Document ID: EPA-HQ-OPP-2007-1151-0003
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

 

January 2, 2008

MEMORANDUM:

Subject:	Revised Dietary and Drinking Water Exposure Chapter for
Diiodomethy p-tolyl sulfone for the Reregistration Eligibility Decision
(RED) Document (Case 4009)

To:		K. Avivah Jacob, Chemical Review Manager,

		Regulatory Management Branch II

Antimicrobials Division (7510P)

From: 		Cassi Walls, Ph.D., Chemist

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)

DP Barcode: 		344855

Chemical Name:	Diiodomethyl p-tolyl sulfone	

		

PC Code:		101002 

CAS Registry No. 	20018-09-1 

Attached is a review of the dietary and drinking water exposures and
risks for the antimicrobial uses of diiodomethyl p-tolyl sulfone to
support the Reregistration Eligibility Decision (RED) document.  The
text of this assessment was revised to correct errors identified during
the error only comment period. 

I.	Executive Summary

The Antimicrobials Division (AD) assessed the potential dietary and
drinking water exposures and risks for the antimicrobial uses of
diiodomethyl p-tolyl sulfone.  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 diiodomethy 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 diiodomethy p-tolyl sulfone
to impact drinking water sources is negligible and therefore a
quantitative drinking water assessment was not conducted.

II.  SEQ CHAPTER \h \r 1  	Dietary Exposures and Risks to Diiodomethy
p-tolyl sulfone as an Indirect Food Additive

AD assessed the potential dietary exposure to the active ingredient,
diiodomethy p-tolyl sulfone, from its use as an indirect food additive. 
The US Food and Drug Administration (US FDA) has granted diiodomethy
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 21CFR176.300, US FDA has cleared the use of
diiodomethy 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 diiodomethy p-tolyl sulfone labels for the
pulp and paper slimicide use state for 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 diiodomethy
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 diiodomethy
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 December 2007 and memos obtained from FDA
granting the diiodomethy 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 1.

Table 1. Diiodomethy p-tolyl sulfone Dietary Exposures from Indirect
Food Uses

FDA Clearance

(21 CFR §)	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 21CFR 175.105, diiodomethy p-tolyl sulfone can be
used to preserve adhesive formulations used in food packaging.  Dietary
exposures to diiodomethy 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

 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

Preservative of Can End and Sid- Seam Cements

As regulated under 21CFR 175.300 (Substances for Use as Components of
Coatings – Resinous and Polymeric Coatings), diiodomethy 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 diiodomethy p-tolyl sulfone indirect food
uses, dietary exposures were estimated using the following assumptions:

Diiodomethy 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 diiodomethy 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

Diiodomethy 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

 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% diiodomethy
p-tolyl sulfone by weight.  The AMICAL 48 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 polymeric
based products, coating, adhesives, foams, and sealants.”  Neither one
of these use descriptions gives a clear indication of where the can end
and side seam cements would fall under.  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.

Preservative 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), diiodomethy 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 diiodomethy p-tolyl sulfone indirect food uses, dietary
exposures were estimated using the following assumptions:

Diiodomethy p-tolyl sulfone migrates to all types of food in incidental
contact with caulk containing 1000 mg/kg diiodomethy 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

 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%
diiodomethy p-tolyl sulfone by weight.  The AMICAL 48 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 polymeric
based products, coating, adhesives, foams, and sealants.”  Neither one
of these use descriptions gives a clear indication of where the repeat
use rubber sealant would fall under.  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.  

Cumulative Dietary Exposure

The cumulative estimated dietary intakes (CEDI) of diiodomethy p-tolyl
sulfone from its use as a preservative in adhesives, can end cements,
and repeat-use rubber sealants are presented in Table 2.

Table 2. Diiodomethy p-tolyl sulfone Cumulative Exposures

FDA Clearance

(21 CFR §)	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

	Cumulative

10.4	31.1	15.5	0.00044	0.0010

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

The dietary risks from diiodomethy 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 PAD
of 0.002 mg/kg/day, the dietary risks were estimated and summarized in
Table 3.  None of the uses exceed the Agency’s level of concern for
the chronic exposure durations.  

Table 3. Dietary Risks of Diiodomethy p-tolyl sulfone Indirect Food Uses

FDA Clearance

(21 CFR §)	Use	Dose 

(mg/kg/day)	%cPAD

Adult	Child	Adult	Child

175.105	Preservative in Adhesives	0.00029	0.00067	14%	33%

177.2600 	Preservative in Repeat-use
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sulfone to impact drinking water sources is negligible and therefore a
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IV.  References:

US Food and Drug Administration (US FDA) Center for Food Safety &
Applied Nutrition’s (CFSAN). 2007.  “Preparation of Food Contact
Notifications and Food Additive Petitions for Food Contact Substances:
Chemistry Recommendations.”
http://www.cfsan.fda.gov/~dms/opa3pmnc.html. December.

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. 

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