MEMORANDUM							July 27, 2005

SUBJECT: 		Data Evaluation Records (DER) for the Product Chemistry of
Iodine                                                                  
                                                                        
                                                                        
                                                                        
                                 

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

Regulatory Management Branch II

Antimicrobials Division (7510C)

To:			Ben Chambliss, Team Leader,

Regulatory Management Branch II

Antimicrobials Division (7510C)

Thru:			Tim McMahon, Senior Toxicologist and Chair: AD Tox Committee

Antimicrobials Division (7510C)

And

Michelle Centra, Member ADTC and Science Coordinator for Iodine-Iodophor
RED

Regulatory Management Branch II

Antimicrobials Division (7510C)

And

Heather Garvie, CRM for Iodine/Iodophor RED

Regulatory Management Branch II

Antimicrobials Division (&510C)

And

Mark Hartman, Chief

Regulatory Management Branch II

Antimicrobials Division

PRODUCT CHEMISTRY CHAPTER

IODINE

A.  Chemical Overview 						

The chemical Iodine is most commonly used in: sanitation, animal feed
and pharmaceutical production.

B.  Chemical Identification

Name:			Iodine

Chemical Family: 		Halogen 

Common/Trade Names:	None

CAS Number:		7553-56-2

Molecular Formula:		I2	

C.  Physical/Chemical Properties

The following characteristics have been reported for iodine: 

Technical Grade Active Ingredient (TGAI):

Molecular Weight:			253.809

Color:				Bluish-black

Physical State:			Solid; scales or plates

Specific gravity:			4.93

Dissociation Constant:		No data available

pH:				No data available

Stability:			No data available

Melting point:			113.6(C

Boiling point:                                      185.24(C

Water Solubility:			330mg/L at 25(C

Log Kow				0.40

Vapor Pressure:			0.305 mm Hg at 25oC 



POTASSIUM  IODIDE

A.  Chemical Overview 						

The chemical Potassium iodide is most commonly used in: sanitation,
animal feed, catalysts, and for treatment of radioiodide poisoning
resulting from nuclear accidents.

B.  Chemical Identification

Name:			Potassium iodide

Chemical Family: 		Halogen 

Common/Trade Names:	None

CAS Number:		7681-11-0

Molecular Formula:		KI	

C.  Physical/Chemical Properties

The following characteristics have been reported for potassium iodide: 

Technical Grade Active Ingredient (TGAI):

Molecular Weight:			166.02

Color:				Colorless or white

Physical State:			Solid; crystals, granules, or powder

Specific gravity:			3.12

Dissociation Constant:		N/A: Completely ionized in aqueous medium

pH:				No data available

Stability:			Stable , but turn yellowish over prolonged period of time

Melting point:			680(C

Boiling point:                                      1323(C

Water Solubility:			1429 g/L at 25(C

pH;				Aqueous Solution: neutral to basic: 7-9

Log Kow:			0.04

Vapor Pressure:			9.9 x 10-18 mm Hg

SODIUM IODIDE

	Chemical Over view:

This chemical is used in sanitization.

CHEMICAL IDENTIFICATION:

Name:				Sodium Iodide

Chemical Family:	Halogen

Common/Trade Name:	None

CAS#:				7681-82-5

Molecular Formula:	NaI

Physical/Chemical Properties:

 

Following Characteristics have been reported for Technical Grade Active
Ingredient(TGAI):

Molecular Weight:	149.89

Color:				White, which on prolonged exposure to air turns brown as it
releases Iodine

Physical State:		Solid

Melting Point:		321 o C

Boiling Point:		732 o C

Specific Gravity:	3.67

pH:				Basic in aqueous medium: 8- 9.5

Stability:			Delinquent, absorb moisture from air and become brown

Water Solubility:	22 g/L

Dissociation Constant:	N/A: Completely ionized in water.

Log Kow			0.04

Henry Law Constant:	2.8 x10-23 atm-m3/mol

Vapor Pressure:		9.9 x 10-18 mm Hg

AA.  Chemical Overview of  Iodophors4			

I. Subgroup A (Propoxyethoxy (PO/EO) Copolymer Carriers)

Butoxypolypropoxypolyethoxyethanol

Butoxypolypropoxypolyethoxyethanol is synthesized by the ethoxylation
reaction of

propylene oxide (PO) and ethylene oxide (EO) with a butanol "starter."
For iodophor

production, so-called block copolymers are used. In the synthesis of
these molecules, PO

and EO are added in sequential steps (rather than simultaneously) to
form "blocks" of

polypropoxy and polyethoxy units within the molecule. The final
polyalkylene glycol

(PAG) is not a single compound but is a mixture of polymer chains which
have an

approximate normal distribution around the desired molecular weight. The
molecular

weights used in iodophor production range from 2000 to 4000 a.m.u. 

Polypropoxypolyethoxyethanol

Polypropoxypolyethoxyethanol is synthesized by the ethoxylation reaction
of propylene

oxide (PO) and ethylene oxide (EO) with a water "starter." Except for
the initiator, these

polymers are the same as the butoxypolypropoxypolyethoxyethanol
carriers.

Alkyl(polypropoxy)polyethoxyethanol

The alkyl EO and PO/EO carriers,
alpha-alkyl-omega-hydroxypoly(oxyethylene) and alkyl (C12-15)
poly(oxypropylene)poly(oxyethylene), are synthesized by the ethoxylation
reaction of propylene oxide (PO) and/or ethylene oxide (EO) with a
longer alkyl chain (than butanol) "starter". The
alpha-alkyl-omega-hydroxypoly(oxyethylene) is a linear alcohol
ethoxylate identical to those used extensively in soaps, detergents, and
many other common products. Except for the initiator, the alkyl (C12-15)
poly(oxypropylene)- poly(oxyethylene) polymers are the same as the
butoxypolypropoxypolyethoxyethanol carriers and the approach to the
toxicology profile is identical.

Structurally-related Polyalkylene Glycols (used in toxicological
evaluation of Subgroup A)

Polyethylene glycols (PEGs; CAS No. 25322-68-3) have been used
extensively in thousands of applications including drug excipients,
direct food additives, cosmetics, and many others that lead to
substantial human contact. These products are produced in ethoxylation
reactions similar to those for the Iodophor carriers and are essentially
the same chemicals without the propylene oxide components. Polypropylene
glycols (PPG) are similar and a FIFRA Registered fly repellent,
Stabilene, is simply the polypropylene glycol equivalent of a PEG with a
molecular weight of approximately 700 a.m.u.  The following is the
chemical structure for PEG:



II. Subgroup B (Phenoxypolyethoxyethanol Carriers)

Nonylphenoxypolyethoxyethanol

Nonylphenoxypolyethoxyethanols (nonylphenol polyethoxylates; NPE; CAS
No. 9016-45-9 or 26027-38-3) are commonly used surfactants in industrial
cleaners, pesticide adjuvants, and, for the most commonly made 9-mole
ethoxylate, spermicides. A wide range of ethoxylation (approximately 4
to 100 moles of EO) are used to provide different properties. The NPEs
are produced by introducing the preferred molar ratio of EO and
nonylphenol (NP) into a reactor.  The C9 chain of the NP is comprised of
approximately 25-30 isomers with different branching. As with the EO/PO
polymers discussed above, the final products are not a single compound
but are mixtures of chains which have an approximate normal distribution
around the desired molecular weight. For example, the most commonly
produced 9-mole ethoxylate (known as Nonoxynol in spermicide use)
contains congeners ranging from approximately 5 to 16 moles of EO.
Therefore, each NPE is a complex mixture of isomers of the nonene chain
and congeners of the EO chain.  Nonylphenoxypolyethoxyethanol is in the
form a blue liquid, with a specific gravity of 1.01.
Nonylphenoxypolyethoxyethanol has a listed pH factor of 9.5 ( 2.  

Octylphenoxypolyethoxyethanol

Octylphenoxypolyethoxyethanols (octylphenol polyethoxylates; OPE; CAS
No. 9002-93-1) also known as Triton X-100 are surfactants similar to the
NPEs but are less commonly used. They are produced in a similar process
replacing octylphenol (OP) for NP. Approximately 97% of the OP is the
tertiary branched isomer and, therefore, the OPEs are less heterogeneous
than the NPEs (but retain the normal distribution of EO chain lengths).
OPEs are more costly to produce and, therefore, are generally used only
in specialized applications.  The physical and chemical properties of
technical grade octylphenoxypolyethoxyethanol found are listed below:

Molecular weight:	206.1534

Molecular Formula:	C14H22O ( (C2H4O)n

Color:		Clear to slightly hazy

Physical state:	Liquid

Specific gravity:	1.082

pH:		6-8

Melting point:	7 (C

Boiling point:	270 (C

Water Solubility:	Soluble in water

Vapor pressure:	< 1mm Hg at 25 (C

III. Subgroup C (Polyvinylpyrrolidone Carriers)

Polyvinylpyrrolidone (Povidone)

Povidone (PVP; CAS No. 9003-39-8) is a synthetic polymer principally
consisting of linear 1-vinyl-2-pyrrolidone groups, produced as a series
of products having mean molecular weights ranging from about 10,000 to
about 1 million a.m.u. or greater.  The monomer molecular weight is 11.1
a.m.u  In addition to its use in disinfectants, it is used as a
dispersing agent, and has been used as a tablet binder, coating agent,
and viscosity-increasing agent in pharmaceutical preparations.  The
chemical formula is (C6H9NO) x.

 

PVP is an odorless faintly yellow powder and is soluble in water,
ethanol, and chloroform and insoluble in ether.  PVP has a specific
gravity of 1.1-1.3 and a pH ranging from 3.0 to 7.0 in a 1:20 solution. 
The melting point is 100oC.  The amide region of the pyrrolidone
substituent absorbs in the UV region at wavelengths below 235 nm. 

IV. Amino Acid Complex

Tetraglycine Hydroperiodide

For the iodophor used for emergency water disinfection (tetraglycine
hydroperiodide), the iodine complex is formed by a catalyst driven
reaction with the essential amino acid glycine, to produce the complex:
2[(CH2NH2COOH)8 ( (HI)2 2.5I2]

V. Iodinated Resin Complex

Quat Amine divinylbenzene/ styrene copolymer

Triosyn( resin is produced by thermally fusing pure iodine crystals
under high pressure with a specialized quaternary amine
divinylbenzene/styrene polymer. During this process, a stable
electrochemical bond is formed between the iodine and the polymer,
allowing no free release of iodine in the media employed. This
electrochemical bond serves as a demand-release mechanism that allows
iodine molecules to be released from Triosyn( resin in the presence of
demand-causing microorganisms and in amounts required to eliminate the
source of the demand. Triosyn( is activated by the strong ionic charge
of surface proteins that cover microorganisms and then interacts with
organisms through ionic transfer. Upon contact with a microorganism,
ionic molecular iodine is transferred from Triosyn( resin, to the more
strongly charged surface proteins of the microbe. The iodine immediately
devitalizes the microorganism by removing electrons from the organism's
surface proteins which are necessary for life and reproduction.

This process provides disinfectant properties to items such as tent
fabric and outdoor paint. There is little human contact with the
poymeric Triosyn( resin.

NOTE:	 It has been noted by the Agency that when Iodine is present in
the iodophor ( matrixed in one of the polymeric structures discussed
below, the vapor pressure of iodine decreases considerably. A one page
document provided by Iodophors Joint Venture Group (Nov. 24, 2004),
shows that  iodine present  at  use level of 300 ppm in an iodophor, 
its vapor pressure decreases from 0.3 mm Hg to

 6.6 x10-6 mm Hg, which is a considerable reduction.



BIBLIOGRAPHY

MRID#					CITATION

--------------------	1. Budavari S, O(Neil MJ, Smith A, et al., eds.
1998. The Merck index: An encyclopedia of chemicals, drugs, and
biologicals. Whitehouse Station, NJ: Merck and Co., Inc.

---------------------	2. Chemfinder. 2001. Iodine. Chemfinder.com:
Database and internet searching. http://www.chemfinder.com.

---------------------	3.  Lide DR, ed. 2000. CRC Handbook of Chemistry
and Physics. 81 st ed. Boca Raton, FL: CRC Press.

---------------------	4. Non-MRID  Documents provided by Iodophor Joint
Venture on Iodophors Chemistry Background.

--------------------	5.  Calculations of the Maximum Atmospheric Iodine
Concentration From Solutions of Iodophors..  Memo from Iodophor Joint
Venture, Nov.24, 2004

