August 2, 2006

MEMORANDUM

SUBJECT:	DIETARY RISK ASSESSMENT FOR CHLORINE DIOXIDE AND SODIUM
CHLORITE INDOOR USES AS DISINFECTANTS/SANTIZERS 

From:		A. Najm Shamim, Ph.D, Chemist

		Regulatory Management Branch II

		Antimicrobials Division (7510P)

To:		ShaRon Carlisle,  CRM for Chlorine Dioxide/Sodium Chlorite RED

		Regulatory Management Branch II

		Antimicrobials Division (7510P)

				And

Melba Morrow, D.V.M,  Risk Assessor for Chlorine Dioxide/Sodium Chlorite
RED	

Antimicrobials Division (7510P)

Thru:		Diane Isbell, Team Leader RMBII

		Regulatory Management Branch II

		Antimicrobials Division (7510P)

				

				And

Mark Hartman, Chief

		Regulatory Management Branch II

		Antimicrobials Division (7510C)

Executive Summary

Antimicrobials Division has determined   dietary exposures from chlorine
dioxide /sodium chlorite uses on food contact surfaces, indirect food
contact surfaces, disinfectant use in drinking water,  slimicide use  in
paper/pulp, fruits  and vegetable washes, post-harvest potato treatment.
AD has determined that there are  chronic risks concerns for  less than
one year old infants (cPAD: 145.1%) and non-nursing infants (cPAD:
179.8%) from chlorine dioxide-treated drinking water. 

Background:

In this document Antimicrobials Division has assessed the dietary
exposure and risks due to  the uses of chlorine dioxide and sodium
chlorite in the residential scenarios, sanitizer/disinfectant use on
hard surfaces  resulting in  direct or indirect exposure and risks, 
paper/pulp slimicide use which may result in exposure and risks, and
chlorine dioxide use as disinfectant for  drinking water  and resulting
exposure and risks.

Table 1 summarizes the use/site/application rates for chlorine dioxide
and sodium chlorite.

				Table 1

Use Sites and Application Rates for Chlorine Dioxide and Sodium Chlorite

Use Site	EPA Reg #	Method of Application	 Application Rates

Mushroom Facilities (food contact)	74602-2, 9150-2, 9150-3, 9804-1	Flush
equipment with sanitizing solution	100-200 ppm total available chlorine
dioxide 

Potato Storage: Potato rinse and humidification	9804-5, 5335-20, 21164
Fogger	200-400 ppm

Poultry house disinfection: poultry chiller water/carcass spray	74602-2,
74602-3, 9150-2,  9150-3,  9150-7,  9150-8	Dip carcass	For chiller
water: 50-150 ppm;

For carcass spray: 500-1200 ppm

Egg room/hatching area, incubator room, tray washing room and loading
platform	9150-2, 9150-3, 74602-2	 High pressure spray	20 ppm for pre
wash with sprayer

Chick room, chick grading box and sex room	9150-2, 9150-3, 74602-2,
Fogger, mop	1000 ppm with fogger

Food processing plants (poultry, meat, fish)

Food contact surfaces	9150-2, 9150-3, 9150-7, 9804-1, 9804-9

53345-14, 53345-19	1 minute contact time	200-1000 ppm total available
chlorine dioxide

Dairies, breweries, and bottling plants

Food contact surface sanitizer	9150-2, 9150-3, 9150-7, 9150-8,
53345-14,19, 20, 21, 21164-6,8,9, 9804-9, 74602-2, 5382-46, 74517-1,	1
minute contact time	200-1000 ppm total available chlorine dioxide 

Fruits, vegetables	9150-8	Spray or dip	500-1200 ppm

Fruits and vegetable rinses	9150-2, 9150-3, 9804-1, 9150-7, 9150-8,
45631-22, 45631-19, 53345-20, 	Immersion, spray	5 ppm

Pulp/paper mills	9150-2, 9150-3, 9804-1, 9804-9,  53345-22, 69151-3, 4,
21164, 6,8, 9, 21	None stated	4.5 gallons product per 100 tons of paper:
1.25-5 ppm (3.2 12.8 fluid ounces per 1000 gallons of water)

Potable drinking water	

69151-3,5, 21164-6,8,9,21	

None stated	 

5 ppm



Mushroom House Treatment

Mushrooms: A number of AD use labels  (74602-2, 9150-2, 9150-3, 9804-1)
indicate  the application of chlorine dioxide as a sanitizer  in
mushroom facilities is applied to the equipment used in the processing
of Mushroom rooms (application rate varies between 100-200 ppm), and
method of application is flush equipment); however, any transfer of
residue levels on mushrooms is not indicated.. The Agency at this is not
requiring any tolerances of chlorine dioxide on mushroom uses and or
does not have any exemption  from the requirement  of tolerance it its
regulatory database.  The Agency has not, at this time conducted any
dietary risk assessment for mushroom use of chlorine dioxide as no
dietary risks are indicated.

Fruits and Vegetable Washes

These uses are covered under FDA 21 CFR 173.300(b)(2) for chlorine
dioxide under 21CFR 173.325 for  similar uses of acidified sodium 
chlorite. However, the Agency still conducted dietary exposure
assessment  as the label language was not clear enough. Table II
indicates that the Agency has no  dietary concerns for %cPAD for all
ages.

Label changes similar to the following wording might help reduce the
exposure concerns for fruits and vegetable washes: “Water containing
up to 3 ppm residual chlorine dioxide may be used for washing fruits and
vegetables that are not raw agricultural commodities in accordance  with
the 21 CFR 173.300 Treatment of the fruits and vegetables with chlorine
dioxide must be followed by blanching, cooking or canning.”

AD conducted  chronic  risk assessment for the  fruits and vegetable
washes (post –harvest) with chlorine dioxide and sodium chlorite and
chronic risk risks appear to be below the levels of concerns ( adults:
7.5% cPAD and child between the ages of one and two  years the% cPAD is
42.4%). This includes apple and orange juices..

If the suggested label changes as stipulated above are made by industry,
it is likely the levels of concerns  (% cPAD) for all populations,
including one to two years old children would reduce drastically.

				Table II

Reference dose (RfD, Chronic) = 0.03 mg/kg bw/day

COMMENT 1: All Fresh Fruit and Vegetables, including apple and orange
juices

         Total exposure by population subgroup

------------------------------------------------------------------------
--

                                                    Total Exposure

                                        		--------------------

          		Population                         mg/kg            

 Percent of   

           		Subgroup                       body wt/day             Rfd 
     

--------------------------------------   -------------      

U.S. Population (total)                     0.003292               
11.0%

U.S. Population (spring season)             0.003315               
11.1%

U.S. Population (summer season)             0.003568               
11.9%

U.S. Population (autumn season)             0.003138               
10.5%

U.S. Population (winter season)             0.003145               
10.5%

Northeast region                            0.004045               
13.5%

Midwest region                              0.003062               
10.2%

Southern region                             0.002774                
9.2%

Western region                              0.003686               
12.3%

Hispanics                                   0.004079               
13.6%

Non-hispanic whites                         0.003120               
10.4%

Non-hispanic blacks                         0.003100               
10.3%

Non-hisp/non-white/non-black                0.004787               
16.0%

All infants (< 1 year)                      0.003493               
11.6%

Nursing infants                             0.001821                
6.1%

Non-nursing infants                         0.004128                

42.6%

3.		DRINKING WATER EXPOSURE ASSESSEMNT

Chlorine dioxide is used as a disinfectant in water treatment plants in
the USA. Chlorite ion (ClO2-) is present in drinking water and there are
two possible ways it ends up in the drinking water: First, chlorine
dioxide is produced via sodium chlorite used as a starting material and
incomplete conversion of sodium chlorite into chlorine dioxide leaves
residual chlorite ion in water and second, a major breakdown product of
chlorine dioxide in water is chlorite ion. Because of the health
concerns of the presence of chlorite ion and its subsequent  conversion
to chlorate ion, Agency  wanted to make sure that the presence of
chlorite ion did not exceed  certain limits. In 1996  USEPA instituted 
Information Collection rule (ICR) and most extensive monitoring data on
the occurrence of chlorite ion in drinking water was collected between
July 1997 to December  1998. 

Public Water Systems (PWSs) serving a population of at least 100,000 to
report, under ICR , treatment plant design and operational data and
conduct monitoring for specific microbial contaminants and disinfection
byproducts like chlorite ion .Chlorine dioxide treating plants conducted
monthly monitoring for chlorite ion concentration in samples of finished
water leaving the plant as well as three sample points in the
distribution system: near  the first customer, an average residence time
and a maximum residence time. 

Monitoring data were collected  from 22 water systems using chlorine
dioxide treatment (29 treatment plants) The minimum reporting level
(MRL) was established at 20 µg/L . all samples below this value were
considered zero. Data from 418 samples (point of entry to the
distribution) showed chlorite ion concentration ranged from 20 µg/L to
2,029 µg/L. Data from 1,115 samples ( collected from within the
distribution system) showed the concentration of chlorite ion between 20
µg/L to 1,850 µg/L.  The average concentration of chlorite ion from
27/29 treatment plants when averaged from the three distribution system
sample points (first customer, average residence time and maximum
residence time) ranged from 20µg/L to 801 µg/L.

Based on the results from this ICR monitoring data, the Agency in 1998
established a stage  1  Disinfectant/Disinfectant Byproduct Rule (Stage
1 DBPR) which established a maximum contaminant level goal (MCLG) and
maximum contaminant level (MCL) for chlorite ion: 0.8 mg/L and 1.0 mg/L
respectively.

Based on the ICR Rule for the MCL of chlorite ion, treatment plants
using chlorine dioxide as the disinfectant treatment, are required to:
1) conduct monthly monitoring at three sample points in the distribution
system. Compliance is met if the average chlorite ion concentration does
not exceed 1.0 mg/L. Compliance is determined monthly. 2) Water plants,
in addition to monthly monitoring, must also analyze daily samples of
water entering the distribution system. Chlorite ion concentration must
not exceed 1.0 mg/L If the entry point data shows the exceedence from
1.0 mg/L, the water treatment system must sample at three distribution
system sample points within 24 hours and verify that the chlorite ion
concentration has not exceeded 1.0 mg/L.

g/L) - ICR Data Adjusted for MCL Compliance

	

	Chlorine Dioxide Water Treatment Plants (WTPs)

	Distribution System Entry Point	Near First Customer	Average Residence
Time	Maximum Residence Time	Distribution System Average2

10th Percentile	60	52	58	30	45

20th Percentile	99	79	87	81	84

50th Percentile	440	380	360	310	390

80th Percentile	590	580	600	510	550

90th Percentile	660	660	640	650	630

Maximum	800	740	680	680	700

# WTPs	29	27	27	27	27

# PWSs	22	21	21	21	21



The Agency conducted a drinking water risk assessment  using 90th
percentile annual average of 0.630 mg/L,  following exposure values are
obtained (Memo by David Herdy (HED) to Jennifer Slotnick (AD):

				Table IV

90th percentile annual avg = 0.630

Reference dose (RfD, Chronic) = .03 mg/kg bw/day

NOEL (Chronic) = .03 mg/kg bw/day

       Total exposure by population subgroup

--------------------------------------------------------

                                                    Total Exposure

                                        
-----------------------------------

          Population                         mg/kg       Margin of  
Percent 

           Subgroup                       body wt/day   Exposure 1/  

of RfD 

--------------------------------------   -------------  ---------- 
---------

U.S. Population (total)                     0.013279            2    

		   44.3%

U.S. Population (spring season)             0.013162            2      
43.9%

U.S. Population (summer season)             0.014264            2      
47.5%

U.S. Population (autumn season)             0.012836            2      
42.8%

U.S. Population (winter season)             0.012838            2      
42.8%

Northeast region                            0.012113            2      
40.4%

Midwest region                              0.013425            2      
44.7%

Southern region                             0.012622            2      
42.1%

Western region                              0.015214            2      
50.7%

Hispanics                                   0.015073            2      
50.2%

Non-hispanic whites                         0.012955            2      
43.2%

Non-hispanic blacks                         0.012605            2      
42.0%

Non-hisp/non-white/non-black                0.016279            2      
54.3%

All infants (< 1 year)                      0.043535            1     
145.1%

Nursing infants                             0.016146            2      
53.8%

Non-nursing infants                         0.053927            1     
179.8%

Children 1-6  yrs                           0.018552            2      
61.8%

Children 7-12 yrs                           0.012062            2      
40.2%

Females 13-19 (not preg or nursing)         0.009344            3      
31.1%

Females 20+ (not preg or nursing)           0.013255            2      
44.2%

Females 13-50 yrs                           0.012846            2      
42.8%

Females 13+ (preg/not nursing)              0.012912            2      
43.0%

Females 13+ (nursing)                       0.018397            2      
61.3%

Males 13-19 yrs                             0.009770            3      
32.6%

Males 20+ yrs                               0.011898            3      
39.7%

Seniors 55+                                 0.013036            2	 43.5%

Children 1-2 yrs                            0.019719            2      
65.7%

Children 3-5 yrs                            0.018460            2      
61.5%

Children 6-12 yrs                           0.012733            2      
42.4%

42.4%

Youth 13-19 yrs                             0.009599            3      
32.0%

Adults 20-49 yrs                            0.012398            2      
41.3%

Adults 50+ yrs                              0.013044            2      
43.5%

Females 13-49 yrs                           0.012347            2      
41.2%

EPA’s Office of Water also determined (Memo by Pat Fair, OW to
Jennifer Slotnick, AD) that: a) Overall percent of water treatment
plants using ClO2 as a disinfectant is low (~ 6%) and b)Exceedences from
monitoring data can not be generalized to all populations. tc "5.4
Drinking Water Exposures and Risks " \l 2 

In addition, the Agency subsequently has reviewed additional study on:
a) Determination of Chlorite in Baby Formula Prepared From Water
Containing Residual Chlorite ( by T.V. Tran, Report #: TR05-01) The
Agency does agree generally with the conclusions of the studies that: 1)
the components of the baby formula, including vitamin C,  do react with
the chlorite in drinking water and may not be available  in drinking
water or baby formula formulated with drinking water;  however, at this
time the Agency has no quantitative tool (a model etc.) to assess the
extent of reduction in  exposure to chlorine dioxide from specific
chemicals  present in baby formula. Due to these uncertainties, the
Agency believes  that  for all infants (< 1 year old) as well as 
non-nursing infants (< 1 year old), the % cPAD may likely  be less than
100.

Poultry Hatcheries:

AD label searches  ( EPA Reg#: 9150-2, 9150-3) indicates that chlorine
dioxide  is used   in poultry hatching area, incubator room, tray
washing room and loading platform  as disinfectant. High pressure
sprayer is used to deliver the chemical @  rate of 20 ppm. 

In these poultry hatcheries, eggs are produced  for the production of
chicks and not for human consumption and although it is likely some of
sanitizer/disinfectant chemicals may penetrate the egg shells and
bioaccummulate in the developing chicks, at this time the Agency
believes that the amount of the chemical transferred to the developing
chicks is not likely to adversely affect in the development of chicks
and will have even a smaller transfer into humans. 

A similar label searches ( EPA Reg#: 74602-2) indicate the same uses for
sodium chlorite at the same application rate.  The Agency has no
concerns for this use.

The use of chlorine dioxide and sodium chlorite  in poultry hatcheries
can be classified as non-food use. Agency has no concerns at this time
for this use.

Food Handling Establishments:

	Hard Surface  Indirect Food Contact Surfaces

Use of chlorine dioxide and sodium chlorite  on  sites where there is a
likelihood of exposure (and migration ) of these chemicals into food. An
example of direct food contact would be antimicrobials  post-harvest
treatment  of fruits and vegetables. Sanitizing and or disinfecting use
of antimicrobials to hard non-porous  surfaces which come into contact
with food are classified as indirect food contact surfaces. Eating
establishments (food tables), kitchen counter tops etc fall in this
category. 

Using FDA methodology, EPA has  calculated the Estimated Daily Intake
(EDI) of a chemical by using  the relationship:

EDI (mf/kg/day) = AR  x SA  x F (100% or
10%)/BW…………………..(1)

Where: SA = Surface area of the treated hard surface which comes into
contact with food ( fruits, vegetables, meats) = 2000 cm2

AR =  1 mg/cm2 of dilute  product x a.i. (active ingredient) =
application rate

F = Fraction of the pesticide transferred or migrated from the treated
surface into food.  It could be 10% or 100%.

BW = Body weight: adult man = 70 kg; adult woman = 60 kg;  child = 15
kg.

Maximum application rate ( labels: 9150-2, 9150-3, 53345-14, -19, and
-20) = 1000 ppm of chlorine dioxide or sodium chlorite = 1000 µg/1000
mg (ppm)

Using eq. 1:

1000 µg/1000mg(ppm) x 0.10 mg/cm2 x 2000 cm2/ BW

EDI = 200 µg a.i. /BW

  Food consumption  is 3000 g/day: for an adult------------a

Estimated EDI for an adult = 200µg  /g x 1/3000 g a.i./BW

= 0. 0666 µg food/BW

Estimated Daily Dietary Dose for an adult-7

= 0.0666µg/70kg =  0.00095µg /kg/day
------------------------------------ (1)

Food consumption is 1500  g for a child  ------------------------------b

EDI for a child = 200 µg a.i./1500 g /day BW

=  0.1333 µg /day/BW

Estimated Daily Dietary Dose for a child

= 0.1333 µg/15 kg/day

= 0.0088 µg/kg/day  
-----------------------------------------------------(2)

	aPAD and cPAD dietary for chlorine dioxide and sodium chlorite  is the
same: 0.03 mg/kg/day

 1 mg = 1000 µg

Daily Dietary Dose  for an adult= 9.5 x 10-4 µg x 1 mg/1000 µg = 9. 5
x 10-7 mg/kg/day 
------------------------------------------------------------------------
- (3)

Daily Dietary Dose for a child = 8.8 x 10-3 µg x 1 mg/1000µ g = 8.8 x
10-6 mg/kg/day  -

--------------(4)

a or cPAD are 0.03 mg/kg/day

% PAD = exposure /a or c PAD x 100
-------------------------------------------------(5)

For an adult., % a or cPADs are:  9.5 x10-7  mg/kg/day / 0.03 mg/kg/day
x 100 =  3.16 x 10-7 

For a child , % a or c PAD are: 8.8 x10-6 mg/kg/day/0.03mg/kg/day  x 100
= 2.93 x 10-6   

Agency does not  have any concerns from this exposure.

 

6.	Post –Harvest Potato Treatment:

	The Agency has allowed the use of chlorine dioxide  in the form of
spray, mist and fogger in the limit of 200-400 ppm in the post-harvest
treatment of potatoes  places in the storage area before these are sent
out for retail market.( label: 9804-5)

AD had asked  States of Idaho and Washington  to collect the analytical
data on the residues on the chlorine dioxide treated post-harvest
potatoes ( AD Memo by Tim McMahon, and A. Najm Shamim, March, 1998).

A six month residue monitoring  data from chlorine dioxide treatment on 
stored potatoes  (February through July 1999) were submitted in
August/September  , 1999  Analytical Sciences Laboratory, a contracting
lab. 42 samples were (duplicate) were analyzed.

1) 42/42 samples showed  chlorite to be non-detect ( at practical
quantitation limit of 0.1 ppm level)

2) 39/42 samples showed the presence of chlorate below the quantitation
limit of 0.1 ppm and only three samples showed the chlorate level 
between 0.97 to 1.1 µg/g. Both chlorate and chlorite are considered the
breakdown products of chlorine dioxide.

The Agency did not see any concerns for the presence of chlorate at
these levels  in a few samples. 

A Memo by Health Effects Division (Christina Swatrz, 1994)  noted: “
Residue Chemistry data reviews of data submitted in support of existing
tolerance exemptions concluded that there is no likelihood of transfer
of residues (of sodium chlorate) to meat/milk/poultry/eggs). It also
noted that ‘ based on the likelihood of reduction of sodium chlorate
residues through hydrolysis on cooking, and based on a lack of toxicity
concern, and residue levels found on crops during field trials, CBRS (
HED’s Branch), continues to support the existing tolerance exemption.

The Agency has no concerns at this time for use of chlorine dioxide and
sodium chlorite for stored potato treatment and subsequent interstate
commerce of this commodity.

Poultry House Disinfection, Poultry Chiller Water/ Carcass Spray or Dip

Food Contact Surface Sanitizer Use of Chlorine dioxide and Sodium
chlorite: Food Processing Plants (Meat, Fish)

These uses fall under the perview of FDA and not under FIFRA and there
the Agency has decided not to assess these uses.

Dairies, Breweries, Bottling Plants, Food Contact Surfaces (application
rates: 200-1000 ppm)

Labels: 53345-14, 19, 20, 21; 9150-7,8; 21164-6, 8, 9; 74602-2; 
5382-46;  74517-1;  73139-1

The use scenario for this application includes sanitizing food contact
surfaces,  processing equipments, utensils in dairies, breweries,
canning operations, meat and vegetable processing plants.

FDA reviewed a similar application and made a few assumptions ( FDA Memo
by Susan Carberry, Ph.D: HFS-247, Chemistry Review Branch, Document
Number 2B4334, 1993).

We have used the FDA assumptions  for residues and also calculated the
EDI, DDDs, and  percent aPADs  and cPADs based on our toxicity  numbers.

FDA Assumptions: 1)  residue exposure : 1 mg/cm2; 2) Major exposure
scenarios and foods from this application are: brewery, beverage,
egg/mayonnaise industries; 3)  at eaters level, following foods will
have the residues: beer, beverages, egg/mayonnaise products, and milk.
Weight of food/ surface area for some foods are as follows:

Milk (dairy): 			6.6 

Egg/mayonnaise		64

Beer, beverages		150;

weight/ surface are ratios are in g/cm2

4) FDA used the intake data ( 14 day average from MRCA (1982-87) menu
census survey and USDA/NFCS  survey data (1987-1988) for portion sizes.
Following represents the average eaters only  food category and food
intake averages:

Beverages, alcoholic/beer:			182 g/p/d

Beverages,  non-alcoholic			240 g/p/d

Egg products					9 g/p/d

Salad dressing/mayonnaise			6 g/p/d

Milk						124 g/p/d

5) FDA also assumed that there is no loss of chlorine dioxide as a gas,
and  the treatment is 100% with the product present in the formulation.

Calculations:

Using the maximum application rate of 1000 ppm

1000 ppm = 1000 mg/kg x 1 kg/1000g x 1000 µg/1 mg = 1000 µg/g =
1000µg/1000 mg. Using  the assumptions 1 through 4 and data inputs from
above:

Beverages, alcoholic , beer: 

Estimated Daily Intake (EDI) = 1000µ/ 1000mg x 1 mg/cm2  x 182
g/person/day x 1 cm2/150 g = 1.2 µg/person/day
------------------------------1

Beverages, non-alcoholic, 

EDI = 1.6 µg/person/day 
--------------------------------------------------2

Egg products, salad dressing, mayonnaise

EDI = 0.14 µg/person/day
--------------------------------------------------3

Milk

EDI = 19. µ g/person/day 
--------------------------------------------------4

From (1):Adult  Daily Dietary Dose = 1.2 µg/person/day x mg/1000µg =
1.2 x 10-3  mg/person/day x person/70 kg =  1.7 x 10-5 mg/kg/day
------------------1a

Child DDD =  8 x 10-5 mg/kg/day
--------------------------------------------1b

From(2) Adult  Daily Dietary Dose =  1.6 µg/person/day x mg/1000µg =
1.6 x 10-3 mg/person/day x person/70 kg = 2.4 x 10-5 mg/kg/day
-------------------2a

Child DDD =  1.0 x 10-4 mg/kg/day 
------------------------------------------2b

From(3) Adult Daily Dietary Dose = 0.14 µg/person/day x mg/1000µg =
1.4 x 10-4 mg/person/day x person/70 kg = 2.0 x 10-6 mg/kg/day
--------------------3a

Child DDD = 9.33 x 10-5 mg/kg/day
-------------------------------------------3b

From (4) Adult Daily Dietary Dose =19.0 µg/person/day x mg/1000µg =
1.9 x 10-2 

mg/person/day x person/70 kg =  2.7 x 10-4 mg/kg/day
---------------------4a

Child DDD = 6.6 x 10-4 mg/kg/day
----------------------------------------------4b

For chlorine dioxide and sodium chlorite, acute and chronic ( aPAD and
cPAD) are the same, i.e. = 0.03 mg/kg/day
---------------------------------------------------(5)

% aPAD and cPAD are calculated in Table V

				Table V

Food Type	 Daily Dietary Dose (DDD) mg/kg/day)	% a PAD or cPAD

= Exposure (DDD)/ aPAD (or cPAD) x 100

Beverages, alcoholic, beer	Adult: 1.7x10-5

Child: 8x10-5	Adult: 0.56%

Child: 0.26%

Beverages, non-alcoholic	Adult:2.4x10-5

Child: 1.0x10-4	Adult: 0.08%

Child:0.33%

Egg products, mayonnaise	Adult: 2.6x10-6

Child:9.3x10-5	Adult: 0.0086%

Child: 0.31%

Milk	Adult: 2.7x10-4

Child:6.6x10-4	Adult: 0.66%

Child:2.2%



None of the % PADs exceed 100 and hence Agency does not have any concern
for uses in these sites and at the level of applications.

	

Chlorine Dioxide and Sodium Chlorite’s antimicrobials uses include: 
slimicide  use in paper/pulp. AD has, therefore, assessed the potential
dietary exposure to such uses applying the FDA methodologies.

	 AD’s label searches identified a number of chlorine dioxide and/or
sodium chlorite products use as slimicides in the manufacture of
pulp/paper products. Label of SLEME-TROL RX-33 ( EPA Reg#: 74655-2) 
showed highest concentration of sodium chlorite (25%) at use level . The
application rate is 2 lbs/ton of finished paper. Same label shows that
in polymer slurries preservative in paper coatings and as adhesives in
paper products, the maximum amount of chlorine dioxide /sodium chlorite
is 1000 ppm of the active. The Agency has note that at the use sight,
sodium chlorite generates chlorine dioxide. Hence whether  the label is
that of chlorine dioxide or  sodium chlorite, these are treated as one
and the same.

10.	Dietary Exposures and Risks Resulting From Use of Chlorine
Dioxide/Sodium Chlorite as Slimicides in Paper/Pulp Products (Indirect
Food  Additives).

	FDA  Method makes a number of assumptions for calculating migration of
actives (chlorine dioxide/sodium chlorite) from food contact surfaces
(paper): 1. Food contact surface (paper) can be a one time use/day or a
repeat use material; 2. Consumption factor (CF) or fraction of daily
food which comes in to contact with the packaging surface (paper). CF
represents the actual weight of food that comes into contact with the
paper to the weight of all food packaged with paper; 3. The CF varies
from one type of packaging (type of paper) to the other (type of paper).
FDA methodology of migration of active assumes a 100% migration to the
food commodities (This represents a worst case scenario).

		

						

I	Data Input Parameters for Chlorine Dioxide and Sodium Chlorite Used as
Paper Slimicide

		Rate of Application of Active: Maximum of 2 lbs Chlorine
dioxide/sodium chlorite/ton of paper ( = 1.0  kg/1000 kg of paper)

		Paper slurry: Prior to entering paper manufacturing machine: 1% ( 99%
water and 1% pulp). This is  an FDA assumption

		Concentration of Slurries Entering Driers: 33% pulp and 67% water (FDA
Assumption)

		Standard Paper Weight: 50 mg/in2 (FDA Assumption)

		Finished Paper: 8% water and 92% pulp ( RASSB Memo by Bob Quick, based
on FDA Assumption)4

		Mass of Food in Contact with Surface Area of Treated Paper: 10 g/in2
(FDA Assumption)

		Consumption Factor (CF)  for Treated Paper ) 0.10 ( FDA Assumption)

		Daily Average Food Intake (Adult) = 3000 g

		Daily Average Food Intake (Child) = 1500 g

	Calculations:

		As the active is only 25%, from parameters 1 & 2 above, 2 lb/ton paper
= 0.5 lbs/1000 lbs paper or 1 lb active = 2000 lbs paper =  200,000 lb
slurry x 1% paper slurry = 1 lb/2000 lbs of finished paper = 2. 5 ppm of
active in the paper slurry. (This is derived from FDA assumption).

		From in put parameter 3, the concentration of the active (Chlorine
dioxide/sodium chlorite) present in the pulp prior to entering the
driers: Application Rate x % water/ % pulp

= 2.5 ppm active =2. 5 g active/g pulp slurry x 0.67 water/0.33 g
pulp = 5 µg active/g pulp.

	OUTPUT:

	

Based on input parameters	 1 through 7 and calculations a and b, the
outputs are:

		1a: Concentration of Chlorine dioxide/sodium chlorite in Food:

µg of chlorine dioxide/sodium chlorite/mass of pulp x mass of pulp/mass
of paper x standard mass of paper x mass of food/surface area
---------------------------------------------------------i

5 µg chlorine dioxide/sodium chlorite/mass of pulp x 0.92 g pulp/g of
paper x 0.05 g/in2 x 1 in2 /10 g food

		= 0.023 µg of  chlorine dioxide/sodium chlorite/g food

Taking into account of CF 0f 0.10, the actual dietary concentration of
chlorine dioxide/sodium chlorite in daily diet would be: 0.023 µg
chlorine dioxide/sodium chlorite/g food x 0.10 = 0.0023 µg of active/g
food -----ii

1b.	Estimated Daily Intake (EDI) for an Adult = 0.0023 µg of chlorine
dioxide/sodium chlorite/ g food x 3000 g food = 6.9 µg chlorine
dioxide/sodium chlorite/person/day -----------------------iii

		1c.	Estimated Daily Intake (EDI) for a Child = 0.0023 µg of chlorine
dioxide /sodium chlorite/g food x 1500 g food = 3.45 µg chlorine
dioxide/sodium chlorite/person/day -----------------------------iv

Estimated Daily Dietary Dose:

EDI/Body Weight:

Adult: 6.9µg x mg/1000µg / 70 kg/day =   9.8 x 10-5  mg/kg BW/day

Child:  3.45 µg x mg/1000µg /15 kg /day =	2.3 x 10-4 mg/kg BW/day

According to the Agency’s memo ( Memo by EPA’s  Wanda Henson to 
Hercules Incorporated’s Kathryn Ingram, May 9th, 2006) Agency has
accepted the following  label change from the label SLIME-TROL RX 33 (
USA EPA Reg #: 74655-2): “ Deletion of Preservation Section”. The
Preservation Section stated: “This product should be added to the
material to be  preserved prior to manufacturing into finished product
i.e. pul, broke, polymer, defoamer, alum, emulsions, adhesives, paper
mill coatings, pigment slurries and paper products….”

Based on this information, the Agency has decided to exclude the dietary
assessment for: 

Polymer Slurries as Filler in Paper, Chlorine Dioxide and Sodium
Chlorite Use as Paper Adhesive Preservative, and Chlorine Dioxide and
Sodium chlorite Use as Paper Coating Preservative 



			

Table VI.  Summary of Dietary Exposure and Risk for Chlorine Dioxide

Use Site	Food Type	Population Subgroup	EDI (mg/person/day)	Chronic
Dietary





Dietary Exposurea (mg/kg/day)	% cPAD b

Indirect Food Use

Food handling establishments/ kitchens	NA	Adult	2.00 x 10-1	9.5E-07
0.00316



Child

8.8E-06	0.0293

Dairies, Breweries, Bottling Plants, Food Contact Surfaces/Food
Processing Plants for Meats and Fishd	Beverages, alcoholic, beer	Adult
1.2 x 10-3	1.70E-05	0.56

	Beverages, non-alcoholic	Adult	1.6 x 10-3	2.40E-05	0.08



Child

1.00E-04	0.33

	Egg Products, Mayonnaise	Adult	1.4 x 10-4	2.00E-06	0.0086



Child

9.33E-06	0.031

	Milk	Adult	1.9 x 10-2	2.70E-04	0.66



Child

1.30E-03	4.2

Pulp/Paper, Polymer Slurries, Paper Adhesive, Paper Coating	NA	Adult	1.1
x 10-1	9.8E-05	0.326 



Child

2.3E-04	0.766

Total Indirect Food-Contact Exposure	Adult	3.3 x 10-1	4.12E-04	1.64

	Child

1-2 years	2.7 x 10-1	1.65E-03	5.35

	Infant

<1

	<5.35 f

Direct Food Use

Post Harvest Application 	Fruit and Vegetable Wash	Adult	 	2.24E-03c,
e	7.5



Child	 	1.27E-02 c, e	42.3

Total Direct Food-Contact Exposure	Adult	 	2.24E-03	7.5

	Child

1-2 years 	 	1.27E-02	42.3g

	Infant

<1

3.49E-03	11.6 f

Inorganic Chlorate Use

Highest Exposure from 

Agricultural Use	Child 

1 – 2 years

	 	8.38E-03c	28

	Infant 

<1 year

4.511E-03	15 f

Total Dietary Exposure

Total Direct and Indirect Food-Contact Exposure	Adult	 	2.65E-03	9.1

	Child 

1-2 years	 	2.27E-02	75.7

	Infant

<1 year

	<31.95 f

a-- For adults, acute and chronic exposure analysis is based on a body
weight of 70 kg.  For adult females, the body weight is 60 kg.  For
children, exposure is based on a body weight of 15 kg.  

b--%PAD = dietary exposure (mg/kg/day) * 100 / cPAD, where cPAD for
adults and children = 0.03 mg/kg/day;   

c--children 1-2 years of age, adults 20-49 years of age

d--food processing plants for meats/fish have exposures which are
similar to other food contact surfaces, exposure numbers not included
for this scenario.

e-- includes all fruits and vegetables and apple and orange juices;
assumes 100% of fruit is washed with chlorine dioxide.

f--Infants (<1 year) are included in this table for comparison purposes
and were not added to the total dietary exposure as it was not the most
highly exposed subpopulation.

g--Assuming 50% of fruits/vegetables are treated, the dietary risk for
children (1 – 6) would represent 21% of the cPAD.

Formation of Chlorate From Chlorine Dioxide, Sodium Chlorite, Sodium and
Calcium Hypochlorites and Dietary Risks

The main source of chlorate ion exposure in the environmental media
(soil, water, animal or humans and in food) is through the agricultural
applications of sodium chlorate. However, it is likely that some
chlorate in these media is formed/found through antimicrobial
applications (disinfectant) of chlorine dioxide, sodium chlorite, and
sodium/calcium hypochlorites.

In aqueous media, these oxyanions(chlorite, chlorate, hypochlorite)
exist because of the unique chemistry of chlorine which has a chemical
tendency to change its oxidation states (charges). Thus, in chlorate,
chlorine has a +5 charge, in chlorite it bears a +3 charge, in
hypochlorite a + 1 charge, while in chloride a net -1 charge exists.
These variations in charges  (hence the speciations) are dependent on
many factors including: pH of the medium, temperature,  redox potential
of the medium, presence of oxidizing or reducing species etc. 
Similarly, chlorate itself can under go reodix reactions, depending on
the pH of the aqueous medium  to form, chloride,  chlorine,
hypochlorite, chlorous acid, chlorine dioxide.

The Agency lacks definite data which can help in quantifying the amounts
of chorate formed from  chlorine dioxide, sodium chlorite,
sodium/calcium hypochlorite. Simultaneous or concurrent conversions of
these species into chlorate are not likely to occur as these
interconversions depend on factors some of which are mentioned above and
these factors do not work in tandem. Thus at this time, any additional
dietary risks from interconversions in drinking water (non-cancer or
cancer risks), and food (non-cancer risks) can not be estimated. The
Agency has determined no additional risks exist other than the ones
which have estimated in chlorine dioxide/sodium chlorite RA and sodium
chlorate RA.

MRID# 			BIBLIOGRAPHY

1.  AD Memo by Tim McMahon, and A. Najm Shamim to Norm Cook, March,
1998).

FDA Memo: 1994, FAP: 4A4433

 FDA Memo, 1993 by Susan Carberry,  Ph.D: HFS-247, Chemistry Review
Branch, Document Number 2B4334

 David Hrdy, 2006. A Memo  from David Hrdy (HED) to Jennifer
Slotnick(AD) on Fruits and Vegetable Washes for Chlorine Dioxide Use.

David Hrdy, 2006. A Memo from David Hrdy to Jennifer Slotnick (AD) on 
Drinking Water Risks from Chlorine Dioxide Treated Water

Pat Fair, 2006.  A Memo from Office of Water  to Jennifer Slotnick, OPP
(AD) on Monitoring Data of Chlorine Dioxide Disinfectant Use by Water
Treatment Plants in the USA.

7.  Tim McMahon et al., 2005ADTC Memo on Hazard Identification (End
Point Selection)  for Chlorine Dioxide and Sodium Chlorite.

8.  A. Najm Shamim: AD Document on: Dietary Risk Assessment for
Dihalogen Dialkyl  and  MethylolHydantoins , 2003. This document lists
the FDA assumptions of pesticide migration form paper to food through
indirect food contact.	

9. A. Najm Shamim, 2005,  AD Document on Dietary Risk Assessment for
1,2-Benzisothaizolin-3-one.

10.. Bob Quick, 2001 AD Memo on Review of Lonza Registration Request for
5,5- Dimethylhydantoins as Slimicide and Preservative in Paper
Manufacture. Additional FDA assumptions on pesticide migration into food
from treated paper.  

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摧ᐔༀ. RASSB Memo by Bob Quick, 2001, with additional comments on
February 2001 Document (Reference 10)

12. Lonza Document op cit reference 4.

13. T.V. Tran, 2005 (?) ERCO Worldwide Research Report by  ERCO Report
#: TR-05-01

14 Wanda Henson to Kathryn Ingram, A Memo for the Acceptance of Label
Change on Hercules Incorporated Label Slime-Trol RX-33, May 2006.

