**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

WASHINGTON, D.C. 20460![](media/image1.png){width="1.5833333333333333in"
height="1.5402777777777779in"}

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

April 4, 2006

**[MEMORANDUM]{.underline}**

**DATE:** 4/04/2006

**SUBJECT:** 2-(Thiocyanomethylthio)benzothiazole Dietary Assessment for
the Reregistration Eligibility Document

**REVIEWER:** Robert Quick, Chemist

Risk Assessment & Science Support Branch

Antimicrobials Division (7510C)

**THROUGH:** Norm Cook, Chief

Risk Assessment & Science Support Branch

Antimicrobials Division (7510C)

**TO:** Kathryn Avivah Jakob, Chemical Review Manager

Regulatory Management Branch

Antimicrobials Division (7510C)

**PC CODES:** 035603

**DP BARCODES:** D322616

**I. Introduction**

**2-(Thiocyanomethylthio)benzothiazole (TCMTB) Dietary Exposure**

The Antimicrobials Division has assessed the potential antimicrobial
dietary exposure to the active ingredient
2-(Thiocyanomethylthio)benzothiazole (TCMTB). The dietary exposure use
for this chemical results from a pulp and paper use.

The paper uses for TCMTB include uses as a slimicide, a wood chip use, a
bacteriostatic paper use, a paper adhesive preservative use and an
agricultural mulch paper use. The registrant stated at the SMART meeting
that he plans to cancel the wood chip use, bacteriostatic paper use and
the agricultural mulch paper use. There is a use for wood treatment but
the registrant states that the use is not intended for fruit and
vegetable packing crates.

There is a Food & Drug Administration (FDA) regulation for the use of
TCMTB as a slimicide (21 CFR 176.300).

21 CFR 176.170 relates to "Components of paper and paperboard in contact
with aqueous and fatty foods". The 21 CFR 176.170 (a)(4) states, "
Substances that by regulation in Parts 170 through 189 of this chapter
may be safely used without extractives limitations as components of the
uncoated or coated surfaces of paper or paperboard in contact with
aqueous or fatty food, subject to the provisions of such regulation".
Our AD interpretation of this paragraph (personal communication between
Mr. Dennis Edwards, RMB I Branch Chief and Robert Quick, RASSB) is that
this paragraph would also permit TCMTB to be used as a paper coating
that is permitted to contact aqueous or fatty food.

2-(Thiocyanomethylthio)benzothiazole (TCMTB) can be used to preserve
paper-coating formulations. Several labels bear paper coating uses but
the use rate for application to the coating is unclear. Example: EPA
Reg.# 1448-37. The label states: *"Rate of application will vary per
coating rate."* **[The registrant must clarify the labeling to show the
label rates(ranges) for the paper coating uses.]{.underline}**

The registrant has been requested by the CRM, Kathryn Avivah Jakob, to
clarify the use pattern for coatings. In the registrant's latest e-mail
response dated 12/14/2005, the registrant states, "It might be more
efficient to put limitations in the label use directions in which text
is added stating in effect of 'Not for use in coatings intended for food
contact'. Will this suffice?" AD does not consider label restrictions
such as, "Not for food contact use", to be practical. **AD would
consider a label restriction(s) for paper that defines the type of paper
that is to be treated; e.g., use sites such as wallboard paper,
insulation backing, newsprint, photographic paper, drawing paper, etc.
for label restrictions that preclude food contact as practical. These
types of paper are not likely to be used for food contact.**

**The registrant could also revise the slimicide use on the labels in
the same manner that AD has suggested above for the paper coating use;
i.e. define the type of paper that is to be treated. This would help
preclude food contact with TCMTB-treated paper.**

There are agricultural food uses for TCMTB which are for seed treatment
uses to a variety of crops. These agricultural food uses will be
reviewed by the Health Effects Division.

The chemical, 2-mercaptobenzothiazole, is the main mammalian metabolite
of TCMTB (Timothy McMahon memo dated 12/22/2005). This chemical and its
sodium and potassium salts are also permitted for use as slimicides by
the Food & Drug Administration in pulp and papermaking (21 CFR 176.300).
Residues of this chemical may also be present as a result of this use of
TCMTB in papermaking. See **Other Issues** below.

**II. Dietary Exposure for TCMTB**

[Slimicide Use]{.underline}

As regulated under 21CFR 176.300, TCMTB can be used for controlling
bacteria, fungi and yeasts which cause deterioration of paper and
paperboard products. Dietary exposure to TCMTB as a slimicide in these
paper mill systems were estimated using the following assumptions:

-   The slimicide is added to the pulp slurry at a maximum application
    rate of 2.0 lbs of slimicide per ton of dry fiber produced, which is
    equivalent to 1.2 lbs of TCMTB per 2000 lbs of paper (EPA Reg. No.
    1448-37 is 60.0% ai). Since there is no control over how the paper
    will be used in commerce, AD assumes that all paper can contact food
    and have therefore assessed the dietary exposure using maximum
    application rate which comes from the non-food use. Since paper pulp
    is diluted with water to form the paper slurry, the application rate
    must be adjusted to account for only the pulp/paper present in the
    slurry. Prior to entering the paper machine, the paper slurry
    consists of less than 1% paper pulp. Therefore, the adjusted
    application rate was 6.0 ppm (or μg ai/g pulp).

-   Prior to entering the driers, the slurry consists of 33% pulp and
    67% water. The application rate was further adjusted to account for
    the amount of pulp present in the finished paper.

-   The finished paper (after paper making) contains 92% pulp and 8%
    water.

-   The standard basis weight of paper is 50 mg/in^2^.

-   The amount of food contacting the paper packaging is 10 g of
    food/in^2^ of paper.

-   The consumption factor (percentage of food packaging that contacts
    food) is 10%.

-   There is 100% migration of TCMTB from the treated paper into food.

-   Adult food consumption is 3 kg/day; child food consumption is 1.5
    kg/day.

-   Adult body weight is 70 kg for a male; 60 kg for a female and 15 kg
    for a child.

Calculations:

Determination of the application rate in terms of ai and finished paper
is:

Application rate on label:

> 1.2 lbs ai/2000 lbs of finished paper

Pulp slurry (e.g., water/paper pulp mixture) is 1% pulp therefore,

> 2000 lbs paper/0.01 = 200,000 lbs of slurry

1.2 lbs ai/200,000 lbs of slurry = 6.0 ppm of ai in the slurry

Conc. of ai in the pulp prior to entering the driers is:

> Adjusted application rate x water/pulp ratio
>
> (6.0 μg ai/g slurry water) x (67 g water/33 g pulp) = 12.2 μg ai/g
> pulp

Conc. of ai in the finished paper is:

> Adjusted application rate x percentage of pulp in finished paper:
>
> (12.2 μg ai/g pulp) x (0.92 g pulp /g finished paper) = 11.2 μg ai/g
> paper

Determination of dietary concentration:

App rate x Basis paperweight x Surface area contacting food x
Consumption factor x % migration

(11.2 μg ai/g paper) (0.05 g paper/in^2^ paper) (in^2^ paper/10 g food)
(0.1) (100%) =

0.0056 μg ai/g food or 5.6 ppb

Determination of the Estimated Daily Intake (EDI):

Dietary conc. x Daily food consumption

Adult: (0.0056 μg ai/g food) (3000 g food /day) = 16.8 μg ai/person/day

Child: (0.0056 μg ai/g food) (1500 g food /day) = 8.4 μg ai/person/day

Determination of the Daily Dietary Dose:

EDI / Body Weight

Adult: (16.8 μg ai /day) (mg/1000 μg) / (70 kg) = 0.00024 mg ai/kg
bw/day

Adult: (16.8 μg ai /day) (mg/1000 μg) / (60 kg) = 0.00028 mg ai/kg
bw/day

# Child: (8.4 μg ai/day) (mg/1000 μg) / (15 kg) = 0.00056 mg ai/kg bw/day

[Paper Coating Preservative Use]{.underline}

The label use appears to permit the use of coated paper for both dry and
wet food.

2-(Thiocyanomethylthio)benzothiazole (TCMTB) can be used to preserve
paper-coating formulations. Several labels bear paper coating uses but
the use rate for application to the coating is unclear. Example: EPA
Reg.# 1448-37. The label states: *"Rate of application will vary per
coating rate."* **[The registrant must clarify the labeling to show the
label rates(ranges) for the paper coating uses.]{.underline}**

In the case of EPA Reg. \# 1448-81, label directions state: "To inhibit
the growth of bacteria and fungi in paper making additives (including
alum solutions, animal glue solutions, pigment slurries, coating
formulations, and starch slurries and solutions) Busan 1009 is added to
these materials in concentrations of 50-400 ppm (weight/weight)".The
calculations for TCMTB residues in the paper coating and in food are:

Dietary exposures to TCMTB from this formulation were estimated using
the following assumptions:

-   The preservative is added to paper coating formulations at a maximum
    application rate of 400 ppm, which is equivalent to 40 ppm on an ai
    basis (EPA Reg. No. 1448-81 contains 10.0% ai).

-   The paper coating is approximately 10%, by weight, of paper.

-   The standard basis weight of paper is 50 mg/in^2^.

-   The amount of food contacting the paper packaging is 10 g of
    food/in^2^ of paper.

-   The consumption factor (CF) (percentage of daily diet expected to
    contact paper coatings) is 20%.

-   There is 100% migration of TCMTB from the treated paper into food.

-   Adult food consumption is 3 kg/day; child food consumption is 1.5
    kg/day.

-   Adult body weight is 70 kg for a male and 60 kg for a female; child
    body weight is 15 kg.

In the case of EPA Reg.# 1448-81, the calculations for TCMTB residues in
the paper coating and in food are:

Calculations:

Determination of dietary concentration:

App rate x % of paper that is coating x Basis paperweight x Surface area
contacting food x Consumption factor x % migration

(40 μg ai/g coating) (0.10 g coating/g paper) (0.05 g paper/in^2^ paper)
(in^2^ paper/10 g food) (0.2) = 0.004 μg ai/g food or 4.0 ppb

Determination of the Estimated Daily Intake (EDI):

Dietary conc. x Daily food consumption

Adult: (0.004 μg ai/g food) (3000 g food /day) = 12.0 μg ai/person/day

Child: (0.004 μg ai/g food) (1500 g food /day) = 6.0 μg ai/person/day

Determination of the Daily Dietary Dose:

EDI / Body Weight

Adult: (12.0 μg ai /day) (mg/1000 μg) / (70 kg) = 0.00017 mg ai/kg
(0.17ppb) bw/day

Adult: (12.0 μg ai /day) (mg/1000 μg) / (60 kg) = 0.0002 mg ai/kg (0.2
ppb) bw/day

Child: (6.0 μg ai/day) (mg/1000 μg) / (15 kg) = 0.0004 mg ai/kg (0.4
ppb) bw/day

# [Paper Adhesive Preservative Use]{.underline}

Several labels claim that TCMTB can be used to preserve paper-adhesive
formulations. However, it does not appear that this use has been cleared
by the US FDA under 21 CFR175.105. Although the adhesive use has not
been officially cleared by US FDA, it was included in this assessment in
order to determine the total dietary exposure from all paper uses.
Dietary exposures to TCMTB from this type of use were estimated using
the following assumptions:

-   Based on FDA's guidance document, it was assumed that a chemical
    used as "an adhesive or adhesive component in accordance with the
    limitations of 21CFR175.105, migration levels for the substance
    generally will be assumed to be no greater that 50 ppb. Applying a
    CF (consumption factor) of 0.14 for adhesives gives a dietary
    concentration of 7 ppb" (US FDA, 2002). Note: CF is the percentage
    of daily diet expected to contact paper adhesives.

-   Adult food consumption is 3 kg/day; child food consumption is 1.5
    kg/day.

Adult body weight is 70 kg for a male, 60 kg for a female and for a
child 15 kg.

Calculations:

Determination of the Estimated Daily Intake (EDI):

Dietary conc. x Daily food consumption

Adult: (0.007 μg ai/g food) (3000 g food /day) = 21.0 μg ai/person/day

Child: (0.007 μg ai/g food) (1500 g food /day) = 10.5 μg ai/person/day

Determination of the Daily Dietary Dose:

EDI / Body Weight

Adult: (21.0 μg ai /day) (mg/1000 μg) / (70 kg) = 0.00030 mg ai/kg
bw/day

Adult: (21.0 μg ai /day) (mg/1000 μg) / (60 kg) = 0.00035 mg ai/kg
bw/day

#  Child: (10.5 μg ai/day) (mg/1000 μg) / (15 kg) = 0.0007 mg ai/kg bw/day

**TABLE 1**

Cumulative Estimated Dietary Intake of TCMTB

+----------------+---------------+------------------+-----------------+
| **Use**        | **Dietary     | **Estimated      | **Daily Dietary |
|                | Conc.**       | Daily Intake**   | Dose**          |
|                |               |                  |                 |
|                | **(ppb)**     | **(              | **(mg/kg        |
|                |               | μg/person/day)** | bw/day)**       |
+----------------+---------------+------------------+-----------------+
| Pulp/Paper     | 5.6           | 16.8 (adult M)   | 0.00024(adult)  |
| Slimicide      |               |                  |                 |
|                |               | 16.8 (adult F)   | 0.00028 (adult) |
|                |               |                  | 0.00056 (child) |
|                |               | 8.4(child)       |                 |
+----------------+---------------+------------------+-----------------+
| Paper Coating  | 4             | 12 (adult M)     | 0.00017 (adult) |
| Preservative   |               |                  |                 |
|                |               | 12 (adult F)     | 0.0002 (adult)  |
|                |               |                  |                 |
|                |               | 6 (child)        | 0.0004 (child)  |
+----------------+---------------+------------------+-----------------+
| Paper Adhesive | 7             | 21 (adult M)     | 0.00030 (adult) |
|                |               |                  |                 |
| Preservative   |               | 21 (adult F)     | 0.00035 (adult) |
|                |               |                  |                 |
|                |               | 10.5 (child)     | 0.0007 (child)  |
+----------------+---------------+------------------+-----------------+
| Cumulative     | 16.6          | 49.8 (adult)     | 0.00071(adult   |
|                |               |                  | M)              |
|                |               | 24.9 (child)     |                 |
|                |               |                  | 0.00083 (adult  |
|                |               |                  | F)              |
|                |               |                  |                 |
|                |               |                  | 0.0017 (child)  |
+----------------+---------------+------------------+-----------------+

Utilizing the acute RfD or aPAD of 0.25 mg/kg day taken from the Timothy
McMahon memo dated 12/22/2005, the dietary risks were estimated and
summarized in Table 2.

Utilizing the chronic RfD or cPAD of 0.013 mg/kg day taken from the
Timothy McMahon memo, the dietary risks were estimated and summarized in
Table 2.

> **TABLE 2**

Dietary Risks of TCMTB

+-----------------+-----------------+-----------------+-----------------+
| **USE**         | **Daily         | **% aPAD**      | **%cPAD**       |
|                 | Dietary**       |                 |                 |
|                 |                 |                 |                 |
|                 | **Dose**        |                 |                 |
|                 |                 |                 |                 |
|                 | **(mg/kg        |                 |                 |
|                 | bw/day)**       |                 |                 |
+-----------------+-----------------+-----------------+-----------------+
| Pulp/Paper      | 0.00024 (adult  | 0.096 (adult M) | 1.8 (adult M)   |
|                 | M)              |                 |                 |
| Slimicide       |                 | 0.11 (adult F)  | 2.2 (adult F)   |
|                 | 0.00028 (adult  |                 |                 |
|                 | F)              | 0.22 (child)    | 4.3 (child)     |
|                 |                 |                 |                 |
|                 | 0.00056 (child) |                 |                 |
+-----------------+-----------------+-----------------+-----------------+
| Paper Coating   | 0.00017 (adult  | 0.07 (adult M)  | 1.31 (adult M)  |
| Preservative    | M)              |                 |                 |
|                 |                 | 0.08 (adult F)  | 1.54 (adult F)  |
|                 | 0.0002 (adult   |                 |                 |
|                 | F)              | 0.16 (child)    | 3.08 (child)    |
|                 |                 |                 |                 |
|                 | 0.0004 (child)  |                 |                 |
+-----------------+-----------------+-----------------+-----------------+
| Paper Adhesive  | 0.00030 (adult  | 0.12 (adult M)  | 2.3 (adult M)   |
| Preservative    | M)              |                 |                 |
|                 |                 | 0.14 (adult F)  | 2.7 (adult F)   |
|                 | 0.00035 (adult  |                 |                 |
|                 | F)              | 0.28 (child)    | 5.38 (child)    |
|                 |                 |                 |                 |
|                 | 0.0007 (child)  |                 |                 |
+-----------------+-----------------+-----------------+-----------------+
| Cumulative      | 0.00071 (adult  | 0.29 (adult M)  | 5.41 (adult M)  |
|                 | M)              |                 |                 |
|                 |                 | 0.33 (adult F)  | 6.44 (adult F)  |
|                 | 0.00083 (adult  |                 |                 |
|                 | F)              | 0.66 (child)    | 12.8 (child)    |
|                 |                 |                 |                 |
|                 | 0.0017 (child)  |                 |                 |
+-----------------+-----------------+-----------------+-----------------+

**[Other Issues]{.underline}**

1\. The chemical, 2-mercaptobenzothiazole, is the main mammalian
metabolite of TCMTB (Timothy McMahon memo dated 12/22/2005). This
chemical and its sodium and potassium salts are also permitted for use
as slimicides by the Food & Drug Administration in pulp and papermaking
(21 CFR 176.300). Residues of this chemical may also be present as a
result of this use of TCMTB in papermaking.

**The registrant must address the question of whether the use of TCMTB
in pulp and papermaking will result in residues of
2-mercaptobenzothiazole in paper produced using TCMTB and provide
information on the level of 2-mercaptobenzothiazole that will occur in
paper.**

**The EPA OPPIN reference does not show any active registrations for
2-mercaptobenzothiazole.**

2\. The registrant must clarify the labeling to show the label rates
(ranges) for the paper coating uses.

3\. In the registrant's latest e-mail response dated 12/14/2005, the
registrant states, "It might be more efficient to put limitations in the
label use directions in which text is added stating in effect of 'Not
for use in coatings intended for food contact'. Will this suffice?" AD
does not consider label restrictions such as, "Not for food contact
use", to be practical. AD would consider a label restriction(s) for
paper that defines the type of paper that is to be treated; e.g., use
sites such as wallboard paper, insulation backing, newsprint,
photographic paper, drawing paper, etc. for label restrictions that
preclude food contact as practical. These types of paper are not likely
to be used for food contact.

The registrant could also revise the slimicide use on the labels in the
same manner that AD has suggested above for the paper coating use; i.e.
define the type of paper that is to be treated. This would help preclude
food contact with TCMTB-treated paper.