Document ID: EPA-HQ-OPP-2007-1151-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-01-16T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460

OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES

 

1/10/08

MEMORANDUM:

SUBJECT:	Diiodomethyl p-tolyl sulfone. P.C. Code: 101002. Human Health
and Ecological Effects Risk Assessments for the Reregistration
Eligibility Decision (RED) Document. Case  4009. CAS Registry No.
20018-09-1. DP Barcode 344851.

TO:		Kathryn Avivah Jakob, Chemical Review Manager

		Regulatory Management Branch II

Antimicrobials Division (7510P)

FROM: 		William J. Hazel, Ph.D., Chemist, Risk Assessor

		Jonathan Chen, Ph.D., Toxicologist

		Nathan Mottl, Occupational/Residential Assessor

		Cassi Walls, Ph.D., Dietary Assessor

		Najm Shamim, Ph.D., Chemist, Product Chemist

		Siroos Mostaghimi, Modeling for Ecological Effects

		William Erickson, Ecological Effects 

		James Breithaupt, Environmental Fate

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (7510P)

THRU:		Norm Cook, Branch Chief

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (7510P)

This document is a revision of the 11/20/07 combined human health risk
assessment and ecological effects assessment for the Reregistration 
Eligibility Decision (RED) Document of the antimicrobial pesticide known
as Diiodomethyl p-tolyl sulfone.  This assessment reflects Agency
incorporation of relevant error comments provided 12/20/07 by The Dow
Chemical Company deemed.  In the next phase of the reregistration
process, the public will be given the opportunity to comment on this
document and the Agency will respond as appropriate.

The following disciplinary chapters are discussed in this
EPA/Antimicrobial Division Risk Assessment for diiodomethyl p-tolyl
sulfone and are attached as Appendices:

Diiodomethyl p-tolyl sulfone RED Use Summary Updated Appendix A. 
10/1/2007.

Diiodomethyl p-tolyl sulfone:  Draft Hazard Assessment.  Jonathan Chen. 
1/9/08.  DP 344852.

Amended Product Chemistry of Benzene,
1-((diiodomethyl)sulfonyl)-4-methyl or Diiodomethyl p-tolyl sulfone for 
Reregistration Eligibility Decision (RED).  A. Najm Shamim.  1/9/08.  DP
348167.

Revised Dietary and Drinking Water Exposure Chapter for Diiodomethyl
p-tolyl sulfone for the Reregistration Eligibility Decision (RED)
Document (Case 4009).  Cassi Walls.  1/2/08.  DP 344855.

Occupational and Residential Exposure Chapter for
Diiodomethyl-p-tolylsulfone.  Nathan Mottl.  1/9/08. DP 344853.

Environmental Fate Assessment of Diiodomethyl p-tolyl sulfone for RED
Case No. 4009.  James Breithaupt.  1/9/08.  DP 344849.

Revised Environmental Hazards and Ecological Risk Assessment for the
Diiodomethyl p-tolyl sulfone RED.  William Erickson.  1/8/08.  DP
344848.

Diiodomethyl p-tolyl sulfone – Incident Report Summary.  Jonathan
Chen.  1/9/08.  DP 344852.

TABLE OF CONTENTS

EXECUTIVE
SUMMARY………………………………………………………
……4

PHYSICAL AND CHEMICAL
PROPERTIES…………………………………...10

HAZARD
CHARACTERIZATION………………………………………………
…11

Hazard Profile/Dose-Response Assessment ………………..……….11

FQPA
Considerations…………………………………………………
…..20

Endocrine
Disruption……………………………………………………..
.20

Incident
Reports………………………………………………………
……………20

Human Exposure Assessment and
Characterization……………………….21

Summary of Registered
Uses……………………………………………21

Dietary Exposure and
Risk……………………………………………….21

Drinking Water Exposure and
Risk……………………………………..28

Residential Exposure and
Risk………………………………………….28

Aggregate Risk Assessment and Characterization………………….30

Cumulative Exposure and
Risk………………………………………….31

Occupational Exposure and
Risk……………………………………………….31

Environmental
Fate…………………………………………………………
……..35

Ecological Effects and
Risks…………………………………………………….37

Deficiencies/Data
Needs………………………………………………………….
38

References……………………………………………………
……………………..41

Appendices……………………………………………………
…………………….49

EXECUTIVE SUMMARY

Diiodomethyl p-tolyl sulfone is the Dow Chemical Company trademark for
their antimicrobial properly named Diiodomethyl p-tolyl sulfone, which
is a List D chemical having the P.C Code 101002 in Case No. 4009. 
Diiodomethyl p-tolyl sulfone is an algicide, bactericide, and fungicide
in eight EPA-registered Wettable Powders (WP) or Flowable Concentrate -
Liquid (FlC-L) products.  One of these products (EPA Reg. No. 464-671)
will be cancelled.  Diiodomethyl p-tolyl sulfone products are used for: 
dry film mildewicide/algicide in paints, air duct coatings, and
fire-retardant coatings; pigment dispersions, inks, emulsions, and
extender slurries as fungal preservatives; adhesives, caulks, and
sealants for dry film mildew control and as a fungal preservative; for
wood preservation; rubber and plastic surface fungal protection; textile
dry-film fungal protection; leather in-process fungal protection; paper
production to protect pulp and slurries; paper/paperboard for dry-film
fungal protection; wetlap storage as a fungal preservative; and
nitrocellulose fungal preservative.  Commitment has been made to cancel
the uses for metalworking fluid and drain, trap, and septic system
fungal control.  Refer to Appendix A for the details of the Diiodomethyl
p-tolyl sulfone use pattern.

Diiodomethyl p-tolyl sulfone is moderately toxic following acute
exposure and is classified as Toxicity Category II via the inhalation
route and as Toxicity Category IV via both the oral and dermal routes. 
It causes severe irritation to ocular tissue of rabbit and is classified
as Toxicity Category I for primary eye irritation.  Diiodomethyl p-tolyl
sulfone is not a dermal sensitizer.  It causes minimal irritation to
rabbit skin and is classified as Category IV for primary skin
irritation.

For several short-term (ST) dermal and incidental oral risk assessments,
an oral 30-day rabbit developmental study was selected in which effects
were clinical signs, reduced body weight gain, and reduced food
consumption of maternal animals (NOAEL = 4.0 mg/kg/day).  There are two
subchronic studies: one dog 90-day capsule dosing study and one rat
90-day feeding study.  Dogs appear to be the more sensitive species to
Diiodomethyl p-tolyl sulfone exposure.  In the dog, the LOAEL was 2
mg/kg/day based on decreased body weight gain, decreased activity,
dehydration, ocular discharge, abnormal feces, and thyroid degeneration.
 This dose was selected to be used as the hazard component of risk in
chronic dietary, and all intermediate-term (IT) and long-term (LT)
durations of exposure except the inhalation route.

As an oral dosing toxicity study was used for dermal risk assessment, a
dermal adsorption factor was calculated to be 12% based on rat
pharmacokinetics and metabolism. An inhalation absorption factor of 100%
was used (equivalency to oral absorption was assumed) for all inhalation
exposure durations since the MOE calculations were based on an oral
endpoint.  The uncertainty factors or “target” margins of exposure
(MOE) serving as the standard Levels of Concern (LOC) in the assessment
of nondietary risks to Diiodomethyl p-tolyl sulfone are:

A MOE of 100 is applicable to short-term oral and dermal risk
assessments (10x for interspecies extrapolation and 10X for intraspecies
variation).

A MOE of 300 is applicable to intermediate-term oral and dermal risk
assessments (10x for interspecies extrapolation, 10X for intraspecies
variation, and 3X for using a LOAEL).

A MOE of 300 is selected for all durations of inhalation exposure risk
assessments (10x for interspecies extrapolation, 10X for intraspecies
variation, and 3X for using a LOAEL).  However, if a MOE of 3000 is not
achieved, a route-specific inhalation toxicity study will be needed
(hence the extra 10x).  

There are no chronic and/or cancer studies.  At this point in time, the
only long-term/high exposure scenario triggering the requirement for
chronic studies and cancer studies (two species) is use in metal working
fluid.  However, the technical registrant (Dow), in 10/07 committed to
cancel the metalworking fluid uses which would negate the need for
chronic toxicity and cancer studies.

No direct food uses are associated with the registered Diiodomethyl
p-tolyl sulfone labels.  There are, therefore, no FQPA concerns.

It was not appropriate to assess acute dietary risks because there were
no adverse effects attributable to a single dose.  The chronic dietary
risks from the combined use of Diiodomethyl p-tolyl sulfone as an
indirect food additive in the preservation of adhesives, can side-seam
cements, and repeat-use rubber sealants were calculated using the
chronic RfD of 0.002 mg/kg/day.  The sum of the risks from these three
indirect food uses (22% in adults and 52% in children) do not exceed the
Agency’s Level of Concern (100% of the chronic RfD).    

Based on the use patterns, the potential for Diiodomethyl p-tolyl
sulfone to impact drinking water sources is negligible and, therefore, a
quantitative drinking water assessment was not conducted.

For the ST residential handler dermal risk assessment, calculated MOEs
are above the target MOE of 100, i.e., below the Agency’s level of
concern (except the MOE 40 for painting with an airless sprayer).
However, the calculated IT dermal MOEs for applying paint and wood
preservative are all below the target MOE of 300, i.e., of Agency
concern. The inhalation MOE for painting with an airless sprayer (MOE
230) is the only scenario that is below the Agency’s target MOE of
300. However, none of the inhalation MOEs  exceeded 3,000; therefore, a
confirmatory inhalation toxicity study is warranted based on the results
of these exposure scenarios. 

For the residential postapplication risk assessments, MOEs are below the
respective target MOEs (ST dermal  = 100, inhalation = 3,000, and
incidental ingestion = 300) for the following scenarios and, therefore,
are of concern:

Dermal contact of children with treated carpet (ST MOE 9 and IT MOE 4).

Dermal contact to treated wood products (IT MOE 99).

Incidental oral exposure to treated carpet (ST MOE 49 and IT MOE 51).

The likelihood and appropriateness of ST and IT aggregate exposures to
Diiodomethyl p-tolyl sulfone were assessed for adults and children.  As
risks associated with one or more residential scenarios exceed the
Agency’s Level of Concern, no aggregate risks were calculated.

For occupational handlers at baseline (without gloves) dermal, all of
the dermal IT MOEs are below the target MOE of 300 and, therefore,
exceed the level of concern except:  preservation of slurries (liquid
pump); preservation of paper (liquid pump); diptank operator; treatment
assistant; and application of wood preservative (airless sprayer).

For baseline (without gloves) dermal, all of the dermal ST MOEs are
below the target MOE of 100 and, therefore, exceed the level of concern
except:  preservation of adhesives and caulks (liquid pump);
preservation of slurries (liquid pump); preservation of emulsions
(liquid pump); preservation of paper (liquid pump); application of wood
preservative by professionals (brush and airless sprayer); chemical
operator (wood preservative); blender/spray operator; diptank operator;
treatment operator; and treatment assistant.

For PPE (gloves) dermal, all of the dermal IT MOEs are above the target
MOE of 300 and are below the applicable level of concern except. 

Preservation of Paint for liquid pump (MOE 188) and liquid pour (MOE
88).

Application of Paint by professionals for brush (MOE 197) and airless
sprayer (MOE 34).

Preservation of Adhesives and Caulks by liquid pour (MOE 288).

Preservation of Rubber and Plastic for liquid pour (MOE 56) and liquid
pump (MOE 120).

Preservation of Leather for liquid pour for raceway (MOE 34), mixers
(MOE 168), and tanning drum (MOE 84).

Preservation of Textiles for liquid pour (MOE 182). 

For PPE (gloves) dermal all of the dermal ST MOEs are above the target
MOE of 100 and are less than the level of concern except:

Application of Paint by professionals for airless sprayer (MOE 67).

Preservation of Leather for liquid pour for raceway (MOE 67).

For baseline (without respirator) inhalation the following scenarios are
below the target MOE of 300 (at all exposure levels) and do exceed the
level of concern except:

Application of Paint (airless sprayer) with MOE 68.

Preservation of Rubber and Plastic for liquid pour (MOE 261) and liquid
pump (MOE 224).

Preservation of Leather for liquid pour for raceway (MOE 157)

For PPE (respirators) inhalation all the scenarios were above the target
MOE of 300. However, even with PPE, some of the calculated inhalation
MOEs (e.g., painting with an airless sprayer = MOE 341) were less than
the target MOE of 3,000. Therefore, a confirmatory inhalation toxicity
study is warranted based on the results of this assessment of paint.

For occupational postapplication, the inhalation MOEs for treated HVAC
systems and for cleanup activities at lumber mills exceeded the target
MOE of 300.  However, they did not exceed the target MOE of 3,000;
therefore, a confirmatory inhalation toxicity study is warranted based
on the results of this assessment.

For the occupational postapplication risk assessment, dermal ST MOEs are
above the respective target MOEs ((ST dermal  = 100) for all scenarios
except for the following:

Cleanup activities at a lumber mill (MOE 70).

For the occupational postapplication risk assessment, dermal IT MOEs are
above the respective target MOEs ((IT dermal  = 300) for all scenarios
except for the following: 

Millwright at lumber mill (MOE 152).

Cleanup activities at a lumber mill (MOE 35).

Chemical operator (MOE 198)

Limitations and uncertainties associated with the residential handler
and postapplication exposure assessments need to be eliminated by
submission of data/information to refine the following: confirmatory
monitoring data to support the values used in these assessments;
quantities of Diiodomethyl p-tolyl sulfone handled/treated need to be be
further refined based on registrant input; low pressure spray data used
herein could easily reflect an underestimation of exposure; the method
use to estimate exposure from toddlers mouthing toys is considered to be
overly conservative.  Also, since the Chemical Manufacturers Association
(CMA) data used to support the occupational scenarios are of poor
quality, the Agency requests that confirmatory data be submitted to
support the occupational scenarios assessed in this document.

Diiodomethyl p-tolyl sulfone is stable to hydrolysis at pH 5, but it
degrades with half-lives of 2-4 days at pH 7 and 9. 
Monoiodomethyl-p-tolylsulfone (MIMPTS; loss of one iodo group) was the
major degradate formed, and increased until the end of the study (30
days).  Methyl-p-tolylsulfone (MPTS; loss of both iodo groups) and
p-toluene sulfonic acid (PTSA; parent minus methyl group) reached minor
concentrations.  Soil photolysis half-lives of 13 days (linear) and 5.3
days (non-linear) were observed for parent compound. MIMPTS was stable
in the dark control but degraded with a half-life of 12.5 days in an
irradiated sample.  Volatiles and non-extractables were negligible.

Degradation by microorganisms will reduce Diiodomethyl p-tolyl sulfone
concentrations in the environment, but residues are expected to
partition to water in the presence of soil or sediment.  In aerobic soil
(the top layer of non-flooded soil), the non-linear parent, MIMPTS, and
MPTS half-lives were 1.5, 32, and 53 days, respectively.   The linear
half-life of MPTS was 173 days.  In the anaerobic soil metabolism study
(the second layer of soil), the half-lives of parent Diiodomethyl
p-tolyl sulfone were 1.7 and 4.2 days in aerobic (non-flooded) and
anaerobic (flooded soil) portions of the study, respectively. 
Diiodomethyl p-tolyl sulfone was found in equal portions in water and
sediment.  MIMPTS was a major degradate with a half-life of 21 days and
was found predominantly in water.  MPTS reached 81% by the end of the
study and was primarily found in water.  Anaerobic aquatic metabolism
(representing bottom sediment) degrades parent and MIMPTS with total
system half-lives of 9.6 and 11 days, respectively.  MPTS was the
terminal metabolite and increased to 95% by 4-6 months.  Aqueous
residues were greater than sediment residues for parent, MIMPTS, and
MPTS for 7, 180, and 60 days, respectively.

Diiodomethyl p-tolyl sulfone was mobile in columns of soil that were
leached with water.  The amounts of parent compound that leached through
12-inch columns were 73, 84, 34, and 8% in sand, silt loam, sandy loam,
and clay soils.  An average of 2, 1.5, 5, and 8% of applied compound was
present in each inch of the columns, respectively.

The Log Kow (Log P) for parent Diiodomethyl p-tolyl sulfone is 2.66, and
the estimated (EPI-SUITE) Log Kow values for MIMPTS, MPTS, and PTSA were
2.2, 1.1, and 0.56, respectively.  None of these compounds are expected
to bioconcentrate significantly because the Log Kow values are below
3.0.  

An average of 43% of Diiodomethyl p-tolyl sulfone from wooden tongue
depressors leached into pH 5, 7, and 9 unfiltered buffers over a 30-day
study (median of 42%).  Maximum residues in water were observed at day
zero, followed by a decrease to the minimum values at day 7 and then a
general increase.  In filtered samples, the aqueous residues averaged
4.3%, indicating that some sorption to organic materials may occur in
the environment.  

There was no inhibition of microorganisms in sewage sludge treated at 9
mg/l.

Three available acute avian oral/dietary studies indicate that
Diiodomethyl p-tolyl sulfone is practically nontoxic to birds (LD50
>2000 mg ai/kg bw) when ingested and an avian precautionary statement is
not required on product labels.  The guidelines for avian acute oral
toxicity (OPPTS 850.2100) and avian dietary toxicity (OPPTS 850.2200)
are satisfied.  

Diiodomethyl p-tolyl sulfone is practically nontoxic to mammals as
indicated by several available studies reflecting the oral (rat LD50
>5000 mg ai/kg bw) and dermal (rabbit LD50 >20,000 mg/kg) routes of
exposure.  Refer to the human toxicology chapter for more details on
these and other mammalian toxicity studies submitted for the human
health assessment.

No data are available regarding effects of Diiodomethyl p-tolyl sulfone
on honeybees.  For wood preservative use, a study addressing
honey/beeswax residues and acute toxicity of treated wood residues to
bees is required or, in lieu of this study, product labels with wood
preservative use can include a statement prohibiting use of Diiodomethyl
p-tolyl sulfone-treated wood for beehive construction.

Three acceptable acute toxicity studies with the TGAI have resulted in
Diiodomethyl p-tolyl sulfone being categorized as very highly toxic to
freshwater fish.  Therefore, a precautionary label statement is
required.

Results from three available studies categorize technical-grade
Diiodomethyl p-tolyl sulfone as being moderately to very highly acutely
toxic to freshwater invertebrates.  Therefore, a precautionary label
statement is required.

Acute toxicity testing with estuarine/marine organisms using the TGAI is
required when the end-use product is intended for direct application to
the marine/estuarine environment or the active ingredient is expected to
reach this environment in significant concentrations because of its
expected use and mobility.  Data are required to support the wood
preservative uses of Diiodomethyl p-tolyl sulfone.  No data are
available.  

The Agency’s level of concern (LOC) is exceeded for listed (i.e.,
endangered and threatened) species for all three dilution-rate scenarios
from antisapstain treatment (refer to the Ecological Effects Chapter). 
The LOC is not exceeded for non-listed invertebrates for any scenario
but is exceeded for listed (i.e., endangered and threatened) species for
all three dilution-rate scenarios from antisapstain treatment.  

Because Diiodomethyl p-tolyl sulfone is practically nontoxic to birds
and mammals, minimal acute risk is presumed for all registered uses. 
Toxicity data are not available to assess risk to honey bees.  However,
if use of treated wood is prohibited for construction of bee hives,
minimal exposure and risk are presumed.

For certain use categories, including most Diiodomethyl p-tolyl sulfone
uses, the Agency assumes there will be minimal environmental exposure,
and only a minimal toxicity data set is required (Overview of the
Ecological Risk Assessment Process in the Office of Pesticide Programs
U.S. Environmental Protection Agency - Endangered and Threatened Species
Effects Determinations, 1/23/04, Appendix A, Section IIB, p. 81).  Uses
in these categories do not undergo a full screening-level risk
assessment and are considered to fall under a no effect determination.  

The assessment for antisapstain wood treatment uses indicates that there
is a potential for Diiodomethyl p-tolyl sulfone exposure of listed
freshwater and aquatic invertebrate species and that a more refined
assessment is warranted, to include direct, indirect and habitat
effects.  The refined assessment should involve clear delineation of the
action area associated with proposed use of Diiodomethyl p-tolyl sulfone
and best available information on the temporal and spatial co-location
of listed species with respect to the action area.  This analysis has
not been conducted for this assessment.  An endangered species effect
determination will not be made at this time.  The label statement
required for wood preservative products is expected to provide some
mitigation until a full endangered species assessment is conducted.

2.0	PHYSICAL AND CHEMICAL PROPERTIES

CAS#:			20018-09-1

Chemical Name:	Benzene, 1-((diiodomethyl)sulfonyl)-4-methyl

Common Names: 	Diiodomethyl p-tolyl sulfone/AmicalTM

Chemical Formula:	C8H8 I2O2S

Mol. Wt:		422.01

Molecular Structure:

Color:			Tan

Physical State:		Solid at room temeprature

MP:			136 oC  / 149-152 oC				

BP:			394 oC   

Specific Gravity:	  	~1   at 25 oC

Vapor Pressure:		1.87 x 10-6  mmHg  / 5.2 x 10-8  mmHg at 25 oC

Solubility:			10 mg/L   at 25 o C  in water 

Henry Law Constant:	6.03 x 10-7  atm-m3/mole

Persistence in Air:	23.4 Hours

Log KOW :			2.66 

Stability:			Stable at room temperature and stable at 54±2 oC 					for
two weeks 

Redox Potentials: 	Not oxidizing

Flammability:		60 oC

Explodability:		Does not contain explosive material

Log KOC:			2.788 

3.0	HAZARD CHARACTERIZATION

	3.1	Hazard Profile/Dose-Response Assessment

As summarized in Table 1, Diiodomethyl p-tolyl sulfone is moderately
acutely toxic and classified as Toxicity Category II for inhalation
routes and Category IV for both oral and dermal routes. It causes severe
irritation to ocular tissue of Rabbit and is classified as Category I
for primary eye irritation.  Diiodomethyl p-tolyl sulfone is not a
dermal sensitizer.  It causes minimal irritation to skin of Rabbit and
is classified in Category IV for primary skin irritation. 

Table 1.  Acute Toxicity Decisions for Diiodomethyl p-tolyl sulfone.

Guideline

 No.	

Study Type	

MRID #(S).	

Results	

Toxicity

 Category

870.1100

(81-1)	

Acute Oral	

41765401, 43008702, and 42586801	LD50  > 5000 mg/kg 

(for both male and female)

	

IV

870.1200

(81-2)	

Acute Dermal

(Rats)	

00141066	

LD50 (Males) = 20,000 mg/kg

	

IV

870.1300

(81-3)	

Acute Inhalation	43660901 and

00087842	LC50 (combined)= 0.96 mg/L

LC50 (male) = 1.15 mg/L 

LC50 (female) = 0.77 mg/L	

II

870.2400

(81-4)	

Primary Eye Irritation	41765402 and 43008703

	

Severe irritant to ocular tissue of Rabbit	

I

870.2500

(81-5)	

Primary Skin Irritation	41765403, 43008704, and 00141066	

Minimum irritant to skin of Rabbit	

IV

870.2600

(81-6)	Dermal Sensitization	00230726 and 00054963	Not a Dermal
Sensitizer

	ACUTE REFERENCE DOSE (aRfD)  A study of the appropriate dose/duration
to determine acute toxicity is not available.

	

	CHRONIC REFERENCE DOSE (cRfD)

	90-day Oral (Dog)  870.3150

MRID Nos.: 42054403 and 43246402

Executive Summary:   Four groups, each consisting of 4 male and 4 female
beagles, were administered Diiodomethyl p-tolyl sulfone at doses of 0,
2, 10 or 60 mg/kg/day in gelatin capsules for at least 3 months. 
Clinical signs of toxicity, which were observed 1-4 hours after dosing
in the high dosage group, included decreased activity, dehydration,
mucoid eye discharge, weakened condition, and abnormal feces (mucoid and
occasionally blood-tinged).  Eye discharge and abnormal feces in the
intermediate dosage group were also considered treatment-related. 
Females in all of the treated groups had decreases in mean body weight
gain from Day 0 to 91 of at least 20% in comparison to the control
value.

Mean hematology evaluations of the treated animals were not
statistically significant from those of the control animals, although
the white blood cell counts and neutrophil counts of the males in the 60
mg/kg/day group were higher than the control and other treated groups. 
The high dosage group males also had significantly decreased mean
calcium, albumin, albumin: globulin ratio and total protein values on
one or two evaluations during the treatment period.  On gross necropsy,
the only findings were changes in the gastrointestinal tract (patchy-red
discoloration of the stomach and mucoid appearance of the small
intestines) in three males in the high dosage group.  Absolute and
relative organ weight did not differ from the control values,
essentially.  On histopathology, degeneration of the thyroid gland was
observed in males and females in the high and intermediate dosage
groups.  Sialadenitis, gastritis, necrosis of the small intestine and
keratitis were also seen in the high dose group.  The clinical and
pathologic findings were considered to be a result of iodine toxicity
induced by the iodine moiety of Diiodomethyl p-tolyl sulfone.

In this study, the NOAEL and LOAEL for males and females are as follows:

Males:

NOAEL = 2 mg/kg/day and LOAEL = 10 mg/kg/day based on decreased
activity, dehydration, mucoid ocular discharge, weakened appearance,
abnormal feces, and degeneration of the thyroid.

Females 

NOAEL < 2.0 mg/kg/day and LOAEL = 2 mg/kg/day based on decreased body
weight gain.

Dose and Endpoint for Risk Assessment:

LOAEL = 2 mg/kg/day (based on decreased body weight gain)

Proposed Uncertainty Factor(s): 

1000 [10x for interspecies, 10x for intraspecies, 3x for database
uncertainty (missing chronic and cancer studies) and 3x for using LOAEL]

 

Comments about Study/Endpoint

In the study, females in all of the treated groups had decreases in mean
body weight gain from Day 0 to 91 of at least 20% by comparison to the
control value. 

  

	Occupational/Residential Exposure

	Short-Term Incidental Oral Exposure (1 – 30 days)

Developmental Toxicity - Rabbit	§   870.3700a

MRID No.: 41161801

Executive Summary: 

In a developmental toxicity study (MRID # 42243801), pregnant New
Zealand White Rabbits from Hazleton Dutchland, Inc. (Denver PA.)
received 0, 4, 15, or 60 mg/kg/day diiodomethyl p-tolyl sulfone (95%
a.i., Lot No. 66-207-CB) by gavage from gestation day 6 through 18,
inclusive.

 

Maternal toxicity was noted as deaths and abortions primarily in the
high dose group, clinical signs in the mid and high dose group, reduced
body weight gain and food consumption in the mid and high dose groups.
The Maternal Toxicity LOAEL was 15 mg/kg/day and the Maternal Toxicity
NOAEL was 4 mg/kg/day, based on clinical signs, reduced body weight gain
and reduced food consumption.

Dose and Endpoint for Risk Assessment:

The maternal NOAEL was 4 mg/kg/day (100% a.i) based on clinical signs,
reduced body weight gain and reduced food consumption.

Proposed Uncertainty Factor(s): 

100 (10x for interspecies extrapolation and 10x for intraspecies
variation).

Comments about Study/Endpoint

The appropriateness of using the rabbit developmental maternal NOAEL of
4 mg/kg/day in the study (MRID 41161801) as endpoint is confirmed by the
second rabbit developmental study (MRID47242202). At the highest dose
tested in the second developmental study (2 mg/kg bw/day), no
toxicologically adverse maternal effects or developmentally adverse
fetal effects were seen.   

	Intermediate-Term Incidental Oral Exposure (1 – 6 months)

90-day Oral (Dog)	§ 870.3150

MRID No.:  42054403 and 43246402

Executive Summary: 

See above under Chronic Reference Dose (aRfD).

Dose and Endpoint for Risk Assessment

LOAEL = 2 mg/kg/day and NOAEL of < 2 mg/kg/day based on decreased body
weight gain.

Comments about Study/Endpoint/Margins of Exposure: 

It is based an appropriate exposure period and the dog is considered to
be a more sensitive species.  The total Margin of Exposure of 300 has be
used [10x for interspecies extrapolation, 10x for intraspecies
variation, and 3x for using a LOAEL].

	Relative Dermal Absorption Rate

There is no guideline acceptable dermal penetration study.  There is
some dermal absorption information in the newly available
pharmacokinetic and metabolism study (MRID 47078801).

In the study, Fischer 344 rats (4 males and 4 females) were dosed
dermally by applying C14-Diiodomethyl p-tolyl sulfone on the shaved back
(between scapula), covering the site with mesh, and washing the site 6
hours after application. Dose suspension for the dermal application was
prepared at the target concentration of ~8.8 mg/ml and applied at a dose
volume of 10 µl/cm2 to 12 cm2, which resulted in a dose of ~5 mg/kg. 
Absorption of the dermally applied DIIODOMETHYL P-TOLYL SULFONE
antifungal agent was 7-12% of the dose . Between 5 and 7% of the applied
dose was excreted in urine; fecal elimination was negligible (~0.3%).
The level of radioactivity and free iodide in the plasma of the dermally
dosed animals remained <LOQ throughout the study. The dermally applied
dose was slowly absorbed from the site of application and rapidly
eliminated in urine accounting for 23-30% and 38-45% of the absorbed
dose within 24 hours and 48 hours, respectively. The total amount of
iodide found in the urine of the dermally dosed rats was 10-40% higher
than the total radioactivity, which was opposite to what was observed in
the orally dosed animals, indicating higher metabolism/liberation of one
or both of the iodide from the parent molecule. Elimination of
radioactivity and iodide in urine continued during the analysis period
due to slow continuous absorption of 14C-diiodomethyl p-tolyl sulfone
antifungal agent from the application site.

Because there were only 6 hr of exposure, there was only one dosage
treatment concentration group, absorption from the site of application
was very slow, and eliminated in the urine was very rapid, it is very
possible that more absorption would have occurred under some of these
other exposure conditions.  Therefore, the Agency is uncertain considers
all the unabsorbed portion of the 14C-diiodomethyl p-tolyl sulfone in
the skin to be considered absorbable.  The appropriate dermal absorption
factor to be used risk in risk assessment should be around 12%.

	Short-Term Dermal (1-30 days) Exposure

Developmental Study (Rabbit)    MRID No.: 42243801

Executive Summary: 

In a developmental toxicity study (MRID 42243801), pregnant New Zealand
White Rabbits from Hazleton Dutchland, Inc. (Denver PA.) received 0, 4,
15, or 60 mg/kg/day diiodomethyl p-tolyl sulfone (95% a.i., Lot No.
66-207-CB) by gavage from gestation day 6 through 18, inclusive.

 

Maternal toxicity was noted as deaths and abortions primarily in the
high dose group, clinical signs in the mid and high dose group, reduced
body weight gain and reduced food consumption in the mid and high dose
groups. The Maternal Toxicity LOAEL is 15 mg/kg/day and the Maternal
Toxicity NOAEL is 4 mg/kg/day, based on clinical signs, reduced body
weight gain and reduced food consumption.

Dose and Endpoint for Risk Assessment: 

NOAEL = 4 mg/kg/day (based on maternal toxic effects on clinical signs,
reduced body weight gain and reduced food consumption.).

Comments about Study/Endpoint/Margins of Exposure:

It is based on appropriate exposure period and dog is considered a more
sensitive species.  Margin of Exposure (MOE) = 100x (10x for
interspecies, 10x for intraspecies)

	Intermediate-Term Dermal (1 to 6 Months) Exposure

Proposed Study: 90-day Oral  (Dog)	§  870.3150

MRID No.:  42054403 and 43246402

Executive Summary: 

See Above (Chronic Reference Dose).

Dose and Endpoint for Risk Assessment

LOAEL = 2 mg/kg/day and NOAEL of < 2 mg/kg/day (based on decreased body
weight gain.).

Comments about Study/Endpoint/Margins of Exposure: 

It is based on appropriate exposure period and the dog is considered to
be the more sensitive species.  Margin of Exposure is 300x [10x for
interspecies extrapolation, 10x for intraspecies variation, and 3x for
using LOAEL].

	Long-Term Dermal (More than 6 Months to Life-Time) Exposure

Proposed Study: 90-day Oral  (Dog)	§  870.3150

MRID No.: 42054403 and 43246402

Executive Summary: 

See Above (Chronic Reference Dose).

Proposed Dose and Endpoint for Risk Assessment

LOAEL = 2 mg/kg/day and NOAEL of < 2 mg/kg/day (based on female based on
decreased activity, dehydration, mucoid ocular discharge, weakened
appearance, abnormal feces, and degeneration of the thyroid).

Comments about Study/Endpoint/Margins of Exposure: 

It is based on an appropriate exposure period and the dog is considered
to be the more sensitive species.  The Margin of Exposure is 300x [10x
for interspecies extrapolation, 10x for intraspecies variation, and 3x
for using a LOAEL].

	

	Inhalation Exposure (All Durations)	

Proposed Study: 90-day Oral  (Dog)	§ 870.3150

MRID No.: 42054403 and 43246402

Executive Summary: 

See above (Chronic Reference Dose).

Proposed Dose and Endpoint for Risk Assessment

LOAEL = 2 mg/kg/day and NOAEL of < 2 mg/kg/day day based on decreased
body weight gain in females.

Comments about Study/Endpoint/Margins of Exposure: 

There is no appropriate inhalation study.  A target MOE of 300x is
selected (10x for intraspecies extrapolation, 10x for interspecies
variation, and 10x for using a LOAEL) and, if a MOE of 3000 is not
achieved, a route-specific inhalation toxicity study will be needed
(hence the extra 10x).  The 90-day inhalation toxicity study is
considered as the primary data gap for inhalation exposure scenarios.

	

	Margins of Exposure for Occupational/Residential Risk Assessments

A MOE of 100 is selected for short-term oral and dermal risk assessment
(10x for interspecies extrapolation, and 10x for intraspecies
variation). 

A MOE of 300 is selected for intermediate-term oral and dermal exposure
risk assessments (10x for interspecies extrapolation, 10x for
intraspecies variation, and 3x for using a LOAEL)

A MOE of 300 is selected for all term inhalation dermal exposure risk
assessments (10x for interspecies extrapolation, 10x for intraspecies
variation, and 3x for using LOAEL).  However, and if a MOE of 3000 is
not achieved a route-specific inhalation toxicity study will be needed
(hence the extra 10x).  

	

	Classification of Carcinogenic Potential

There are no chronic and/or cancer studies.  At this point in time, the
only long-term/high exposure scenario triggering the requirement for
chronic studies and cancer studies (two species) is use in metal working
fluid.  However, the technical registrant (Dow) in 10/07, proposed to
cancel the metalworking fluid uses which would negate the need for
chronic and cancer.

Table 2.   Summary of Toxicological Dose and Endpoints for Diiodomethyl
p-tolyl sulfone

Exposure

Scenario	

Dose Used in Risk Assessment, UF 	

Special FQPA SF* and Level of Concern for Risk Assessment	

Study and Toxicological Effects

Acute Dietary

 (All populations)	No appropriate end-point can be selected for Acute
RfD.

Chronic Dietary

(All populations)

[No direct food uses exist.]	Oral LOAEL =2 mg/kg/day

UF = 1000

[10x for interspecies, 10x for intraspecies, 3x for lack of chronic and
cancer studies, and 3x for using LOAEL]	

N/A	90-day Oral  (Dog)

MRID 42054403 and 43246402

based on decreased body weight gain, decreased activity, dehydration,
mucoid ocular discharge, weakened appearance, abnormal feces, and
degeneration of the thyroid.

 

Short-Term Incidental Oral (1-30 days)

	

Oral Maternal NOAEL =4 mg/kg/day 

UF = 100

(10x for interspecies, 10x for intraspecies)

	

N/A	

Rabbit Developmental Toxicity – 

(MRID  41161801)

based on clinical signs, reduced body weight gain and food consumption.

 

Intermediate-Term Oral (1- 6 months)

	

Oral LOAEL =2 mg/kg/day

MOE = 300 

[10x for interspecies, 10x for intraspecies, and 3x for using LOAEL]	

N/A	

90-day Oral  (Dog)

MRID 42054403 and 43246402

based on decreased body weight gain, decreased activity, dehydration,
mucoid ocular discharge, weakened appearance, abnormal feces, and
degeneration of the thyroid.

Dermal Ad. Factor

	

12% [based on the Rat Pharmacokinetics and Metabolism (MRID 47076641]

Dermal (System, Short-Term)	Oral Maternal NOAEL =4 mg/kg/day 

MOE = 100

(10x for interspecies, 10x for intraspecies)

	N/A	Rabbit Developmental Toxicity – 

(MRID  41161801)

based on clinical signs, reduced body weight gain and food consumption.

Dermal (Intermediate-term)	

Oral LOAEL =2 mg/kg/day

MOE = 300 

[10x for interspecies, 10x for intraspecies, 3x for using LOAEL]	

N/A	90-day Oral  (Dog)

MRID 42054403 and 43246402

based on decreased body weight gain, decreased activity, dehydration,
mucoid ocular discharge, weakened appearance, abnormal feces, and
degeneration of the thyroid.

Dermal (long-term)

[No applicable use scenarios remain as metal working uses are to be
cancelled.]	

Oral LOAEL =2 mg/kg/day

MOE= 1000

[10x for interspecies, 10x for intraspecies, 3x for lack of chronic and
cancer studies, and 3x for using LOAEL]	

N/A

	

 90-day Oral  (Dog)

MRID 42054403 and 43246402

based on decreased body weight gain, decreased activity, dehydration,
mucoid ocular discharge, weakened appearance, abnormal feces, and
degeneration of the thyroid.based on lymphocytic infiltration in females
and erosion of gastric mucosa and prominence of limiting ridge of the
stomach in males

Inhalation (All Exposure Terms)	

Oral LOAEL =2 mg/kg/day

MOE = 3000 

[10x for interspecies, 10x for intraspecies, 10x for route-to-route
extrapolation  and 3x for using LOAEL]	

N/A

	

 90-day Oral  (Dog)

MRID 42054403 and 43246402

based on decreased body weight gain, decreased activity, dehydration,
mucoid ocular discharge, weakened appearance, abnormal feces, and
degeneration of the thyroid.based on lymphocytic infiltration in females
and erosion of gastric mucosa and prominence of limiting ridge of the
stomach in males

Cancer (oral, dermal, inhalation)	

	

	

no cancer data available

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL =
no observed adverse effect level, LOAEL = lowest observed adverse effect
level, PAD = population adjusted dose (a = acute, c = chronic) RfD =
reference dose, MOE = margin of exposure, LOC = level of concern, NA =
Not Applicable

 

 3.2		FQPA CONSIDERATION

No direct food uses are associated with the registered Diiodomethyl
p-tolyl sulfone labels.  Therefore, there are no FQPA concerns.

3.3	Endocrine Disruption

  SEQ CHAPTER \h \r 1 EPA is required under the FFDCA, as amended by
FQPA, to develop a screening program to determine whether certain
substances (including all pesticide active and other ingredients) “may
have an effect in humans that is similar to an effect produced by a
naturally occurring estrogen, or other such endocrine effects as the
Administrator may designate.”  Following recommendations of its
Endocrine Disruptor and Testing Advisory Committee (EDSTAC), EPA
determined that there was a scientific basis for including, as part of
the program, the androgen and thyroid hormone systems, in addition to
the estrogen hormone system.  EPA also adopted EDSTAC’s recommendation
that the Program include evaluations of potential effects in wildlife. 
For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an
effect in humans, FFDCA authority to require the wildlife evaluations. 
As the science develops and resources allow, screening of additional
hormone systems may be added to the Endocrine Disruptor Screening
Program (EDSP).

4.0	INCIDENCE REPORTS

	Incident Reports.   tc "8.0	INCIDENTS" The Agency consulted the
following databases for poisoning incident data for Diiodomethyl p-tolyl
sulfone; no incidents involving Diiodomethyl p-tolyl sulfone were
discovered (J. Chen, 11/19/07):

OPP Incident Data System (IDS) - The Incident Data System of The Office
of Pesticide Programs (OPP) of the Environmental Protection Agency (EPA)
contains reports of incidents from various sources, including
registrants, other federal and state health and environmental agencies
and individual consumers, submitted to OPP since 1992.  Reports
submitted to the Incident Data System represent anecdotal reports or
allegations only, unless otherwise stated.  Typically no conclusions can
be drawn implicating the pesticide as a cause of any of the reported
health effects.  Nevertheless, sometimes with enough cases and/or enough
documentation risk mitigation measures may be suggested.

Poison Control Centers - as the result of a data purchase by EPA, OPP
received Poison Control Center data covering the years 1993 through 2002
for all pesticides.  Most of the national Poison Control Centers (PCCs)
participate in a national data collection system, the Toxic Exposure
Surveillance System, which obtains data from about 65-70 centers at
hospitals and universities.  PCCs provide telephone consultation for
individuals and health care providers on suspected poisonings, involving
drugs, household products, pesticides, etc.

  SEQ CHAPTER \h \r 1 California Department of Pesticide Regulation
(1982-2004) - California has collected uniform data on suspected
pesticide poisonings since 1982.  Physicians are required, by statute,
to report to their local health officer all occurrences of illness
suspected of being related to exposure to pesticides.  The majority of
the incidents involve workers.  Information on exposure (worker
activity), type of illness (systemic, eye, skin, eye/skin and
respiratory), likelihood of a causal relationship, and number of days
off work and in the hospital are provided.

National Pesticide Telecommunications Network (NPTN) - NPTN is a
toll-free information service supported by OPP.  A ranking of the top
200 active ingredients for which telephone calls were received during
calendar years 1984-1991, inclusive, has been prepared.  The total
number of calls was tabulated for the categories human incidents, animal
incidents, calls for information, and others.

HUMAN EXPOSURE ASSESSMENT AND CHARACTERIZATION

Summary of Registered Uses

Diiodomethyl p-tolyl sulfone is an active ingredient used as a
fungicide, algaecide, bacteriostat, insecticide, and miticide used in
materials preservatives, and wood preservatives.  The Agency determines
potential exposures to handlers of the product by identifying exposure
scenarios from the various application methods that are plausible, given
the label uses.  Based on a review of product labels, products
containing Diiodomethyl p-tolyl sulfone are intended for use as a
materials preservative for a variety of products (Use Site Category VII)
and as a wood preservative (Use Site Category X).  Examples of
registered uses for Diiodomethyl p-tolyl sulfone products as material
preservatives include application to paints (in-can), HVACs, coatings,
caulks, fire retardants, adhesives, sealants, slurries,
dispersions/emulsions/solutions/ suspensions, rubber products,
plastic/pvc/vinyl products, hides/leathers/leather products, textiles,
papermaking, and paper and paperboard, and  wood preservative uses.  Dow
has committed to cancel use in metalworking fluids and in drains, grease
traps, and septic tanks.

  SEQ CHAPTER \h \r 1 5.2 	Dietary Exposures and Risks to DIIODOMETHYL
P-TOLYL SULFONE as an Indirect Food Additive

The potential dietary and drinking water exposures and risks for the
antimicrobial uses of diiodomethyl p-tolyl sulfone were assessed.  The
potential dietary exposures include the following: indirect food
additive from paper products when used as a preservative in adhesives,
can end and side-seam cements, and sealants and caulking materials for
repeated use food contact surfaces.   None of the dietary risks exceeded
the Agency’s level of concern.  However, it is recommended that the
diiodomethyl p-tolyl sulfone labels be revised to clearly state which
set of use directions is intended for the indirect food uses cleared by
FDA.  Furthermore in order to accept non-food contact paper language,
examples of non-food contact paper (i.e., newsprint, Kraft paper, brown
paper mills, sheets for corrugated board) must also be listed on the
labels. 

Based on the use patterns, the potential for diiodomethyl p-tolyl
sulfone to impact drinking water sources is negligible and therefore a
quantitative drinking water assessment was not conducted.

AD assessed the potential dietary exposure to the active ingredient,
diiodomethyl p-tolyl sulfone, from its use as an indirect food additive.
 The US Food and Drug Administration (US FDA) has granted diiodomethyl
p-tolyl sulfone indirect food clearances for the following uses:

175.105 Substances for Use Only as Components of Adhesives

175.300 Substances for Use as Components of Coatings – Resinous and
Polymeric Coatings (Can End and Side Seam Cements) with a limitation of
not to exceed 0.3% by wt in can-sealing cements;

176.300  Substances for Use as Basic Components of Paper and Paperboard
Components – Slimicides with a limitation of not to exceed 0.2 pounds
per ton of dry weight of fiber; and	

177.2600 Substances for Use as Basic Components of Repeated Use Food
contact Surfaces – Rubber Articles Intended for Repeated Use with a
limitation of not to exceed 0.3% by wt of sealants and caulking
materials.

It should be noted that in 21 CFR 176.300, US FDA has cleared the use of
diiodomethyl p-tolyl sulfone as an indirect food additive for its use as
a pulp and paper slimicide at a maximum level of 0.20 pound per ton of
dry weight fiber.  However, this use was not assessed in this document
because all of the current diiodomethyl p-tolyl sulfone labels for the
pulp and paper slimicide use restrict use to non-food contact paper
only.  Although EPA accepts this language on the labels, examples of
non-food contact paper (i.e., newsprint, Kraft paper, brown paper mills,
sheets for corrugated board) must also be listed.  Most of the
diiodomethyl p-tolyl sulfone labels will need to be updated to include
non-food contact paper examples.

No residue data have been submitted in support of the diiodomethyl
p-tolyl sulfone antimicrobial dietary uses.  Therefore, a
screening-level assessment has been conducted using the US FDA’s
Center for Food Safety & Applied Nutrition’s (CFSAN) approach as
presented in “Preparation of Food Contact Notifications and Food
Additive Petitions for Food Contact Substances: Chemistry
Recommendations” dated April 2002 and memos obtained from FDA granting
the diiodomethyl p-tolyl sulfone clearances.  Using the maximum
application rates and US FDA’s default assumptions, “worst-case”
dietary concentration values were calculated by AD and are summarized in
Table 3.

Table 3.  Diiodomethyl p-tolyl sulfone Dietary Exposures from Indirect
Food Uses

FDA Clearance	Use	Dietary Conc (ppb)	EDI 

(µg/person/day)	Dose

 (mg/kg/day)

	Adult	Child	Adult	Child

175.105	Preservative in Adhesives	6.7	20.0	10.0	0.00029	0.00067

177.2600	Preservative in Repeat-use Rubber Sealants and Caulking
Materials	1	3	1.5	0.000043	0.00010

175.300	Preservative in Can Side-Seam Cements	2.7	8.1	4.1	0.00012
0.00027

 

Preservative of Paper Adhesives

As regulated under 21 CFR 175.105, diiodomethyl p-tolyl sulfone can be
used to preserve adhesive formulations used in food packaging.  Dietary
exposures to diiodomethyl p-tolyl sulfone from this type of use were
estimated using the following assumptions:

Based on FDA’s guidance document, it was assumed that “If the
adhesive is either separated from food by a functional barrier, or the
quantity of adhesive that contacts aqueous and fatty food is limited to
the trace amount at seams and edges, then migration levels for the
substances generally will be assumed to be no greater than 50 ppb.
Applying a CF (consumption factor) of 0.14 for adhesives gives a dietary
concentration of 7 ppb” (US FDA, 2007).  It should be noted that for
components of adhesives, FDA assumes that the food concentration of 50
ppb is for the finished additive, not adhesive (US FDA, 1999).  Note: CF
is the percentage of daily diet expected to contact paper adhesives.

The finished additive, AMICAL 48 (EPA Reg. No. 464-670), contains 95%
active ingredient

Adult food consumption is 3000 g/day; child food consumption is 1500
g/day.

Adult body weight is 70 kg; child body weight is 15 kg.

Calculations:

Determination of the Dietary Concentration (DC):

Food conc. x CF x %ai

	(50 ng adhesive/g food) (0.14) x (95% ai) = 6.7 ng ai/g food

Determination of the Estimated Daily Intake (EDI):

Dietary conc. x Daily food consumption

Adult: (0.0067 μg ai/g food) (3000 g food /day) = 20.0 μg
ai/person/day

Child: (0.0067 μg ai/g food) (1500 g food /day) = 10.0 μg
ai/person/day

Determination of the Daily Dietary Dose:

EDI / Body Weight

Adult: (20.0 μg ai /day) (mg/1000 μg) / (70 kg) = 0.00029 mg ai/kg
bw/day

        Child: (10.0 μg ai/day) (mg/1000 μg) / (15 kg) = 0.00067 mg
ai/kg bw/day

Preservation of Can End and Side-Seam Cements

As regulated under 21CFR 175.300 (Substances for Use as Components of
Coatings – Resinous and Polymeric Coatings), diiodomethyl p-tolyl
sulfone also can be used to preserve can end and side seam cement
formulations with the limitation of not to exceed 0.3% by weight.  Based
on FDA’s 1999 memo clearing diiodomethyl p-tolyl sulfone indirect food
uses, dietary exposures were estimated using the following assumptions:

Diiodomethyl p-tolyl sulfone migrates to all types of food in contact
with side seam cements at a rate of 14 ng ai/g food per day (FAP 6B3961
memorandum dated 10/10/86 and 2/9/87)

Maximum Diiodomethyl p-tolyl sulfone concentration in cement is 0.3%

Cement quantity per can is 80 mg

Can volume is 177 ml (or 0.177 L)

1% of  cement surface contacts food

Diiodomethyl p-tolyl sulfone migration from cement to food is 100%

The consumption factors (CF) is 0.20

Polymer coated can CF = 0.17

Uncoated can CF = 0.03  

Adult food consumption is 3000 g/day; child food consumption is 1500
g/day.

Adult body weight is 70 kg; child body weight is 15 kg.

Calculations:

Determination of the food concentration:

(Cement Quantity x %ai) / Can Volume x Cement Surface Contact with Food

((80 mg) (0.3%ai) / (0.177 ml)) (1%) = 0.014 mg ai/L (or 14 ng ai/g
food)

Determination of the Dietary Concentration (DC):

Food conc. x CF

	(14 ng ai/g food) (0.20) = 2.7 ng ai/g food

Determination of the Estimated Daily Intake (EDI):

Dietary conc. x  Daily food consumption

Adult: (0.0027 μg ai/g food) (3000 g food /day) = 8.1 μg ai/person/day

Child: (0.0027 μg ai/g food) (1500 g food /day) = 4.1 μg ai/person/day

Determination of the Daily Dietary Dose:

EDI / Body Weight

Adult: (8.1 μg ai /day) (mg/1000 μg) / (70 kg) = 0.00012 mg ai/kg
bw/day

Child: (4.1 μg ai/day) (mg/1000 μg) / (15 kg) = 0.00027 mg ai/kg
bw/day

It should be noted that the FDA clearance for the can side seam cement
preservative use provides a limitation of not to exceed 0.3%
diiodomethyl p-tolyl sulfone by weight.  The diiodomethyl p-tolyl
sulfone label (EPA Reg. No. 464-670) provides use instructions for
“use in adhesives, caulks and sealants” as well as “use in rubber
and plastic products”.  The “use in adhesives, caulks and
sealants” provides a use rate of 0.0098 – 0.29% ai for “adhesives,
binders, e.g. joint compounds, tile mastics, wallpaper pastes, carpet
backing, air filter and foil scrim Kraft laminate; and sealants and
caulks.”  The “use in rubber and plastic products” provides a use
rate of 0.095 – 0.76% ai for “PVC, polyurethane, rubber,
thermoplastic rubber and other polymer-based products, coatings,
adhesives, foams, and sealants.”  Neither of these use descriptions
gives a clear indication of whether it would include can end and side
seam cements.  Based on discussions during the SMART meeting, the
registrant stated that the can end and side seam cements would fall
under the “use in adhesives, caulks and sealants”; therefore, the
maximum application rate of 0.3% ai was used in this assessment.  It is
recommended that the labels be revised to clearly state which set of use
directions is intended for the indirect food uses cleared by FDA.

Preservation of Repeat-Use Rubber Sealants and Caulking Materials

As regulated under 21CFR 177.2600 (Substances for Use as Basic
Components of Repeated Use Food contact Surfaces – Rubber Articles
Intended for Repeated Use), diiodomethyl p-tolyl sulfone also can be
used to preserve can end and side seam cement formulations with the
limitation of not to exceed 0.3% by weight.  Based on FDA’s 1999 memo
clearing diiodomethyl p-tolyl sulfone indirect food uses, dietary
exposures were estimated using the following assumptions:

Diiodomethyl p-tolyl sulfone migrates to all types of food in incidental
contact with caulk containing 1000 mg/kg Diiodomethyl p-tolyl sulfone at
a rate of 20 ng ai/g food per day (FAP 7B3321 memorandum dated 10/21/77
and 2/17/78)

The consumption factors (CF) is 0.05 for repeat-use rubber articles

Adult food consumption is 3000 g/day; child food consumption is 1500
g/day.

Adult body weight is 70 kg; child body weight is 15 kg.

Calculations:

Determination of the Dietary Concentration (DC):

Food conc. x CF

	(20 ng ai/g food) (0.05) = 1.0 ng ai/g food

Determination of the Estimated Daily Intake (EDI):

Dietary conc. x Daily food consumption

Adult: (0.001 μg ai/g food) (3000 g food /day) = 3.0 μg ai/person/day

Child: (0.001 μg ai/g food) (1500 g food /day) = 1.5 μg ai/person/day

Determination of the Daily Dietary Dose:

EDI / Body Weight

Adult: (3.0 μg ai /day) (mg/1000 μg) / (70 kg) = 0.000043 mg ai/kg
bw/day

Child: (1.5 μg ai/day) (mg/1000 μg) / (15 kg) = 0.00010 mg ai/kg
bw/day

It should be noted that the FDA clearance for the repeat use rubber
sealant preservative use provides a limitation of not to exceed 0.3%
diiodomethyl p-tolyl sulfone weight.  The diiodomethyl p-tolyl sulfone
label (EPA Reg. No. 464-670) provides use instructions for “use in
adhesives, caulks and sealants” as well as “use in rubber and
plastic products”.  The “use in adhesives, caulks and sealants”
provides a use rate of 0.0098 – 0.29% ai for “adhesives, binders,
e.g. joint compounds, tile mastics, wallpaper pastes, carpet backing,
air filer and foil scrim Kraft laminate; and sealants and caulks.” 
The “use in rubber and plastic products” provides a use rate of
0.095 – 0.76% ai for “PVC, polyurethane, rubber, thermoplastic
rubber and other polymer-based products, coatings, adhesives, foams, and
sealants.”  Neither of these use descriptions gives a clear indication
of whether it would include can end and side seam cements.  Based on
discussions during the SMART meeting, the registrant stated that the
repeat use rubber sealant would fall under the “use in adhesives,
caulks and sealants”; therefore the maximum application rate of 0.3%
ai (rather than 0.76% ai) was used in this assessment.  It is
recommended that the labels be revised to clearly state which set of use
directions is intended for the indirect food uses cleared by FDA.  

Diiodomethyl p-tolyl sulfone Indirect Food Additive Dietary Exposure

The additive estimated dietary intakes (CEDI) of diiodomethyl p-tolyl
sulfone from its use as a preservative in adhesives, can end cements,
and repeat-use rubber sealants are presented in Table 4.

Table 4. Diiodomethyl p-tolyl sulfone Indirect Food Additive Exposures

FDA Clearance	Use	Conc in Food (ng/g)	Dietary Conc (ppb)	EDI
(µg/person/day)	Dose 

(mg/kg/day)

Adult	Child	Adult	Child

175.105	Preservative in Adhesives	47.5	6.7	20.0	10.0	0.00029	0.00067

177.2600	Preservative in Repeat-use Rubber Sealants and Caulking
Materials	20	1	3	1.5	0.000043	0.00010

175.300	Preservative in Can Side-Seam Cements	14	2.7	8.1	4.1	0.00012
0.00027

	Additive

10.4	31.1	15.5	0.00044	0.0010

Dietary Risks from diiodomethyl p-tolyl sulfone as an Indirect Food
Additive 

The dietary risks from diiodomethyl p-tolyl sulfone used as an indirect
food additive in preservative of adhesives, can side-seam cements, and
repeat-use rubber sealants were calculated using the toxicological data
provided from ADTC (DP Barcode D314321).  There was no appropriate
endpoint selected attributable to an acute exposure, therefore the acute
dietary risks were not necessary to assess.  Utilizing the chronic RfD
of 0.002 mg/kg/day, the dietary risks were estimated and summarized in
Table 5.  None of the uses exceed the Agency’s level of concern for
the chronic exposure durations.  

Table 5. Dietary Risks of Diiodomethyl p-tolyl sulfone Indirect Food
Uses

FDA Clearance	Use	Dose 

(mg/kg/day)	% cRfDa

Adult	Child	Adult	Child

175.105	Preservative in Adhesives	0.00029	0.00067	14%	33%

177.2600	Preservative in Repeat-use Rubber Sealants and Caulking
Materials	0.000043	0.00010	2%	5%

175.300	Preservative in Can Side-Seam Cements	0.00012	0.00027	6%	14%

	Additive	0.0004	0.0010	22%	52%

aRfD = 0.002 mg/kg/day.

5.3	Drinking Water Exposure

Based on the use patterns, the potential for Diiodomethyl p-tolyl
sulfone to impact drinking water sources is negligible and, therefore, a
quantitative drinking water assessment was not conducted.

Residential Exposure and Risk

According to the labels, typical end users for registered end users
include building lumber, furniture, frames, fences, decking, shingles
and siding, logs and poles.  For residential residential
post-application exposure to children and adults exposed to Diiodomethyl
p-tolyl sulfone-treated wood.  The highest concern would be to decking
or playground equipment. Currently, there are no study data that can be
used to estimate either exposure to adults from inhalation of wood dusts
during construction of wood decks or to children exposed to treated
wood.  To complete an assessment, dislodgeable wood residues would need
to be generated (i.e., wipe studies).  Incidental ingestion exposure for
adults is expected to be negligible and dermal contact for adults is
expected to be lower than children for crawling on wood decks.  Because
children are more likely than adults to contact wood surfaces, and
because children have a higher surface area to body weight ratio, they
have been used to represent the maximum exposed individual. The
potential outdoor residential postapplication exposure pathways for
children are:  (i) dermal contact with Diiodomethyl p-tolyl
sulfone-treated wood products (e.g., residential playground equipment
and decks); (ii) incidental ingestion via hand-to-mouth contact with
Diiodomethyl p-tolyl sulfone-treated wood products; (iii) incidental
ingestion of soil contaminated with Diiodomethyl p-tolyl sulfone; and
(iv) dermal contact with soil contaminated with Diiodomethyl p-tolyl
sulfone (e.g., soil contaminated by treated decks and playground
equipment).  

Available data to assess the levels of diiodomethyl p-tolyl sulfone in
soil contaminated with diiodomethyl p-tolyl sulfone-treated wood do not
exist at this time.  Because of this data gap, EPA was not able to
estimate dermal and incidental ingestion residential postapplication
exposures to soil contaminated with diiodomethyl p-tolyl sulfone-treated
wood.  In this assessment, incidental ingestion and dermal exposures to
children from contact with treated wood were estimated using surrogate
data.  

At present, there are no available data to assess the levels of
diiodomethyl p-tolyl sulfone residues in soil contaminated from
diiodomethyl p-tolyl sulfone-treated wood (above ground fabricated
components of decks or playsets).  Because of this data gap, EPA was not
able to estimate residential post-application dermal and incidental
ingestion exposures to soil contaminated with diiodomethyl p-tolyl
sulfone.  In this assessment, incidental ingestion and dermal exposures
to children from contact with treated wood were estimated using
surrogate data.

Surrogate Data 	

	

μg/cm2 and call-in confirmatory data.  The 1 μg/cm2 value accounts for
the skin reduction factor, or “transfer efficiency” from a cloth
wipe (i.e., cloth wipe surface residues are higher than that available
to the skin).  This high end residue value is higher than the maximum
residue seen for chromium and non chromium-based wood preservatives.

The routes of exposure evaluated in this assessment include: short-term
(ST) [1-30 days], intermediate-term (IT) [1-6 months], and long-term
(LT) [>6 months] dermal, inhalation and incidental oral exposures.  For
the dermal exposure routes, the doses used in risk assessment for ST is
an oral NOAEL of 4 mg/kg/day and for IT/LT an oral LOAEL of 2 mg/kg/day.
 A human dermal absorption factor of 12% was used because the dermal MOE
calculations were based on oral endpoints.  An inhalation absorption
factor of 100% was used (default value, assuming oral and inhalation
absorption are equivalent) in all inhalation exposure since the
inhalation MOE calculations were based on an oral endpoint.  For
short-tem incidental oral exposures an oral maternal NOEAL of 4
mg/kg/day was used and for intermediate-term oral (1-6 months) an oral
LOAEL of 2 mg/kg/day was used.   

The uncertainty factor or “target” margin of exposure (MOE) for the
ST dermal exposure scenario is 100 [10X for interspecies and 10X for
intraspecies] and 300 [10X for interspecies, 10X for intraspecies and 3X
for database uncertainty factor] for IT.  For inhalation exposure
scenario the MOE is 300 [10X for interspecies, 10X for intraspecies, and
3X for using a LOAEL] for all durations.  It should be noted that if a
MOE of 3000 is not achieved a route-specific inhalation toxicity study
will be needed (hence the extra 10x). For short-term incidental oral
exposure scenario the MOE is 100 [10X for interspecies, 10X] and for the
intermediate-term incidental oral exposure scenario the MOE is 300 [10X
for interspecies, 10X for intraspecies, and 3X for using a LOAEL].    

Based on examination of product labels, it has been determined that
exposure to handlers can occur in a variety of occupational and
residential environments.  Additionally, postapplication exposures are
likely to occur in these settings.  The representative scenarios
selected by the Antimicrobials Division (AD) for this assessment were
evaluated using maximum application rates as stated on the product
labels. 

To assess the handler risks, AD used surrogate unit exposure data from
the following proprietary resources: Chemical Manufacturers Association
(CMA) antimicrobial exposure study, the Pesticide Handlers Exposure
Database (PHED), and the proprietary sapstain study (task force #
73154), Measurement and Assessment of Dermal and Inhalation Exposures to
Didecyl Dimethyl Ammonium Chloride (DDAC) Used in the Protection of Cut
Lumber (Phase III) (Bestari et al., 1999, MRID 455243-04). 
Additionally, the EPA’s Health Effects Division’s (HED) Standard
Operating Procedures (SOPs) for Residential Exposure Assessments, was
used when estimating postapplication/bystander exposures.

Handlers

For the residential handler ST dermal risk assessment, the ST dermal
MOEs are above the target MOE of 100 and below the Agency’s level of
concern (except for painting with an airless sprayer MOE 40). However,
the IT dermal MOEs for applying paint and wood preservative are all
below the target MOE of 300. The inhalation MOE for painting with an
airless sprayer (MOE 230) is the only scenario that is below the
Agency’s target MOE of 300. However, all the inhalation MOEs did not
exceed 3,000; therefore, a confirmatory inhalation toxicity study is
warranted based on the results of these exposure scenarios. 

Postapplication for children

For the residential postapplication risk assessment, MOEs are below the
respective target MOEs (ST dermal  = 100, inhalation = 3,000, and
incidental ingestion = 300) for the following scenarios and therefore
are of concern:

Dermal contact of children contact treated carpet (ST MOE 9 and IT MOE
4).

Dermal contact to treated wood products (IT MOE 99).

Incidental oral exposures with treated carpet (ST MOE 49 and IT MOE 51).

     Aggregate Risk Assessment and Characterization

Short- and intermediate-term aggregate exposures and risks were assessed
for adults and children that could be exposed to Diiodomethyl p-tolyl
sulfone residues from the use of products in nonoccupational
environments. The adult scenarios were not aggregated because their use
patterns are not likely to co-occur.  Because the calculated residential
ST dermal MOEs for children exceeded the Agency’s LOC for both
painting with an airless sprayer and postapplication exposure to carpet
and IT for applying paint/wood preservative and postapplication exposure
to decks and carpets, the aggregate MOEs were not calculated.  Any
additional contribution of Diiodomethyl p-tolyl sulfone residues to
human exposure is expected to be absent or negligible from drinking
water or indirect food additive sources.  Aggregation with residential
scenarios was not performed because Diiodomethyl p-tolyl sulfone is not
subject to FQPA and because the LOC is already exceeded. 

5.6	CUMULATIVE EXPOSURE AND RISK

Another standard of Section 408 of FFDCA which must be considered in
making an unreasonable adverse effect determination is that the Agency
considers "available information” concerning the cumulative effects of
a particular pesticide's residues and "other substances that have a
common mechanism of toxicity.” 

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 Diiodomethyl p-tolyl sulfone
and any other substances and Diiodomethyl p-tolyl sulfone does not
appear to produce a toxic metabolite produced by other substances.  For
the purposes of this tolerance action, therefore, EPA has not assumed
that Diiodomethyl p-tolyl 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/.

6.0	OCCUPATIONAL EXPOSURE AND RISK tc "7.0	OCCUPATIONAL EXPOSURE AND
RISK"  

It should be noted that the Dow Chemical Company has proposed to cancel
the following uses: (1) metal working fluids; (2) nitrocellulose; (3)
and preservation of drains, grease traps and septic systems. These uses
have not officially been cancelled; however, the Agency is working with
the technical registrant to ensure that the necessary steps are taken to
cancel these uses. As a result, these uses will not be assessed in the
risk assessment at this time.   

The routes of exposure evaluated in this assessment include: short-term
(ST) [1-30 days], intermediate-term (IT) [1-6 months], and long-term
(LT) [>6 months] dermal, inhalation and incidental oral exposures.  For
the dermal exposure routes, the doses used in risk assessment for ST is
an oral NOAEL of 4 mg/kg/day and for IT/LT an oral LOAEL of 2 mg/kg/day.
 A human dermal absorption factor of 12% was used because the dermal MOE
calculations were based on oral endpoints.  An inhalation absorption
factor of 100% was used (default value, assuming oral and inhalation
absorption are equivalent) in all inhalation exposure since the
inhalation MOE calculations were based on an oral endpoint.  For
short-tem incidental oral exposures an oral maternal NOEAL of 4
mg/kg/day was used and for intermediate-term oral (1-6 months) an oral
LOAEL of 2 mg/kg/day was used.   

The uncertainty factor or “target” margin of exposure (MOE) for the
ST dermal exposure scenario is 100 [10x for interspecies and 10x for
intraspecies] and 300 [10X for interspecies, 10X for intraspecies and 3X
for database uncertainty factor] for IT.  For inhalation exposure
scenario the MOE is 300 [10X for interspecies, 10X for intraspecies, and
3X for using a LOAEL] for all durations.  It should be noted that if a
MOE of 3000 is not achieved a route-specific inhalation toxicity study
will be needed (hence the extra 10x). For short-term incidental oral
exposure scenario the MOE is 100 [10X for interspecies, 10X] and for the
intermediate-term incidental oral exposure scenario the MOE is 300 [10X
for interspecies, 10X for intraspecies, and 3X for using a LOAEL].    

Based on examination of product labels, it has been determined that
exposure to handlers can occur in a variety of occupational and
residential environments.  Additionally, postapplication exposures are
likely to occur in these settings.  The representative scenarios
selected by the Antimicrobials Division (AD) for this assessment were
evaluated using maximum application rates as stated on the product
labels. 

To assess the handler risks, AD used surrogate unit exposure data from
the following proprietary resources: Chemical Manufacturers Association
(CMA) antimicrobial exposure study, the Pesticide Handlers Exposure
Database (PHED), and the proprietary sapstain study (task force #
73154), Measurement and Assessment of Dermal and Inhalation Exposures to
Didecyl Dimethyl Ammonium Chloride (DDAC) Used in the Protection of Cut
Lumber (Phase III) (Bestari et al., 1999, MRID 455243-04). 
Additionally, the EPA’s Health Effects Division’s (HED) Standard
Operating Procedures (SOPs) for Residential Exposure Assessments, was
used when estimating postapplication/bystander exposures.

Handler Risk Summary

For occupational handlers at baseline (without gloves) dermal all of the
dermal IT MOEs are below the target MOE of 300 and exceed the level of
concern except:

Preservation of Slurries (liquid pump).

Preservation of Paper (liquid pump).

Diptank Operator.

Treatment Assistant.

Application of Wood Preservative (airless sprayer)

For baseline (without gloves) dermal all of the dermal ST MOEs are below
the target MOE of 100 and exceed the level of concern except:

Preservation of Adhesives and Caulks (liquid pump)

Preservation of Slurries (liquid pump).

Preservation of Emulsions (liquid pump).

Preservation of Paper (liquid pump).

Application of Wood Preservative by professionals (brush and airless
sprayer).

Chemical Operator (Wood Preservative).

Blender/spray Operator

Diptank Operator.

Treatment Operator.

Treatment Assistant

For PPE (gloves) dermal, all of the dermal IT MOEs are above the target
MOE of 300 and are below the level of concerns except. 

Preservation of Paint for liquid pump (MOE 188) and liquid pour (MOE
88).

Application of Paint by professionals for brush (MOE 197) and airless
sprayer (MOE 34).

Preservation of Adhesives and Caulks by liquid pour (MOE 288).

Preservation of Rubber and Plastic for pour liquid (MOE 56) and pump
liquid (MOE 120).

Preservation of Leather for pour liquid for raceway (MOE 34), mixers
(MOE 168), and tanning drum (MOE 84).

Preservation of Textiles for pour liquid (MOE 182). 

For PPE (gloves) dermal all of the dermal ST MOEs are above the target
MOE of 100 and are less than the level of concern except:

Application of Paint by professionals for airless sprayer (MOE 67).

Preservation of Leather for pour liquid for raceway (MOE 67).

For baseline (without respirator) inhalation the following scenarios are
below the target MOE of 300 (at all exposure levels) and do exceed the
level of concern except:

Application of Paint (airless sprayer) with MOE 68.

Preservation of Rubber and Plastic for pour liquid (MOE 261) and pump
liquid (MOE 224).

Preservation of Leather for pour liquid for raceway (MOE 157)

For PPE (respirators) inhalation all the scenarios were above the target
MOE of 300. However even with PPE some of the calculated inhalation MOEs
(e.g., painting with an airless sprayer MOE 341) were less than the
target MOE of 3,000. Therefore, a confirmatory inhalation toxicity study
is warranted based on the results of this assessment of paint.

 

Post-application/Bystander Risk Summary

For occupational postapplication, the inhalation MOEs for treated HVAC
systems and for cleanup activities at lumber mills exceeded the target
MOE of 300.  However, they did not exceed the target MOE of 3,000
therefore, a confirmatory inhalation toxicity study is warranted based
on the results of this assessment.

For the occupational postapplication risk assessment, dermal ST MOEs are
above the respective target MOEs ((ST dermal  = 100) for all scenarios
except for the following:

Cleanup activities at a lumber mill (MOE 70).

For the occupational postapplication risk assessment, dermal IT MOEs are
above the respective target MOEs ((IT dermal  = 300) for all scenarios
except for the following:

Millwright at lumber mill (MOE 152).

Cleanup activities at a lumber mill (MOE 35).

Chemical operator (MOE 198)

Aggregate exposure risk summary

	Short- and intermediate-term aggregate exposures and risks were
assessed for adults and children that could be exposed to diiodomethyl
p-tolyl sulfone residues from the use of products in non-occupational
environments. The adult scenarios were not aggregated based on the use
patterns.  Because the calculated residential short-term and
intermediate dermal MOEs to children were unacceptable for both
short-term (painting with an airless sprayer, postapplication exposure
to carpet) and intermediate-term (applying paint and wood preservative,
postapplication exposure to deck (IT) and carpet), the aggregate MOEs
were not calculated.

Data Limitations and Uncertainties:

	There are a number of uncertainties associated with this assessment and
these have been reiterated from Sections 4.4.3 (residential) and 6.3
(occupational) respectively.

The data limitations and uncertainties associated with the residential
handler and postapplication exposure assessments include the following:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998) (See Appendix A for summaries of
these data sources). Most of the CMA data are of poor quality therefore,
AD requests that confirmatory monitoring data be generated to support
the values used in these assessments.  

The quantities handled/treated were estimated based on information from
various sources, including HED’s Standard Operating Procedures (SOPs)
for Residential Exposure Assessments (USEPA 2000, and 2001) and standard
AD assumptions that can be further refined from input from registrants. 

The low pressure spray unit exposure data from PHED were used to assess
outdoor applications to hard surfaces (exterior of homes).  As the low
pressure spray data are representative of treating low to mid level
shrubs and the scenario assessed in this document represents treatments
above the waist, the unit exposure value may underestimate exposure to
the head and the upper body.

The data limitations and uncertainties associated with the occupational
handler and postapplication exposure assessments include:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998) (See Appendix A for summaries of
these data sources).   Since the CMA data are of poor quality, the
Agency requests that confirmatory data be submitted to support the
occupational scenarios assessed in this document.

ENVIRONMENTAL FATE

Diiodomethyl p-tolyl sulfone is stable to hydrolysis at pH 5, but
degraded with half-lives of 2-4 days at pH 7 and 9.  MIMPTS
(Monoiodomethyl-p-tolylsulfone, parent minus one iodo group) was the
major degradate formed, and increased until the end of the study (30
days).  MPTS (methyl-p-tolylsulfone, parent minus both iodo groups) and
PTSA (p-toluene sulfonic acid, parent minus methyl group) was a minor
metabolite.  Soil photolysis half-lives of 13 days (linear) and 5.3
(non-linear) were observed for parent compound. MIMPTS was stable in the
dark control but degraded with a half-life of 12.5 days in an irradiated
sample.  Volatiles and nonextractables were negligible.

Diiodomethyl p-tolyl sulfone was mobile in columns of soil that were
leached with water.  The amounts of parent compound that leached through
12-inch columns were 73, 84, 34, and 8% in sand, silt loam, sandy loam,
and clay soils.  An average of 2, 1.5, 5, and 8% of applied compound was
present in each inch of the columns, respectively.  

™ is 2.66, and the estimated (EPI-SUITE) Log Kow values for MIMPTS,
MPTS, and PTSA were 2.2, 1.1, and 0.56, respectively.  None of these
compounds are expected to bioconcentrate significantly because the Log
Kow values are below 3.0.  

An average of 43% of Diiodomethyl p-tolyl sulfone from wooden tongue
depressors leached into pH 5, 7, 9 unfiltered buffers over a 30-day
study (median of 42%).  Maximum residues in water were observed at day
zero, followed by a decrease to the minimum values at day 7 and a
general increase.  In filtered samples, the aqueous residues averaged
4.3%, indicating that some sorption to organic materials may occur in
the environment.  

A.	Abiotic

Diiodomethyl p-tolyl sulfone forms sequential metabolites MIMPTS (parent
minus one iodo group), MPTS (parent minus both iodo groups), and PTSA
(parent minus methyl group).  The degree of formation of metabolites
depends on the level of oxidation potential present in the test system. 
Diiodomethyl p-tolyl sulfone  and its metabolites are largely present in
water in the presence of soil/sediment and degradation forms compounds
that are more polar and water soluble than parent compound.   

B.	Biotic

Under aerobic soil conditions, parent Diiodomethyl p-tolyl sulfone and
MIMPTS degraded with non-linear half-lives of 1.5 and 32 days in sandy
loam soil, respectively.  The next sequential metabolite was MPTS which
degraded with calculated non-linear and linear half-lives of 53 (poor
fit) and 173 (better fit) days, respectively.  Based on the increase in
non-extractable residues, the decrease in extractable residues, and the
formation of CO2, complete mineralization of some of the product in
aerobic soil was occurring.  

Degradation by microorganisms will reduce Diiodomethyl p-tolyl sulfone
concentrations in the environment, but residues are expected to
partition to water in the presence of sandy loam soil or sediment.   In
aerobic soil (the top layer of non-flooded soil), the non-linear parent,
MIMPTS, and MPTS half-lives were 1.5, 32, and 53 days, respectively.  
The linear half-life of MPTS was 173 days.  In the anaerobic soil
metabolism study (the second layer of soil), the half-lives of parent
Diiodomethyl p-tolyl sulfone were 1.7 and 4.2 days in aerobic
(non-flooded) and anaerobic (flooded soil) portions of the study,
respectively.  Diiodomethyl p-tolyl sulfone was found in equal portions
in water and sediment.  MIMPTS was a major degradate with a half-life of
21 days and was found predominantly in water.  MPTS reached 81% by the
end of the study and was primarily found in water.  Anaerobic aquatic
metabolism (representing bottom sediment) degrades parent and MIMPTS
with total system half-lives of 9.6 and 11 days, respectively.  MPTS was
the terminal metabolite and increased to 95% by 4-6 months.  Aqueous
residues were greater than sediment residues for parent, MIMPTS, and
MPTS for 7, 180, and 60 days, respectively.

Under anaerobic aquatic conditions (sandy loam sediment, water, and
nitrogen atmosphere), the total system, non-linear half-lives of
Diiodomethyl p-tolyl sulfone and MIMPTS were 9.6 and 11 days,
respectively.  Parent compound was associated more with water than
sediment through 7 days and more in sediment afterwards.  MIMPTS reached
16.2 % by 7 days, and then declined to <1% by 3-6 months.  MIMPTS was
associated more in water than sediment for 60 days and then in equal
portions thereafter.  MPTS increased to 94.5 by 4-6 months, and was
associated with water rather than sediment over the duration of the
study.  PTSA did not reach significant levels in the study.  Extractable
residues were 23-31% (0-14 days) and 16-18% by 30-180 days, and
non-extractable residues never exceeded 2%.  Water soluble residues
ranged from 68 to 85% and volatiles did not exceed 0.8%.

In columns of sand, silt loam, sandy loam, and clay soils, 73, 84, 34,
and 8% of radioactivity passed through the columns into the leachate,
respectively.  An average of 2, 1.5, 5, and 8% of applied Diiodomethyl
p-tolyl sulfone was detected in each inch of the 12-inch columns.  These
results indicate that Diiodomethyl p-tolyl sulfone residues will
eventually leach through the columns.  

An average of 43% of Diiodomethyl p-tolyl sulfone from wooden tongue
depressors leached into pH 5, 7, 9 unfiltered buffers over a 30-day
study (median of 42%).  Maximum residues in water were observed at day
zero, followed by a decrease to the minimum values at day 7 and a
general increase.  The wood extract accounted for 2.1-6% of applied for
pH 5, 7, and 9.  In filtered samples, the aqueous residues averaged
4.3%, indicating that some sorption to organic materials may occur in
the environment.  

There was no inhibition of microorganisms in sewage sludge treated at 9
mg/l.

Ecological Effects and Risks

Three available acute avian oral/dietary studies indicate that
Diiodomethyl p-tolyl sulfone is practically nontoxic to birds (LD50
>2000 mg ai/kg bw) when ingested and an avian precautionary statement is
not required on product labels.  The guidelines for avian acute oral
toxicity (OPPTS 850.2100) and avian dietary toxicity (OPPTS 850.2200)
are satisfied.  

Diiodomethyl p-tolyl sulfone is practically nontoxic to mammals as
indicated by several available studies reflecting the oral (rat LD50
>5000 mg ai/kg bw) and dermal (rabbit LD50 >20,000 mg/kg) routes of
exposure.  Refer to the human toxicology chapter for more details on
these and other mammalian toxicity studies submitted for the human
health assessment.

No data are available regarding effects of Diiodomethyl p-tolyl sulfone
on honeybees.  For wood preservative use, a study addressing
honey/beeswax residues and acute toxicity of treated wood residues to
bees is required or, in lieu of this study, product labels with wood
preservative use can include a statement prohibiting use of Diiodomethyl
p-tolyl sulfone-treated wood for beehive construction.

Three acceptable acute toxicity studies with the TGAI have resulted in
Diiodomethyl p-tolyl sulfone being categorized as very highly toxic to
freshwater fish.  Therefore, a precautionary label statement is
required.  The guideline for freshwater fish acute toxicity (OPPTS
850.1075) is satisfied.

Results from three available studies categorize technical-grade
Diiodomethyl p-tolyl sulfone as being moderately to very highly acutely
toxic to freshwater invertebrates.  Therefore, a precautionary label
statement is required.  The guideline requirement (OPPTS 850.1010) is
satisfied.

Acute toxicity testing with estuarine/marine organisms using the TGAI is
required when the end-use product is intended for direct application to
the marine/estuarine environment or the active ingredient is expected to
reach this environment in significant concentrations because of its
expected use and mobility.  Data are required to support the wood
preservative uses of Diiodomethyl p-tolyl sulfone.  No data are
available.  

The Agency’s level of concern (LOC) is exceeded for listed (i.e.,
endangered and threatened) species for all three dilution-rate scenarios
from antisapstain treatment (refer to the Ecological Effects Chapter). 
The LOC is not exceeded for non-listed invertebrates for any scenario
but is exceeded for listed (i.e., endangered and threatened) species for
all three dilution-rate scenarios from antisapstain treatment.  

Because Diiodomethyl p-tolyl sulfone is practically nontoxic to birds
and mammals, minimal acute risk is presumed for all registered uses. 
Toxicity data are not available to assess risk to honey bees.  However,
treated wood is prohibited from use for construction of bee hives,
minimal exposure and risk are presumed.

For certain use categories, including most Diiodomethyl p-tolyl sulfone
uses, the Agency assumes there will be minimal environmental exposure,
and only a minimal toxicity data set is required (Overview of the
Ecological Risk Assessment Process in the Office of Pesticide Programs
U.S. Environmental Protection Agency - Endangered and Threatened Species
Effects Determinations, 1/23/04, Appendix A, Section IIB, p. 81).  Uses
in these categories do not undergo a full screening-level risk
assessment and are considered to fall under a no effect determination.  

The assessment for antisapstain wood treatment uses indicates that there
is a potential for Diiodomethyl p-tolyl sulfone exposure of listed
freshwater and aquatic invertebrate species and that a more refined
assessment is warranted, to include direct, indirect and habitat
effects.  The refined assessment should involve clear delineation of the
action area associated with proposed use of Diiodomethyl p-tolyl sulfone
and best available information on the temporal and spatial co-location
of listed species with respect to the action area.  This analysis has
not been conducted for this assessment.  An endangered species effect
determination will not be made at this time.  The label statement
required for wood preservative products is expected to provide some
mitigation until a full endangered species assessment is conducted.

9.0	DEFICIENCIES/DATA NEEDS/LABEL RECOMMENDATIONS

Toxicology

The following study is recommended as a data gap:

(1). 90-day inhalation toxicity study

Occupational/residential handler and postapplication exposure
assessments  

Since the surrogate dermal and inhalation unit exposure values were
taken from CMA data and are of poor quality, the Agency requests that
confirmatory data be submitted to support the occupational scenarios
assessed in this document.

Currently, no exposure data are available to assess the bystanders’
inhalation exposure to Diiodomethyl p-tolyl sulfone vapors in industrial
settings.  Appropriate air monitoring data in the manufacturing setting
are needed to support the preservative uses. 

For the wood preservative pressure treatment scenarios, surrogate CCA
exposure data were used for lack of chemical-specific exposure data for
this use pattern. For the wood preservative non-pressure treatment
scenarios, surrogate DDAC exposure data were used for the lack of
chemical-specific exposure data.  Limitations and uncertainties
associated with the use of these data include:

The assumption was made that exposure patterns for workers at treatment
facilities using CCA and DDAC would be similar to exposure patterns for
workers at treatment facilities using diiodomethyl p-tolyl sulfone, and
therefore the exposures could be used as surrogate data for workers that
treat wood with diiodomethyl p-tolyl sulfone-based formulations.

For environmental modeling, it was assumed that the leaching process
from wood treated with diiodomethyl p-tolyl sulfone would be similar to
that of CCA and DDAC. However, due to the lack of robust data for
diiodomethyl p-tolyl sulfone-treated wood, it is not possible to verify
this assumption. 

The quantities handled/treated were estimated based on information from
various sources, including Agency standard assumptions, HED’s Standard
Operating Procedures (SOPs) for Residential Exposure Assessments (USEPA,
2000 and 2001), and professional judgment based on Agency understanding
of industrial practices.  In certain cases, no standard values were
available for some scenarios.  Assumptions for these scenarios were
based on AD estimates and could be further refined with input from
registrants.

Ecological Effects

	•  Estuarine/marine fish acute study (850.1075); TGAI 

	•  Estuarine/marine shrimp acute study (850.1035); TGAI     

	•  Estuarine/marine mollusk acute study (850.1025); TGAI

	•  Aquatic invertebrate (freshwater) life-cycle study (850.1300);
major degradate

	•  Fish early life-stage (freshwater) study (850.1400); major
degradate

	•  Freshwater diatom (850.5400); TGAI or EP

	•  Marine diatom (850.5400); TGAI or EP

	•  Blue-green cyanobacteria (850.5400); TGAI or EP

	•  Freshwater green alga (850.5400); TGAI or EP

	•  Freshwater floating macrophyte duckweed (850.4400); TGAI or EP

	•  Freshwater rooted macrophyte rice seedling emergence (850.4225);
EP

	•  Freshwater rooted macrophyte rice vegetative vigor (850.4250); EP

	•  A study addressing honey/beeswax residues and acute toxicity of
treated wood residues to bees is required if bee hives might be
constructed of treated wood or if any product is intended for
application to a bee hive.  The study is a combination of Guidelines
171-4 and 850.3030 (see information regarding residue data requirements
for uses in beehives in the residue chemistry section of 40 CFR part
158).  The toxicity portion of this study is conducted in lieu of a
honeybee contact LD50 test. The number of bees tested and the
methodology for collection/ introduction of bees into hives, feeding,
and observations for toxicity and mortality must be consistent with
those described in OPPTS Guideline 850.3030, “Honey Bee Toxicity of
Residues on Foliage”.  However, this study will be waived if product
labels with wood preservative use are amended to prohibit the use of
treated wood for beehive construction (see section IV Label Hazard
Statements). 

	Required Label Statements – Ecological Effects

All product labels must have the following ENVIRONMENTAL HAZARDS
statement:  

"This pesticide is toxic to fish and aquatic invertebrates. Do not
contaminate water when disposing of equipment washwaters.  Do not
discharge effluent containing this product into lakes, streams, ponds,
estuaries, oceans, or other waters unless in accordance with the
requirements of a National Pollutant Discharge Elimination System
(NPDES) permit and the permitting authorities are notified in writing
prior to discharge.  Do not discharge effluent containing this product
to sewer systems without previously notifying the local sewage treatment
plant authority.  For guidance contact your State Water Board or
Regional Office of the EPA."

Product labels having antisapstain use must have the following
DIRECTIONS FOR USE statement:

"Treated lumber must be stored under cover, indoors, or at least 100
feet from any pond, lake, stream, wetland, or river to prevent possible
runoff of the product into the waterway.  Treated lumber stored within
100 feet of a pond, lake, steam, wetland, or river must be either
covered with plastic or surrounded by a berm to prevent surface water
runoff into the nearby waterway.  If a berm or curb is used around the
site, it should consist of impermeable material (clay, asphalt,
concrete) and be of sufficient height to prevent runoff during heavy
rainfall events."

Products with wood preservative uses:  if honeybee studies 850.3030 and
171-4 are waived, the following label statement is required:  

“Treated wood shall not be used in the construction of beehives.”

Products with wood preservative uses almost must have a statement
prohibiting use of pretreated wood in structures located in surface
waters and prohibiting application of Diiodomethyl p-tolyl sulfone to
existing structures located or to be placed in surface waters.

10.  	REFERENCES tc \l1 "7.0	REFERENCES 

Toxicology

Brusick, D.J. (1977) Mutagenicity Evaluation of A-47685 50/50 Mixture
with Dipropylene glycol: LBI Project No. 2683.. Final rept., rev. 11 p.
MRID 00054962.  Unpublished.

Brusick, D.J. (1977) Mutagenicity Evaluation of A-47685: LBI Project No.
2683. Final rept., rev. (Unpublished study received Jun 15, 1977 under
275-33; prepared by Litton Bionetics, Inc., MRID 00054961 submitted by
Abbott Laboratories, North Chicago, Ill.; CDL: 230726-E)

Carney, E. W., Zablotny, C. L., and Johnson, K. A. (2006) Amical 48: 
one-generation dietary reproduction toxicity study in CD rats. 
Toxicology & Environmental Research and Consulting, The Dow Chemical
Company, Midland, MI.  Laboratory Project Study ID.:  031007, April 28,
2006.  MRID 46913302.  Unpublished.

Carney, E., K. Brooks, R. Rasoulpour, et al. (2007) AMICAL™ 48,
antifungal agent: oral gavage developmental toxicity study in New
Zealand white rabbits. The Dow Chemical Company. Laboratory Project
Study ID 061146, August 29, 2007. MRID 47242202. Unpublished.

Carney, E.W., C.L. Zablotny, J.F. Quast, and K.A. Johnson (2006) Amical
48: two-generation dietary reproductive toxicity study in CD rats. 
Toxicology & Environmental Research and Consulting, The Dow Chemical
Company, Midland, MI.  Laboratory Project Study ID.:  031007, May 15,
2006.  MRID 46913301.  Unpublished.

Cifone, M. (1985) Evaluation of A-9248 in the Rat Primary Hepatocyte
Unscheduled DNA Synthesis Assay: LBI Project No. 20991: Final Report.
MRID 00160072 

Cifone, M. (1985) Mutagenicity of A-9248 in a Mouse Lymphoma Mutation
Assay: LBI Project No. 20989: Final Report. MRID 00160070 Unpublished
study prepared by Litton Bionetics, Inc. 17 p.

Creighton, J. (1986) Three-Month Toxicity Study of Amical 48
Administered Orally to Dogs: Lab Project Number: TB85-158. Abbot labs. 
MRID 42054403.  Unpublished

Creighton, J.; Bollmeier, A. (1986) Three-Month Toxicity Study of AMICAL
48 Administered Orally to Dogs: Supplemental Data: Lab Project Number:
TB85/158. Abbott Labs. 22 p. MRID 43246402. Unpublished.

Davis, J. and Erhardt, S.  (2005) Amical 48 antifungal agent: 
Pharmacokinetics and metabolism in Fisher 344 rats. The Dow Chemical
Company, Midland, Michigan. Laboratory report number not reported,
January 18, 2007. MRID 47076601. Unpublished. 

Dudley, R. (1986) Three-Month Toxicity Study of Amical 48 Administered
Via the Diet to Rats: Lab Project Number: TA85-096. Abbot Laboratories. 
MRID010504. Unpublished 

Ema M, Itami T, Kawasaki H. (1992).Teratological assessment of
diiodomethyl p-tolyl sulfone in rats. Toxicol Lett. 62(1):45-52.

FitzGerald, G. (1992) Acute Oral Limit Study: Amical WP: Lab Project
Number: 92G-1490. Toxikon Corp. MRID 42586801. Unpublished.

Ivett, J. (1986) Clastogenic Evaluation of A-9248...in the in vivo Mouse
Micronucleus Assay: HB Project No. 20996: Final Report. MRID
00160071Unpublished study prepared by Hazleton Biotechnologies. 20 p.

Kesterson, J.; Majors, K.; Moore, L.; et al. (1976) Acute Dermal
Toxicity of Amical 48 (Dry Powder) and an Amical 48 Dispersion in
Rabbits: Study Nos. 76-245 and 76-246. (Unpublished study received Jun
16, 1976 under 275-30; submitted by Abbott Labora- tories, North
Chicago, IL; CDL:225439-A.  MRID 00123023.  Unpublished.

Kesterson, J.; Majors, K.; Moore, L.; et al. (1976) Acute Dermal
Toxicity of Amical 48 (Dry Powder) and an Amical 48 Dispersion in
Rabbits: Study Nos. 76-245 and 76-246. submitted by Abbott Laboratories,
North Chicago, IL; CDL:225439-A.  MRID 00123023. Unpublished.

Kreuzmann, J. (1990) Acute Oral Toxicity in Rats--Limit Test of AMICAL
48: Supplemental Information: Lab Project Number: 90/4015/21/A. Hill Top
Biolabs, Inc. MRID 43008702.  Unpublished. 

Kreuzmann, J. (1990) Acute Oral Toxicity in Rats-Limit Test: Amical 48:
Lab Project Number: 90-4015-21 Hill Top Biolabs, Inc. MRID 41765401
Unpublished. 

Lehrer , SB (1985). Evaluation of the Effects of Orally Administered
AMICAL® 48 on the Embryonic and Fetal Development of the Rat - Segment
II, TFR Abbott Laboratories, North Chicago, IL MRID 42054404. 
Unpublished.

Lehrer , SB (1986). Evaluation of the Effects of Orally Administered
AMICAL® 48 on the Embryonic and Fetal Development of the Rat - Segment
II, TFR Supplement to Study TA85-022. Abbott Laboratories, North
Chicago, IL MRID 42054405.  Unpublished.

Lehrer, S. (1985) Evaluation of the Effects of Orally Administered
Amical 48 on the Embryonic and Fetal Development of the Rat: Segment II,
TFR: Lab Project Number: TE85-022. MRID 42054404  Unpublished study
prepared by Abbott Labs. 56 p.

Lehrer, S. (1985) Evaluation of the Effects of Orally Administered
AMICAL 48 on the Embryonic and Fetal Development of the Rabbit--Segment
II, TFR: Lab Project Number: TE85-054. MRID 42243801 Unpublished study
prepared by Abbott Labs. 64 p. 

Lehrer, S. (1986) Evaluation of the Effects of Orally Administered
Amical 48 on the Embryonic and Fetal Development of the Rat: Segment II,
TFR: Supplement to Study TA85-022: Lab Project Numb- er TE85-230. MRID
42054405.Unpublished 

Lehrer, S.; Bollmeier, A. (1985) Evaluation of the Effects of Orally
Administered AMICAL 48 on the Embryonic and Fetal Development of the
Rabbit--Segment II, TFR: Supplement: Lab Project Number: TE85/054.
Abbott Labs. 179 p. MRID 43246404 Unpublished.

Putman, D.; Curry, P.; Schadly, E. (1994) Chromosome Aberrations in
Chinese Hamster Ovary (CHO) Cells (Amical 48 Preservative): Final
Report: Lab Project Number: TD585/337. MRID 43120601. Unpublished study
prepared by Microbiological Associates, Inc. 30 p.

Saghir, S., Brzak, K., Clark, A., et al. (2007) Amical 48 antifungal
agent:  Pharmacokinetics and metabolism in Fisher 344 rats. The Dow
Chemical Company, Midland, Michigan. Laboratory report number not
reported, January 18, 2007. MRID 47076601. Unpublished. 

Occupational and Residential

American Chemistry Council (ACC). 2002.  Assessment of Potential
Inhalation and Dermal Exposure Associated With Pressure Treatment of
Wood with Arsenical Wood Products.  MRID 4550211-01.

Bestari et al., 1999 Measurement and Assessment of Dermal and Inhalation
Exposures to Didecyl Dimethyl Ammonium Chloride (DDAC) Used in the
Protection of Cut Lumber (Phase III).  (MRID 455243-04, Task force
#73154).

Cinalli, Christina, et al. A Laboratory Method to Determine the
Retention of Liquids on the Surface of Hands.  Exposure Evaluation
Division. September 1992. 

National Institute for Occupational Safety and Health (NIOSH): Criteria
for a Recommended Standard-Occupational Exposure to Metalworking Fluids.
 Department of Health and Human Services (DHHS) NIOSH Publication
#98-102 (1998).

SIMetric, 2005.  Mass, Weight, Density, or Specific Gravity of Bulk
Materials.  http://www.simetric.co.uk/si_materials.htm, last accessed
June 2005.

USEPA.  1997.  Standard Operating Procedures (SOPs) for Residential
Exposure Assessments.  EPA Office of Pesticide Programs(Human Health
Effects Division (HED). Dated December 18, 1997.

USEPA.  1997a.  Exposure Factors Handbook. Volume I-II.  Office of
Research and Development.  Washington, D.C.  EPA/600/P-95/002Fa.

USEPA. 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure
from the Pesticide Handler Exposure Database Version 1.1.   Washington,
DC:  U.S. Environmental Protection Agency.

USEPA.  1999.  Evaluation of Chemical Manufacturers Association
Antimicrobial Exposure Assessment Study.  Memorandum from Siroos
Mostaghimi, Ph.D., USEPA, to Julie Fairfax, 

USEPA.  2000.  Residential SOPs.  EPA Office of Pesticide Programs Human
Health Effects Division. Dated April 5, 2000.

USEPA.  2001.  HED Science Advisory Council for Exposure. Policy Update,
November 12. Recommended Revisions to the Standard Operating Procedures
(SOPs) for Residential Exposure Assessment, February 22, 2001. 

USEPA. 2003.  Assessment of the Proposed Bardac Wood Preservative
Pressure Treatment Use.  Memorandum from Tim Leighton and Siroos
Mostaghimi.  February 11, 2003.

USEPA. 2004.  Occupational and Residential Exposure Assessment for
Carboquat WP-50.  Memorandum from Siroos Mostaghimi, USEPA to Velma
Noble, USEPA.   Dated November 4, 2004. DP Barcodes D303714 and D303938.

USEPA.  2005.  Antimicrobials Division’s Draft Standard Operating
Procedures for Occupational and Residential Exposure Assessments.  July,
2005. (Unpublished Internal Guidance).

USEPA.  2005a.  A Probabilistic Exposure Assessment for Children Who
Contact CCA-Treated Playsets and Decks.  Final Report, February, 2005. 
US EPA Office of Research and Development, National Exposure Research
Laboratory.

Whatman, 2005.  Whatman Absorbent Sinks. 
http://www.whatman.com/products/?pageID=7.32.42, Accessed March 2005.

  

Environmantal Fate

Carpenter, M. (1988) Hydrolysis as a Function of pH at 25(degrees)C of
?carbon 14|-Amical: Lab Project Number: 36019. Unpublished study
prepared by Analytical Bio-Chemistry Labs., Inc. 756 p.  MRID 41765404. 

Williams, M.; Heim, L. (1993) Hydrolysis of AMICAL  as a Function of pH
at 25 (degrees) C: Lab Project Number: 40886. Unpublished study prepared
by ABC Laboratories, Inc. 63 p.  MRID  43008701.

Madsen, S. and M.D. Williams.  (1991)  Determination of the Photolysis
Rate of 14C-Amical  on the Surface of Soil.  ABC Laboratories Final
Report No. 38727.  No MRID.

Cranor, W. (1990) Aerobic Soil Metabolism of ?carbon 14|-Abbott- 9248
(Amical 48): Lab Project Number: 36608. Unpublished study prepared by
Analytical Bio-Chemistry Labs., Inc. 955 p.  MRID 41765405.

Madsen, S.; Williams, M. (1990) Anaerobic Soil Metabolism of ?carbon
14|-Amical 48: Lab Project Number: 38730. Unpublished study prepared by
Analytical Bio-Chemistry Labs., Inc. 461 p.  MRID 41765406

Madsen, S.; Williams, M. (1991) Anaerobic Aquatic Metabolism of ?carbon
14| Amical 48: Final Report: Lab Project Number: 38729. Unpublished
study prepared by ABC Labs, Inc. 532 p.  MRID 42177201.

Daly, D.; Cranor, W. (1987) Leaching Characteristics in Soil with
?carbon 14|-Amical-48 (Abbott-9248): Lab Project Number: 36021.
Unpublished study prepared by Analytical Bio-Chemistry Labs., Inc. 277
p. 41765407.

Williams, M.; Bradley, A. (1996) Aqueous Availability of AMICAL 48:
Final Report: Lab Project Number: 42782: ABC 42782. Unpublished study
prepared by ABC Laboratories Europe, Ltd. 78 p.   MRID 43997001.

Gonsior, S.J., M.A. Rivard, and M.K. Stock.  August 12, 2002.  Activated
Sludge Respiration Inhibition Test (OECD 209) for Amical 48
Preservative.  Unpublished study submitted by The Dow Chemical Company. 
No MRID.

Ecological Effects

Bollmeier, A. (1990) Angus Chemical Company Phase 3 Summary of MRID
00149729. Acute Toxicity of AMICAL to Daphnia magna: Static Acute
Toxicity: Report No. 31947. Prepared by ABC Labs., Inc. 1 p.  MRID
94039006

Bollmeier, A. (1990) Angus Chemical Company Phase 3 Summary of MRID
00149731. Acute Toxicity of AMICAL to Bluegill Sunfish: Static Acute
Toxicity: Report No. 31945. Prepared by ABC Labs. Inc. 10 p.  MRID
94039004

Bollmeier, A. (1990) Angus Chemical Company Phase 3 Summary of MRID
00149730. Acute Toxicity of AMICAL to Rainbow Trout: Static Acute
Toxicity: Report No. 31946. Prepared by ABC Labs., Inc. 1 p.  MRID
94039005

Fink, R.; Beavers, J.; Grimes, J.; et al. (1978) Acute Oral LD50--
Bobwhite Quail: A-9248: Project No. 161-104. Final rept. (Unpublished
study received Sep 7, 1979 under 275-21; prepared by Wildlife
International Ltd. and Washington College, submitted by Abbott
Laboratories, North Chicago, IL; CDL:240936-C)  MRID 123643

Fink, R.; Beavers, J.; Joiner, G.; et al. (1978) Eight-day Dietary
LC50--Bobwhite Quail: A-9248: Project No. 161-105. Final rept.
(Unpublished study received Sep 7, 1979 under 275-21; prepared by
Wildlife International Ltd. and Washington College, submitted by Abbott
Laboratories, North Chicago, IL; CDL:240936-B)  MRID 123642

Fink, R.; Beavers, J.; Grimes, J.; et al. (1978) Eight-day Dietary
LC50--Mallard Duck: A-9248: Project No. 161-106. Final rept.
(Unpublished study received Sep 7, 1979 under 275-21; prepared by
Wildlife International Ltd. and Washington College, submitted by Abbott
Laboratories, North Chicago, IL; CDL:240936-A)  MRID 124488

Forbis, A.; Burgess, D.; Georgie, L. (1984) Acute Toxicity of Amical to
Daphnia magna: Static Acute Toxicity Report # 31947. Unpublished study
prepared by Analytical Biochemistry Laborato- ries, Inc. 38 p.  MRID
149729

Forbis, A.; Georgie, L.; Burgess, D. (1984) Acute Toxicity of Amical 48
to Rainbow Trout (Salmo gairdneri): Static Acute Toxicity Report #31946.
Unpublished study prepared by Analytical Bio- chemistry Laboratories,
Inc. 60 p.   MRID 149730

Forbis, A.; Georgie, L.; Burgess, D. (1984) Acute Toxicity of Amical 48
to Bluegill Sunfish (Lepomis macrochirus): Static Acute Toxicity Report
#31945. Unpublished study prepared by Analyti- cal Biochemistry
Laboratories, Inc. 63 p.  MRID 149731

Hamlin, J. (1972) Report to: Abbott Laboratories, Chemical Division:
Four-Day Static Fish Toxicity Studies with Amical and Amical 77 in
Rainbow Trout and Bluegills: IBT No. A1244. (Unpublished study received
Mar 9, 1972 under 275-22; prepared by Industrial Bio-Test Laboratories,
Inc., submitted by Abbott Laboratories, North Chicago, Ill.;
CDL:002251-H)  MRID 55326	

Krahn, P.; Strub R. (1990)  Standard Leaching Test for Antisapstain
Chemicals:  Regional Program Report 90-10.  Environment Canada,
Conservation and Protection, Pacific and Yukon Region North Vancouver,
BC.

Marino, T. A. (2007) AMICAL: An Acute Toxicity Study with the Rainbow
Trout; The Dow Chemical Company; Guideline 72-1; 42 pages.

Marino, T. A. (2007) AMICAL: An Acute Toxicity Study with the Daphnid,
Daphnia magna; The Dow Chemical Company; Guideline 72-2; 42 pages.

Suprenant, D.; Ziencina, M. (1978) Acute Toxicity of A-9248 to the Water
Flea (Daphnia magna): Report #BW-78-9-308. (Unpublished study received
Sep 7, 1979 under 275-21; prepared by EG & G, Bionomics, submitted by
Abbott Laboratories, North Chicago, IL; CDL:240936-D)  MRID 123644

Trueblood, A. (1990) Angus Chemical Company Phase 3 Summary of MRID
00123643. Acute Oral Toxicity Study of AMICAL in Bobwhite Quail: Project
#161-104. Prepared by Wildlife International, Ltd. 13 p.  MRID 94039001

Trueblood, A. (1990) Angus Chemical Company Phase 3 Summary of MRID
00123642. Eight-Day Dietary Toxicity Study of AMICAL in Bobwhite Quail:
Project #161-105. Prepared by Wildlife International Ltd. 12 p.  MRID
94039002

Trueblood, A. (1990) Angus Chemical Company Phase 3 Summary of MRID
00124488. Eight-Day Dietary Toxicity Study of AMICAL in the Mallard
Duck; Project No. 161-106. Prepared by Wildlife International, Ltd. 12
p.  MRID 94039003

Aschacher G and Gruendlinger R, 2000.  Methods to evaluate the
ecotoxicological risks of anti-sapstain preservatives.  Holzforschung,
Austria Research and Development. 
www.holzforschung.at/english/img_eng/ascha200.pdf.

EPA, 2007.  “Amical Environmental Fate Data Based on Jim Breithaupt
Power Point Presentation,” document provided by Siroos Mostaghimi,
U.S. Environmental Protection Agency, October 4, 2007.

EPA, 2004. Wood Leaching Model: Chemical Concentration Screening Tool,
v1.0. USEPA/OPPT/AD.

Krahn P and Strub R, 1990.  Standard Leaching Test for Antisapstain
Chemicals:  Regional Program Report 90-10.  Environment Canada,
Conservation and Protection, Pacific and Yukon Region North Vancouver,
BC.

Lee R, 2004.  WLM recommendation regarding chemical generalization. 
Memorandum to Siroos Mostaghimi, USEPA.  December 15, 2004.

Versar, 2005. "ADBAC Antisapstain Modeling (TAF 1-4-10, CM-43),"
memorandum to Najim Shamim, U.S. EPA, from Ron Lee and Jignasha Patel,
Versar, Inc., December 5, 2005.

Dietary Exposure

US Food and Drug Administration (US FDA) Center for Food Safety &
Applied Nutrition’s (CFSAN). 2002.  “Preparation of Food Contact
Notifications and Food Additive Petitions for Food Contact Substances:
Chemistry Recommendations.”   HYPERLINK
"http://www.cfsan.fda.gov/~dms/opa2pmnc.html" 
http://www.cfsan.fda.gov/~dms/opa2pmnc.html . April.

US Food and Drug Administration (US FDA) 1999. Memorandum from the
Division of Product Manufacture and Use, Chemistry Review Team HFS-246. 
to the Division of Petition Control, HFS-215 Attn: M. Hepp, Ph.D. 
“FAP 9B4668 (MATS #1055 M2.0 and 2.1): Angus Chemical Co,; submission
of 5/5/99. 4-(Diiodomethylsulfonyl) toluene as a slimicide in the
manufacture of paper and paperboard.”  August 12. 

US Food and Drug Administration (US FDA) 1987. Memorandum from the
Regulatory Food Chemistry Branch, HFF-458.  to the Indirect Additives
Branch, HFF-335 Attn: M. Stephens.  “FAP 6B3961-Abbott Laboratories.
Submission dated 11/4/86. 4-(Diiodomethylsulfonyl) toluene (DIMST) for
use as a component of side seam cements.”  February 9. 

US Food and Drug Administration (US FDA) 1986. Memorandum from the
Regulatory Food Chemistry Branch, HFF-458.  to the Indirect Additives
Branch, HFF-335.  “FAP 6B3961-Abbott Laboratories.
4-(Diiodomethylsulfonyl) toluene (DIMST) for use as a component of side
seam cements. Submission dated 8/8/86.”  October 10. 

Appendices



Use

(

v

w

Ë

Ì

Ï

Ð

2

(

P

w

ª

Ê

Ë

ê

6

g

p



¶

¹

Á

਀&䘋

਀&䘋

hã

਀&䘋

਀Ħ䘋

਀&䘋

 hã

hã

hã

h

@

Æ

Ø	@

Æ

Ø	@

Ø	@

Ø	@

Ø	@

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

̤̀옍

̤̀옍

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

@

@

gdj

~

@

~

~

hj

hj

hj

hj

hj

hj

~

~

@

gdj

hj

hj

hwp

  hwp

hj

hj

hj

 hwp

hj

hwp

hj

hj

hj

„Ð]„¦ÿ^„Ðgdj

@

gdj

„Ð^„Ðgdj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

@

gdj

@

gdj

„Ð`„Ðgdj

„àã^„ð-`„àãgdj

„Ð^„Ðgdj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

`„€égdj

hw.

hw.

hj

hj

hj

hw.

hj

hw.

hj

hj

hj

hj

hj

 hw.

hj

 hw.

hw.

hw.

hj

hj

hj

hj

hj

hj

hw.

hj

hj

hw.

hw.

hj

hj

hj

hj

hj

hj

@

gdj

„Ð`„Ðgdj

gdj

„Ð^„Ðgdj

„àã^„ð-`„àãgdj

hj

hj

hj

hj

hj

hj

hj

hw.

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

hj

B*

hj

hj

hj

hj

Ø	@

Ø	@

 h{

 h{

옍



Ø	@

㄀Ĥ摧偓,ࠀ

y

z

—

˜

Ø	@

㄀Ĥ摧徵¦ࠀ

Ö

Ü

y

z

–

—

˜

™

 

«

Ö

Û

û

ü

&

Ø	@

萏ؠ葞ؠ摧

摧

萏˘萑ﴰ葞˘葠ﴰ摧

萑ː葠ː摧

Ø	@

Ø	@

Ø	@

@

Ø	@

Ø	@

옍īː

ᴡ਀&䘋 옍)

 hj

ᴦ਀&䘋 옍īː

옍īː

옍īː

㄀Ĥ摧⫈

␱䀁द摧撥`

옍)

 hG

옍)

옍)

萏޼萑葞޼葠摧⢍Ý

옍)

h

 hG

(

h

Ff

Ff

lb/1000 lb dry fabric	Non-clothing

	Ultra-Fresh 15	10466-37	Add	Dry-film fungal protection	3.3	33.4	lb/1000
lb dry fabric	Non-clothing

Leather Tanning	AMICAL 48	464-670	Detailed on Label	In-process mold and
mildew protection	0.01%	0.30%	w/w	 

	AMICAL WP	464-672	Detailed on Label	In-process mold and mildew
protection	0.02%	0.61%	w/w	 

	AMICAL Flowable	464-673	Detailed on Label	In-process mold and mildew
protection	0.02%	0.66%	w/w	 

	Ultra-Fresh 15	10466-37	Detailed on Label	In-process mold and mildew
protection	0.053%	1.2%	w/w	 

Paper Production	AMICAL 48	464-670	Add to system where mixing occurs
Protection of water system, pulp, additives, and slurries	0.0008	0.8
lb/ton paper	Not for food contact

	0.004	3.32	lb/1000 gal

AMICAL WP	464-672	Add to system where mixing occurs	Protection of water
system, pulp, additives, and slurries	0.0016	1.6	lb/ton paper	Not for
food contact

	0.008	6.78	lb/1000 gal

AMICAL Flowable	464-673	Add to system where mixing occurs	Protection of
water system, pulp, additives, and slurries	0.0019	1.92	lb/ton paper	Not
for food contact

	0.0096	7.97	lb/1000 gal

Ultra-Fresh 15	10466-37	Add to system where mixing occurs	Protection of
water system, pulp, additives, and slurries	0.0051	5.13	lb/ton paper	Not
for food contact

	0.026	21.3	lb/1000 gal

	Mold Inhibition in Paper and Paperboard	AMICAL 48	464-670	Add to
whitewater or stock	Dry-film fungal protection	0.02	3.4	lb/ton paper	 

	Applicator rolls or shower

0.02	3.4	lb/ton paper	 

	Size press or water box

80	8000	ppm	 

	AMICAL WP	464-672	Add to whitewater or stock	Dry-film fungal protection
0.04	6.9	lb/ton paper	 

	Applicator rolls or shower

0.04	6.9	lb/ton paper	 

	Size press or water box

163	16300	ppm	 

	AMICAL Flowable	464-673	Add to whitewater or stock	Dry-film fungal
protection	0.54	8.21	lb/ton paper	 

	Applicator rolls or shower

0.048	8.16	lb/ton paper	 

	Size press or water box

200	20000	ppm	 

	Ultra-Fresh 15	10466-37	Add to whitewater or stock	Dry-film fungal
protection	0.13	21.8	lb/ton paper	 

	Applicator rolls or shower

0.13	21.8	lb/ton paper	 

	Size press or water box

540	54000	ppm	 

	Intace Fungicide B-6773	74075-1	Add	Dry-film fungal protection	350	2500
ppm	 

Paper Plant Storage	AMICAL 48	464-670	Add to material to be preserved
Fungal Preservative	0.2	400	ppm	 

	AMICAL WP	464-672	Add to material to be preserved	Fungal Preservative
0.4	816	ppm	 

	AMICAL Flowable	464-673	Add to material to be preserved	Fungal
Preservative	0.2	400	ppm active	 

	Ultra-Fresh 15	10466-37	Add to material to be preserved	Fungal
Preservative	0.2	400	ppm active	 

Nitrocellulose	AMICAL 48	464-670	Add to material	Fungal Preservative
0.05%	0.30%	w/w	 

Drain, Grease Trap and Septic System	AMICAL Flowable	464-673	Add	Fungal
Control	125	1000	ppm	 

 PAGE   

Page   PAGE  1  of   NUMPAGES  53 

	

 PAGE   

Page   PAGE  53  of   NUMPAGES  53 

Page   PAGE  49  of   NUMPAGES  53