Document ID: EPA-HQ-OPP-2006-0599-0012
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-06-03T04:00Z

ECOLOGICAL HAZARD AND ENVIRONMENTAL RISK ASSESSMENT

Iodine and Iodine Complexes

CASE 3080

PC CODES 046905 (iodine), 075701 (potassium iodide), 046901
(butoxypolypropoxypolyethoxyethanol -iodine complex), 046904
(polypropoxypolyethoxyethanol-iodine complex), 046921
(alpha-alkyl-omega-hydroxypoly(oxyethylene)-iodine complex), 046918
(alkly(C12-15)poly(oxypropylene)poly(oxyethylene)-iodine complex),
046903 (nonylphenoxypolyethodyethanol-iodine complex), 046915
(octylphenoxypolyethodxyethanol-iodine complex), 046914
(polyvinylpyrrolidone-iodine complex),  046923 (amino acid-iodine
complex), and 046905 (iodinated resins)

Kathryn V. Montague, M.S.

Antimicrobials Division

Office of Pesticide Programs

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, DC 20460

Table of Contents

1.  Ecological Toxicity Data . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

a.  Toxicity to Terrestrial Animals . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . .1

1.  Birds, Acute and Subacute . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . 1

2. Mammals, Acute and Chronic . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . .3

b.  Toxicity to Aquatic Animals . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . 4

1.  Freshwater Fish, Acute . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . .4

2.  Freshwater Invertebrates, Acute . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . .4

3.  Estuarine and Marine Organisms, Acute . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . 5

4.  Aquatic Organisms, Chronic . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . .5

c.  Toxicity to Plants . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.  Risk Assessment and Risk Characterization . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

a.  Environmental Fate Assessment Summary . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . .7

b.  Environmental Exposure Assessment . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . .8

c.  Environmental Risk Assessment . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . .8

d.  Endangered Species Considerations . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .8

	Ecological Effects Hazard and Environmental Risk Assessment

	Iodine and Iodine Complexes

Iodine and various iodine complexes are used for a variety of indoor
antimicrobial uses.  They all function as microbiocides by releasing
iodine.  The complexes are grouped into several categories for the
purposes of this RED:

1.  Iodine [PC Codes 046905 (iodine) and 075701 (potassium iodide)]

2.  Surfactant-iodine complexes, which includes several subgroups:

a.  Polypropoxypolyethoxyethanol-iodine complexes (PC codes 046901,
046904, 046921, and 046918)

b.  Phenoxypolyethoxyethanol-iodine complexes (PC codes 046903 and
046915)

c.  Polyvinylpyrrolidone-iodine complexes (PC Code 046914)

3.  Amino acid-Iodine Complex (PC Code 046923)

4.  Iodinated Resins (PC Code 046905)

Currently registered uses include emergency drinking water purification,
fresh food sanitization, food-contact surface sanitization, hospital
surface disinfection, materials preservation, and recirculating
industrial water system treatment.  Registered antimicrobial products
account for approximately 2 million pounds of iodine annually.

I.	Ecological Toxicity Data

  The toxicity endpoints presented below are based on the results of
ecotoxicity studies submitted to EPA to meet the Agency’s data
requirements for the uses of iodine and iodine complexes (iodophores).
Since the iodine complexes function by releasing elemental iodine,
iodine is the chemical of concern for this assessment.  Iodine was
registered at one time for once-through cooling system treatment, but
that use was subsequently dropped, and the associated ecotoxicity data
requirements (e.g., marine/estuarine organism testing) were no longer
applicable.

A.	Toxicity to Terrestrial Animals

(1)	Birds, Acute and Subacute

In order to establish the toxicity of iodine and iodophores to avian
species for indoor uses, the Agency required an acute oral toxicity
study using the TGAI.  The preferred test species is either mallard duck
(a waterfowl) or bobwhite quail (an upland game bird).  The results of
one toxicity study are provided in the following table (Table 1).

Table 1.  Acute Oral Toxicity of Iodine and Iodophores to Birds

Species

	

chemical, % Active Ingredient (ai)	

Endpoint

(mg/kg)	

Toxicity Category (TGAI)	

Satisfies Guidelines/

Comments	

Reference

Northern bobwhite

(Colinus virginianus)	

Iodine, 99.8%		

LD50 > 2000 mg ai/kg

NOEL = 500 mg ai /kg	

Practically non-toxic	

Yes

(  core study

(  14-day test duration

(  NOEL based on reduced body weight gain in males	

431384-01

Northern bobwhite

(Colinus virginianus)	

Tetraglycerine hydroperiodide, 100%	

LD50 >250 mg/kg

NOEL = 250 mg/kg	

Moderately toxic	

Supplemental information

- did not test at high enough levels and did not achieve and LD50

- actual toxicity may be less than (moderately toxic( 	

423283-01

Northern bobwhite

(Colinus virginianus)	

Nonylphenoxypolyethodyethanol-iodine complex, 100%	

LD50 = 1700 mg/kg, NOEL = 631 mg/kg	

Slightly toxic	

Yes

- core study

- NOEL based on mortality, weight loss, and signs of toxicity	

ACC238200

The results indicate that iodine is moderately toxic to practically
non-toxic to avian species on an acute oral basis. The iodine study
fulfills guideline requirements (71-1/OPPTS 850.2100).

A subacute dietary study using the TGAI may be required on a
case-by-case basis depending on the results of lower-tier ecological
studies and pertinent environmental fate characteristics in order to
establish the toxicity of a chemical to avian species.  This testing was
not required for the indoor uses of iodine.  However, several studies
were available in the OPP database. Results of these studies are
provided in Table 2.

Table 2.  Subacute Dietary Toxicity of Iodine and Iodophores to Birds

Species

	

% Active Ingredient (ai)	

Endpoint

(ppm)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

Bobwhite quail

(Colinus virginianus)	

Iodine, 99.8%	

LC50 > 5620 ppm ai 

NOEC =562 ppm ai	

Practically non-toxic (TGAI)

	

Yes

- Core study

- NOEC based on signs of toxicity	

431917-01

Bobwhite quail

(Colinus virginianus)	

Tetraglycine hydroperiodide, 100%	

LC50 > 5000 ppm ai 

NOEC= 2500 ppm ai	

Practically non-toxic

	

Supplemental study

- analytical data for diet not provided

- NOEC based on reduction in body weight 	

423291-01

Bobwhite quail

(Colinus virginianus)	

Nonylphenoxypolyethodyethanol-iodine complex, 100%	

LC50 > 5620 ppm

NOEC = 5620 ppm	

Practically non-toxic	

Yes

- core study

	

ACC238200

Mallard (Anas platyrhynchos)	

Nonylphenoxypolyethodyethanol-iodine complex, 100%	

LC50 > 5620 ppm

NOEC = 3160 ppm	

Practically non-toxic	

Yes

- core study

- NOEC based on signs of toxicity	

ACC238200

The results indicate that iodine is practically non-toxic to avian
species on a subacute dietary basis. Several studies are acceptable and
fulfill guideline requirements (71-2/OPPTS 850.2200).

(2)	Mammals, Acute and Chronic Toxicity

Wild mammal testing was not required by the Agency.  In most cases, rat
toxicity values obtained from studies conducted to support data
requirements for human health risk assessments substitute for wild
mammal testing.  These toxicity values are reported below (Table 3).
Further information on the mammalian toxicology of iodine and iodophores
may be found in the Toxicology Disciplinary Chapter of this RED
document.

Table 3.  Acute Toxicity of Iodine and Iodophores to Mammals (excerpted
from Toxicology Chapter)

Species

	

Test Type	

LD50

(mg/kg)	

Toxicity Category	

Reference

(MRID)

Rat	

Acute oral 	

315 mg/kg	

II	

42326704

Rat	

Acute dermal	

3,333 mg/kg	

III	

42326705

Rat	

Acute inhalation	

0.363 mg/L	

II	

42961002

Rabbit	

Primary skin irritation	

corrosive, severe erythema, edema 	

I	

42326706

Guinea pig	

Dermal sensitization	

no sensitization observed (Buehler method)	

N/A	

42326707

Acute toxicity of iodine is low for dermal toxicity, but is somewhat
higher for acute oral and inhalation toxicity and dermal irritation. 

B.	Toxicity to Aquatic Animals

(1)	Freshwater Fish, Acute

In order to establish the acute toxicity of pesticides to freshwater
fish, the Agency requires freshwater fish toxicity studies using the
TGAI.  The preferred test species are rainbow trout (a coldwater fish)
or bluegill sunfish (a warmwater fish).  Results of freshwater fish
acute testing for iodine and iodophores are presented in Table 4.

Table 4.  Acute Toxicity of Iodine and Iodophores to Freshwater Fish

Species

	

% Active Ingredient (ai)	

Endpoints

(ppm)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

Bluegill sunfish

(Lepomis macrochirus)	

Igepal CO-630 (technical(	

96hr LC50 = 7.9 mg/L	

Moderately toxic	

No

- supplemental study

- test substance did not include iodine complex	

ACC238200

Bluegill sunfish

(Lepomis macrochirus)

	Iobio

99.8% iodine	96-hour LC50 = 0.61 mg/L

NOEC= 0.16 mg/L	Highly toxic	Yes	MRID #430445-01

(2)	Freshwater Invertebrates, Acute

The Agency requires a freshwater aquatic invertebrate toxicity study
using the TGAI to establish the acute toxicity of pesticides to
freshwater invertebrates.  The preferred test species is Daphnia magna. 
Results of the submitted studies for iodine and iodophores are provided
in the following table (Table 5).

Table 5.  Acute Toxicity of Iodine and Iodophores to Freshwater
Invertebrates

Species

	

% Active Ingredient (ai)	

Endpoints

(ppm)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

Waterflea

(Daphnia magna)	

Iodine, 99.8%

	

48-hr. EC50 = 0.33 (95% conf. limits 0.20 - 0.37) mg ai/L

NOEC = 0.09 mg ai/L	

Very highly toxic 

	

Yes

(	Core study

- NOEC based on signs of toxicity

	

429610-01



The results of this study indicate that iodine is very highly toxic to
freshwater invertebrates.  The guideline requirement has been fulfilled
(850.1010/72-2).

(3)	Estuarine and Marine Organisms, Acute

Acute toxicity testing with estuarine and marine organisms using the
TGAI is required when the end-use product is intended for direct
application to the marine/estuarine environment or effluent containing
the active ingredient is expected to reach this environment. This
testing is not required for iodine or iodophores, as all the currently
registered uses are indoor applications.

(4)  Aquatic Organisms, Chronic

Chronic toxicity testing (Fish early life stage, 850.1300/72-4a and
aquatic invertebrate life cycle, 850.1400/72-4b) is required for
pesticides when certain conditions of use and environmental fate apply. 
This testing is not required for iodine and iodophores as all the
currently registered uses are indoor applications.

C.  Toxicity to Plants

Phytotoxicity testing is required for pesticides when certain conditions
of use and environmental fate apply.  This testing is not required for
iodine and iodophores as all the currently registered uses are indoor
applications.

Risk Assessment and Characterization

Risk assessment integrates the results of the exposure and ecotoxicity
data to evaluate the likelihood of adverse ecological effects. One
method of integrating the results of exposure and ecotoxicity data is
called the quotient method.  For this method, risk quotients (RQs) are
calculated by dividing exposure estimates by ecotoxicity values, both
acute and chronic:  

       

           RQ = EXPOSURE/TOXICITY 

 

RQs are then compared to OPP's levels of concern (LOCs).  These LOCs are
criteria used by OPP to indicate potential risk to nontarget organisms
and the need to consider regulatory action.  The criteria indicate that
a pesticide used as directed has the potential to cause adverse effects
on nontarget organisms.  LOCs currently address the following risk
presumption categories: (1) acute high - potential for acute risk is
high, and regulatory action may be warranted in addition to restricted
use classification; (2) acute restricted use - the potential for acute
risk is high, but this may be mitigated through restricted use
classification; (3) acute endangered species - the potential for acute
risk to endangered species is high, and regulatory action may be
warranted; and (4) chronic risk - the potential for chronic risk is
high, and regulatory action may be warranted.   Currently, AD does not
perform assessments for chronic risk to plants, acute or chronic risks
to nontarget insects, or chronic risk from granular/bait formulations to
mammalian or avian species.

The ecotoxicity test values (i.e., measurement endpoints) used in the
acute and chronic risk quotients are derived from the results of
required studies.  Examples of ecotoxicity values derived from the
results of short-term laboratory studies that assess acute effects are:
(1) LC50 (fish and birds) (2) LD50 (birds and mammals) (3) EC50 (aquatic
plants and aquatic invertebrates) and (4) EC25 (terrestrial plants). 
Examples of toxicity test effect levels derived from the results of
long-term laboratory studies that assess chronic effects are: (1) LOEC
(birds, fish, and aquatic invertebrates) (2) NOEC (birds, fish and
aquatic invertebrates) and (3) MATC (Maximum Allowable Toxic
Concentration) (fish and aquatic invertebrates).  For birds and mammals,
the NOEC value is used as the ecotoxicity test value in assessing
chronic effects.  Other values may be used when justified.  Generally,
the MATC (defined as the geometric mean of the NOEC and LOEC) is used as
the ecotoxicity test value in assessing chronic effects to fish and
aquatic invertebrates.  However, the NOEC is used if the measurement
endpoint is production of offspring or survival.

Risk presumptions, along with the corresponding RQs and LOCs are
tabulated below.

Risk Presumptions for Terrestrial Animals

Risk Presumption	

RQ	

LOC

Birds and Wild Mammals

Acute High Risk	

EEC1/LC50 or LD50/sqft2 or LD50/day3	

0.5

Acute Restricted Use	

EEC/LC50 or LD50/sqft or LD50/day (or LD50 < 50 mg/kg)	

0.2

Acute Endangered Species	

EEC/LC50 or LD50/sqft or LD50/day 	

0.1

Chronic Risk	

EEC/NOEC	

1

 1 abbreviation for Estimated Environmental Concentration (ppm) on
avian/mammalian food items   

 2    mg/ft2             	3 mg of toxicant consumed/day

   LD50 * wt. of bird             	LD50 * wt. of bird  

 

Risk Presumptions for Aquatic Animals	 

Risk Presumption	

RQ 	

LOC

Acute High Risk	

EEC1/LC50 or EC50	

0.5

Acute Restricted Use	

EEC/LC50 or EC50	

0.1

Acute Endangered Species	

EEC/LC50 or EC50	

0.05

Chronic Risk	

EEC/MATC or NOEC	

1

 1 EEC = (ppm or ppb) in water

Risk Presumptions for Plants	

	

Risk Presumption	

RQ	

LOC

Terrestrial and Semi-Aquatic Plants 

 tc \l2 "Terrestrial and Semi-Aquatic Plants  

Acute High Risk	

EEC1/EC25	

1

Acute Endangered Species	

EEC/EC05 or NOEC	

1

Aquatic Plants

 tc \l2 "Aquatic Plants 

Acute High Risk	

EEC2/EC50	

1

Acute Endangered Species	

EEC/EC05 or NOEC 	

1

 1 EEC = lbs ai/A 

 2 EEC = (ppb/ppm) in water 

A.  Environmental Fate Assessment Summary (excerpted from the
Environmental Fate Science Chapter of this RED document)

Iodine is an element ubiquoutously present in water, air, and soils. It
is a part of human diet. Iodine is not likely to volatilize from
iodophors due to lower vapor pressure.   Iodine is likely mobile in
soils; iodine as iodide and iodate exist in water and the iodophor use
is not likely to contaminate the surface waters. The estimated log Kow
is about 2.5, which makes it less likely to bioaccumulate in aquatic
organisms like fish.

Iodine is not hydrolyzed in water as are other halogens proceeding it in
the halogen family. It is photolytically unstable in the atmosphere as
it can form iodine radicals.

The transfer of iodine from air, water, and land is due to the
volatility of iodine.  The wet deposition of iodine is  predominantly
into soil.  Iodine in water exists as iodide and iodate, at a 55:45
ratio.  Mobility of iodine in soil depends on the soil porosity,
saturation and the amount of organic matter and iron/ aluminum oxides in
the soil.  In most soils it is immobile to moderately immobile.  

OPP’s Lower Risk Pesticide Chemical Group (LRPCG), in its Science
Assessment for iodine chemicals as active and inerts, did not observe
any real or potential environmental concerns for these pesticides
(Chemicals assessed were: Iodine, Potassium Iodide, Sodium Iodide,
Hydroiodic Acid, Potassium Iodate)3

B.  Environmental Exposure Assessment

Environmental exposure modeling was not conducted for iodine and
iodophores as all the currently registered uses are indoor applications.
Industrial water treatment requires a NPDES permit in order to discharge
effluents.  Little or no environmental exposure is expected from these
uses.  

C.  Environmental Risk Assessment

The uses of iodine and iodophores considered in this RED make it
unlikely that any appreciable exposure to terrestrial or aquatic
organisms would occur. 

Endangered Species Considerations 

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to insure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means "to engage in an action that reasonably would
be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species." 50 C.F.R. ( 402.02.

To facilitate compliance with the requirements of the Endangered Species
Act subsection (a)(2) the Environmental Protection Agency, Office of
Pesticide Programs has established procedures to evaluate whether a
proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the
Agency’s screening-level risk assessment is performed, if any of the
Agency’s Listed Species LOC Criteria are exceeded for either direct or
indirect effects, a determination is made to identify if any listed or
candidate species may co-occur in the area of the proposed pesticide
use.  If determined that listed or candidate species may be present in
the proposed use areas, further biological assessment is undertaken. 
The extent to which listed species may be at risk then determines the
need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

For certain use categories, 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, pg.81).  Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
“No Effect” determination.  The registered uses of iodine and
iodophores fall into this category.

REFERENCES

ACC238200.   

1.  Fink, R.  1978. Acute Oral LD50 - Bobwhite Quail Biopal NR-20. 

2.  Fink, R.  1978. Eight-day Dietary LC50 - Bobwhite Quail Biopal
NR-20.

3.  Fink, R.  1978. Eight-day Dietary LC50 - Mallard Duck Biopal NR-20.

Unpublished data.  Conducted by Wildlife International for GAF
Corporation.

4.  Macek, K.J. and S.F. Krzeminski.  1975.  Susceptibility of Bluegill
sunfish (Lepomis macrochirus) to Nonionic Surfactants.  Bul. Env.
Contam. Toxicol. 13(3):377-384.	

MRID 42328301. Pedersen, C.A. 1991.  Tetraglycine Hydroperiodide: 21-day
Acute Oral LD50 Studt in Bobwhite Quail. Unpublished data.  Conducted by
Bio-Life Associates for the U.S. Army Natick Research Development and
Engineering Center.

MRID 42329101.  Pedersen, C.A.  1991.  Tetraglycine Hydroperiodide:
8-day Acute Dietary LC50 Study in Bobwhite Quail.  Conducted by Bio-Life
Associates for the U.S. Army Natick Research Development and Engineering
Center.

MRID 42961001.  Zelinka, E.A., C.M. Holmes, K.H. Martin, and J.P.
Swigert.  1993.  A 48-hour Flow-through Acute Toxicity Test with the
Cladoceran (Daphnia magna).  Unpublished data.  Conducted by Wildlife
International for the Baltimore Aircoil Company.

MRID 43138401. Campbell, S.M. and J.B. Beavers.  1994.  IOBIO: An Acute
Oral Toxicity Study with the Northern Bobwhite.  Unpublished data. 
Conducted by Wildlife International for the Baltimore Aircoil Company.

MRID 43191701. Campbell, S.M., and J. B. Beavers.  1994.  IOBIO: A
Dietary LC50 Study with the Northern Bobwhite.  Unpublished data. 
Conducted by Wildlife International for the Baltimore Aircoil Company.

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