' 

~ 

( 

.~ 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 • 

00988tl 

lo-{ S '1 IH3 o 3 4 'f t' 2-/ OFFICE OF 

PR£VENTIOH, PESTICIOEI 

AND TOXIC IUIIITANCU '-1 H (!J <; c ':i VINOV 2 7 ilj r)' ' 

'· 

MEMORANDUM 

SUBJECT: 

FROM: 

THRU: 

TO: 

Rereg;stratlon Eligibility Document (RED) for Iron Salts 

Case #4058 ',A~ 

Jane Smith, Chemist !tu(,fYf - Chemical Coordination ~hch Health Effects Division (H7509CI 

Esther 

Chemical 

Saito, 

Coordination 

Acting Branch 

Branch 

Chief ~ ~ 

Health Effects Division (H7509CI 

and 

Penelope Fenner-~J"h.D, Direct()[ )•"' 

Health Effects Di~sMir" (H7509CI utV' 

Jay Ellenberger, Chief 

Accelerated Reregistration Branch 

Special Review and Reregistration Branch (H7508WI 

Attached please find the Human Health Ass;;,ssment for the Iron Salts (to Include ferric 

sulfate and ferrous sulfate he pta-and monohydrate) Reregistration Eligibility Document. 

This chapter includes the Hazard Assessment from Beth Doyle and Pat Mclaughlin of 

Toxicology II and the Occupationai/Resid,ntial Exposure Assessment from Judy Smith. 

There are no active labels involving pesticidal uses on food or a11imal feed. Therefore, 

there are no tolerances or exemptions from the requirements cr tolerances established 

for Iron salts. Since there are no toxicological endpoints of concern and no food uses, 

no risk assessment was performed for dietary exposure. Ferrous sulfate is generally 

recognized as safe as noted in 40 CFR§180.2(a). The Food and Drug Administration 

has affirmed that ferric sulfate and ferrous sulfate (hepta· and monohydrate) are 

generally recognized as safe (GRAS) for use in food as a flavoring agent and a nutrient O 

supplement, respectively, with no limitations other than current good manufacturi7 {) / 

@ ........ ns:;•I'R:eu•b 

_ .. ..... ...... ,.. ....... .. 
practice. Basad on these factors, the human risks from both dietary and occupational 

exposures are considered to be negligible. No additional hazard or exposure data are 

required for reregistration eligibility. 

cc: Marcia Van Gernert 

Beth Doyle 

Pat Mclaughlin 

Larry Dorsey 

AI Nielsen 

Judy Smith 

Attachments 

009885 
B. Hyman Health Assessment 

00~)385 1 . Toxicology Assessment 

TEST 

Oral LD50 rat 

The toxicological data base on ferric sulfate, ferrous sulfate 

heptahydrate, and ferrous sulfate monohydrate Is adequate and 

will support reregistration eligibility. 

a. Acyte and Sybchronic Toxicity 

Ferric sulfate, in an acute oral toxicity study ~, rats, had an 

LD50 of 1487 mg/kg In females and of 2102 mg/kg in males. An 

acute dermal toxicity test In rabbits with ferric sulf Jte found an 

LD50 greate; than 2000 mg/kg. An acute inhalation toxicity study 

in rats with ferric sulfate found an LC50 greater than 1 . 10 mg/L. 

Ferrous sulfate heptahydrate, in an acute oral study in rats, 

showed an LD1

• of 1389 mg/kg; an acute oral study in rabbits 

showed an LD1

• of 2778 mg/kg (4). The LD50 found for this 

compound in mice was 1520 mg/kg (4). A sensitization study in 

guinea pigs with ferrous sulfate monohydrate found no indication 

of contact sensitization by this compound. The table below 

summarized the toxicity values and categories: 

Acute Toxicity Data--FERRIC SULFATE 

RESULT CATEGORY 

1487- 2102 mg/kg Ill 

Inhalation LC., rat >1.1 mg/L Ill 

Dermal LD50 rabbit >2000 mg/kg Ill 

b. Mytagenicity 

A mutation study in .E... !t.2ll reported positive results at 30 

umoi/L (4). With due regard for the continuing exposure that 

hun1an beings have had to the Iron and sulfate components of 

these chemicals over many, many generations, it is considered 

unlikely that this reported result in microorganisms has any 

bearing on probable effects in humans or other mammals at the 

levels expected from use of these compounds as pesticides. 

3 
c. Matabgllam 009885 

Iron and sulfate are normal constituents of the diet and are 

metabolized and utilized by the body. 

d. Other Toxicolog .a! Considerations 

The toxicological data on Iron sulfates with the agsncy and 

in the literature are adequate for assasslng risk to humans. Not 

all of the toxicity data usually required for pesticide registration 

are necessary for the present uses of iron sulfates. There are 

some unusual factors In this case which Indicate that specific 

studies to fulfill the usual data requirements are not necessary to 

regulate these substances as pesticides. Iron sulfates are 

normally present in the environment. They may be present in 

foods naturally and as added Ingredients. There Is no reason to 

expect reasonable pesticide usage to constitute any hazard 

beyond that from ordinary exposure. 

2. Exposyre Assessment 

a. Qletary 

·Dietary exposure to ferric sulfate, ferrous sulfate 

heptahydrate, and ferrous sulfate monohydrate is not expected to 

occur from pesticidal use. There are no active labels involving 

pesticidal uses on food or animal feed. Therefore, there are no 

tolerances or exemptions from the requirements of tolerances 

established for Iron salts. Since there are no toxicological 

endpoints of concern and no food uses, no risk assessment was 

performed for dietary exposure. Ferrous sulfate is generally 

recognized as safe as noted In 40 CFR§180.2(a). The Food and 

Drug Administration has affirmed that ferric sulfate and ferrous 

sulfate (hepta- and mom1hydratel are generally recognized as safe 

(GRAS) for use in food as a flavoring agent and a nutrient 

supplement, respectively, with no limitations other than current 

good manufacturing practice. 

b. Occypatjgnal and hesjdentjal 

Ferric sulfate and ferrous sulfate h3pta- and monohydrate 

are applied to turf and ornamental lawns using drop and broadcast 

4 
009885 

spreaders, sprlroKier cans, and by hand. These lnorgan!c salts are 

formulated as a granular and soluble concentrate (liquid and solid), 

They are used as a herbicide to control moss on residential lawns 

and ornamental turf. The potential for mixer/loader/applicator 

exposure exists; however, these Inorganic salts are of little 

concern from a toxicity perspective. Any mixer/loader/applicator 

exposure to these Inorganic salts Is considered Inconsequential 

and no additional exposure data are required for reregistration 

eligibility. 

3. Risk Cbaracterizatjon 

The human risks from both dietary and occupational 

exposures are considered to be negligible. The general knowledge 

of ferric sulfate and ferrous sulfate hepta- ao1d monohydrate 

Indicate low toxicities associated with these compounds. They 

are used by humans as a food flavorint~ agent and food nutrient 

supplement, and have inherent function in the metabolic pathways 

of humans and domestic animals. No additional hazard or 

exposure data are required for reregistration eligibility. 

5 
BIBLIOGRAPHY 

(1) MRID# 42171701 

(2) MAID# 42171702 

(3) MAID# 42171703 

(4) Sax, N. 1., and Lewis, R. J. SR, 1989. Qangeroua Properties of 

!ndystrlal Materials, 7th Ed. Van Nostrand Reinhold, New York. 

(5) MAID# 41763701 

6 
, __ ,• 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WAaHINGTON, D.C. 10 .. 0 

• 

AUG 2 7 1992 

009885 

MEMQRANQUM: OP'P'IC. OP 

P.8TICIII.8 AIIID TOXIC 8U.aTAIIICU 

Subject: 

To: 

From: 

Thru: 

Thru: 

Chemical: 

Caset: 

Chemicalt: 

Company: 

Defer toa 

Review of potential Occupational and Reaidential Expoaure 

to Iron for the Reregiatration Phaae 4 Reviuw and the 

Reregistration Eligibility Document (RED). 

!ather Saito, Chief 

Science Adminiatration Section 

Science Analyaia ' coordination Branch (SACB) 

Health Effects Division (~09C) 

Judy Smith, PhD, Chemist ') ~j)L '/+r/?.z.. 

Reregiatration Section iz/1 

Occupational and Resident~al Exposure Branch 

Health ~~f,cts Division (H7509C) ()1..~ 

Alan Nialaen, Chief 

Reregistration Section II 

occupational and Residential Exposure Branch 

Health Effects Division (H7509C) 

Larry Dorsey, Acting Chief 

Occupational and Residential Exposure Branch 

Health Effects Division 

p~ C/, o-~-4 i-")1,;,,_ 

Ferric sulfate 

034902 

000802 Chas. H. Lilly Company 

Biological ADalyaia Br&Dcb/BBAD 

Accalarata4 Raraqiatratioa Braach/SRRD 

TB-Iaaactici4e/Rc4aatici4a Support lactioa 

TB-Rarbici4e/WU.qici4e/ADtiaiorobial 

1 

•..• idf .. &ilt*:.!·y ·'·~fi'~. 4t·;@;it&h;·, :.,~. --~~- ,tt~en'1·•rt-•ti,il~_,~. "'~~--.. ~~~.~W~. ~~U.l;." -~.-414 
caael tOll ••qe 2 of J 

Ch .. iaall OJtiOI 

009885 

PHASE ' DATA REQUIREMENTS 

Guideline f: 1l2-1Cal Deacription: Foliar Raaidut Qissipation 

Ia requirement applicable? (Y/N): _1_ 

Diacussion: Irgn i• u1ed '' a be~igidg to contrgl moat on turf 

and ornamental 1ayn1. Tht potential fgr exposure to 

treated foliage oxiata. Howoyor. ;ron is of little 

cons;ern frgm a tgxigity par•p•gtiya. Thoro fort. ORIB 

do•• not roquir• a foliar r••idut di•aipatign wtcdv 

fgr roreq!ttration. 

Guidoline t: 13&-lCbl Doacription: Soil Residue Qissipation 

Is requirement applicable? (Y/N): _a_ 

Discussion: trgn is ueed os a hefbicide to control mo•• qn tyrt 

and ornamantal lawnt. The potential for expoapro dut 

tg contact with the traotad soil axi1t1. Howayer. 

iron is o;. little concern from a toxicity 

perspoctiya; Tb•r•fgra. OBEB doe• not require a •gil 

retidue ditsipotiqn study fgr rereqiatrotiqn. 

Guideline f: 133-3 Description: Dermal Exposure 

Is requirement applicable? (Y/N): _H_ 

Dtscussion: Irgn is used aa o berbfcide to cpntrpl moss gn turt 

and ornamtntal lawns. Tha pgtontiol for postappligptipn dermal expgsure exists. Howayar. iron i' 

of little concern from a toxicity perspectiye. 

Thareforo. OREB doe1 ngt require 1 dermol axposure 

study for reregistration. 

Guideline f: 133-4 Description: Inhalation Exposure 

Is requirement applicable? (Y/N): _u_ 

Discussion: Iron is used as a herbicide to control moss on turf 

and grnamental lawns. 1 The potential fgr inhalation 

expgsure may axist. However. irfn is of little 

concern frgm ' tgxigity perspective; Therefore. QREB 

dgas not requir• on inhalation axpg•urt 1tudy fgr 

reregistration. 

I 

2 

UN tnf-tton ta beald on t~e LUIS report dltld J.,_ry 27, 199Z c- 2119/92) fr .. Phyll ta 

Jollnaon of HAD, 11111 the prooi.lct llbtl CEPA .... Mo. 802•509), 

Toa tnfo,.tlon- retrl- fr .. the toa -·llnor dltod 6/9192 (.cute 111,.1/ .. t....., Ill 

11111 .cute -1/cot....., Ill boald on 19 percent •.I.). 

t ' 
009885 

caset •osa »aqe 3 of 3 

ch .. ioalt 010507 

Applicator Exposure Monitorinq (Subdivision U) 

Guideline 1231: Estimation of Dermal Expcsure at outdoor Site• 

Estimation of Inhalation Exposure at Outdoor sites 

Estimation of Dermal Exposure at Indoor Sites 

Estimation of Inhalation at Indoor sites 

Guideline 12321 

Guideline f233: 

Guideline f234: 

lron is applied to turf and ornamental lawns usinq drop and broadcast 

spreaders, sprinkler cans, and by hand. 1 The potential for 

mixer/loader/applicator exposure exists. However, iron is of little 

concern from a toxicity perspective. 2 Therefore, OREB does not 

require a mixerjloader;applicator exposure study for rereqistration. 

Cpp•ptwa 

Iron, formulated as a qranular and soluble concentrate (liquid and 

solid), is used as a herbicide to control moss on residential lawns 

and ornamental turf. 1 Homeowners apply iron usinq drop and broadcast 

spreader11, sprinkler cans, e.nd by hand. 1 

cc: 

1 

Linda Kutney/SACB Pat McLauqhlin/TOX II 

Circulation 

Correspondence 

Chemical File 

UH lnf-tlan Ia biNd an the LUll report •ttd J.,...ry Z7, 1992 c- 2/19/92) f,_ Pllyllla J......., of IUD, and the procNct labela CEPA les. lloa. 7404·4, i'001·290, 3234•44, andl02•558). 

2. TDillcolltc•l lnf-tlon retrl.,... fr,. tha tDil -·liner dlttd 7131192; IIC\Ite 

oral/.,..1/lnhelatiOII/ .. t_., Ill biNd an 1191 a.l. 
UNiftD ITATU INVIIIIOHIIIDTAL PR011CTIOH AOINCY 

WASHINGTON, D.C. 20480 

• 

009885 

Z661 8 I AON OffiCI Of 

PEITICIDEI AND TlliKIC 

IUIITAHCEI 

MEMORANDUM 

subject: Toxicoloqy Review for the Rereqistration 

Document on Iron Sulfates 

Eliqibility 

To: 

From: 

Thru: 

Esther Saito, Actinq Chief 

Chemical Coordination Branch 

Health Effects Division (H7509C) 

Patricia McLauqhlin, Ph.D. 5' /l ~ ltj;;~.J/17- Toxicoloqy II Branch, HED (H7509C) 

Elizabeth Doyle, Ph.D., Head ~- a • ~0 I {/ ).;_3 section IV, Toxicoloqy II Branch, HED (H7509C!_. Q ;· 

Marcia van Gernert, Ph.D., Chief 1?7 fJ) __ ,} 

Toxicoloqy II Branch, HED (H7509C) t(~~ 

Chemicals: Ferric sulfate, ferrous sulfate heptahydrate, ferrous 

sulfate monohydrate case/chemical number: 4058/34902, 50502, 50507 

Products: Herbicides for lawns 

Considerations: 

The Food and oruq Administration has affirmed ferric sulfate as 

qenerally recoqni~ed as safe (GRAS) for use as a food flavorinq 

aqent. Also, FDA has affirmed ferrous sulfate (heptahydrate and 

monohydrate) as GRAS for use in food as a nutrient supplement with 

no limitation other than current qood manufacturinq practice. The toxicoloqical data on iron sulfates with the aqency and in 

the literature are adequate for assessinq risk to humans. Not all 

of the toxicity data usually required for pesticide reqistration 

are necessary for the present uses of iron sulfates. There are 

some unusual factors in this case which indicate that specific studies to fulfill the usual data requirements are not necessary to 

requlate these substances as pesticides. Iron sulfates are 

normally present in the environm£..:-.t. They may be present in foods 

naturally and as added inqredients. There is no reason to expect reasonable pesticide usaqe to constitute any hazard beyond ordinary 

exposure. 
,•• 

. 1. Toxicology Data Base 0098[i5· 

The toxicological data base on ferric sulfate, ferrous sulfo.te 

heptahydrate, and ferrous sulfate monohydrate is adequate and will 

support reregistration eligibility. 

a. Acute Toxicity 

TEST RESULT CATEGORY 

LDSO rat 1487 3 

Inhalation rat >1.1 3 

an LDSO of 1487 mg/kg in females and of 2102 rnq/kg in males. An 

acute dermal toxicity test in rabbits with ferric sulfate found an 

LD50 greater than 2000 rnq/kg, An acute inhalation toxicity study 

in rats with ferric sulfate found an LC50 greater than 1.10 rnq/L. 

Ferrous sulfate heptahydrate, in an acute oral study in rats, 

showed an LDlo of 1389 rnq/kg; an acute oral study in rabbits showed 

an LOla of 2778 mg/kg (4). The LDSO found for this compound in 

mice was 1520 rnq/kg (4) . A sensitization study in guinea pigs with 

ferrous sulfate monohydrate found no indication of contact 

sensitization by this compound. 

b. Metabolism 

Iron and sulfate are normal constituents of the diet and are 

metabolized and utilized by the body. 

c. Mutagenicity 

A mutation study in ~ 2Q!i reported positive results at 30 

umol/L (4). With due regard for the continuing exposure that human 

beings have had to the iron and sulfate components of these 

II 
• 

··. 

009885 ch~aicals over many, many generations, it is considered ~nlikely 

that this reported result in microorganisms has any bearing on 

probable effects in humans or other mammals at the levels expected 

from use of these compount.:·• as pesticides. 

BIBLIOGRAPHY 

(1) 42171701 

(2) 42171702 

(3) 42171703 

(4) Sax, N. I., and Lewis, R. J. SR, 1989. Dangerous Properties of 

Industrial Materials, 7th Ed. Van Nostrand ~einhold, New York. 

(5) 41763701 

ONE-LINERS