, gums and lignosulfonate. Dimethoxane is also registered for use in textile 

chemicals and finishes, leather processing liquors and distillation fuels. The product application 

rate for all these uses ranges from 0.01% to 0.2% by weight. Given that the product contains 

87.0% dimethoxane, the application rates in terms of active ingredient range from 0.0087% to 

0.174%. 

The RED for Dimethoxane was completed in 1996 and all of the above uses were found to be 

eligible for registration provided that the labels were modified to include precautionary language 

regarding skin sensitization and a label statement about the use of dimethoxane in food contact 

adhesives and coatings. In 2009, the registrant requested a label amendment to include 

preservation of household, industrial and institutional water based products. The human health 

aspects of this request were evaluated in D356732 (EPA, 2009) and it was determined that a 90 

day inhalation study and a dermal sensitization study would be needed to support these uses. 

These requirements were re-iterated in D371458/D371587 (EPA, 2010) which was written in 

response to waiver requests 

2.3 Summary of Use Data 

 

 According to the Specialty Biocides North America Report 2004-2005 (Kline, 2006), 

dimethoxane (listed as Bioban DXN) is used in paints and coatings with a market share of 2 

percent by volume and 1 percent by value and in adhesives with a market share of 6 percent by 

volume and 5 percent by value. 

Page 4 of 22 
3.0 TOXICOLOGY 

 

The toxicological database for the dimethoxane registration review case is comprised of 

studies that were available to the Agency when the RED was written in 1996 and additional 

studies that were submitted after the RED. The additional studies include the following: 

• Unscheduled DNA Synthesis – Rat Hepatocyte, MRID 457183-01 

• Micronucleus Test – Mouse Bone Marrow Erythrocyte, MRID 457195-01 

Both these studies were reviewed and found to be acceptable. The micronucleaus test 

indicated that dimethoxane does not cause a change in the frequency of micronuclei in mouse 

bone marrow erythrocytes. The unscheduled DNA Synthesis test indicated that dimethoxane 

does not cause unscheduled DNA synthesis. 

3.1 Acute Toxicity 

 A complete database of acute toxicity data was available to the Agency at the time the RED 

was written. A summary of the findings, which are detailed in the RED, is included in Table 3. 

These findings indicate that dimethoxane is of low to moderate acute toxicity by all routes of 

exposure and that dimethoxane is a strong sensitizer. 

Table 3 - Acute Toxicity Values for Dimethoxane. 

Test (species) Result Toxicity Category 

81-1 Oral Toxicity (rat) LD50 >2000 mg/kg III 

81-2 Dermal Toxicity (rabbit) LD50 > 2000 mg/kg III 

81-3 Inhalation Toxicity (rat) LC50 > 4.0 mg/L III 

81-4 Eye Irritation (rabbit) Mild Irritation III 

81-5 Skin Irritation (rabbit) Slight Irritation IV 

81-6 Dermal sensitization (guinea pig) Strong sensitizer N/A 

3.2 Subchronic and Chronic Toxicity 

The most recent hazard assessment for dimethoxane is included in D356732 (EPA, 2009) and a 

summary of this assessment is included below: 

Dermal Toxicity

90 Day Dermal Toxicity Study: During a dermal toxicity study (MRID #406502-01) doses of 

0, 100, 300, or 1000 mg/kg/day of dimethoxane were applied to the skin of rats for 6 hrs/day, 5 

days/week, for three months. The test material was administered undiluted and the test site was 

covered with gauze. The gauze was removed after six hours and the test site was cleaned with 

water. There were signs of dermal irritation in females during the first three weeks of treatment, 

however, the irritation subsided after the use of water to clean the dosing site was discontinued 

and during the last month of the study irritation (eschar formation and superficial necrosis) were 

observed only on one male and two females in the 1000 mg/kg/day dose group. Systemic 

effects were also observed at 300 and 1000 mg/kg/day and included decreased body weight gain 

Page 5 of 22 
and hepatic lesions. The lesions consisted of minimal or slight necrosis, inflammation or 

hemorrhage. The NOAEL for systemic effects was 100 mg/kg/day.

Subchronic Oral Toxicity

NTP 16-day oral gavage study: The National Toxicology Program (NTP) conducted a 16-day 

study, during which groups of five rats and five mice of each sex were administered 0, 125, 250, 

500, 1,000, or 2,000 mg/kg dimethoxane in corn oil per day. The rats were 6 weeks old and mice 

were 8 weeks old when placed in the study. Deaths occurred in rats and in male mice that 

received 2,000 mg/kg. Body weights of rats and mice were similar to those of vehicle controls. 

Compound-related clinical signs were not seen in surviving rats. Hemorrhage and necrosis of the 

stomach were observed in rats in the 2,000 mg/kg group which died before the end of the studies. 

Lesions of the forestomach, including inflammation, hyperplasia, hyperkeratosis, and ulceration, 

occurred in rats that received 250-2,000 mg/kg. Mice that received 500-2,000 mg/kg 

dimethoxane had lesions of the forestomach including erosion, ulceration, hyperplasia, and 

hyperkeratosis. Forestomach lesions were not seen at 125 or 250 mg/kg. 

NTP 13-week oral gavage study: The NTP conducted a 13-week rat and mice gavage study 

with commercial grade dimethoxane (80% pure, none of these impurities exceeded 3%) in corn 

oil. Groups of 10 rats and 10 mice of each sex were administered levels of 0, 31, 62, 125, 250, 

or 500 mg/kg/day by gavage. No compound-related deaths occurred in rats. The final mean body 

weights of rats that received 500 mg/kg were 17% lower than that of vehicle controls for males 

and 5% lower for females. Ulceration, inflammation, and acanthosis with hyperkeratosis of the 

stratified squamous epithelium of the forestomach were seen in rats that received 500 mg/kg. 

Forestomach lesions were not seen in males that received 31 mg/kg or in females that received 

31, 62, or 125 mg/kg. 

All mice lived to the end of the studies and final mean body weights of dosed and vehicle control 

mice were similar. Minimal-to- mild acanthosis and hyperkeratosis of the squamous epithelium 

of the forestomach were seen in 4/10 high dose male and 1/10 high dose female mice. 

Because of the forestomach lesions observed in rats and mice and reduced body weight observed 

for male rats, doses selected for the 2-year studies were 0, 62.5, or 125 mg/kg dimethoxane in 

corn oil, given by gavage 5 days per week to groups of 60 male rats; 0, 125, or 250 mg/kg to 

groups of 60 female rats; and 0, 250, or 500 mg/kg to groups of 58 or 60 mice of each sex. Ten 

animals per sex and species from each dose group were killed 15 months after initiation of the 

studies to determine toxicity, pre-neoplastic lesions, and early induced neoplasia. 

Chronic Oral Toxicity and Carcinogenicity

NTP 15-month oral gavage study: The NTP conducted a 15-month rat and mice gavage study 

with commercial grade dimethoxane in corn oil. Groups of 60 male rats were administered 0, 

62.5, or 125 mg/kg/day and groups of 60 female rats were administered at levels of 0, 125, or 

250 mg/kg/day. Groups of 58 or 60 mice of each sex were administered at levels of 0, 250, and 

500 mg/kg/day. Minimal diffuse acanthosis and hyperplasia of the forestomach were seen in 

7/10 female rats at 250 mg/kg, 7/10 males at 125 mg/kg, and 1/9 male and 1/9 female vehicle 

controls. Acanthosis of the forestomach was seen in 7/10 male and 6/10 female mice at 500 

Page 6 of 22 
mg/kg. Harderian gland adenomas were seen in one high dose male and one high dose female 

mouse. A harderian gland adenocarcinoma was seen in a second high dose female mouse. No 

compound-related effects were observed for clinical chemical or hematologic values or for organ 

weights for rats or mice. The NOAEL was 125 mg/kg/day. 

NTP two-year cancer study: The NTP conducted carcinogenicity studies on rats and mice with 

commercial grade dimethoxane (80% pure). The male rats were given 0, 62.5, or 125 mg/kg/day 

and the female rats were given 0, 125 or 250 mg/kg/day dimethoxane in corn oil by gavage for 

two years. Acanthosis and hyperkeratosis were increased in the forestomach of high dose rats. 

The male and female mice were given 0, 250, or 500 mg/kg/day by gavage for two years. 

Acanthosis, hyperkeratosis, focal hyperplasia, and chronic inflammation were increased in the 

forestomach of dosed mice. Mean body weights of dosed and vehicle control rats and mice of 

each sex were generally similar. No significant differences in survival were observed between 

any groups of rats or mice. 

There was no evidence of carcinogenic activity of dimethoxane for male rats receiving 62.5 or 

125 mg/kg or for female rats receiving 125 or 250 mg/kg per day. There was equivocal evidence 

of carcinogenic activity of dimethoxane for male mice, as indicated by an increased incidence of 

forestomach neoplasms. There was no evidence of carcinogenic activity for female mice 

receiving 250 or 500 mg/kg per day. Acanthosis and hyperkeratosis occurred at increased 

incidences in the forestomach of high dose rats. Inflammation, acanthosis with hyperkeratosis, 

and focal hyperplasia occurred at increased incidences in the forestomach of dosed mice. 

 

Developmental Toxicity

MRID # 411514- 01 - Dimethoxane (92.0% a.i.) was administered to groups of 24-26 pregnant 

female rats by gavage on gestation days 6-15 inclusive at dose levels of 0, 60, 300, and 900 

mg/kg/day. Excessive salivation and was noted in all high dose females at one or more intervals 

during treatment. Food consumption was decreased in high dose females and body weight gain 

was significantly decreased. There were no adverse effects noted on pregnancy incidence or 

number of females with live pups at any dose level; cesarean section observations were also 

unremarkable. Filamentous tail was observed in one high dose pup. One mid dose pup was 

observed with abnormal origin and course of the right subclavian artery off the aortic arch; this 

same pup was observed to be edematous and pale in color. Tortuous ureter was also observed 

among the dose groups but were within historical control incidence and did not demonstrate a 

dose-response. Several skeletal variations were observed in the mid- and high-dose pups in this 

study which were slightly increased over control, and included incomplete ossification of several 

bones; however, these increases were not statistically significant. Based on the results of this 

study, the Maternal NOAEL is determined to be 300 mg/kg/day, and the Maternal LOAEL is 

determined to be 900 mg/kg/day, based on reduced body weight gain and food consumption, and 

excessive salivation. The Developmental NOAEL is considered to be 900 mg/kg/day. 

Page 7 of 22 
Reproductive Toxicity

There are no reproductive toxicity studies available for dimethoxane. 

Mutagenicity

The following summary is obtained from TR-354, “Toxicology and Carcinogenesis Studies of 

Dimethoxane (Commercial Grade) in F344/N Rats and B6C2F1 Mice.” 

Dimethoxane was mutagenic in strain TA100 of S. typhimurium in the presence but not the 

absence of exogenous metabolic activation; it was not mutagenic in strains TA98, TA1535, or 

TA1537 with or without activation. Dimethoxane induced sister chromatid exchanges and 

chromosomal aberrations in Chinese hamster ovary (CHO) cells both with or without exogenous 

metabolic activation. Dimethoxane induced sex-linked recessive lethal mutations in Drosophila 

when administered by abdominal injection to adult males; no induction of reciprocal 

translocations was observed in adult males after injection of dimethoxane.

In studies submitted to and reviewed by the Agency, dimethoxane was found to be nonmutagenic in the Ames Salmonella assay in five tester strains. In the CHO assay, dimethoxane 

was clastogenic at concentrations of 100 and 150 μg/ml under conditions of metabolic activation, 

but was non-clastogenic under conditions of non-activation. 

3.3 Metabolites and Degradates of Toxicological Concern 

As discussed in the Product Chemistry, Environmental Fate and Ecotoxicity Data 

Summary (EPA, 2010), the available data indicate that the major route of degradation is abiotic 

hydrolysis aided by microbial mediated degradation. Further, the data indicate that dimethoxane 

is highly unstable in water with over 50% of the compound hydrolyzed in 2 hours. Dimethoxane 

is purported to react with water to form acetic acid and a transient intermediate, dioxinol. The 

dioxinol then breaks down into acetaldehyde and aldol (i.e. 3-hydroxybutanal). The breakdown 

into acetic acid and dioxinol is completed in 14 hours. 

3.4 Toxicological Endpoints Used for Risk Assessment 

A summary of the endpoints that could be used for risk assessment was included in D356732 

(EPA, 2009) and these endpoints are listed in Table 4. Endpoints are not available to assess 

dermal sensitization effects or effects from inhalation exposures. 

Page 8 of 22 
Table 4. Summary of Doses and Endpoints Selected for Dimethoxane Risk Assessments. 

Exposure 

Scenario 

Dose Used in 

Risk Assessment 

Level of Concern for 

the MOE 

Study and Toxicological Effects 

Incidental Oral - Short 

and Intermediate Term 

(1-30 days) 

NOAEL=125 

mg/kg/day 

Residential/Occupational 

MOE = 100A

NTP fifteen-month rat study 

LOAEL = 250 mg/kg/day 

Based on diffuse acanthosis and 

hyperplasia in the forestomach 

Dermal – All Durations NOAEL= 100 

mg/kg/day 

Residential/Occupational 

MOE = 100A

90-Day Dermal Toxicity – Rats 

LOAEL = 300 mg/kg/day 

based on hepatocellular alterations 

Dermal SensitizationB No study available (data gap); this risk assessment IS required for specific dermal 

exposure concern. The chemical is a strong dermal sensitizer. 

InhalationC – All 

Durations 

No study available (data gap); this risk assessment IS required. 

Cancer (all routes) Suggestive evidence of carcinogenicity to humans; quantitative risk assessment not 

required. 

A. Includes 10x for inter-species variation, and 10X for intra-species variation. 

B. Dimethoxane is a strong dermal sensitizer and a dermal sensitization study that can be used to identify a 

threshold for dermal sensitization risk assessment is needed. 

C. A data gap exists for a 90-day inhalation toxicity study in rats was identified by the OPP Hazard Identification 

Assessment Review Committee (2000). This study is required due to the significant vapor pressure (0.111 mm 

Hg at 23°C). Inhalation is considered as an important route of exposure. 

Toxicity Data Needs

Several toxicology studies will be needed to complete registration review. These studies are 

listed in Section 10. 

4.0 DIETARY ASSESSMENT 

Dietary Exposure

Dimethoxane is not registered for any direct or indirect food uses, nor does it have any FDA 

approvals for such uses. The label contains the following statement which was required by the 

RED: 

“THE PRODUCT HAS NOT BEEN CLEARED UNDER THE FEDERAL, FOOD, DRUG, 

AND COSMETIC ACT FOR USE IN THE MANUFACTURE OF COATINGS THAT MAY 

COME IN CONTACT WITH FOOD.” 

Drinking Water Exposure

There is a potential for drinking water exposure from the material preservative uses. The 

Agency expects that the environmental fate data that are being required will be useful to evaluate 

Page 9 of 22 
this potential. Therefore, the need for a drinking water assessment will be determined after the 

environmental fate data are received and reviewed. 

5.0 OCCUPATIONAL/RESIDENTIAL EXPOSURE 

At the time of the RED, it was determined that there were no toxicological endpoints of 

concern due to low toxicity and minor effects and therefore no assessment was required for 

occupational or residential risks. It was also determined incorrectly that there would be 

minimal post application exposure due to the chemical properties (low vapor pressure, etc.) and 

small amounts contained in treated products such as paints. Because dimethoxane actually has a 

fairly high vapor pressure of 0.11 mm Hg at 25 C, this determination needs to be reconsidered. 

It will also be necessary to evaluate the exposures from acetaldehyde which is a degradate of 

dimethoxane. Based on these factors and the use patterns, physical/chemical properties and 

hazard data, the following exposures will need to be assessed: 

• Occupational dermal and inhalation exposure to dimethoxane from the open pour 

application of dimethoxane during paint preservation. 

• Occupational inhalation exposure to acetaldehyde released from dimethoxane during 

paint preservation. 

• Occupational and residential dermal and inhalation exposure to dimethoxane from the use 

of dimethoxane treated paints. 

• Occupational and residential inhalation exposure to acetaldehyde from the use of 

dimethoxane treated paints. 

• Residential dermal and incidental oral exposures to textiles treated with textile chemicals 

and finishes that have been preserved with dimethoxane. 

• Residential dermal and incidental oral exposures to leather products treated with 

processing liquors that have been preserved with dimethoxane. 

Exposure Studies Needed for Registration Review

A listing of the exposure studies that will be needed for registration review is included in 

Section 10 and detailed justifications are included in Appendix A. 

 

6.0 AGGREGATE AND CUMULATIVE EXPOSURE 

 In examining aggregate exposure, EPA takes into account the available and reliable 

information concerning exposures to pesticide residues in food and drinking water, as well as 

non-occupational pesticide exposures. An aggregate risk assessment may be needed for 

dimethoxane if it is determined that a drinking water exposure could occur based on the 

environmental fate data. 

 Section 408(b)(2)(D)(v) of 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 yet determined whether dimethoxane has a common 

Page 10 of 22 
mechanism with other compounds; consequently, a cumulative assessment will not be performed 

at this time. 

7.0 INCIDENTS 

There are no incidents reported for dimethoxane in the OPP incident database. There is one 

report in the literature (Shmunes and Kempton, 1980) of allergic contact dermatitis resulting 

from the use of dimethoxane in a textile spin finish. 

8.0 TOLERANCES 

There are no tolerances or exemptions from tolerances for dimethoxane. As mentioned in 

Section 4.0, dimethoxane is not approved for use as an indirect food additive. 

9.0 ENDOCRINE DISRUPTION EFFECTS 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors. 

Dimethoxane is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

Page 11 of 22 
10.0 ANTICIPATED DATA NEEDS 

To assess the exposures listed in Section 4 (dietary) and Section 5 (occupational/residential) 

the toxicological and exposure studies listed in Tables 5 and 6 will be needed. Detailed 

justifications for these studies are provided in Appendix A. 

Table 5 – Human Toxicology Studies Needed for Dimethoxane Registration Review

Study Needed Guideline Rationale 

Dermal Sensitization 

Threshold Quantification 

N/A This study is needed to identify a threshold for dermal sensitization risk 

assessment for dimethoxane in treated materials such as paints, textiles and 

leather products. 

90 Day Inhalation - rat 870.3465 This study is needed to assess occupational inhalation risk from openpouring of liquids during materials preservation and the occupational and 

residential inhalation risks during the use of dimethoxane treated paints. 

Table 6 –Exposure Studies Needed for Dimethoxane Registration Review

Study Needed Guideline Rationale 

Indoor Exposure 

(Open Mixing/Loading Liquids) 

875.1200 (Dermal) 

875.1400 (Inhalation) 

875.1600 (Data Reporting/Calculations) 

Exposure may occur during open pour 

addition of dimethoxane* during material 

preservation and fuel treatment. 

Indoor Exposure 

(Interior Painting) 

875.1200 (Dermal) 

875.1400 (Inhalation) 

875.1600 (Data Reporting/Calculations) 

Exposures to paint aerosols and vapors of 

dimethoxane and to vapors of acetaldehyde 

may occur during interior applications of 

dimethoxane treated paints. 

Leaching Study on Textiles No Guideline Dermal and incidental oral exposures may 

occur from wearing and mouthing clothing, 

towels and blankets made from textiles 

treated with dimethoxane preserved textile 

chemicals and finishes. 

Leaching Study on Leather No Guideline Dermal and incidental oral exposures may 

occur from wearing and mouthing leather 

products treated with dimethoxane 

preserved liquors. 

Product Use Information 875.1700 Use information can be used to evaluate 

exposures and assist in the planning of 

exposure studies. 

*If the labels are amended to require closed mixing and loading, then the exposure studies will not be needed 

for the open loading/mixing scenario. 

Page 12 of 22 
11.0 REFERENCES 

Dow Chemical, 2002. Product Information for BIOBAN DXN, Form No. 253-01219-10/10/02. 

EPA, 1996. Dimethoxane Reregistration Eligibility Decision (RED), May 1996, 

http://www.epa.gov/pesticides/reregistration/status.htm

EPA, 2009. Dimethoxane: Hazard Assessment for the Proposed New Use as an Antimicrobial in 

Preservation of Household, Industrial and Institutional Water Base Products. D356732, May 7, 

2009 

EPA, 2010. Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the 

Dimethoxane Registration Review Decision Document. D382303, October, 2010. 

Kline, 2006. Specialty Biocides North America 2004-2005, Kline and Company, Inc. 

Shmunes and Kempton, 1980. Allergic Contact Dermatitis to Dimethoxane in a Spin Finish, 

Contact Dermatitis: 6 (6), pp 421-424, October, 1980. 

Page 13 of 22 
Page 14 of 22 

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Appendix A – Justification for the 

Toxicology and Exposure Studies Needed fo

Registration Review of Dimethoxane 

Page 15 of 22 
Appendix A, Table 1 - Toxicology Study Justifications 

Guideline Study Title Practical Utility of the Data 

870.3465 90-Day Inhalation 

Toxicity Study (Rat) 

1) What is the value of the study? The Agency currently does not have a repeated dose inhalation toxicity stud

and is therefore required to extrapolate from a repeated dose oral toxicity st

of inhalation exposure. Since the effects of a chemical can vary greatly wit

administration, the use of a route specific study will greatly increase the acc

assessment. 2) How would the data be used? The study will be used to assess risks from inhalation exposures to dimethoopen pour addition of liquids during materials preservation and painting wit

dimethoxane. The study will be used to determine inhalation specific endpto assess the inhalation exposures and it will eliminate the uncertainty that estudies are used to assess inhalation exposures. 3) How could the data affect the risk assessment? The study will allow the selection of a route specific endpoint which may b

route extrapolated endpoint that would otherwise be used. It is possible tha

uncertainty factor that is associated with using route to route extrapolation c

removed, resulting in a lower level of concern for the uncertainty factor. 

4) What is triggering the need for this data? The potential inhalation exposures that might occur during open pour additi

material preservation and painting with dimethoxane treated paints are the t

inhalation risk assessment which in turn requires an inhalation toxicity stud

Page 16 of 22 
Appendix A, Table 1 - Toxicology Study Justifications 

Guideline Study Title Practical Utility of the Data 

N/A Dermal 

Sensitization Threshold Quantification 

1) What is the value of the study?This study is needed to quantify the dermal sensitization effects that have bacute animal study (MRID 419367-03) where dimethoxane was found to be 

guinea pigs. 2) How would the data be used?The data would be used to identify a threshold for the dermal sensitization Specifically the data would be used to identify a safe threshold level for the 

sensitization which is protective of induction as recommended by the FIFRThis level would then be used to assess the risk of dermal sensitization from dimethoxane. 3) How could the data affect the risk assessment?Currently it is not possible to assess the risks of sensitization from exposur

because the acute animal study does not provide a threshold level. 4) What is triggering the need for this data? The need for this data is triggered by residential dermal exposures from the 

use, the positive result for dermal sensitization seen in the acute study and t

dermal sensitization in a textile worker exposed to spinning fluids treated w

Note 1 - Transmittal of Minutes of the FIFRA Scientific Advisory Panel Meeting Held May 4-6, 2004: A ConsulSensitization Issues for Exposures to Pesticides, Memorandum of 1 July 2004.

Page 17 of 22 
Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 

875.1200 875.1400 875.1600 

Applicator Indoor Exposure (Open Pour Liquids) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to dimethoxane and inhalation expacetaldehyde are expected during the open pour addition of liquids preservation. In addition, dermal and inhalation exposures from opare evident in exposure studies in the Pesticide Handlers Exposure DThe existing Chemical Manufacturer Association (CMA) data base scenarios are limited in scope for QA/QC and the number of replicatimes a worker is monitored for a specific activity). EPA presented additional handler exposure data to the January 2007 Science Adviswell as to the April 2007 Human Studies Review Board (HSRB) anthat additional data are warranted. 2) How would the data be used? The data would be used to assess dermal and inhalation exposures topen pour addition of liquids during materials preservation. 3) How could the data affect the risk assessment? The exposure data would be used to assess the risks to occupational determine if mitigation measures, such as closed system loading, arthese risks. 4) What is triggering the need for this data? The need for the exposure study is based on the potential for exposuaddition of liquids during the materials preservation uses listed on t

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Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1200 875.1400 875.1600 

Applicator Indoor Exposure (Brush/Roller Painting) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to dimethoxane and inhalation expacetaldehyde are expected during interior brush/roller application opreserved paints. There are no studies available to assess these exp2) How would the data be used? The exposure data would be used to assess dimethoxane and acetaldresult from brush/roller application of dimethoxane preserved paint3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of dimeth

acetaldehyde resulting from the use of dimethoxane in paints and ththis use are unknown. The exposure data would be used to assess thdetermine if mitigation is needed to reduce these risks. 4) What is triggering the need for this data? Dimethoxane is labeled for use as a preservative in “Paints”.

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Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data N/A Textile Leaching Study 1) What is the value of the study? 

Dermal and incidental oral exposures to dimethoxane are expected and linens made from textiles that are treated with textile chemicals preserved with dimethoxane. There are no leaching studies availab

exposures. 2) How would the data be used? The leaching data would be used to assess dimethoxane exposures tof clothing and blankets treated with textile finishes and chemicals preserved with dimethoxane. 3) How could the data affect the risk assessment? Currently there are no leaching data available to assess the dermal aexposure of dimethoxane resulting from the use of dimethoxane in tfinishes and thus the risks from this use are unknown. 4) What is triggering the need for this data? Dimethoxane is labeled for use as a preservative in “Textile Chemic

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Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data N/A Leather Leaching Study 1) What is the value of the study? 

Dermal and incidental oral exposures to dimethoxane are expected goods made from leather that is processed with leather processing lipreserved with dimethoxane. There are no leaching studies availab

exposures. 2) How would the data be used? The leaching data would be used to assess dimethoxane exposures tof leather processed with leather processing liquors that are preserv3) How could the data affect the risk assessment? Currently there are no leaching data available to assess the dermal aexposure of dimethoxane resulting from the use of dimethoxane in lliquors and thus the risks from these exposures are unknown. 4) What is triggering the need for this data? Dimethoxane is labeled for use as a preservative in “Leather Proces

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Page 22 of 22 

Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1700 Product Use Information 1) What is the value of the study? 

Product use information is a description of how the product is actuafield study. A description of how this product is used would providrealistic assessment of its potential applications. 2) How would the data be used? The product use information will be used to define and characterize scenarios that will be assessed in the risk assessment. 3) How could the data affect the risk assessment? A complete description of product use would ensure that the risk asof the types of exposures occurring during use and that these exposu

assessed. 4) What is triggering the need for this data? The need for a risk assessment under Registration Review in turn neassessor understand how the product is used.