UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, DC 20460 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

10/13/11 

MEMORANDUM 

SUBJECT: Bis(trichloromethyl)sulfone: Human Health Effects Scoping 

Document for the Registration Review Decision 

PC Code: 035601 DP Barcodes: D394302 

Decision No.: 455122 Registration No(s).: Multiple 

Petition No(s).: NA Regulatory Action: Registration Review 

Risk Assess Tvpe: Sinale Chemical Case No.: 2055 

TXR No.: NA CAS No: 3064-70-8 

MRID No(s).: NA 40 CFR: NA 

TO: 

FROM: 

THRU: 

Seiichi Murasaki, Chemical Review Manager 

Regulatory Management Branch II 

Antimicrobials Division (7510P) 

Jenny 

Talia Lindheimer, 

J. Tao, Toxi

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gist ~ tial Assessorc;;:{e,~ Jonathan Chen, Ph.D., Incident Data ~ 

William J. Hazel, Ph.D., Risk Assesso ~ _ / 

Risk Assessment and Science Support Br h" --r-r 

Antimicrobials Division (7510P) 

Nader Elkassabany, Ph.D., Chief vf1tt{~ Lr~ - Risk Assessment and Science Support Branch - (5-

Antimicrobials Division (7510P) 

INTRODUCTION 

The Antimicrobials Division (AD) has generated this Human Health Effects 

Scoping Document for the Registration Review Decision on the broad-spectrum 

antimicrobial pesticide bis(trichloromethyl)sulfone. The hazard and exposure 

databases were examined as were any available risk assessments conducted in 

support of the registration or reregistration of all pesticide products containing 

bis(trichloromethyl)sulfone. The Agency will also determine whether current 
2

science policies, use patterns, or available data materially affect the overall risk 

picture. The purpose of this scoping document is to determine whether sufficient 

data are available to support registration review, whether new human health risk 

assessments are needed to support registration review, and to report why the 

Agency feels it may be appropriate to require additional data and/or conduct new 

risk assessments under the registration review process. A Reregistration 

Eligibility Decision (RED) document was issued for bis(trichloromethyl)sulfone in 

September 1995; this was the primary source of information for this human 

health effects scoping document.

EXECUTIVE SUMMARY

Bis(trichloromethyl)sulfone is an organosulfur antimicrobial active ingredient in 

nine registered products. There are three manufacturing-use products (MP) all

registered to Verichem, Inc. Five end-use products (EP) containing one or more 

other active ingredients are registered to Hercules, Inc. and Nalco Co.; one 

single active ingredient product is registered to Verichem. All EP products are 

used as slimicides to control bacterial and fungal slimes in pulp and paper mill 

process water systems and as a preservative of paper-making chemicals. These 

products are added to systems and industrial products using open-pouring and 

pumping methods. Verichem’s EP also bears uses in industrial air washing

systems, commercial and industrial process and water systems, oil and gas field 

water systems, and as a material preservative in a wide range of household and 

construction materials including paints, coatings, and fuels; closed 

loading/application methods must be used in the water systems.

Bis(trichloromethyl)sulfone is corrosive to the eyes and strongly irritating to the 

skin and the lungs (all are Toxicity Category I). Acute oral (Toxicity Category III) 

and dermal (Toxicity Category IV) toxicities are low to moderate. It is not a 

dermal sensitizer.

In a 21-day rat dermal toxicity study, the systemic NOAEL was 2.0 mg/kg/day; 

systemic adverse effects at the LOAEL of 5.0 mg/kg/day were changes in 

hematology and clinical chemistry. The NOAEL for dermal irritation was 2.0 

mg/kg/day.

Two developmental toxicity studies are available for bis(trichloromethyl)sulfone, 

one in rats and the other in rabbits. In rats, the maternal toxicity NOAEL was 2 

mg/kg/day based on decreased body weight gain and food consumption at the 

LOAEL of 10 mg/kg/day. The developmental NOAEL was 10 mg/kg/day. 

Decreased fetal body weight and increases in skeletal and external anomalies

occurred at the developmental LOAEL of 50 mg/kg/day. In rabbits, the maternal 

toxicity NOAEL was 20 mg/kg/day based on decreased body weight gain and 

food consumption and increased incidence of clinical signs at the maternal 

LOAEL of 45 mg/kg/day. No developmental toxicity was observed in rabbits at 
3

any dose; therefore, the high dose of 45 mg/kg/day is considered to be the 

developmental NOAEL.

Preliminary studies have shown adverse affects of bis(trichloromethyl)sulfone on 

fertility in male rats which, in turn, resulted in lower reproductive rates in female 

rats. In addition, bis(trichloromethyl)sulfone has been shown to immobilize rat 

spermatozoa in vitro at a lower concentration and within a very short period of 

time. Therefore, a two-generation reproductive toxicity study is anticipated to be 

needed.

Based on the registered uses, chronic dietary exposure to bis(trichloromethyl)-

sulfone via both food and drinking water sources as well as residential exposure 

are expected to be aggregated. Although residential exposures are likely to be 

short-term and intermediate-term in duration, the dietary sources would be 

chronic. Therefore, an oral chronic toxicity study is needed.

A carcinogenicity study is expected to be needed due to chronic human exposure 

to bis(trichloromethyl)sulfone via food and drinking water sources, due to a 

number of positive mutagenicity studies, and the potential for degradation of 

bis(trichloromethyl)sulfone to chloroform, a probable human carcinogen.

There are several mutagenicity studies available for bis(trichloromethyl)sulfone. 

In three repeated Ames assays, the compound was mutagenic to the same 

bacterial strain under both nonactivated and S9-activated conditions as well as to 

a second strain under nonactivated condition in one study. In a mouse lymphoma 

cell line, bis(trichloromethyl)sulfone was also found to be positive under both 

nonactivated and S9-activated conditions in a sister chromatid exchange assay. 

Although negative results were shown in the other mutagenicity assays, they do 

not negate the positive gene mutation results.

A rat metabolism study is anticipated to be needed because: (i) there is an 

unknown mode of antimicrobial action of bis(trichloromethyl)sulfone; (ii) there is 

an unknown mechanism of mammalian irritation as well as systemic mammalian 

toxicity; and (iii) there are no solid clues regarding metabolism from 

environmental fate data because the database is very limited and of poor quality.

No additional acute toxicity data are anticipated to be needed. Based on the 

vapor pressure of bis(trichloromethyl)sulfone and the currently registered uses, 

the Agency anticipates that a subchronic inhalation toxicity study is needed to 

assess inhalation risks. No additional subchronic oral, subchronic dermal, or 

developmental toxicity studies are needed. A two-generation rat reproduction 

toxicity study is anticipated to be necessary due to concern for adverse effects on 

sperm motility observed in a published study. Resulting from the potential for 

chronic dietary exposure (food and drinking water), a chronic toxicity study is 

anticipated to be needed. A carcinogenicity study is expected to be needed due 

to chronic human exposure to bis(trichloromethyl)sulfone via food and drinking 
4

water sources, a number of positive mutagenicity studies, and the potential for 

degradation of bis(trichloromethyl)sulfone to chloroform, a probable human 

carcinogen. In addition, a metabolism study is needed to better understand the 

behavior of bis(trichloromethyl)sulfone under biological conditions.

Dietary (food) exposure to bis(trichloromethyl)sulfone is likely because it is used 

as a slimicide in food contact paper and paperboard production and to preserve 

paper-making chemicals. Migration of bis(trichloromethyl)sulfone from paper 

packaging to the food contents may occur to some extent. The FDA regulates 

bis(trichloromethyl)sulfone as an indirect food additive in paper, adhesives, and 

coatings. A migration study is anticipated to be needed as will a dietary (food 

source) risk assessment.

The registered uses of bis(trichloromethyl)sulfone may result in human exposure 

via drinking water resulting from industrial discharges of treated water. However, 

the need for a dietary (drinking water) exposure assessment will be determined 

upon review of environmental fate data the Agency anticipates requiring.

Bis(trichloromethyl)sulfone may be used to preserve a number of construction 

and household materials that may be used in the home and other sites such that 

nonoccupational exposures may occur. Preserved paints are of particular 

concern in the residential setting. Both dermal and inhalation exposures of 

homeowner handlers and bystanders (including children) are expected. 

Postapplication exposure including mouthing of treated plastic toys of children 

may also occur; a restriction against use of treated materials for toys may negate 

the need for this assessment. Data are anticipated to be needed to estimate 

exposures associated with residential paint use. A residential risk assessment is 

also needed.

Potential contributors to aggregate risk are exposures via food, nonoccupational, 

and possibly via drinking water sources. Aggregate risk assessments combining 

the applicable bis(trichloromethyl)sulfone sources of exposure associated with 

registered uses will be conducted during the risk assessment stage of 

Registration Review.

Occupational exposure to bis(trichloromethyl)sulfone is expected based on its 

use as an antimicrobial in industrial water systems and as a preservative of a 

wide range of water-based liquid solutions, dispersions, and emulsions. Most 

water systems must be treated using closed loading/application or a meter-pump 

system whereas open-pour loading may be used for material preservation. Both 

dermal and inhalation exposure of workers to bis(trichloromethyl)sulfone is

expected. Due to the relatively high vapor pressure of bis(trichloromethyl)sulfone

(1.1 x 10-3 mmHg), worker inhalation exposure is likely to be due to vapor phase 

as well as aerosolized parent compound. Dermal and inhalation exposure 

studies, product use, and human activity data are expected to be needed and 

any available relevant Industrial Hygiene air sampling data in commercial 
5

facilities should be submitted. Occupational applicator and postapplication/

bystander risk assessments are anticipated to be necessary.

Section 1. Chemical Identity and Generic Physical/Chemical Properties

Table 1.1 Chemical Identity of bis(trichloromethyl)sulfone

Common Name Bis(trichloromethyl)sulfone

Chemical Names Trichloro(trichloromethylsulfonyl)methane; Methane, 

sulfonylbis(trichloro-); Hexachlorodimethyl sulfone; 

Sulfone, bis(trichloromethyl)

Trade Names N-1386®; Spectrum®; Nalcon®7642

Molecular Formula C2Cl6O2S

Molecular Weight 300.8

PC Code 035601

CAS Registry Number 3064-70-8

Registration Review 

Case No.

2055

Chemical Structure

 

Bis(trichloromethyl)sulfone is solid at room temperature although it melts at 37°C. 

It has a pungent, aromatic odor. Bis(trichloromethyl)sulfone has a low water 

solubility (70 ppm at 20-22 °C). The log Ko/w is estimated to be 3.3. The vapor 

pressure is estimated to be 1.1 x 10-3 mmHg at 25oC and the Henry's Law 

Constant to be 1.2 x 10-8atm•m

3

/mole at 25oC.

Section 2. Toxicology

The toxicology database for the bis(trichloromethyl)sulfone registration review 

case is primarily comprised of studies submitted to the Agency before the RED 

for bis(trichloromethyl)sulfone was issued in 1995. The toxicity database consists

of acute toxicity studies, a subchronic dermal toxicity study, developmental 

toxicity studies, and mutagenicity studies. 

a. Acute Toxicity

Bis(trichloromethyl)sulfone is corrosive to the eyes and strongly irritating to the 

skin (both are Toxicity Category I) but it is not a dermal sensitizer. In addition, the 

compound is strongly irritating to the lungs via the inhalation route (Toxicity 

Category I). Acute oral (Toxicity Category III) and dermal (Toxicity Category IV) 

toxicities are of less concern. The acute toxicity data are adequate to support 

registration. The Agency does not anticipate that any additional acute toxicity 

information on the technical is needed. 
6

b. Subchronic Dermal and InhalationToxicity

In a 21-day dermal toxicity study (MRID 40050701), bis(trichloromethyl)sulfone 

was administered to young adult rabbits of the Hra:(NZW)SPF strain in doses of 

0, 0.8, 2.0, or 5.0 mg/kg/day. Systemic toxicity, such as reduced red blood cell

and white blood cell counts and reduced hemoglobin, hematocrit, neutrophils 

(leukocytes), and blood glucose, was noted in the males of the high dose group. 

No similar findings were observed in the females. The systemic LOAEL was 5.0 

mg/kg/day for males and not established for females (>5.0 mg/kg/day). The 

systemic NOAEL was 2.0 mg/kg/day for males and ≥5.0 mg/kg/day for females 

based on changes in hematology and clinical chemistry. Dermal irritation was 

noted in the high dose groups as compared to control animals. The LOAEL for 

dermal irritation was 5.0 mg/kg/day for both sexes and the NOAEL for dermal 

irritation was 2.0 mg/kg/day based on dermal irritation scores compared to 

control animals.

Based on the vapor pressure and currently registered use patterns, the Agency 

anticipates that inhalation exposure to bis(trichloromethyl)sulfone will occur in 

both occupational and residential settings. The Agency therefore anticipates the 

need for a subchronic inhalation toxicity data to assess inhalation exposure risks. 

A 90-day rat inhalation toxicity study was called in 1/1/89 but has not been 

received.

c. Developmental Toxicity

There are two developmental toxicity studies available for bis(trichloromethyl)-

sulfone, one in rats (MRID 40149101) and another in rabbits (MRID 43156602).

In rats, bis(trichloromethyl)sulfone technical was administered by gavage to 

Charles River Crl:CD BR albino rats at doses of 0, 2, 10 or 50 mg/kg/day on 

gestation days 6 through 15. The maternal toxicity NOAEL was 2 mg/kg/day 

based on decreased body weight gains and reduced food consumption occurring 

at the LOAEL of 10 mg/kg/day. The developmental NOAEL was 10 mg/kg/day 

based on decreased fetal body weight and an increase in skeletal and external 

anomalies observed at the LOAEL of 50 mg/kg/day.

In rabbits, bis(trichloromethyl)sulfone technical was administered by gavage to 

groups of 20 pregnant New Zealand white rabbits at doses of 0, 10, 20, or 45 

mg/kg/day on gestation days 6 through 18. The maternal toxicity NOAEL was 20 

mg/kg/day based on a statistically significant decrease in maternal body weight 

gain, reduced food consumption, and increased incidence of clinical signs of 

toxicity observed at the LOAEL of 45 mg/kg/day. There was no developmental 

toxicity observed at any dose level tested. The NOAEL for developmental toxicity 
7

was considered to be 45 mg/kg/day (highest dose tested). A LOAEL was not 

established for developmental toxicity.

d. Reproductive Toxicity

There is no reproductive toxicity study available for bis(trichloromethyl)sulfone in 

the Agency’s hazard database. A study described in the open literature 

addressed the infertility effects of bis(trichloromethyl)sulfone in rats. Male 

Sprague-Dawley (SD) rats (10/dose) were administered bis(trichloromethyl)-

sulfone by gavage at doses of 0, 10 mg/kg/day, or 30 mg/kg/day. Animals were 

dosed once daily, 6 times a week, for 8 weeks (10 mg/kg/day) or 4 weeks (30 

mg/kg/day). Female animals were not treated with bis(trichloromethyl)sulfone. A 

dose-related, statistically significant (p<0.001) reduction in both number and

motility of the spermatozoa in the cauda epididymides was demonstrated 

compared to the controls. A corresponding lower pregnancy rate (p<0.001) was 

shown in female animals. There were no effects of bis(trichloromethyl)sulfone on 

body weight, sexual behavior, blood testosterone level, or histopathology of the 

treated male animals. An in vitro study was also performed and it was found that 

bis(trichloromethyl)sulfone, at a concentration of 0.31mg/ml, immobilized rat 

spermatozoa within 20 seconds (MRID 48638801). 

Due to the adverse effects on fertility observed in this published study, a twogeneration rat reproduction toxicity study is anticipated to be necessary.

e. Chronic Toxicity

Resulting from the potential for chronic dietary exposure (food and drinking 

water), a chronic toxicity study is anticipated to be needed to characterize chronic 

hazard and to calculate chronic dietary risks.

f. Carcinogenicity

Carcinogenicity studies are also needed for bis(trichloromethyl)sulfone to 

evaluate its potential to induce cancer for the following reasons: 

Positive results evidenced in mutagenicity assays (three repeated 

Ames assays and a sister chromatid exchange assay)

Potential dietary exposure to bis(trichloromethyl)sulfone, including food 

and drinking water sources

In an anaerobic aquatic metabolism study (MRID 40317101), one of 

the metabolites of bis(trichloromethyl)sulfone (half life <0.5 day) was 

hexachloroethane. The Agency has concerns that chloroform may be 

an active intermediate in the process. Chloroform is classified as “a 

Group B2; probable human carcinogen” by the Agency (U.S. EPA, 

2006).
8

g. Mutagenicity

A number of mutagenicity studies are available for bis(trichloromethyl)sulfone

with both positive and negative mutagenic responses. The studies and results of 

the tests are summarized below:

In two Ames bioassays, bis(trichloromethyl)sulfone was tested in strains 

of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, and 

TA100). The test material was positive as indicated by increased 

numbers of revertants in strain TA1535 under both nonactivated and S9-

activated conditions (MRIDs 00152330 and 00152331).

In another gene mutation assay, bis(trichloromethyl)sulfone was tested in 

strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, and 

TA100) and found to be positive to TA1535 under both nonactivated and 

S9-activated conditions and also positive to TA100 under nonactivated 

conditions (MRID 00152332).

In a forward mutation assay using Fischer mouse lymphoma L5178Y cells 

(MRID 00152333), bis(trichloromethyl)sulfone did not elicit a mutagenic 

response (negative) under either nonactivated and S9-activated 

conditions.

In a sister chromatid exchange assay in mouse lymphoma L5178Y cells 

(MRID 00152335), bis(trichloromethyl)sulfone was found to be positive

under both nonactivated and S9-activated conditions.

In a multiple endpoint (gene mutation, chromosomal aberration, sister 

chromatid exchange) assay using mouse lymphoma L5178Y cells (MRID 

00152334), an equivocal positive result in gene mutation was observed in 

the absence of S9, but was negative in the presence of S9. Negative 

results were found in the chromosomal aberration and sister chromatid 

exchange assays; however, the tested doses were not considered 

adequate to reveal full mutagenic potential. Therefore, these two assays 

(chromosomal aberration and sister chromatid exchange) were classified

as unacceptable.

In a mouse bone marrow micronucleus assay (MRID 42372701), 

bis(trichloromethyl)sulfone technical was tested at doses of 100, 200, or

400 mg/kg/day in males and 150, 300, or 600 mg/kg/day in females for 2 

consecutive days. There was no significant increase in the frequency of 

micronucleated polychromatic erythrocytes (MPEs) in bone marrow 
9

(harvested 24 or 48 hours after final dosing), i.e., the test material was 

negative for genotoxicity.

In a morphologic transformation assay in BALB/3T3 cells (MRID 

00152335), bis(trichloromethyl)sulfone was found to be negative.

In an in vitro malignant transformation assay in BALB/3T3 cells (MRID not 

assigned), there was no indication of a positive response induced by

bis(trichloromethyl)sulfone.

h. Rat Metabolism

A rat metabolism study is anticipated to be needed because: (i) there is an 

unknown mode of antimicrobial action of bis(trichloromethyl)sulfone; (ii) there is 

an unknown mechanism of mammalian irritation as well as systemic mammalian 

toxicity; and (iii) there is no metabolism information in the environmental fate 

database that could be applicable to a mammalian system and the database is 

very limited and of poor quality.

Section 3. Use Directions

Bis(trichloromethyl)sulfone is the active ingredient in nine registered products. 

EPs are formulated as Soluble Concentrate/Liquids (SC/L). There are three 

manufacturing-use products (MP) containing 35-98% ai; all are registered to 

Verichem, Inc. Six end-use products (EP) are registered containing 3.33-20% ai. 

Five of the six EPs also contain one or more other active ingredients; these are 

registered to Hercules, Inc. and Nalco Co. All EP products are used as slimicides 

to control bacterial and fungal slimes in pulp and paper mill process water 

systems and as a preservative of paper-making chemicals (pulp, broke, 

polymers, defoamers, alum, emulsions, adhesives, paper mill coatings, pigment 

slurries, and paper products). These products are added to water systems and 

industrial products using open-pouring and pumping methods.

Only the EP containing 20% bis(trichloromethyl)sulfone as the sole active 

ingredient (Verichem, Inc.; EPA Reg. No. 67869-32; 4/21/11) bears the use to 

control bacteria, fungi, and algae in industrial air washing systems as well as

commercial and industrial process and water systems. This product is also 

approved to control slime-forming and sulfate-reducing bacteria in oil and gas 

field water systems including oil field injection waters, enhanced recovery 

injection fluids, and drilling fluids. It is also used as a material preservative to 

control fungi and bacteria in: adhesives and tackifiers; construction products and 

household products (caulking materials, mastics, ceramic glazes, concrete, 

concrete admixtures, plasters); dispersed pigments (kaolin clay, montmorillonite 

clay, titanium dioxide, calcium carbonate, calcium sulfate, barium sulfate, 

magnesium silicate, and kieselguhr used in paint and paper production); paints, 

coatings, and stains; water-based coatings such as paper coatings; photo 

processing systems; synthetic and natural polymeric latices; and liquid 
10

hydrocarbon fuels and oils (crude oils, aviation fuels, kerosene, heating oils, 

diesel fuels, residual fuel oils, coal slurries, liquefied petroleum gases, and 

petrochemical feedstock). Verichem’s 20% EP (EPA Reg. No. 67869-32) 

requires that a meter-pump system or a closed loading/application system be 

used to load and apply the product to oil recovery drilling muds/packer fluids, 

commercial/industrial water cooling systems, evaporative condenser water 

systems, and heat exchanger systems.

Section 4. Dietary Exposure

a. Food Exposure

Dietary (food) exposure to bis(trichloromethyl)sulfone could potentially occur 

because it is used to inhibit slime-forming bacteria and fungi in paper process 

water systems culminating in production of paper and paperboard that may be 

used for food contact. Also, bis(trichloromethyl)sulfone is used to preserve a 

number of paper-making chemicals as well as paper and paperboard coatings, 

adhesives, dispersed pigments, etc. Bis(trichloromethyl)sulfone is regulated by 

the FDA as an indirect food additive at 21 CFR 176.300 for use as a paper 

slimicide, at 21 CFR 175.105 to preserve food-packaging adhesives, and at 21 

CFR 176.180 to preserve coatings to be used on paper and paperboard in 

contact with dry foods. Migration of bis(trichloromethyl)sulfone from paper 

packaging to the food contents is likely to occur to some extent. Therefore, a 

migration study is expected to be needed as is a dietary (food source) risk 

assessment.

b. Drinking Water Exposure

The registered uses of bis(trichloromethyl)sulfone may result in contamination of 

surface water and possibly ground water as a result of discharges of treated 

water from industries using this antimicrobial in their water systems or as a 

material preservative. Therefore, drinking water exposure is a reasonable 

possibility. However, the need for a dietary drinking water exposure assessment 

for bis(trichloromethyl)sulfone will be determined upon review of environmental 

fate data the Agency anticipates requiring. These environmental fate data will be 

useful to determine if bis(trichloromethyl)sulfone can pass through wastewater 

treatment facilities into drinking water or migrate into residential groundwater 

wells as a result of its current use patterns. Therefore, the need for a drinking 

water assessment will be revisited upon submission and review of the 

environmental fate data anticipated to be needed.

Section 4. Residential Exposure

Bis(trichloromethyl)sulfone may be used to preserve a number of construction 

and household materials that may be used in the home and/or in commercial, 
11

institutional, and industrial settings resulting in residential and other 

nonoccupational exposures. Of the preserved materials, paints are expected to 

result in the highest residential exposure. Both dermal and inhalation exposures 

of homeowner handlers and bystanders (including children) are expected. 

Postapplication exposure of children may also occur as may incidental oral 

exposure from playing with toys made of treated plastic. Data are anticipated to 

be needed to estimate exposures associated with residential paint use. A 

residential risk assessment is also needed.

Section 5. Aggregate Risk

Based on the registered use of bis(trichloromethyl)sulfone as a paper chemical 

preservative and use as a slimicide during the manufacture of paper and 

paperboard that may contact food, dietary exposure may occur. Residues of 

bis(trichloromethyl)sulfone may reach drinking water although this will be 

determined upon review of the environmental fate data anticipated as being 

needed. Also, exposure of adults and children to bis(trichloromethyl)sulfone in 

residential and other nonoccupational settings is likely to occur from the use of 

preserved materials to be represented by preserved paint. Thus, the potential 

contributors to aggregate risk are exposures via food, in the home, and possibly 

via drinking water. Aggregate risk assessments combining the applicable

exposure sources associated with registered bis(trichloromethyl)sulfone use will 

be conducted during the risk assessment stage of Registration Review.

Section 6. Occupational Exposure

Bis(trichloromethyl)sulfone products are added to pulp and paper water systems 

and other industrial water systems as well as to many different materials during 

the manufacturing process. The labels instruct the handler to wear protective 

eyewear (goggles, face shield, or safety glasses), rubber gloves, and protective 

clothing. The EP labels are silent on the type of loading and mixing equipment to 

be used in all cases except Verichem’s 20% EP (EPA Reg. No. 67869-32) which 

requires that a meter-pump system or a closed loading/application system be 

used to load and apply the product to oil recovery drilling muds/packer fluids, 

commercial/industrial water cooling systems, evaporative condenser water 

systems, and heat exchanger systems. Therefore, open-pour loading is 

permissible in most cases.

During open-pour activities, dermal and inhalation exposure of workers to 

bis(trichloromethyl)sulfone is expected. Due to the relatively high vapor pressure 

of bis(trichloromethyl)sulfone (1.1 x 10-3 mmHg), worker inhalation exposure is 

likely to be due to gaseous as well as aerosolized parent compound. Detailed 

product use and human activity information are needed to permit more realistic 

estimates of worker exposure. To estimate occupational exposure, dermal and 
12

inhalation exposure studies are recommended. In lieu of inhalation exposure 

studies, the registrant may opt to conduct small chamber emission studies.

These small chamber studies permit inhalation exposure estimation and are 

recommended for representative scenarios to estimate potential occupational 

(handler, factory bystander, painter) exposure. If chosen to be conducted, small 

chamber study protocols should be approved by the Agency. The generated air 

emissions data will also be useful to estimate residential exposures. It is also 

recommended that relevant Industrial Hygiene air sampling data in commercial 

facilities manufacturing, storing, or using large quantities of bulk or end-products 

made from preserved materials be submitted. Occupational risk assessments for 

handlers and postapplication/ bystanders are expected to be performed.

Section 7. Cumulative Risk

Unlike other pesticides for which EPA has followed a cumulative risk approach 

based on a common mechanism of toxicity, EPA has not made a common 

mechanism of toxicity finding as to bis(trichloromethyl)sulfone and any other 

substances. For the purposes of this Registration Review, therefore, EPA has not 

assumed that bis(trichloromethyl)sulfone has a common mechanism of toxicity 

with other substances. For information regarding EPA’s efforts to determine 

which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see the policy statements released by 

EPA’s Office of Pesticide Programs concerning common mechanism 

determinations and procedures for cumulating effects from substances found to 

have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

Section 8. Endocrine Disruption

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.
13

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 postapplication agricultural scenarios. This list should not be 

construed as a list of known or likely endocrine disruptors.

Bis(trichloromethyl)sulfone 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/.

Section 7. Incidents

Based on a search of OPP’s databases, there have been no reported human 

poisoning incidents associated with bis(trichloromethyl)sulfone.

Section 8. Anticipated Data Needs

a. Data Needs

The Agency anticipates needing the following toxicity studies (utility and 

rationale provided in Appendix A) to characterize the hazards and assess human 

health risks associated with exposure to bis(trichloromethyl)sulfone:

90-day Rat Inhalation Toxicity Study (GLN 870.3465)

Reproductive toxicity study (GLN 870.3800)

Chronic Oral Toxicity Study in Rats (GLN 870.4100)

Carcinogenicity Studies in Two Rodent Species (GLN 870.4200)

Rat Metabolism Study (GLN 870.7485)

The Agency anticipates needing the following exposure studies (utility and 

rationale provided in Appendix A) to assess dietary, occupational, and residential 

risks associated with registered uses of bis(trichloromethyl)sulfone:

Migration Studies (No GLN)

Outdoor Dermal Exposure (GLN 875.1100) or

Indoor Dermal Exposure (GLN 875.1200)
14

Outdoor Inhalation Exposure (GLN 875.1300) or

Indoor Inhalation Exposure (GLN 875.1400)

Applicator Exposure Monitoring Data Reporting for Dermal and Inhalation 

Data (GLN 875.1600)

Product Use Information – Outdoor (GLN 875.1700)

Indoor Surface Residue Dissipation (GLN 875.2300)

Inhalation Exposure (Postapplication) (GLN 875.2500)

Product Use Information – Indoor (GLN 875.2700)

Descriptions of Human Activity (GLN 875.2800)

Data Reporting and Calculations (GLN 875.2900)

b. Risk Assessments Needed

A dietary risk (food) assessment will be needed to determine risks 

resulting from dietary exposure to bis(trichloromethyl)sulfone used in pulp 

and paper mill water systems, coatings, adhesives, and other papermaking chemicals used to manufacture food contact paper/paperboard. If 

a restriction against use in paper-making chemicals other than coatings 

and adhesives is not added to the label (see Label Issues below), these 

will all be assessed for their contributing dietary exposure.

A dietary risk (drinking water) assessment will be needed to reflect 

discharges of bis(trichloromethyl)sulfone residues from industries using 

this antimicrobial as a slimicide and as a preservative. If, upon receipt, the 

environmental fate (biodegradation) studies provide evidence that drinking 

water exposure to bis(trichloromethyl)sulfone residues of toxicological 

concern is not likely, a dietary risk (drinking water) assessment will not be 

needed.

Residential applicator/user dermal and inhalation risks to adults from 

exposure to bis(trichloromethyl)sulfone residues following use of 

consumer products consisting of or containing preserved materials (paints

and construction products).

Residential postapplication dermal and inhalation risks to adults and 

children, including bystanders, from exposure to bis(trichloromethyl)-

sulfone residues following use of products consisting of or containing 

preserved materials (paints, and construction products). Incidental oral 

risks also need to be determined for children handling and mouthing toys 

made of preserved polymers unless a restriction against such use is 

added to Verichem’s 20% product label (EPA Reg. No. 67869-32).

At this point, it appears as though aggregate risk will consist of dietary 

(both food and drinking water) and residential exposures. However, the 

details of any needed aggregate assessments will be determined during 

the risk assessment stage of this Registration Review.

Occupational handler dermal and inhalation risks to bis(trichloromethyl)-

sulfone resulting from open-pour application of the antimicrobial in pulp 

and paper mill water systems and in manufacturing facilities to preserve 

materials should be assessed except for those use sites on Verichem’s 
15

20% product label (EPA Reg. No. 67869-32) for which open pouring is 

prohibited.

Occupational handler dermal and inhalation risk resulting from use or 

application of materials preserved with bis(trichloromethyl)sulfone should 

be assessed including a painting assessment.

Occupational bystander inhalation risk due to bis(trichloromethyl)sulfone

gas exposure resulting from volatilization during and after preservation of 

materials, treatment of industrial water systems, and treatment of oil and 

gas fields should be assessed.

Label Issues

The Verichem 20% label (EPA Reg. No. 67869-32) needs to be 

revised to add the following: (i) weight of product per gallon just under the 

ingredient statement; (ii) a restriction against using the product to preserve 

food contact materials except coatings and adhesives unless the FDA 

regulations are broadened (otherwise, the contribution of each to dietary 

exposure will be assessed); (iii) a restriction against use to preserve 

polymers that may be used for children’s toys (otherwise, incidental oral 

risks to children handling and mouthing toys will be assessed); and (iv) 

restriction against using the product to preserve polymers that may be 

used for human food such as xanthan gum, gum arabic, guar gum, 

starches, etc.

All five other labels should add a restriction against using the 

product to preserve food contact materials except coatings and adhesives 

unless the FDA regulations are broadened (otherwise, the contribution of 

each to dietary exposure will be assessed).

Section 9. References

Bis(trichloromethyl)sulfone Reregistration Eligibility Decision Document 

(RED), September 1995. http://epa.gov/oppsrrd1/REDs/2055red.pdf

Summary of Residential and Occupational Exposure Data for the 

Bis(trichloromethyl)sulfone Registration Review Decision Document. Talia 

Lindheimer. 10/11/11. D394306.

Bis(trichloromethyl)sulfone: Summary of Human Health Effects Data for 

the Registration Review Decision Document. Jenny J. Tao. 10/7/11. 

D394304.
16

Appendix A.

1. Need for, and Uses of, the Data

Guideline Number: 870.3465 

Study Title: 90-Day Inhalation Toxicity (Rat)

Rationale for Requiring the Data

This study is required because several use scenarios involve generation of aerosols (such as 

painting). Also, the relatively high vapor pressure of bis(trichloromethyl)sulfone (1.1 x 10-3

mmHg) is likely to result in the compound in the gaseous phase. There is a likelihood of 

significant repeated inhalation exposure to homeowners and occupational handlers using directpour methods and breathing aerosols and gas during or after use/application of materials 

preserved with bis(trichloromethyl)sulfone, especially while painting with preserved paint or 

coatings. Many preserved homeowner, commercial, and institutional liquid spray products are 

preserved with bis(trichloromethyl)sulfone and will result in significant inhalation exposure 

professionally and in the home. A 90-day inhalation toxicity study has not been conducted and is 

required. The inhalation route is a major route of human exposure to bis(trichloromethyl)sulfone 

per se for a number of scenarios because of aerosols forming and it is a volatile gas. The air 

concentrations of bis(trichloromethyl)sulfone in the chamber should be monitored over time.

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

Residential risk has never been assessed for bis(trichloromethyl)sulfone even though both 

dermal and inhalation routes of exposure are expected. Also, inhalation exposure and risk have 

never been assessed for occupational handlers and bystanders. As a major exposure route is 

inhalation and a subchronic inhalation toxicity study is not available, there is no route-specific 

study to appropriately use in a quantitative risk assessment, particularly via the inhalation route.

2. How will the data be used? 

The data will be used to properly characterize and quantify the inhalation hazard and risks to 

occupational workers as well as residential adults during painting and children exposed to 

materials that have been preserved with bis(trichloromethyl)sulfone, including paint, often a 

scenario resulting in the highest exposures.

3. How could the data impact the Agency’s future decision-making?

In the absence of inhalation toxicity data, the Agency would have to estimate inhalation risks 

using an oral developmental toxicity study and rely on the assumption that absorption and 

toxicity of bis(trichloromethyl)sulfone are the same via the oral and inhalation routes of exposure.

Note that absorption of pesticides into the bloodstream via the lungs is often higher than that via 

the dietary route and often many times higher than via the dermal route. Paired with the 

requested chemical-specific bis(trichloromethyl)sulfone inhalation exposure data, the routespecific 90-day rat inhalation toxicity study on bis(trichloromethyl)sulfone will permit EPA to 

conduct residential and occupational risk assessments that are refined and in which there is a 

high degree of confidence.
17

Guideline Number: 870.3800

Study Title: Reproduction and fertility effects

Rationale for Requiring the Data

The 2-generation reproduction study tor bis(trichloromethyl)sulfone is triggered by evidence from 

a published study that this compound adversely affects male fertility by reducing sperm number 

and motility. 

This guideline (870.3800) for two-generation reproduction testing is designed to provide 

information concerning the effects of a test substance on the integrity and performance of the 

male and female reproductive systems, including gonadal function, the estrous cycle, mating 

behavior, conception, gestation, parturition, lactation, and weaning, and on the growth and 

development of the offspring. The study may also provide information about the effects of the 

test substance on neonatal morbidity, mortality, target organs in the offspring, and preliminary 

data on prenatal and postnatal developmental toxicity and may also serve as a guide for 

subsequent tests. Additionally, since the study design includes in utero as well as postnatal 

exposure, this study provides the opportunity to examine the susceptibility of the 

immature/neonatal animal. 

Practical Utility of the Data

How did the Agency make its earlier regulatory decisions without this data?

The Agency made earlier regulatory decisions in the absence of knowledge of the potential 

reproductive and fertility effects this compound may exert. At this time, EPA would make a 

decision regarding the necessity of adding a database uncertainty factor of 10X in the absence 

of a reproductive toxicity study to conduct the human health risk assessment.

How will the data be used and how could the data impact the Agency’s future decisionmaking?

After review and evaluation of the reproductive toxicity study, EPA will use the data to determine 

whether the 10X database uncertainty factor should remain, be reduced, or removed (reduced to 

zero). A dose and adverse systemic effect from the reproductive toxicity study may be selected 

for use in quantitative risk assessments in which the Agency has high confidence.

Guideline Number: 870.4100

Study Title: Chronic Oral Toxicity Study in Rats

Rationale for Requiring the Data

A chronic toxicity study is expected to be needed due to the chronic (>6 months) human dietary 

exposure to bis(trichloromethyl)sulfone via indirect food and drinking water sources. The study 

would provide insight into toxicity via chronic dietary and long-term exposures. It may also 

provide a toxicity endpoint applicable to risk assessment. Food may be contaminated by the 

migration of residues from paper or paperboard food packaging consisting of treated paper pulp 

and preserved chemicals such as adhesives, coatings, and pigments. Drinking water may be 

contaminated by discharges of waste water from the large number of industrial, high-volume 

types of water systems.

Practical Utility of the Data

How did the Agency make its earlier regulatory decisions without these data?

No earlier regulatory decisions were made that would necessitate a chronic toxicity study. The 
18

Agency has never assessed dietary exposure and risk associated with the registered uses of 

bis(trichloromethyl)sulfone. In the 1995 RED (pre-FQPA), such dietary exposures were referred 

to as being “regulated by FDA” and were not considered further.

How will the data be used?

The data will be used to characterize the long-term effects of bis(trichloromethyl)sulfone via the 

oral route. A dietary risk assessment has never been conducted as noted above. A toxicity 

endpoint may be selected from this study for use in a quantitative chronic risk assessment. With 

the passage of FQPA in 1996 and ARTCA in 1998, EPA’s safety finding for registration under 

FIFRA must also meet the standard of safety for FFDCA sec. 408. This means EPA must make 

a safety finding that aggregate risks are not of Agency concern; aggregate risks include chronic 

dietary risks from food and drinking water as well as residential risks regardless of duration.

How could the data impact the Agency's future decision-making?

This chronic oral toxicity study would greatly increase the Agency’s confidence in the hazard 

profile of bis(trichloromethyl)sulfone which increases the confidence in future risk assessments 

and, hence, regulatory decisions. This study could be used as the source for selection of a 

chronic or long-term toxicity endpoint for use in quantitation of human risks. If the human health 

risks are of EPA concern, mitigation would be necessary.

Guideline Number: 870.4200

Study Title: Carcinogenicity Studies in Rat and Mouse

Rationale for Requiring the Data

Carcinogenicity studies are expected to be needed due to chronic human exposure to 

bis(trichloromethyl)sulfone via food and drinking water sources, due to a number of positive 

mutagenicity studies, and due to the potential for degradation of bis(trichloromethyl)sulfone to 

chloroform, a probable human carcinogen.

Practical Utility of the Data

How will the data be used?

The data will be used to characterize the carcinogenic potential of bis(trichloromethyl)sulfone. A 

cancer assessment has never been conducted due to the lack of cancer studies. If one or both 

of the cancer studies in two different rodent species are positive for carcinogenicity, a toxicity 

endpoint will be selected/calculated for use in a quantitative cancer risk assessment.

How could the data impact the Agency's future decision-making?

These cancer studies would greatly increase the Agency’s confidence in the hazard profile of 

bis(trichloromethyl)sulfone which increases the confidence in future risk assessments and, 

hence, regulatory decisions. Positive results from one or both of these studies would necessitate

evaluation by OPP’s Cancer Assessment Review Committee. This could result in calculation of a 

cancer slope factor or other measure of carcinogenic potency for use in quantitation of human 

cancer risks. A cancer hazard endpoint is often the most sensitive measure of a given 

pesticide’s hazard which may result in human health risks of EPA concern that would 

necessitate mitigation.
19

Guideline Number: 870.7485

Study Title: Rat Metabolism Study

Rationale for Requiring the Data

A rat metabolism study is anticipated to be needed because very little is known about the 

reactions of bis(trichloromethyl)sulfone regardless of the type, e.g., whether abiotic or biological, 

microbial or mammalian, etc. It is unknown whether the compound: is a strong oxidizing agent, 

interferes with an enzyme active site, disrupts cell membranes, etc. EPA doesn’t know the 

chemical species that humans would be exposed to initially via different routes and as the 

compound is distributed to the various compartments and organs. The magnitude and identities 

of residues in the various tissues are not known. The magnitude and identities of the residues 

excreted and at what rate are also not known. If the following were known, these are types of 

information that could provide clues regarding metabolism: mode of antimicrobial action, 

mechanism of mammalian irritation, mechanism of systemic mammalian toxicity, mechanism by 

which it causes bacterial mutations, metabolism information in another system that could be 

applicable to a mammalian system (the environmental fate database is very limited and of poor 

quality).

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

In the case of antimicrobials, the Agency virtually never has a rat metabolism study. Historically, 

the parent compound or its well-known degradates have been assumed to be the only residues 

to which humans are exposed. In many cases, chemicals used as antimicrobials are either 

simple compounds, are naturally-occurring, and/or are well-understood. Many are oxidizing 

agents, surface-active agents, metal ions, etc. Most frequently, they have a fairly generalized, 

nonspecific mode of action. They often disrupt cell membranes of all organisms. They are often 

rapidly acting and rapidly degraded to simple, nontoxic compounds in the process. They often 

are irritating to the eyes and lungs but do not cause systemic adverse effects in mammals. In the 

case of bis(trichloromethyl)sulfone, however, systemic toxicity in mammals and bacterial 

mutations are induced.

2. How will the data be used? 

The data will be used to help understand the absorption, distribution, metabolism, and excretion 

of bis(trichloromethyl)sulfone by mammals, including humans. This study contributes to EPA’s 

understanding of the effects caused by this compound and its metabolites/degradates. The 

metabolism study permits a better characterization of both hazard and exposure.

3. How could the data impact the Agency’s future decision-making?

The metabolism study could serve as the basis for future data requirements or Agency decisions 

on waiver requests. It will allow the Agency to render regulatory decisions based on sound 

science.

Guideline Number: None

Study Title: Migration Study

Rationale for Requiring the Data

Bis(trichloromethyl)sulfone is used to control bacteria and fungi in pulp and paper water systems 

and to preserve paper-making chemicals. Residues of this antimicrobial are likely to remain in 
20

the final food contact paper and paperboard from which they may migrate into food. These 

migration data will allow the Agency to conduct chemical-specific, quantitative assessments of 

dietary exposure and risk based on measured rates of bis(trichloromethyl)sulfone migration from 

the paper/paperboard packaging. If the registrant does not elect to add a label restriction against 

use of registered products to preserve plastics to be used for children’s toys, a study of migration 

from impregnated plastics would be necessary for Verichem’s 20% product label (EPA Reg. No. 

67869-32) only.

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

The Agency has never assessed dietary exposure and risk associated with this use pattern. In 

the 1995 RED, such dietary exposures were referred to as being “regulated by FDA” and were 

not considered further. With the passage of FQPA in 1996 and ARTCA in 1998, EPA’s safety 

finding for registration under FIFRA must also meet the standard of safety for FFDCA sec. 408. 

2. How will the data be used? 

The data will be used to determine the rate of migration of bis(trichloromethyl)sulfone from 

various types of paper and paperboard food packaging to various foods as a result of its use to 

treat pulp slurries and paper chemicals. This migration rate will be used to estimate realistic 

dietary exposures and risks resulting from these uses. These dietary risk estimates will be 

aggregated with other sources of exposure including drinking water and residential.

3. How could the data impact the Agency’s future decision-making?

The data will permit the first EPA assessment of dietary exposure that has ever been conducted 

for bis(trichloromethyl)sulfone. Along with drinking water and residential exposure sources, the 

dietary exposure will be aggregated to conduct the first aggregate risk assessment for this 

antimicrobial as required by FQPA. This information will permit a determination of whether these 

uses in the food-contact paper/paperboard industry are likely to result in exposures less than or 

greater than the Agency’s level of concern, whether they must be supported by additional data, 

and, if they are likely to result in risks of concern, to permit mitigation.
21

Guideline Number: 875.1100 Guideline Number: 875.1200

Study Title: Indoor Dermal Exposure Study Title: Outdoor Dermal Exposure

Rationale for Requiring the Data

The dermal exposure route is very important for scenarios such as those associated with oil and 

gas field activities, pulp and paper mill activities, material preservation, and indoor and outdoor 

painting with brushes, rollers, and airless sprayers where direct contact and splashing may occur 

and aerosols will be generated. However, very limited worker exposure monitoring data are 

available for antimicrobial pesticides, including material preservatives used in paint and other 

consumer products. EPA used these limited data to perform screening level risk assessments for 

the bis(trichloromethyl)sulfone RED. 

The existing data in the Chemical Manufacturers Association (CMA) database and Pesticide 

Handlers Exposure Database (PHED) for worker exposure scenarios are limited in scope and 

quality. The CMA data also has QA/QC problems, including the lack of field fortification, 

laboratory recoveries, and/or storage stability information. In addition the CMA data have an 

insufficient number of replicates. 

EPA presented the need for additional handler exposure data to the January 2007 Science 

Advisory Panel (SAP) as well as to the April 2007 Human Studies Review Board (HSRB) and 

both groups agreed that additional data are warranted. 

To protect workers from dermal exposures to pesticides, EPA requires dermal exposure 

monitoring data. The RED identified the lack of chemical-specific dermal exposure data, which 

this study will provide, as a data need. The data are needed to support handler exposures for the 

industrial and residential uses.

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

The Agency conducted a risk assessment in 1995 using limited, preliminary exposure data. 

There is dermal exposure associated with registered bis(trichloromethyl)sulfone uses. This 

triggers the need for chemical- and use pattern-specific occupational and residential exposure 

data upon which to base a more solid quantitative risk assessment.

2. How will the data be used?

The dermal exposure data will be used to assess the occupational and residential exposure of 

workers using materials preserved in-can, particularly latex paints.

3. How could the data impact the Agency’s future decision-making?

The dermal exposure data will provide more accurate estimations of the dermal risks to 

occupational workers using the formulated products and materials preserved with 

bis(trichloromethyl)sulfone. These data will be used to generate a sound risk assessment to 

more accurately reflect the actual exposure. If future risk assessments are performed in the 

absence of these data, the Agency will have a significant degree of uncertainty in its regulatory 

decision-making process and current mitigation measures (i.e., personal protective equipment) 

may not provide adequate protection for workers that may contact bis(trichloromethyl)sulfone in 

industrial settings. The lack of these data will limit the flexibility of the Agency and registrants 

with respect to decisions made from high-end screening level assessments that may 

overestimate exposures.
22

Guideline Number: 875.1300 Study Title: Outdoor Inhalation Exposure

Guideline Number: 875.1400 Study Title: Indoor Inhalation Exposure

Guideline Number: 875.2500 Study Title: Inhalation Exposure (Post

Application) 

Rationale for Requiring the Data

Note: Inhalation exposure data are needed for both residential and occupational uses. The 

selection of an outdoor versus an indoor site is based on the high end exposure scenario (for 

inhalation the selection is typically indoors). In almost all cases, repeating an exposure study for 

the same scenario outdoors and indoors is not necessary

The inhalation exposure route is very important for indoor painting, outdoor painting, and indoor 

open-pouring of liquids and liquid pumps during preservation.exposures and from painting with a 

brush, paint rollers and airless sprayers where aerosols would be generated. Also, the relatively 

high vapor pressure of bis(trichloromethyl)sulfone (1.1 x 10-3 mmHg) is likely to result in vapor 

formation which affects handlers as well as bystanders. In addition, inhalation exposures from 

liquid pouring are evident in exposure studies in the Pesticide Handlers Exposure Database 

(PHED). The existing Chemical Manufacturer Association (CMA) data base and PHED for these 

scenarios are limited in scope for QA/QC and number of monitoring units. EPA presented the 

need for additional handler exposure data to the January 2007 Science Advisory Panel (SAP) as 

well as to the April 2007 Human Studies Review Board (HSRB) and both groups agreed that 

additional data are warranted. 

This data requirement may be satisfied either by conducting an inhalation exposure monitoring 

study or by cooperating with the Agency to develop and conduct small chamber studies to 

determine air emission rates, which then may be used to estimate inhalation exposure in 

occupational and residential settings.

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

The Agency did not conduct an inhalation risk assessment in 1995, as it was stated that 

inhalation exposures were assumed to be minimal. There is, in fact, significant inhalation 

exposure associated with registered bis(trichloromethyl)sulfone uses due to aerosol and gas 

formation. This triggers the need for chemical- and use pattern-specific occupational and 

residential exposure data upon which to base a solid quantitative risk assessment.

2. How will the data be used?

The inhalation exposure data will be used to assess the residential short-term duration of 

painting with a paint brush/roller and an airless sprayer. For occupational uses, the inhalation 

exposure data would be used to assess the short- and intermediate-term painting as well as 

pouring bis(trichloromethyl)sulfone concentrates (e.g., poured into paint as a preservative in 

manufacturing settings for industrial and household water-based liquids). These data will also be 

used to assess bystander exposures to the vapors that may result from the relatively high vapor 

pressure of bis(trichloromethyl)sulfone.

3. How could the data impact the Agency’s future decision-making?

The inhalation exposure data will be used to estimate inhalation risks to both residential and 

occupational workers using the formulated products and in-can-preserved materials in residential 

and industrial settings; inhalation risks have never been estimated. If future risk assessments are 
23

performed without these data, the Agency will have to assume a significant degree of uncertainty 

in its regulatory decision-making process. The lack of these data could result in underestimation 

or overestimation of handler risks. The former would result in the Agency not protecting human 

health whereas the latter could greatly limit the flexibility of the Agency and registrants with 

respect to decisions made from high-end screening level assessments. If risks warrant 

mitigation, the inhalation exposure data would help EPA decide on the types of mitigation 

necessary such as respiratory protection from respirators or closed systems for commercial uses 

to potential removal of uses from the label.

Guideline Number: 875.1600 and 875.2900

Study Title: Data Reporting and Calculations (Handler and Postapplication)

Rationale for Requiring the Data

This data requirement is linked to the dermal and inhalation exposure data also being required. 

The submission of these data serves as quality assurance and control (QA/QC) information and 

to validate the dermal and inhalation data. These data are intended to ensure that the product 

manufacturer and registrant conducting the study adhere to a defined set of quality criteria and 

meet the study requirements of the Agency. These data allow the Agency to determine if the 

quality of data provided will serve the risk assessment needs of the Agency and support the 

registrant’s goal for product registration review. Submission of data reporting and calculations 

increases the Agency’s confidence in the data submitted. 

Rationale for Requiring the Data/Practical Utility

1. How did the Agency make its earlier regulatory decisions without these data?

There were no chemical-specific data available to assess worker or residential dermal or 

inhalation exposures to bis(trichloromethyl)sulfone. Therefore, there were no reporting data. 

2. How will the data be used?

These studies will be used to validate the data provided from the indoor and outdoor dermal and 

inhalation applicator exposure studies. These data are important because it allows EPA to 

assess the adequacy and quality of the exposure study. Information that must be submitted 

includes a description of the purpose of the study and what requirement(s) it is intended to 

satisfy, a summary of the study, a comprehensive section on materials, methods, and 

calculations, a section interpreting the scientific results of the study, a discussion of quality 

assurance, identification of the location of the raw data, and any references, communications, 

and protocols relevant to the conduct of the study. 

3. How could the data impact the Agency’s future decision-making?

The data will be needed to interpret the dermal and inhalation exposure (indoor and outdoor) 

data expected to be submitted in response to this registration review. If the exposure monitoring 

data reporting is not submitted in conjunction with the indoor and outdoor dermal and inhalation 

applicator exposure studies, the Agency may not be able to utilize the studies to the fullest extent 

to conduct its human health exposure and risk assessments.
24

Guideline Number: 875.1700 and 875.2700

Study Title: Product Use Information (Outdoor and Indoor)

Rationale for Requiring the Data

Product use information is a narrative description of which, when, and how materials are 

preserved when the product is actually applied; it is not a field study. A description of how 

products containing bis(trichloromethyl)sulfone are used will provide a comprehensive, realistic 

assessment of its potential applications and resulting handler and postharvest exposure.

Descriptions are needed of: (i) what specific types of materials are treated; (ii) what stage in the 

manufacturing process each material is treated; (iii) the conditions to which the 

bis(trichloromethyl)sulfone will be exposed (temperatures, pH’s, etc); etc. These will provide a 

comprehensive, realistic assessment of potential residential and occupational exposures. 

Therefore, these data are required.

Product use information permits EPA to more accurately assess pesticide exposure to 

applicators by describing how the pesticide is actually used and applied. EPA requires this 

information because differences in use can translate to significant differences in exposure, and 

thus in risk. 

The guideline for postapplication product use information was presented to the FIFRA Science 

Advisory Panel (SAP) in March 1998. (The draft guideline is available at 

http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm.). The guideline for applicator 

product use information should be substantially similar to the one for postapplication.

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

The Agency used its best professional judgment based on its years of experience and general 

use information from the registered product labels and product chemistry data. 

2. How will the data be used? 

The description of the materials preserved, application techniques, degradation conditions, and

physicochemical disposition will be used to determine the scenarios for which exposure studies 

will be required. These will be used in risk assessment and for the Agency to determine how 

representative the exposure data are of the “real-world” use scenarios.

3. How could the data impact the Agency’s future decision-making?

These data will enable the Agency to understand how the EPs are applied and ensure that the 

risk assessment is inclusive of the types of exposures occurring during pesticide use and from 

any potential postapplication contact. This information will permit a determination of which use 

patterns are expected to result in exposures less than the Agency’s level of concern, which ones 

must be supported by additional data, and which ones are likely to have risks of concern and, 

therefore, must be mitigated.
25

Guideline Number: 875.2300 

Study Title: Indoor Residue Dissipation

Rationale for Requiring the Data

Data will only be required if the bis(trichloromethyl)sulfone-treated plastics are 

manufactured into toys

These leaching/migration data will allow the Agency to conduct chemical specific quantitative 

assessments that utilize the measured quantities of bis(trichloromethyl)sulfone and/or major 

metabolites/degradates leaching/migrating from the preserved polymer. Exposures to these 

residues may occur as a result of dermal and non-dietary contact. In the absence of chemical 

specific migration data, the Agency uses a default leaching rate from plastic of 0.5%. The 

leaching study will be used to confirm or replace this default leaching rate.

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

The Agency did not initially assess this use pattern. Based on professional judgment and general 

information on this use pattern, it is now necessary to consider. 

2. How will the data be used? 

The data would be used to determine the leachability of the active ingredient expressed as a rate 

of migration or percentages of the original preservative incorporated over time. However, the 

registrant may seek a data waiver by proposing a label restriction against preserving plastics that 

may be manufactured into toys. If this is pursued and the labels are revised to include this 

restriction, this will override this data requirement. 

3. How could the data impact the Agency’s future decision-making?

The migration data on bis(trichloromethyl)sulfone in plastic toys will be used to estimate 

children’s dermal and incidental oral exposure and associated risk. This exposure source and 

these routes will be aggregated with dietary, drinking water, and any other co-occurring 

nondietary sources; it is possible that the children’s aggregate risk could represent a risk of 

Agency concern which would necessitate mitigation. This information will permit a determination 

of which use patterns are expected to result in exposures less than the Agency’s level of 

concern, which ones must be supported by additional data, and which ones are likely to have 

risks of concern and, therefore, must be mitigated.
26

Guideline Number: 875.2800 

Study Title: Descriptions of Human Activity

Rationale for Requiring the Data

Very limited worker activity data are available for antimicrobial pesticides, including material 

preservatives used in paint and other consumer products. Worker application parameters are 

generally defined by the physical nature of the formulation (e.g., formula and packaging), by the 

equipment required to deliver the chemical to the use site, and by the application rate required to 

achieve an efficacious dose. The risk assessment noted that many of the use parameters used 

(e.g., amount handled and duration of use) were based on professional judgments. These data 

are needed to fill this data gap and provide information needed to refine the risk assessment.

Practical Utility of the Data

1. How did the Agency make its earlier regulatory decisions without these data?

The Agency used its best professional judgment and general use information from the registered 

product labels, product chemistry data, as well as communication with the registrants of 

registered products. 

2. How will the data be used? 

The discussion of human activity would be used to define the exposure scenarios to be 

assessed in the risk assessment. Additionally, a complete description of activity patterns would 

ensure that the risk assessment is inclusive of the types of exposures occurring during 

residential and occupational use.

3. How could the data impact the Agency’s future decision-making?

This information will allow the Agency to assess, with greater confidence, the risks that may 

result from contact with or use of antimicrobial products containing bis(trichloromethyl)sulfone. 

This information will also permit selection of appropriate label warnings, PPE, and any necessary 

risk mitigation.

Sign-off Date : 10/13/11

DP Barcode No. : D394302