8 

### Federal Register / Vol. 53, No. 98 / Friday, May 20, 1988 / Notices'

ENVIRONMENTAL PROTECTION AGENCY [OPTS-41029; FRL-3381-7]
Twenty-second Report of the Interagency Testing Committee to the Administrator; Receipt of Report and Request for Comments Regarding Priority Listof Chemicals
AGENCY: Environmental Protection Agency (EPA). ACTION: Notice.

SUMMARY: The Interagency Testing Committee (ITC), established under section 4(e) ofthe Toxic Substances Control Act (TSCA), transmitted its Twenty-Second Report to the Administrator ofEPA on May 2, 1988. This report, which revises and updates the Committee's priority list of chemicals, adds 10 chemicals to the list. forpriority consideration by EPA in promulgation oftest rules under section 4(a) of the Act. The Twenty-Second Report is included with this notice. One chemical, 1,6-hexamethylene diisocyanate (CAS No. 822-06-0) is designated for response within 12 months. In response to ITC's designation, EPA will either initiate rulemaking under section 4(a) ofTSCA,

orpublish a Federal Register notice explaining the reasons for not initiating such rulemaking within 12 months. Crotonaldehyde (CAS No. 4170-30-3); imidazolium quaternary ammonium compounds (CAS No. 68122-86-1); and

seven ethoxylated quaternary ammonium compounds (CAS Nos. 68153-35-5,68389-88-8,68389-89-9, 68410-69-5, 68413-04-7, 68554-06-3, and 70914-090-9) are not designated for response within 12 months. EPA invites interested persons to submit written
comments on the report, and to attend Focus Meetings to help narrow and focus the issues raised by the ITC's recommendations.

-Additionally, EPAis soliciting interest in public participation in the consent agreement process for crotonaldehyde, imidazolium quarternary ammonium compounds, and seven ethoxylated quaternary ammonium compounds. *The ITC also has removed 9 chemicals from the priority list.Six aminoanthraquinone dyes (CAS Nos. 128-86-9, 2861-02-1, 6247-34-3, 6424-85- 7, 12217-79-7 and 17418-58--5) have been removed from the list on the basis of relatively low aggregate production.and, sufficient genotoxicity testing to reduce

concerns about these chemicals.' Tributyl phosphate (CAS No. 126-73-8), isopropanol (CAS No. 67-63-0), and methyl tertbutyl ether (CAS No. 1634- 04-41 have been removed because EPA has responded to the ITC's previous recommendations for testing ofthe chemicals. DATES: Written comments should be submitted by June 20, 1988. Submit written notice ofinterest in being designated an "interested party" to development ofconsent agreements for crotonaldehyde, imidazolium quaternary ammonium compounds and seven ethoxylated quaternary ammonium compounds by June 20, 1988. Focus Meetings will be held on June 14 and June 17, 1988. ADDRESS: Send written submissions to: TSCA Public Docket Office (TS-793), Office ofToxic Substances, Environmental Protection Agency, Rm. NE G-004, 401 M Street SW., Washington, DC 20460.

Submissions should bear the

- document control number (OPTS-41029).

Thepublic record supporting this action, including comments,..is available for public inspection in Rm. NE G-004 at the address noted above from 8 a.m. to4 p.m., Monday through Friday, except legal holidays. The Focus Meetings will be held at EPA Headquarters, Rm. 103 NE Mall, 401 M Street SW., Washington, DC. Persons planning to attend the Focus Meetings, and/or seeking to be informed ofsubsequent public meetings

on these chemicals, should notify the TSCA Assistance Office at the address listed below. To ensure seating accommodations at the Focus Meetings, persons interested in attending are asked to notify EPA at least one week ahead of the scheduled date. FOR FURTHER INFORMATION CONTACT: Michael M. Stahl, Acting Director, TSCA Assistance Office (TS-799), Office of Toxic Substances, Environmental Protection Agency, 401 M Street SW., Washington, DC 20460, (202) 554-1404.
:SUPPLEMENTARY INFORMATION: 

### EPA has received the Report ofthe TSCA Interagency Testing Committee to the Administrator.

I. Background

TSCA (Pub. L. 94-469, 90 Stat. 2003 et seq; 15 U.S.C. 2601 etseq.) authorizes the Administrator ofEPA to promulgate regulations under section 4(a) requiring testing ofchemical substances and mixtures in order to develop data relevant to determining the risks that such chemical substances and mixtures may present to health and the environment. Section 4(e) ofTSCA established an Interagency Testing Committee to make recommendations to the Administrator ofEPA on chemical substances and mixtures tobe given priority consideration in proposing test rules under section 4(a). Section 4(e) directs the ITC to revise itslist of recommendations at least every 6 months as necessary. The ITC may "designate" up to,50 substances and mixtures at any one time forpriority. consideration by the Agency. The chemical 1,6-hexamethylene diisocyanate'is a designated chemical. For such designations, the Agency must within 12 months either initiate rulemaking or issue in the Federal Register its reasons for not doing so. The ITC's Twenty-Second Report was received by the Administrator on May 2 and follows this Notice. The Report adds 10 substances to the TSCA section 4(e) priority list.

II. Written and Oral Comments and Public Meetings

EPA invites interested persons to submit detailed comments on the ITC's

new recommendations. The Agency is interested in receiving information

. concerning additional or ongoing health and safety studies on the subject chemicals as well as information, Srelating to the human and environmental

exposure to these chemicals.

A notice is published elsewhere in today's IPederal Register adding 8 ofthe 10 substances recommended in the ITC's Twenty-Second Report to the TSCA section 8(d) Health and Safety Data Reporting Rule (40 CFR Part 716]. Two of the 10 substances, 1,6-hexamethylene diisocyanate (52 FR 16022, May 1, 1987) and crotonaldehyde (51 FR 2890,January 22, 1986), already are subject to this rule, which requires the reporting of unpublished health and safety studies

on the listed chemicals. All 10 chemicals will be added to the TSCA section 8(a) Preliminary Assessment Information Rule (40 CFR Part 712) published elsewhere in this issue. The section 8(a) rule requires the reporting ofproduction volume, use, exposure, and release information on ,the listed chemicals.

Focus Meetings will be held to.discuss relevant issues pertaining to these chemicals and to narrow the range of issues/effects which will be the focus of the Agency's subsequent activities in responding to the ITCrecommendations. The Focus Meetings will be held as follows::

June 14,.1988

9:30 a.m.-Imidazolium quaternary

ammonium compounds 1:00 p.m.-Ethoxylated quaternary

ammonium compounds

June 17, 198.8

9:30 a.m.-Crotonaldehyde 1:00p.m.-1,6-Hexamethylene

diisocyanate mmft I 1 

### 18196.

### Federal Register / Vol. 53, No. 98 / Friday, May 20. 1988 / Notices

-
They will be held at EPA or the environment. It also provides for Headquarters, Rm. 103 NE Mall, 401 M the establishment ofa Committee (ITC), Street SW., Washington, DC. These composed of representatives from eight meetings are intended to supplement designated Federal agencies, to and expand upon written comments recommend chemical substances and submitted in response to this notice. mixtures (chemicals) to which the

Persons wishing to attend these Administrator ofthe U.S. Environmental meetings, or subsequent meetings on Protection Agency (EPA) should give these chemicals, should call the TSCA priority consideration for the Assistance Office at the telephone promulgation of testing rules. number listed above at least one week in advance. Section 4(e)(1)(A) ofTSCA difects the

This notice also serves to invite Committee to recommend to the EPA

persons interested in participating in or Administrator chemicals to which the monitoring negotiations for consent Administrator should give priority agreements for crotonaldehyde, consideration for the promulgation of imidazolium quaternary ammonium testing rulespursuant to section 4(a). compounds, and ethoxylated quaternary The Committee is required to designate ammonium compounds to notify EPA no those chemicals, from among its later than June 20, 1988. Theprocedures recommendations, to which the fornegotiations are described in 40 CFR Administrator should respond within 12 790.22. All written submissions should months by either initiating a rulemaking bear the identifying docket number proceeding under section 4(a) or; (OPTS-41029). publishing the Administrator's reason III. Status ofList for not initiating such a proceeding. At least every 6 months, the Committee In addition to adding the 10 makes those revisions in the TSCA recommendations to the priority list, the section 4(e) Priority'List that it ITC's Twenty-Second Report notes the determines to be necessary and removal of9 chemicals from the list transmits them to the EPA since the last ITC report. Six Administrator. aminoanthraquinone dyes have been Amnsrtr 

### aminantraqinoe dys hve een As a result ofits deliberations, the removed from the list by the ITC on the C i reis eb a setio basis ofrelatively low aggregate Committee is revising the TSCA section production and sufficient genotoxicity 4(e) Priority List by the addition of10 testing toreduce concerns. Subsequent chemicals.
to ITC's preparation ofits Twenty-First The Priority List is divided into three Report, EPA responded to the ITC's parts: Part A'contains those recommendations for three additional recommended chemicals and groups chemicals. The three chemicals removed designated for priority consideration and the dates ofpublication in the and response by the EPA Administrator Federal Register ofEPA's responses to within 12 months. Part B contains the ITC for these chemicals are: tributyl chemicals and groups ofchemicals phosphate (52FR 43346, November 12, recommended with intent-to-designate. 1987); isopropanol, (53 FR 8638, March This category was established by the 16, 1988); and methyl tertbutyl ether (53 Committee in its seventeenth report (50 FR 10391, March 31, 1988). FR 47603; November 19, 1985) to take

The current list contains 1 designated advantage ofrules promulgating substance, 2 chemicals recommended automatic reporting requirements for with intent-to-designate, and 14 non-designated ITC recommendations recommended substances. under the section 8(a) Preliminary

Authority: 15 U.S.C. 2603. Assessment rule and the TSCA.section Dated: May 11, 1988. 8(d) Health and Safety Data Reporting J.Merenda, rule. Information received following Director, ExistingChemicdlAssessment 

### recommendation with intent-to- Division.

- designate -mayinfluence the'Committee
to either designate ofnot designate the Twenty-Second Report of the.TSCA chemicals or groups ofchemicals in a Interagency Testing Committee to the subsequent report to the Adminisfiator. Administrator, Environmental Protection Part C contains chemicals'and'groups of Agency • chemicals that have been recommended Summary

.. for priority consideration by EPA

.Section4 ofthe Toxic Substances without being designated for response Control Act of1976 (TSCA,Pub. L. 94- within.12 months. The changes to,the. 469) provides forthe testing of! Priority List are presented, together with chemicals in commerce that-may present the types of testing recommended, in the
an unreasonable risk ofinjury to health following Table 1:, TABLE 1-ADDITIONS TO THE SECTION 

### 4(e) PRIORITY LIST, MAY 1988

Chemical/Group

A. Designated for

response within 12 months: 1,6-

Hexamethylene diisocyanate I CAS No. 822- 06-0.

B. Recommended

with Intent-toDesignate: Crotonaldehyde 2

CAS No. 4170- 30-3.

C. Recommended

WithoutBeing Designated for Response Within 12 Months: Imidazolium

Quaternary Ammonium Compounds 3 (CAS No. 68122-86-1).

Ethoxylated

Quaternary Ammonium Compounds 4 (CAS Nos. 68153-35-5, 68389-88-8, 6889-89-9, 68410-69-5, 68413-04-7; 68554-06-3, and 70914-09- 9). Recommended studies

Health Effects: Chronic toxicity, including oncogencity; reproductive and developmental effects.

Chemical Fate: None Ecological Effects: None

Health Effects: None

Chemical Fate: Volatilization

rate from water;, aerobic aquatic biodegradation rate.

. I Ecological Effects: Acute

toxicity to algae, fish and aquatic invertebrates.

Health Effects: Chronic toxic-

.iy

studies to evaluate potential ' effects through long-term dermal exposures.

Chemical Fate: Aerobic and

anaerobic biodegradation of the chemical sorbed to' freshwater and estuarine sediments. Ecological Effects: Acute

and chronic effects on representative freshwater and estuarine benthic organisms. Health Effects: Chronic toxicity

studies to evaluate potential effects through long-term dermal exposures.

Chemical Fate: Aerobic and

anaerobic biodegradation of the chemicals sorbed'to freshwater and estuarine sediments. Ecological Effects: Acute

and chronic effects 6n representative freshwater and benthic organisms.

CA Index Names (9CI) 'Hexane1 t,6 diisocyanato-. 2-Butenal. 3 Imidazolium compounds, 4,5-dihydro-1;methyl-2- nortallow alkyl--(2-tallow amidoethyl), Me sulfates.

4 Ethanaminium, 2-amino-N-(2-aminoethyl)-N.(2-hydroxyethyl)-N-methyl-, NN'-ditallow acyl derivs., Me sulfates (salts); CAS No. 68153-35-5,

.

Poly(oxy-1,2-ethanediyl), a-t2-[bis(2-aminoethy)- methylammonio]-ethylJ--hydroxy. N.N'-dicoco acyl derivs., Me sulfates (salts); CAS No: 68389-88-8,

Poly(oxy-1,2.ethanediyl), a-[2-[bis(2-aminoehy)- methylammonio]-ethyl].-o-hydroxy. I N,N'- IR1017 lfilOq

Recommended studies

### Federal Register / Vol. 53, No. 98 / Friday, May 20, 1988 / Notices

bis(hydrogenated tallow atyl) defies., Me sulfate (salts); CAS No. 68389-89-9,

Poly(oxy-1,2-ethanediy), a-[2-[bis(2-aminoethyl)

. methylammonio]-ethyl]-w-hydroxy-... N,N'-ditalloi

acyl devs., Me.sulfates (salts); CAS No. 68410-69 5,Polytoxy(methyl-1,2-ethanediyl)], a-t2-[bis(2 aminoethyi)-methytammonio]-methylethyl]-i,)- hydroxy-, N,N'-, ditallow acyl derivs., Me sulfate (salts); CAS No 68413-04-7,

Poly(oxy-1,2-ethanediyl). a-[3-Ebis(2-aminoethyl) methylammonio ]-2-hydroxypropyl] -&-hydroxyo, I

coco acyl derivs.. Me sulfates (salts); CAS Nc 68554-06-3. and

Poly(oxy-1,2-ethanediyl). a-[2-[bis(2-aminoethyl] methylammonio]-ethyl]-w-hydroxy-, N.N'-di-C,,-, acyl defivs., Me sulfates (salts);CAS No. 70914-09 9

TSCA InteragencyTesting Committee Statutory Member Agencies and Their Representatives
Council on Environmental Quality

Joseph Jehl, Member 1 Department of Commerce

Partick D. Cosslett, Member Raimundo Prat,.Alternate Environmental Protection Agency

John D. Walker, Member Laurence S. Rosenstein, Alternate National Cancer Institute

Richard Adamson, Member Elizabeth K. Weisburger, Alternate National Institute ofEnvironmental Health Sciences James K. Selkirk. Member and

Chairperson National Institute for Occupational

.. Safety andHealth Bryan D. Hardin, Member and Vice

Chairperson Rodger L. Tatken, Alternate National Science Foundation

Rodger W. Baier, Member Jarvis L. Moyers, Alternate Occupational Safety and Health Administration Robert Turnage, Member 2 Stephen Mallinger, Alternate

Liaison Agencies and Their Representatives
Consumer Product Safety Commission

Lakshmi C. Mishra Department ofAgriculture

Richard M. Parry,Jr. Elise A.B. Brown Department ofDefense

Vacant Department ofthe Interior

Sarah Gerould Food and Drug Administration

Arnold Borsetti NationalLibrary ofMedicine

Vera Hudson National Toxicology Program,

Dorothy Canter

Committee Staff
Robert H. Brink, Executive Secretary

IAppointed on October 30,1987.

2 Appointed on October 26, 1987. s Norma Williams, ITCProgram Specialist Support Staff
Alan Carpien--Office ofthe General Counsel, EPA The Committee acknowledges and is grateful for the assistance and support given the ITC by the staff ofDynamac Corporation (technical support contractor) and personnel ofthe EPA Office ofToxic Substances.

Chapter 1-Introduction

1.1 Background. The TSCA Interagency Testing Committee (Committee) was established under section 4(e) of the Toxic Substances Control Act of 1986 (TSCA,Pub. L. 94- 469). The specific mandate of the Committee is to recommend to the Administrator ofthe U.S. Environmental Protection Agency (EPA) chemical substances and mixtures in commerce that should be given priority consideration for the promulgation of testing rules to determine their potential hazard to human health and/or the environment. TSCA specifies that the Committee's recommendations shall be in the form ofa Priority List, which is to be published in the Federal Register. The Committee is directed by section 4(e)(1){A) ofTSCA to designate those chemicals on the Priority List to which the EPA Administrator should respond within 12 months by either initiating a rulemaking proceeding under section 4(a) or publishing the Administrator's

reason fornot initiating such a proceeding. There is no statutory time limit for EPA response regarding chemicals that ITC has recommended but not designated forresponse within 12 months.

At least every 6 months, the Committee makes those revisions in the section 4(e) Priority List that it determines to be necessary and transmits them to the EPA Administrator.

The Committee is composed of representatives from eight statutory member agencies and seven liaison agencies. The specific representatives and their affiliations are named in the front ofthis report. The Committee's chemical review procedures and priority recommendations are described in previous reports (Refs, 1 through 6).

.1.2 Committee's previousreports. Twenty-one previous reports to the EPA Administrator have been issued by the Committee and published in the Federal Register (Refs. 1 through 6). Ninety-six entries (chemicals and groups of chemicals) were recommended for priority consideration by the EPA *Administrator and designated for

response within 12 months: In addition, 

### fourteen chemicals and one group of chemicals were recommended without being so designated..

1.3 Committee'sactivitiesduring this reporting period. Between October 16,1987 and April 21, 1988, the 

### Committee continued to .review chemicals from its fifth and sixth scoring exercisesxand from nominations by Member Agencies, Liaison Agencies and State Agencies.

The Committee contacted chemical manufacturers-and trade associations to request information that would be of value in its deliberations. Most ofthose contacted provided unpublished information on current production, exposure, uses, and effects ofchemicals under study by the Committee,

During this reporting period, the Committee reviewed available information on eighty-four chemicals. Ten were selected for addition to the section 4(e) PriorityList, and twentyfour were deferred indefinitely. The remaining chemicals are still under study.

In its twentieth report to the EPA Administrator (Ref. 5,ITC, 1987), the Committee placed ethylbenzene (CAS No. 100-41-4) on the Priority List on the 

### "Recommended with Intent-toDesignate" category. The Committee recommended that ethylbenzene be tested for acute toxicity to freshwater algae and invertebrates and.to saltwater algae,invertebrates and fish. Subsequently, the Committee learned that acute toxicity testing of ethylbenzene with freshwater invertebrates had recently been completed at theUniversity of Wisconsin As noted in thetwenty-first report, the Committee also was informed that a consortium ofethylbenzene -producers,the Styrene and Ethylbenzene Association, voluntarily sponsored studies on the other acute toxicity tests recommended by the Committee. The Committee deferred a decision on whether or not todesignate ethylbenzene pending a review ofthe data developed during the-above studies. The Committee has reviewed the data developed in those studies and has concluded that all ofthe datagaps identified in the,twentieth report have been satisfactorily resolved with the' exception ofsaltwater invertebrate testing. Industry has volunteered to sponsor additional studies with saltwater inver'tebrates. The Committee has decided to continue to defer a decision on whether or not to designate ethylbenzenepending a review ofdata from the additional invertebrate tests.

In its twenty-first report to the EPA -Administrator,the Committee 18198

### Feder#1 Register / Vol. 53, No. 98 / Friday, May 20, 1988 / Notices

recommended genotoxicity testing on six aminoanthraquinone dyes (CAS Nos. 128-86-9,2861-02-1,6247-34-3,6424-85- 7, 12217-79-7 and 17418-58-5). Subsequent to the recommendation the Committee had an opportunity to examine the TSCA section 8(a) Preliminary Assessment rule and TSCA section 8(d) Health and Safety Data Reporting rule information submitted to the EPA. That information included
current production and use information

on those dyes and additional data on genotoxicity tests.As a result ofits review of that information, the Committee has concluded that the six aminoanthraquinone dyes with the above CASnumbers should be removed from the Priority List on the basis of relatively low aggregate production and sufficient genotoxicity testing to reduce

concerns.

1.4 The TSCA section4(e)Priority List.Section 4(e](1](B) ofTSCA direct the Committee to: " * * make such revisions in the [priority] list as it determines to be necessary and * * * transmit them to the Administrator together with the Committee's reasons for the revisions." Under this authority, the Committee is revising the Priority List by adding ten chemicals: 1,6- hexamethylene diisocyanate (GAS No. 822-06-0), crotonaldehyde (CAS No. 4170-30-3), imidazolium quaternary ammonium compounds (CAS No. 68122- 86-1) and ethoxylated quaternary ammonium compounds (CAS Nos. 68153-35-5,68389-88-8,68389-89-9, 68410-69-5, 68413-04-7, 68554-06-3 and 70914-09-9). Nine chemicals are being removed from the Priority List at this time. Tributyl phosphate (GAS No. 126- 73-8) was the subject ofa Notice of Proposed Rulemaking (52 FR 43346; November 12, 1987). Isopropanol (GAS No. 67-63-0) also was the subject ofa Notice of Proposed Rulemaking (53 FR 8638; March 16, 1988) and methyl tert butyl ether (CAS No. 1634-04-4) was the subject ofa Testing Consent Oider (53 FR 10391; March 31, 1988). In addition, six aminoanthraquinone dyes (GAS Nos. 128-86-9,2861-02-1,6247-34-3,6424-85- 7, 12217-79-7 and 17418-58-5) are being removed for the reasons given in section 1.3.

With the ten new recommendations and nine removals noted in this report, seventeen entries now appear on the section 4(e) Priority List. The Priority List is divided in the following Table 2 into three parts; namely, A. Chemicals and Groups ofChemicals Designated for Response Within'12 Months, B. Chemicals and Groups ofChemicals Recommended with Intent-to-Designate, and C. Chemicals and Groups of 

### Chemicals Recommended WithoutBeing Designated forResponse Within 12 Months. Table 2follows:

TABLE 2-THE TSCA SECTION 

### 4(e) PRIORITY LIST, MAY 1988

Date of Entry designation

A. Chemicals and Groups of Chemicals Recommended and Designated for Response Within 12 Months: 1. 1,6-Hexamethylene diisocyanate. B. Chemicals and Groups of Chemicals Recommended with Intent-toDesignate: 1. Ethylbenzene

............................... 2. Crotonaldehyde

............................ C. Chemicals and Groups of Chemicals Recommended Without Being Designated for Response Within 12 Months: 1. Diisodecyl phenyl phosphite. 2. C.I. Disperse Blue 79

.................. 3. Methyl ethyl ketoxime

................. 4. N-[5-[bis[2-

(acetyloxy)ethyl]amino]-2-[(2- bromo-4,6-dinitrophenyl)azo]-4- methoxy phenylJ-acetamide. 5. N-5-4bis[2-

(acetyloxy)ethyllamino]-2-[2- chloro-4,6-dinitrophenyl)azo]-4- methoxy phenylJ-acetamide. 6. N-[5-[bis[2-

(acetyloxy)ethyl]amino]-2-[(2- chloro-4,6-dinitrophenyl)azo]-4- ethoxy phenyl]-acetamide. 7. Imidazolium compounds, 4,5-

dihydro-l-methyl-2onortallow alkyl-l-(2-tallow amidoethy), Me sulfates. 8. Ethanaminium,2-amino-N-(2-

aminoethyl)-N-(2-hydroxyethyl)- N-methyl-, N,N'-ditallow acyl derivs., Me sulfates (salts). 9.. Poly(oxy-1,2-ethanediyt),a-I2-

[bis(2-aminoethyl)-. methylammonio]-ethyl-jhydroxy-, N,N'-dicoco acyl derivs.,'Me sulfates (salts). 10. Poly(oxy-1,2-ethanediyl),a-[2-

[bis(2-aminoethyl)- methylammonioJ -ethyl]-o-

- hydroxy-, N,N'-bis(hydrogenated tallow acyl) derivs., Me sulfates (salts). 11. Poly(oxy-1,2-ethanediyl),a-[2-

[bis(2-aminoethyl)-methylammonio-ethyl]-whydroxy-, NN'-ditallow acyl derivs., Me sulfates (salts). 12. Polytoxy(methyl-1,2-

ethanediyl)],a-2-[bis(2-aminoethyl)-methylammoniolmethylethyl]-w-hydroxy-, N,N'-, ditallow acyl derivs., Me sulfates (salts). 13.. Poly(oxy-1,2-ethanediyl),a-(3-

[bis(2-aminoethyl)- methylammonio]-2- hydroxypropyl]-o)-hydroxy-, Ncoco acyl derivs., Me sulfates (salts). 14. Poly(oxy-1,2-ethanediyl),a-[2-

[bis(2-aminoethyl)-methylammonio]-ethyl]-oihydroxy-, N,N'-di-C,4-s acyl derivs., Me sulfates (salts). May 1988

May 1987 May 1988

Nov. 1985 Nov.1986 Nov. 1986 May 1987

May 1987

May 1987

May 1988

May 1988

May 1988

May 1988

May 1988

May 1988

May 1988

May 1988 References (1] Sixteenth Report of theTSCA Interagency Testing Committee to the Administrator, Environmental Protection Agency. TSCA Interagency Testing Committee, May 21, 1985, 50 FR 20930-20939. Includes references to Reports I through 15 and an annotated list ofremovals.

(2)Seventienth Report ofthe TSCA Interagency Testing Committee to the Administrator, Environmental Protection Agency. TSCA Interagency Testing Committee, November 19, 1985, 50 FR47603- 47612.

(3] Eighteenth Report ofthe TSCA Interagency Testing Committee to the Administrator, Environmental Protection Agency. TSCA Interagency Testing Committee, May 19, 1986, 51 FR 18368-18375.

(4] Nineteenth Report oftheTSCA Interagency Testing Committee to the Administrator, Environmental Protection Agency. TSCA Interagency Testing Committee, November 14, 1986, 51 FR 41417- 41432.

(5)Twentieth Report ofthe TSCA Interagency Testing Committee to the Administrator, Environmental Protection Agency. TSCA Interagency Testing Committee, May 20,1987, 52 FR 19020-19026.

(6)

Twenty-first Report ofthe TSCA Interagency Testing Committee to the Administrator,Environmental Protection Agency. TSCA Interagency Testing Committee, November 20, 1987, 52FR 44830- 44837. Chapter 2-Recommendationsofthe Committee

2.1 Chemicalsrecommended for priorityconsiderationby theEPA Administrator. As provided by section 4(e)(1)(B) ofTSCA, the Committee is adding the following chemical substances to the section 4(e) Priority List: 1,6-hexamethylene diisocyanate (CAS No. 822-06-0), crotonaldehyde (CAS No. 4170-30-3), imidazolium quaternary ammonium compounds (CAS No. 68122-86-1) and ethoxylated quaternary ammonium compounds (CAS Nos. 68153-35-5, 68389-88-8, 68389-89-9, 68410-69-5, 68413-04-7, 68554-06-3 and 70914-09-9). The recommendation of these chemicals is made after considering the factors identified in section 4(e)(1)(A) and other relevant information, as well as the professional judgment "of Committee members. 2.2 Chemicals .designated forresponse within 12months-2.2.a1,6- Hexamethylene diisocyanateSummary ofrecommendedstudies.It is recommended that 1,6-hexamethylene diisocyanate be tested for the following:

1. Chemical fate:None. 2.Healtheffects: Chronic toxicity (including oncogenicity) and reproductive and developmental effects studies.

3.Ecologicaleffects: None. 

### 18199

### Federal Register / Vol. 53, No. 98 /.Friday, May 20, 1988 

## / totices

Physical and Chemical Information

CASNumber:822-06-0 Synonyms:Hexane, 1,6-diisocyanato-;

Hexamethylene diisocyanate; 1,6- Diisocyanatohexane Acronym: HDI TradeNames:Desmodur H; Mondur HX Structural Formula: OCNCH2CH2CH2C H2C2CH 2NCO

OCNC H 2 CH 2CH 2 C H 2 C H2 CH 2NCOEmpiricalFormula: CsH 12 N

202 MolecularWeight 168.0 Appearance: Liquid BoilingPoint-212.8'C at 760 mmHg

(Ref. 22, NIOSH, 1978) VaporPressure: 0.05 mmHg at 24 °C (Ref. 22, NIOSH, 1978] Specific Gravity:1.04 (Ref.22, NIOSH,

1978) Flashpoint140 'C (Ref. 22, NIOSH, 1978] Solubility:Poorly soluble inwater;

readily soluble in organic solvents (Ref. 22,-NIOSH, 1978) Log Octanol/Water Partition Coefficient(logP): -1.9 (Est'd., Ref. 14, Leo et al., 1971).

Rationale for Recommendations

I. ExposureInformation

A. ProductiornUse/Disposal/ Environmental Release

Hexamethylene diisocyanate (HDI) is produced in commercial quantities at Baytown, TX; current annual production is about 11 million pounds (Ref.19, Mobay, 1988b). Laboratory quantities of HDI are also produced by M6rton Thiokol, Inc. at its Danvers, MA plant (Ref.10, ICF, 1986). Thepublic portion of the TSCA Inventory lists U.S. " production at1 to 10 million pounds in 1977 (Ref. 27, USEPA, 1988). No import data are reported for HDI. In 1981, approximately 2 to 3 million pounds

were exported '(Ref.16, Mobay, 1982).

The manufacturing process forHDI, similar to that ofother diisocyanates, employsphosgenation ofhexamethylene diamine. In response to a request for information, Mobay estimated that the quantity ofHDI that enters the -environment during production and use does not exceed 20,000 pounds per year (Ref. 16,Mobay, 1982).

HDIis usedin the manufacture of higher molecular weight biuret polyisocyanate products. These.are commercially used as curing agents in the formulation ofpolyurethane paint systems for.automobile refinishing, industrial maintenance, marine coatings,. and otherhigher performance coating systems (Ref. 16, Mobay, 1982). B. Evidence forHuman and Environmental Exposure

There is no OSHA permissible exposure level (PEL) for HDI.In 1978, NIOSH recommended that OSHA adopt the same standard also recommended for toluene diisocyanate (TDI) and methylene diphenyldiisocyanate (MDI), i.e., an 8-hour time-weighted average of 5ppb (35 ug/m3 }(Ref. 22, NIOSH, 1978). The recommended 10-minute short-term
exposure limit is 0.02 ppm (140 ug/m3) (Ref. 22, NIOSH, 1978). ACGIH earlier recommended the same levels (Ref. 1, ACCII-, 1976). The level immediately dangerous to life and health (IDLH), beyond which irreversible health effects

are known to occur, is 10ppm (Ref.28, Woolrich, 1982).

The National Occupational Hazard Survey (NOHS), conducted by the National Institute for Occupational Safety and Health (NIOSH) from 1972 to 1974, estimated that about 4,490 workers in 238 plants were exposed to HDI through manufacture, processing, or use in 1970. Of these, about 4,000 were involved with coating applications (Ref. 21, NIOSH, 1976). NIOSH also conducted a second workplace survey, the National Occupational Exposure Survey (NOES).from 1980 to 1983 (Ref. 23, NIOSH, 1984). Preliminary data from the NOES indicated that 39workers, including 11 women, were potentially exposed in 1980.

The number ofworkers exposed to HDI is probably underestimated since it is impossible to estimate the workers in trade professions or other operations using products containing HDI. However, data indicate that coatings applications provide the greatest source ofoccupational exposure to HDI. Information obtained from theiJnited Auto Workers suggests that 1,000 to 10,000 workers are potentially exposed
toHDI-containing coatings and adhesives in new car,manufacture (Ref. 26, UAW, 1988). The Automotive Services Association estimated that there are 60,000 to 100,000 private autobody and repaint shops that usually employ 1.5 to 12 persons each, potentially exposing between 90,000 and 1.2 million persons (Ref.4, ASA, 1988): In a 1982 submission to the TSCA Interagency Testing Committee, Mobay estimated that 153,000 autobody repair workers were potentially exposed to HDI (Ref. 16, Mobay, 1982).

Information received from the International Brotherhood of Painters and Allied Trades (IBPAT) indicated that about 60,000 union members use an HDI-containing coating at least once a year. HDI-containing coatings are used several times a year by about 30,000 workers; 3,000use HDI-containing paint exclusively (Ref. 9,IBPAT, 1988). The Communication Workers ofAmerica indicatedthat about 51,000 oftheir members are exposed to multiple diisocyanates, including HDI.Ofthese, about 45,000 telecommunications cable splicers and outside plant technicians work with plugging compounds containing HDI.The remaining 6,000 workers are exposed to diisocyanatecontaining inks and RIM plastics {Ref. 5, CWA, 1988).

The civilian and military aircraft' industry uses aliphatic diisocyanatecontaining paint almost exclusively because ofits stability in ultraviolet light (Ref.8, Hulse, 1984). The number of
persons potentially exposed to HDI through these occupations is not known
at this time.

In summary, excluding individuals exposed through the aerospace industries and the military, it appears thatbetween 265,000 and 1,315,000 workers are potentially exposed to HDIcontaining products.

Between 1978 and 1982, Mobay conducted field industrial hygiene surveys during spray applications of HDI-containing paint systems. Data gathered during six-different surveys demonstrated HDI concentrations between <0.005 ppm and 0.04 ppm (Ref. 16, Mobay,-1982). As shown in a section 8(d) submission from Mobay, oven exhaust from a heat-cured urethane resulted in monomeric HDI concentrations of230 ppb (Ref. 17, Mobay, 1978). This level exceeded the ACGIH threshold limit value (TLV) and NIOSH recommended short-term
exposure limit (STEL) of20 ppb by about 11 times.

A study was conducted to determine the airborne concentrations oftotal reactive isocyanate groups (-NCOs) fromthe application ofconsumeravailable polyurethane products. A twopart HDI-containing polyurethane' enamel was used in a controlled area simulating a workshop/garage. The -productwas sprayed on a metal bookcase. Analyses of personal and

area air samples .collected during the spray application ofthe enamel found

- NCO groups in excess ofthe upper limit ofdetection, >5.0 mg NCO/m 3 or >2.9 ppm (Ref.20, MRI, 1987). This level was almost 300 times the NIOSHrecommended 10-minute STEL of0.02 ppm.
II. ChemicalFate Information Although HDI is likely to be released to the environment, primarily in fugitive air emissions, itis notexpected to persist and shouldbe rapidly

- 

### 18200

### Federal Register / VtL 53, No. 98 

## / Friday. May 20, 1988 J Notices

transformed, especially in the:presence JI. BiologicalEffectsof:Concernto B. Acute (short-term) Effects ofliquid water. Therefore, chemical fate HumanHealth The acute and subacute toxicity of testing is not recommended at this time. A.Metabolism and Toxicdkinetics HDI are summarized in the .followig Tables 3:and 4. No informationwas found.

,TABLE,3.-CRITICAL END POINTS FOR THE ACUTE/SJBACIT-E Toxic .EFFECTS !OFIHDI

Critical toxic effect end points 1from multipledose/concentration 'Test Test subject .studies Reference

ILOELb iNOEL'

Skin irritation

............................. . . .... ..... "Guineapig

................ I

............... 0A mg/anim l :0:2.mg/animal Kondrat'yev and Mustayev (1969, Ref. 13). '(approx) (approx.) Ocular irritation

............. ...... .. ......... Rabbit

. ...... iNE d NE Mobay (1961, Ref. 1:5). Sensory irritation

...... . . .... 'Male mouse

..... . . 0.062 ppm NE Sanglia etal. (1981.,:Ref. 24). (0.43.mgZmr 3 I Pulmonary irritation

.................... Albino rat................. NE' NE Lomonova and Frolova (1968, -as cited in NIOSH, 1,978, Rdf. 2?2). Pulmonary irritation

.................... Rabbit

...................... NE NE ;Frolovaya (1966, 1-968, ,asoitedin Kondrat'yev and Mustayev 1969,,fef. 13). Contact :sensitivity,,induction

...................... Male mouse

.............. 8 ug/aimal 2.1 ug/animal Thorne et al. (1987, Ref. 25). !(0.281mg/kg) i(0:075 mg/ I kg) Contact sensitivity induction

.............................. G inea pig

................................. INE INE Kondrat'yev end Mustayev '(1969, Retf. 13). Contact sensitivity elicitation

.......................... Guinea pig.....

............................. Bug/animal

, NE Kondrat'yev and .Mustayev k(,1969, Ref. 13). (approx) Contact sensitivity elicitation

................................. Male mouse
........................... NE IE Thorne et al. (1987, Ref. 25).

,*With the exception of the mice used in .the Sangha et al. .(1981) study, 1test animal parameters such as sex, age, weight, and strain were not reported. b Lowestobservable-effects level. cNo-ooservable-etfects level.

NE, not-establishedinthis study.

TABLE 4.-ACUTE TOXICI.TY'OF HDI IN :LABORATORY ANIMALS

LC

5 0 Species -Concentration Duration (hours) Reference 'Oral '(mg/kg) 'Dermal (mg/kg) (mg/m 3) (ppm)

Rat

......... ...... 385 56 6 710

................. 'Woolrich'(1982, 'Ref.28). Rat (M

.. 310 45 4

.............................. 'Bunge;et al. ,(1977, as citedinNIOSH, 1978, Ref..22).
Rat (F)

....................... 350 51 4

............................ 'Bungeet.al. (1977, asicited in NIOSH, 1978,,Ref.,22). Rat

....................... ................. i;5

............... Mobay '(l1961,Ref. 15).
Mouse

...................... 30 4 ;2

.............................................. .... :Lomonova and Frolova '(1968, ascited in INIOSH, ;1978,iRef.'22). Rabbit

........ ............ ... ................ ........ ... ................. J....

.. ....... ....................... ................................ ..... 570 Woolrich (4182, ,Ref.28).

Rabbit [---

- I

............ . . . . . . . . . . . . . . .15).
Single dermal doses of -1,000 lo 1:250 mg/kg caused lethality, damage to subcutaneous 'layers iof skin, and systemic injury including -extensive pulmonary congestion.

HDI is known toproduce irritation and inflammation ofthe upper respiratory tract,so-called sensory irritation. Sangha etal.'(Ref. 24, 1981j conducted an acute inhalation study with mice. Depression ofthe respiratory
rate was observed at the lowestdose of EDI tested,,62 ppb (0.43

### .mg/m3). No LOELwas established.

Experiments dealing with the eiicitation ofdermal HDI hypersensitivity wereperformed early in the study ofdiisocyanates. A 'keystudy withguinea pigs pnbulished in 1969by Kondra't'yev and'Mustayev 'Ref. 13, 1969) provided aLOELof'8 ug per animal. Since this is the lowest dose that has been tested in thismanner, it 'is clear that a NOEL hasiotyetbeen established.

Thorne et al. 

### (Ref.'25, 1-987.) induced dermal sensitization to,HDIin mice by application 'ofa single'doseto shaved abdominal ,skin.'Sensitizabion was demonstratedbya sgingle challenge ,does
to the ear. The'SD 5 0 (does predicted to sensitize 50 percent ofthe animals) upon homologous challenge for HDI ,was0.088 mg/kg. TheLOEL for HDI was 8,ugper animal; the)NOEL was 2.1ug,per animal.
C. Genotoxicity.

In the Salmonellaassay,'HDI wasnot mutagenic in,StrainsTAIOO, TA98, or TA1537 with orwithout metabolic activation. A'wide dose'range, up to the highest noninhiblitory dose, was'used (Ref.3,Andetsen et al., 1980). HDIis also reported to 'inhibitmulagenesis induced'by ultravioletlight in an Escherichiacol wild-type strain but not inDNA-repair-enzyme deficient strain (Ref.12,Kawazoeet 

### al., 1981 

### 1 18201

### Federal Register /. Vol. 53, No. 98 / Friday, May 20, 1988 / Notices

D. Oncogenicity

The Mobay Corporation is conducting

a2-year inhalation toxicity/ oncogenicity study for HDI. Male and female Fischer 344 rats were exposed to 0, 0.005, 0.025, and 0.125 ppm for 0 to 4 months and to 0.175 ppm thereafter. The
exposure regimen was 6 hours per day, 5 days per week for approximately 24 months.

Sixtyrats ofeach sex were exposed at each level, and 10 rats ofeach sex at each level for a satellite group. Preliminary review ofthe data indicated

no toxicologically significant effects on body weight, ophthalmology or mortality; no other parameters were. evaluated. The final report is scheduled
to be completed during mid-1989 (Ref. 18, Mobay, 1988a).

E. Chronic (Longterm) Effects

No information was found.

F.Reproductive and Developmental, Effects

No information was found.

G. Observations in Humans

Allegations of adverse health effects following exposure to HDI (and other diisocyanates) were the subject of a TSCA section 8(c) reporting rule (53.FR 1408; January 19, 1988). The rule required only submission of unknown or unreported adverse health effects. Several of these involved a two-part polyurethane enamel. The activator for this enamel contains over 70 percent HDI-polyisocyanate. According to the Material Safety Data Sheet, HDI

monomer is controlled to <0.7 percent by weight. With aging, the monomer content may increase to 1.6 percent by weight (Ref. 6,Dupont, 1981.)

One case study describes an individual who inadvertently stepped into a puddle of two-part polyurethane enamel. This person began to experience immediate "trouble", which gradually worsened to a burning sensation up to mid thigh with aching discomfort and mild weakness in foot muscles. Another case associated " exposure to the two-part polyurethane enamel with subsequent testicular

cancer and terminal chest cancer. A, third case involved 12 men employed in

an unspecified job; all experienced urologicail problems allegedly due to exposure to this enamel (Ref.7, Dupont, 1988).

Another reported incident involved firefighters exposed to the two-part polyurethane enamel. This paint was used in firehouses inBalitmore, MD between January 1982 and March 1984. Of 10 infants fathered during this 15- 

### month interval, 8 died during spontaneous abortion or soon after birth.A similar report involved a man employed in an autobody shop and exposed to this enamel. He claimed that his exposure prior to and subsequent to the conception ofhis son was responsible for severe birth defects (Ref. 7, 

### Dupont, 1988).



### Many case-specific reports suggest adverse health effects following exposure to polymeric HDI. Of particular note is a case described by Malo et al. (1983, as cited in Karol, 1987, Ref. 11), in which an individual exposed to a spray paint containing polymeric HDI experienced shortness ofbreath, wheezing, malaise, and chills late in the afternoon on working days. Symptoms lasted for several hours and were accompanied by wheezing at night. Inhalation challenge under simulated occupational exposure conditions reproduced the symptoms and thereby identified the source ofthe active material.

Arecently published study ofSwedish

car painters exposed both to HDI and biuret-modified HDI at average concentrations of0.001 ppm and 0.013 ppm, respectively, demonstrated that pulmonary closing volume was increased in car painters relative to vital capacity; controls did not exhibit this decrement. The authors found this suggestive of "small airways disease" (Ref. 2,Alexandersson et al., 1987).
H. Rationale for Health Effects Recommendations.

Annual domestic production ofHDI is about 11 million pounds. It is estimated that well over 1million individuals are exposed to this chemical in the workplace, as a result ofits use in coatings. Although one carcinogenicity study is currently being conducted in

one rodent species, data are not available to assess fully the long-term effects ofHDI.Therefore, the Committee recommends that chronic toxicity studies with carcinogenicity as an endpoint be conducted in another species inaccordance with accepted guidelines for carcinogenicity testing; The Committee also is concerned about available human data suggesting potential reproductive impairment. Considering the lack 'ofdefinitive reproductive and developmental effects data, the Commitee recommends that testing addressing these specific endpoints also be conducted.
IV. Ecological Effects ofConcern Since HDI is not expected to persist following release to the environment and should be rapidly transformed in the presence ofwater, ecological effects testing is not being recommended at this 'time.
References

(1)ACGIH. "Threshold Limit Values for Chemical and Physical Agents, 1976," Cincinnati, OH: American Conference of. Governmental Industrial Hygienists.

(2)

Alexandersson, R., Plato, N., Hedenstierna, G., Kolmodin-Hedman, B. "Exposure, lung function, and symptoms in

car painters exposed to hexamethylenediisocyanate and biuret modified hexamethylene-diisocyanate," Archivesof Environmental Health.42:367-373 (1987). (3)

Andersen, M., Binderup, M.L., Kiel, P., Larsen, H. and Maxild, 

### J."Mutagenic action of isocyanates used in the production of polyurethanes," Scandinavian JournalWork EnvironmentalHealth.6:221-226 (1980).

(4)ASA. Personal communication from 

### J. Caldwell, former Executive Secretary, Automotive Services Association (ASA), Laguna, CA, to S'Strassman-Sundy, Risk Analysis Branch, Office ofToxic Substances, U.S. Environmental Protection Agency (March 14, 1988).

(5)CWA. Letter from D.LeGrande, Occupational Safety and Health Coordinator, Communication Workers ofAmerica (CWA), Washington, DC, toS.Strassman-Sundy, Risk Analysis Branch. Office ofToxic Substances, U.S. Environmental Protection Agency (March 31, 1988).

(6)DuPont. Material Safety Data Sheet on 192S Activator. El.du Pontde Nemours & Co., Inc.,(1981).

.

(7)DuPont: Section 8(c) submission number 8CL-0388-0002; E.I. du Pont deNemours & Co, Inc. (March 4,1988).

.(8) Hulse, P.M. "An evaluation ofHDI in polyurethane. spray paint aerosols," Masters: Thesis. The John Hopkins University, Division ofEnvironmental Health Engineering, School ofHygiene & Public Health. Baltimore, MD (1984).

(9)

IBPAT. Personal communication from R. Wolford Health and Safety Officer, International Brotherhood ofPainters and Allied Trades (IBPAT), Washington, DC, to S. Strassman-Sundy, Risk Analysis Branch, Office ofToxic Substances, U.S. Environmental Protection Agency (March 22, 1988).

(10) ICF. "Producers and Users of Diisocyanates," Washington, DC: ICF Incorporated, U.S. EPA Contract No. 68-02- 3976; Work Assignment No. 1-25 (June 30, 1986].

(11) Karol,'M.H. "Respiratory effects of inhaled isocyanates," CRCCritical Reviews in Toxicology. 16(4):349-379 (1987).

( 12) Kawazoe, Y., Kato,M., and Takahashi,' K."Studies on chemical carcinogens. XX. Inhibitory effect ofalkyl isocyanates and isothiocyanates on mutagenesis in E.collby. ultraviolet radiation," Chemicadland Pharmaceutical Bulletin.29:2631-2638 (1981). (13) Kondrat'yev, G.G., Mustayev; R.K. "Study ofthe allergic properties of hexamethylene-diisocyanate in an experiment," (Rus.) GigiyenaPrimeneniya PolimernykhMaterialovi lzdeliyIz Nikh., Nr. 1,pp. 290-293. Translated by: Translation 

### 18202

### Federal Register 

## I Vol. 53,, No. 98 / Friday, May 20, 1988 

## / Notices

Division. Foreign Technology Division. Wright Patterson AFB, Ohio (1969).

(14) Leo, A.R., Hansch. C., andElkins, D. "Partition coefficientsand their uses," ChemicalReviews. 71(6):525-615 f1971).

(15) Mobay. "ToxictyanaSafe~Handing.f 1socyanates. AReview nfthe :Lterature,(TDl,} and Resultsof Toxicity.Screening.Studies on Additional Compounds," Pittsburgh, 'PA Mobay Chemical Company (1961).

(16) Mobay. Letter from C.LH.Howard, Vice President-Scientific, Mobay'Chemrical Corporation to M. Greif, TSCA Interagency Testing Committee (July 20,1982).

(17) Mobay. TSCA Section 8(d) submission number 8-870001276; Mobay Corporation (July 29,1987).

(18) Mobay. Letterfrom Franois J.Rattay, Manager, Regulatory Compliance, Mobay Corporation, Pittsburgh, PA, to Robert Brink, TSCA Interagency TestingCommittee (January 21,1988a).

(19) Mobay.,Personal communication from F.J. Rattay, Manager, Regulatory Compliance, Mobay Corporation, Pittsburgh, PA, toR. Wedge, Dynamac Corporation (March 14, 1988b).

(20) MRI. TotalJsocyanates'-ACE Laboratory Experiment. Xansas City,MI: Midwest Research Institute. U.S. EPA Contract 68-02-4252; Work Assignment No. 51 (October 29, 1987)." " •

(21) NIOSH. National Occupational Hazard Survey (1972-1974) [data base), Cincinnati, OH: National Institute forOccupational Safety and Health, Department ofHealth and Human Services (1976).

(22) NIOSH. "Criteria fora recommended standard occupational exposure to diisocyanates," 'Rockville MD: National Institute for Occupational'Safety -andHealth. NIOSH-78-215. PB81-..26615 (1978].

(23) NIOSH. National Occupational Exposure Survey (1980-1983) (data basej,. Cincinnati, OH: National:Institute for. Occupational Safety-and Health,,Department ofHealth and Human Services :1984).

(24) Sangha, G.K., Matijak, M., Alarie, -Y. "Comparison of some mono- and diisocyanates as sensory irritants," Toxicologyand AppliedPharmocolqgy. 57:241-246 11981).

(25) Thorne,cPS,, Hfllebrand, J.A., 'Lewis, G.R.,Karol, M.H. "Contact sensitivity by diisocyanates:-Potencies and -crossreactivities," ToxicaqgyandAplied Pharmacology. 87:155-165 (1987). (26) UAW. Personal communicationirom.F. Mirer, Health and Safety Director,United Auto Workers, Detroit,.Ml, to L Borghi, Dynamac Corporation (March 16, 1988).

:(27) USEPA. TSCA Chemical Substance Inventory (non-confidential) [data base]. Washington,DC: U.S. Environmental ProtectionAgency !(19881.

'(28) Woolrich, P.F. "Toxicology, industrial hygiene and medical control ofTDI, MDI, and PMPPI," AmericanIndustriot Hygiqne journal.43:89-97 (1982). 2.3 

### Chemicalsrecommended.with intent-to-designate--.2.3a Crotonaldehyde-Summary.of recommendedstudies.Itis recommended that.crotonaldehyde be tested for the.following: 1. Chemical fate:Volatilization rate from water.Aerobic aquatic biodegradation rate.

2.Healtheffects: None. 3.Ecologicaleffects: Acute toxicity'to algae, fish, and aquaticinvertebrates. Physical and Chernical informa'ionCAS.Ntmber 170-30-3 Synonyims:2-iButenal;9 CI);'B-MethyI

acrolein; Crotonal; Crotonic aldehyde; Propylene aldehyde. StructuralFormula.'



# CH3 

# CH=CHCHo

EmpiricalFormul'a: caL0 MolecularWeight:70.1 Melting,Point:.--76.5C I(Ref.6,-Merck, 1983); -69*C (,Ref.9,Sax -and Lewis., 1987) BoilingPoint:104.0°C (Ref. 6, Merck,

.1983); 102*C (Ref.8, Sax and Lewis, 1987) Vapor-Pressure: 30 nmHg -at20*dCt(Ref. 8, Sax and Lewis, 1987);.19 mmHg;at 20C (Ref.11, Verschueren, 1983) Solubilityin .Water:T55:g/L!at209C

(Ref.11, Verschueren, 4983); 18.1-g1100 g at 20°C (Ref. 6,Merck,'1983). : Specfic Gravity:'.853at 20/20°C (.Ref.

Z,"Merck, 1983) Log -Octano7/Water Partition -Coefficient .(Iog P': 0.55 (Est'd;Ref. 7, NRC, 19813 Henry'sLaw Constant:1.7.X 10- 5atm

:m3/mole,,calculated Descrotionof.Chemica" 

### Water white, mobile 'liguid .wtha pungent, suffocating odor (Ref.8, Sax and

- :Lewis, 198)1

Rationale for Recommendation

L Exposure-Information

A. Production/Use/Release to Environment

Most crotonaldehyde is manufactured

,fromacetaldehyde usingcontinuous, enclosed -reactor-systemsvia the aldol condensation route, -althoughavariety ofless,common'methodssnay 'be used (Ref.4, Kirk-Othmer, 1979). Annual currettand projected U:S. production -is from 5,to'15million pounds (Ref. 2, Eastman Kodak, 1987). Crotonaldehyde also maybe formed naturally in :the atmosphere .by the interaction of reactive molecules:such as,ozone and hydroxyl radicals -withhydrocarbons and theirtoxidation products (Ref.7, NRC, 1981). Crotonaldehyde isrused primarily as za,chemicalintermediate for the synthesis ofother organic compounds-such asa-butanol,,sorbic acid, 3-methoxybutanal, and crotonic acid;,(Ret 4, Kirk-Othmer, 1979]. Releases,ofrotonaldehyde ,to,the environment are expected to occurin
wastewater.

B. Evidence fariosure Crotonaldehyde has :been.detected in the effluent of sewage treatment plants (Ref. 9,;Shackelford and.Keith, 1976]. Exhaustfrom cars Without emission controls was foundto contain crotonaldebyde -(Ref. :.,NRC, 1981'). Crotonaldehyde .als6,.has been identified

as a constituent dftobacco smoke '(Ref. 3,Florin et al., 1980) and wood smoke (Ref.5,:Lipari etal., 1984).

17.Chem'calFateInformation

A. Transport

Environmental.-releases iare expected
to be from wastewater. The physical

- and chemical prqpertiesof crotonaldehyde indicate -that-itwill partition tobotbairand water following release to -theenvironment. The Henry's Law'Constantof-1:7 X 

### 10 -5atm!m / mole,allows an estimation ofthe halflife in receiving-stream-water of-60 to 70 hours. Sorption tosolids will not be significant.

B. Persistence

Crotonaldehyde released directly to the atmosphere or evaporated from

_ surface water will -berapidlyidegraded by reactions withlhydroxyl.radicals -and

ozone and by direct sunlight-photolysis. Biodegradation isexpected tobe the
most significant -transformationprocess in water,:but no,aquatic biodegradation
rate data were found.The 5-day ' biochemicaloxygen -demand (-BOD] :for crolonaldehyde was reported as 37 percentof theory4(Ref. 11, Verschueren, 1983) and 51,percentof theory f-Ref. 10, Union Carbide, 1986). The Union " Carbide reference talso 'lists BOD data after 10, 15, and 20 days incubation as 60 percent, 64 percent and 70 percent of theory.,respectivdly.'These data suggest ready andcomplete biodegradation when sewage or sludge, which-may be acclimated-to crotonaldehyde, are-used

as the inoculum, but they do not permit

a determination -ofthebiodegradation half-life in receiving systems.
C. Rationale forChemical Fate Recommendation

Since crotonaldehyde maybe.

, released to,sufiface waters at

- - manufacturing and,use sites, it is
necessary .toobtain.experimental data

on volatilization rates from water.and

on the aerobic,aquatic biodegrad-ition
rate to betterassess ]potential environmental concentrations. 

### -18203

### 18204 Federal Register 

# / Vol. 53, No. 98 

# I Friday, May 20, 1988 

# I Notices.

III.BiologicalEffects ofConcernto HumanHealth

The Committee determined that crotonaldehyde has been studied extensively for health effects and concluded that additional studies are not required. Therefore, health effects testing is not being recommended at this time.

IV. Ecological Effects ofConcern

A.Acute andSubchronic(Short-term) Effects

An 85 percent aqueous solution of crotonaldehyde produced a 96-hour LCo of3.5 mg/L to bluegills (Lepomis .macrochirus) in a static bioassay at 20* C (Ref.1,Dawson et al., 1977). A 96-hour
LCo value of2.8 mg/L with fathead minnows (Pimephales promelas]was reported by Union Carbide (Ref.10, 1986). The 96-hour LC5ofor tidewater silversides (Menidiaberyllina)was reported to be 1.3 mg/L in a static bioassay at 200 C (Ref. 1,Dawson et al. 1977). Percent survival ofsilversides decreased with exposure time.

B. Chronic(long-term)Effects

No information was found.


### C. Other Ecological Effects
Sewage treatment microorganisms

were reported to be adversely affected by 25 to 50 mgfL crotonaldehyde (Ref. 10, Union Carbide, 1986). At concentrations from 0.05 to 1.0 percent, crotonaldehyde produced an immediate loss ofthe metachronic wave in the lateral cilia offreshwater mussels (Lamellibranchiata unio) (Ref. 12, Wynder et al., 1965). At the 0.5 aid 1.0 percent concentrations, total stasis in mussel cilia was observed, with no recovery. D. Bioconcentration andFood-Chain Transport

No information was found, but the high water solubility and low log P of crotonaldehyde make it unlikely that
any sigificant bioconcentration will

occur.
E.Rationale forEcological Effects Recommendation

The available data, from tests using nominal concentrations in static tests, show that crotonaldehyde has significant acute toxicity to both freshwater and marine fish.It is
necessary to develop more reliable
acute toxicity data using measured concentrations ofcrotonaldehyde in flow-through or static-renewal tests, using algae, fish, and aquatic, inverte'rates. * References

(1)Dawson, G.W., Jennings, A.L. Drozdowski, D., Rider, E. "The acute toxicity of47 industrial chemicals to fresh and saltwater fishes," Journal ofHazardous Materials. 1:303-318 (1977).

(2) Eastman Kodak. Letter from R.D. Gerwe, Senior Product Safety Representative; Eastman Kodak Co., Kingsport, TN to R.H. Brink, TSCA Interagency Testing Committee (June 19,1987].

(3] Florin, ., Rutberg, L., Curvall, M., and Enzell, C.R. "Screening oftobacco smoke constituents for mutagenicity using the Ames' test," Toxicology.18:219-232 (1980).

(4] Kirk-Othmer. Kirk-Othmer EncyclopediaofChemicalTechnology.New York, NY: John Wiley &Sons, Inc. Vol. 7, pp. 207-218 (1979).

(5] Lipari, F., Dasch, J.M., Scruggs, W.F. "Aldehyde emissions-from wood-burning fireplaces," EnvironmentalScience and Technology. 18(5):326-330 (1984).

(6] Merck. TheMerckIndex. 10th Ed. Windholz, M., ed. Rahway, NJ: Merck & Company. p. 372 (1983).

( (7) NRC. National Research Council. FormaldehydeandOther Aldehydes. Washington, DC: National Academy Press (1981].

(8] Sax, N.I. and Lewis, R.J., Sr.Howley's CondensedChemicalDictionary. 11th Rev. Ed. New York, NY: Van Nostrand Reinhold Co. p. 323 (1987).

(9] Shackelford, W.M., Keith, L.H. "Frequency oforganic compounds identified in water," Athens, GA: U.S. Environmental Protection Agency, Environmental Research Laboratory. EPA Report No. EPA-600/4-76- 062. p. 102 (1976].

(10] Union Carbide. Letter from D.L. Heywood, Assistant Director, Product Safety, Union Carbide Corp., Danbury, CT to U.S. Environmental ProtectiomAgency (May 2, 1986].

(11) Verschueren, K. Handbookof EnvironmentalDataon OrganicChemicals. 2nd Ed. New York, NY: Van Nostrand Reinhold Co. pp. 410-411 (1983).

(12] Wynder, E.L., Goodman, D.A., Hoffmann. D. "Ciliatoxic components in cigarette smoke. 11. Carboxylic acids and aldehydes," Cancer. 18(4):505-509 (1965).

2.4. Chemicalsrecommendedwithout beingdesignated for-response within12 months-2.4.a Imidazoliumquaternary ammoniumcompounds-Summaryof recommendedstudies.It is recommended that the imidazolium quaternary ammonium compounds, 4,5- dihydro-1-methyl-2-nortallow alkyl-l-(2- tallow amidoethyl], methyl sulfates (IQAC) be tested for the following:

1. Chemical fate:Aerobic and anaerobic biodegradation of IQAC sorbed to freshwater and estuarine sediments.

2.Healtheffects: Chronic toxicity studies to evaluate potential effects through long-term dermal exposure.

3. Ecologicaleffects: Acute'and chronic studies to evaluate effects on 

### representative freshwater and estuarine benthic organisms. Physical and Chemical Information

CAS Number:68122-86-1 

### 9 C!Nane:Imidazolium compounds, 4,5-

dihydro-l-methyl-2-nortallow alkyl-1- (2-tallow amidoethyl), Me sulfates Synonym: Imidazolium quaternary



### ammonium compounds Acronym: "IQAC StructuralFormula:



## R-C 0

CH3C 2

### CH 2

### NHC-R

/ N CH 2



## I

CH 2

where R=tallow Empirical Formula(typically): C37H74N 30 to C4 1 H82N 30 MolecularWeight:577.0 for R

### = C 1

5H3,: 633.1 for R=C 17 -35 BoilingPoint:<260C 

### (Ref.3, Capital

Citq,Products, 1986) Solubility in Water:19.2 mg/L in

deionized water after 16 days of
continuous mixing; 0.5 mg/L in filtered river water after 16 days of continuous mixing.(Ref. 4, Procter and Gamble, 1984a) Specific Gravity:No information was

found. Log Octanol/Water Partition Coefficient(logP):215, measured (Ref.4, Proter and GCmble, 1984a)

Rationale for Recommendations

I.ExposureInformation

A. Production/Use/Release to Environment

IQAC production in 1984 was estimated at about 15 million pounds in the U.S. (Ref., 4, Procter and Gamble, 1984a). The TSCA Inventory update contains confidential 1986 production information for IQAC. The major use of IQAC appears to be in fabric softeners used during the clothes-washing process. Analogs ofIQAC that might also be used infabric softener formulations include chemical mixtures with the following CAS Nos.: 68132-27- 4, 69011-82-1, 70775-90-5, 71060-67-8, 71060-68-9, 72275-90-2, 72623-81-5 and 72623-82-6. Ifthese compounds or Federal Register / Vol. 53, No. 98 / Friday, May 20, 1988 / Notices, 

### 18204 J '

### Federal'Register / Vol. 53, No.' 98 / Friday, May 20, 1988 / Notices

similar imidazolium quaternary ammonium compounds are used now, or in the future, in substantial quantities as ingredients infabric softeners for

consumer use, the Committee would have the same environmental fate, health effects and ecological effects

concerns for them as for IQAC.IQAC and any ofits analogs used in fabric softeners are likely to be released to the environment in wastewater following their use. 

### B.Evidence for Exposure

General population exposure to IQAC may be high given its use in fabric softeners used in laundry washing machines. Consumers who use this type offabric softener are likely to be exposed almost continuously through skin contact with clothing, towels and linens: An assessment by the Office of Toxic Substances (Ref.1, Battin, 1988a) estimated annual consumer dermal exposure to IQAC, from exposure to softened clothing, linens, etc., at 4.06 to 10.14 gper year.Procter and Gamble (Ref.4, 1984a) estimated daily consumer exposure to IQAC, from clothing to skin,
to be 0.07 mg active compound per kg per day for adults and 0.14 

### mg active 

### compound per kg per day for children assuming IQAC isdeposited on fabrics at 0.17 mg/in2. No environmental monitoring studies were found. An assessment by the Office ofToxic Substances (Ref. 1,Battin, 1988a) estimated receiving stream concentrations of1to 1,300 ug/L at manufacturing sites and 0.05 to 50 ug/L

near use sites, depending upon location and stream flows. Procter and Gamble (Ref.4, 1984a) estimated that consumer
use ofIQAC would yield raw wastewater concentrations ofabout 170 ug/L.

II. ChemicalFateInformation

A. Transport



### The physical and chemical-properties ofIQAC indicate that itwill partition significantly to sludge solids and sediments with some remaining dissolved in water.The estimated very low vapor pressure and moderate solubility rule out volatilization as an important factor. The cationic nature of these compounds will contribute to their sorption to sludge and sediment solids which generally are negatively charged and it is expected that IQAC will sorb to solids within a short time after release to the environment.
B.Persistence

No published information was found

on thepersistence ofIQAC. A summary report ofan unpublished study (Ref.4, Procter and Gamble, 1984a) showed about 50 percent biodegradation in 34 days in diluted activated sludge, as determined by following the evolution of radiolabelled carbon dixoide. The concentration ofIQAC Was not I reported. BOD studies reported by Sherex (Ref.6, 1984) showed 2 percent oftheoretical oxygen uptake after 5 days and 19 percent after30 days. While this indicates that IQAC is biodegradable under aerobic conditions, it also indicates that biodegradation in surface waters is likely to be slow. IQAC is expected to partition significantly to sediments following release to the environment and its persistence in sediments, under both aerobic and anaerobic conditions, is unknown. Alsounknown is the persistence ofIQAC under conditions found in estuaries and the ocean. Persistence in saline waters may be different than infresh water. Nitrilotriacetic acid, for example, was found to be resistant to biodegradation in estuarine waters (Ref. 2, Bourquin and Przybyszewski, 1977) although it is readily biodegraded by acclimated' microorganisms in fresh water.
C. Rationale for ChemicalFate Recommendations

'IQAC is likely to sorb strongly to waste treatment sludges and receiving stream organic sediments and may persist forrelatively long time periods following sorption. Since it is being released continuously to both fresh
water and estuarine receiving waters and may persist forrelatively long periods oftime, there may be a tendency for it to accumulate in estuarine, river and lake sediments near discharge points, with gradually increasing concentrations. There is a need to better determine the persistence of IQAC, dissolved in water and sorbed to sediments. It is recommended that those studies be conducted under conditions typical ofboth-fresh surface waters and estuarine waters and that studies with IQAC sorbed to sediment be conducted under both aerobic and anaerobic conditions.Information from these studies is needed to better assess.the potential concentration ofIQAC in receiving waters'and sediment and the potential hazard to aquatic and benthic organisms.
III.BiologicalEffects ofConcernto: HumanHealth

A. MetabolismandToxicokinetics

A summary ofmetabolism studies (Ref.4, Procter and Gamble, 1984a) using radiolabelled IQAC (1 C on the Nmethyl group) suggests that the compound is poorly absorbed inrats via both oral and dermal routes. Upon oral administration, less than 1 percent ofthe oral dose was absorbed and metabolized. Eighty-seven percent of the oral dose was eliminated in feces within 24 hours. A "small but significant amount ofradioactivity was found in the bone marrow" (Ref.4, Procter and Gamble, 1948a. Less than 0.5 percent of the dermal dose was absorbed, with a small amount ofradioactivity found in the bone mairow.

B.Acute andSubchronic(Short-term) Effects.

Summary reports on unpublished data from acute oral, dermal skin irritation, eye irritation, skin sensitization, and subchronic toxicity studies with IQAC

were submitted by Procter and Gamble (Ref.4, 1984a and Ref. 5, 1988). Data from acute oral, skin and eye irritation, and skin sensitization studies were submitted by Sherex (Ref.6, 1984). Acute oral tests with IQAC in rats yielded an LDso of20.8 gfkg in one test (Ref.6, Sherex, 1984) and 2 deaths out of 10 in another test at a dose level of about 18 g active compound per kg (Ref. 4, Procter and Gamble, 1984a). In another study, no deaths were reported with oral doses up to 16 cc ofIQAC dispersion (13.5 wt percent solid) per kg (Ref.6, Sherex, 1984).

Procter and Gamble reported moderate to sev6re irritation for IQAC instilled into the conjunctival sac of rabbit eyes unrinsed after treatment (Ref.4, 1984a). However, itproduced minimal irritation to rinsed rabbit eyes (Ref.4, Procter and Gamble, 1984a; Ref. 6, Sherex, 1984).

Percutaneous studies with IQAC in rabbits yielded a minimum lethal dose ofgreater than 1.8 g active compound per kg (Ref. 4, Procter and Gamble, 1984a).

Primary skin irritation studies conducted with IQAC on intact and abraded rabbit skin indicated moderate
to severe irritation in one study (Ref.4, Procter and Gamble, 1984a) and only mild irritation in another (Ref.6, Sherex, 1984).

Skin sensitization studies with IQAC by Procter and Gamble (Ref. 4, 1984a) showed delayed contact hypersensitivity in 17 out of20 guinea pigs tested. Sherex (Ref.6, 1984), on the other hand, reported that IQAC was not

a strong sensitizer in guinea pigs tested with three different lots. *

In a subchronic toxicity study (Ref. 4, Procter and.Gamble, 1984a) four groups of20 male and-20female rats each were fed a diet containing IQAC at concentrations of0, 10, 100, or 1,000 mg 

### 18205

### Federal Register / Vol. 53,. No. 98,/ Friday, May 20; 1988, / Notices

active compound per kg per'day for 13' weeks. There were no'treatment-related changes in mean body'weights orfood consumption. Lower total,protein and higher serum glutamic-pyruvictransamihase values were observed in blood samples of males in the 1,000mg per kg:group. These males also showed lower absolute and relative liver weights. No treatment-related changes

were observed in bone marrow. The noobservable-effects level (NOEL) was 100 mg per kg per day. According to Procter and Gamble, this level is at least 10 million times the expected daily human, exposure to IQAC in drinking water.

In a percutaneous subchronic toxicity test, two groups of5 male and 5 female rabbits each were treated topically with 2mL per kg per day IQAC at dose levels of3,or27 mg.active compound per kg per day for 13 weeks (Ref. 4, Procter: and Gamble, 1984a). A control group of 5 males and 5 females received the vehicle, distilled water. Slight to moderate erythema, edema, and desquamation were.observed in treated animals atboth doses. No treatmentrelated changes were: observed in clinical pathology, bone marrow smears, body weights, organ weights, microscopic.changes in skin, or histopathologic changes to.internal organs..The NOEL for systemic toxicity,

was.27 mg active compound kg per day.

C. Genotoxicity

IQAC was tested for mutagenicity'in the Salmonellaassay (with and without metabolic: activation), mouse lymphoma assay, rat invitrocytogenetics assay, and for'unscheduled DNA synthesis in human diploid cells (Ref.4, Procter and Gamble, 1984a). IQAC did.not show mutagenic effects in any ofthe assays.
D. Oncogenicity

No information was found.
E. Reproductive and Developmental Effects

Rats,were administered IQAC' (78 percent'active compound) by-gavage at dose levels of 200 of600"mg active. compound per kg daily from days 6 to 12

or 15.ofgestation (Ref. 4, Procter and. Gamble. 1984a). Acontrol groupreceived the vehicle, 15 percent w/v aqueous isopropanol. Doses: were given. to each group of'30 females at a constant. volume of '2mL per kg per day..The animals were observed' formortality, clinical signs, body weight changes, and food consumption. No maternal deaths

were observed. A decrease in food consumption,was found in the 600'mg per kgper day'group during the first3 days. Overall'reproduction parameters and pregnancy'rates-were unaffectedt 

### The incidences ofskeletal and softtissue defects werenot significantly- 'different between the'treated and the, control groups. At the highestdose tested.(600'mg active compound per kg per day) no maternal'or.developmental toxicity was observed.

F. Chronic.(Long-term) Effects

No information wasfound.
G. Observations in Humans

Little orno irritation was observed with human volunteers in a skin irritation test'with a dilute, aqueous dispersion of0.3 mL IQAC per occluded patch (Ref.4, Procterand Gamble, 1984a). IQAC was tested in,three 24- hour exposures over a6-day period at concentrations of0.5, 1.0, and 5.0 percent w/v. In another Procter and Gamble study (Ref.4, 1984a), 217 volunteers received 9exposures to 0.25 percent w'/y aqueous IQAC (0.3 mL per occluded patch) applied fora 24-hour period, 3times a week during a3-week induction period. No skin sensitization

was observed when subjects were challenged 2weeks later with0.25 percent w/v IQAC in a,single 24-hour occluded .patchtest,
H. Rationale for Health Effects Recommendations'

Ithas been estimated that fabric softeners that are applied to the,fabrics: during the washing process: are widely used in' the U.S. Annual U.S. consumption ofimidazolium quaternary ammonium type fabric softeners has been estimated at about 15 million pounds. Itis quite apparent that asignificant portion ofthe population is exposed, on a nearly'continuous basis, to these chemicals in clothing, towels and bed linens. Dermal exposure tests reported to date have'involved only acute or short-term exposures. IQAC produced moderate to severe skin irritation in rabbits and was a skin sensitizer in guinea pigs.

Although exposure.concentrations. used in short-term studies were'reported to be severalfold higher than estimated human exposures from softened fabrics, information from these short-term, intermittent-exposure tests is not useful in predicting what effects might occur with long-term (years)' continuous exposure' It is therefore recommended that IQAC and commercially important. analogsbe testedforchronic.toxicity to evaluate:potential effects,resulting from long-term dermal exposure. IV.Ecological Effects ofConcern


### A. Acute and Subchronic, (Short-term) Effects,.



### Data submitted by'Procter and Gamble (Ref* 4 1984a) show moderate toxicity to bluegills, mysid shrimp and Daphniamagna.The presence of anionic surfactants-or the.use ofnatural surface water with sediments mitigated the effects on bluegills and daphnia. No' data were found for benthic organisms and this is a data gap ofconcern since IQAC will.sorb to and may concentrate in sediments,near wastewater discharge sites.

B.Chronic (Long-term) Effects

No!published information was found but Procter and Gamble (Ref.5,1988) indicated that data have:been.developed with a hydrogenated analog ofIQAC in chronic,studies.with-midge.
C. Other Ecologica*l Effects (Biological, Behavioral, or'Ecosystem Processes).

IQAC was'reported (Ref.4, Procter and'Gamble, 1984a) to, inhibit algal growth at relatively low concentrations The algistatic'concentrations were0.037 mg/L.for a Selenastrumsp.and 0.23 mg/ Lfor aMicrocystissp.
D.Bioconcentration.and'Food-chain Transport,

The measured log Pof2.15 indicates a potential,for some bioconcentration. Procterand..Gamble (Ref. 4, 1984a) reported a measured bioconcentration factor (BCF) of10.7 forbluegills exposed to 8.8,g/LIQACiin a flow-through system.This report is. suspect because thereported concentration ofIQAC is well above its water solubility. Nevertheless,,the evidence is that there may be some bioconcentration.
E. Rationale for Ecological Effects Recommendations.

Environmental fate considerations indicated thatIQAC will sorb strongly to sludge solids and sediments., Itmay persist forrelatively long,time.periods under these conditions and may accumulate in sediments near wastewater discharges. This information plus- the known toxicity of IQAC to fish, aquatic invertebrates,and algae;,raise: concerns forbenthic organisms, Acute-toxicity,data should. be obtained forrepresentative freshwater and estuarine benthic organisms and, ifthese compounds are found,to be relatively persistent, chronic studies,on,the,same organisms maybe warranted. 18206

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### Federal Register / Vol. 53, No. 98 / Friday, May 20, 1988 / Notices

References

(1)Battin, A. Memorandum on exposure and release ofimidazolium quaternary ammonium compounds in liquid fabric softeners from Andrew Battin, Exposure Assessment Branch, Office ofToxic Substances, U.S. Environmental Protection Agency, to John D.Walker,Test Rules Development Branch. (February 2, 1988a.)

(2)Bourquin, A.W. and Przybyszewski, V.A. "Distribution ofbacteria and nitrilotriacetate-degrading potential in an estuarine environment." Appliedand Environmental Microbiology.34:411-418 (1977).

(3] Capital City Products. Material Safety Data Sheet on Accosoft 808 75 and product literature submitted by Capital CityProducts, Janesville, WI (November 12, 1986).,

(4)Procter and Gamble. Letter from T.W. Mooney, Manager, Technical Government Relations, TheProcter and Gamble Co., Cincinnati, OH, to Arthur Stern, TSCA Interagency TestingCommittee. (September 12, 1984a.)

(5)Procter and Gamble. Letter from R.N. Sturm, Associate Director, Bar Soap & Household Cleaning Product Development, Procter and Gamble Co., Cincinnati, OH, to Robert Brink,TSCA Interagency Testing Committee (April 19, 1988).

(6)Sherex. Letterfrom Howard H. Hickman, Manager ofRegulatory Affairs, Sherex Chemical Co., Dublin, OH, to Martin Greif,TSCA Interagency Testing Committee. (January 17,1984.)

2.4.b

- Ethoxylatedquaternary ammoniumcompounds-Summaryof recommendedstudies.It is recommended that ethoxylated quaternary ammonium compounds, EEQ (CAS No. 68153-35-5) and PEQ (CAS No. 68410-69-5) and any commercially important analogs ofPEQ (e.g., CAS Nos. 68389-88-8, 68389-89-9, 68413-44-7, 68554-06-3 and 70914-06-3) be tested for the following:

1. Chemical fate:Aerobic and anaerobic biodegradation ofthe ethoxylated quaternary ammonium compounds sorbed to freshwater and estuarine sediments.

2.Healtheffects: Chronic toxicity studies to evaluate potential effects through long-term dermal exposure.

3. Ecologicaleffects: Acute and chronic effects on representative freshwater and estuarine benthic organisms. • Physical and Chemical Information
CASNo.: 68153-35-5 9 CIName: Ethanaminium, 2-amino-N- (2-aminoethyl)-N-(2-hydroxyethyl)- N-methyl-, N,N'-ditallow acyl derivs., Me sulfates (salts) Synonyms:

Ethoxylated ethanaminium quaternary

ammonium compounds; N,N-Bis(2-tallow amidoethyl)N-(2-

hydroxyethyl)-N-methylammonium methyl sulfate; N,N-Di(2-tallow amidoethyl)-N-(2- hydroxyethyl)-N-methylamm~nium methyl sulfate; Quaternary ammonium compounds,

(hydroxyethyl)-methylbis(2-tallow amidoethyl), Me sulfates Acronym:EEQ Structural Formula:

O CH, O II III
R-C NHCHCH,

- N- CH 2CH 2 NH C-R

CH 2CH2OH

where R = tallow Empirical Formula(typically): C

39 -1oN 30 3 to Q 3H 8 N 30 3 MolecularWeight:

639.1 where R = C15113 695.5 where R = C 17 -3 5 MeltingPoint:170°C, estimated (Ref. 2, Battin, 1988c) BoilingPoint:567°C, estimated (Ref. 2, Battin, 1988c) VaporPressure: 2.86 X 10 - 7mmHg at 25'C, estimated (Ref. 2, Battin, 1988c) Solubilityin Water:35 mg/L in deionized water after 14 days of continuous mixing (Ref. 5, Procter and Gamble, 1984b) Specific Gravity:No information was found. Log OctanollWater Partition Coefficient(logP): 2.48, measured (Ref. 5, Proctor and Gamble, 1984b) Henry'sLaw Constant: 7.71 x 10-19atm m3/mole, estimated (Ref. 2, Battin, 1988c) LogAdsorption Coefficient(logKo)s 2.27, estimated (Ref. 2, Battin, 1988c) Physical and Chemical Information

CAS No.:68410-69-5 9 CIName:Poly(oxy-1,2-ethanediyl), a- [2-[bis(2-aminoethyl)methylammoniolethyl]-co-hydroxy-, N,N-ditallow acyl derivs., Me sulfates (salts) Synonyms:

Methyl tallow diethylenetriamine

condensate, polyethoxylated, methyl sulfate; Quaternary ammonium compounds,

(2-hydroxyethyl) methylbis(2-tallow amidoethyl), Me sulfates, ethoxylated Acronym: PEQ Structural Formula: O CH, O UI 

### Io II R-CNHCHCH,- N- CHCH 2 NHC-R I CH 2 CH 20 (CH 2 CHO )H



### where R==tallow and n=1-7 Empirical Formula(typically):

C41H84N3 0 4 to C 57Hi 16N 30 10 

### MolecularWeight:

683.2 where R=C 5

### H 3 1 and n=1 1,003.9 where R=C17

### 1-b and n=7 

### MeltingPoint:No information was found. BoilingPoint:No information was found. 

### VaporPressure: No information was found. 

### Solubilityin Water:No information Was found.

- 

### Solubilityin Organic Solvents:No information was found. Specific Gravity:No information was found. 

### Log Octanol/Water Partition Coefficient(logP): No information

was found. Henry'sLaw Constant:No information

was found. 

### LogAdsorption Coefficient(logKoc):No

. information was found.


### Rationale forRecommendations
I.ExposureInformation
A. Production/Use/Environmental Release

It was estimated that the market for EEQ in 1984 was about 25 million pounds per year in the U.S. (Ref. 5, Procter and Gamble, 1984b). Information obtained during the ITC review ofthese chemicals indicated that inrecent years PEQ has taken a large share of the market away fromEEQ. TSCA Inventory update information contains a total for 1986 production and import of EEQ that is classified as confidential 

### business information (CBI). Production and import ofPEQ was not reported for the TSCA Inventory update. The lack of PEQ data in the updated Inventory 

### contrasts with reports (toDynamac Corp.) from industry ofsubstantial
current PEQ production. The Committee is unable to obtain current production and import data for PEQ and its analogs 

### because they are classified as polymers and are exempt from Inventory update reporting. However, because ofthe potential forwidespread chronic expbsures they are all recommended for 

### testing.

-

The major use for both EEQ and PEQ is in fabric softeners for industrial and



### consumer applications. Consumer18207

### Federal Register / Vol. 53, No. 98 / Friday, May 20, 1988 / Notices

product formulations typically contain from3.5 to 8percent dispersions ofthe active ingredient. EEQ also is reported
to be used as an anti-static agent, corrosioncontrol agent, foam stabilizer and emulsifier (Ref. 5, Procter and Gamble 1984b). During and after use, these compounds will be released to the environment, mostly in wastewater from clothes-washing operations.

Analogs ofPEQ, which also) may be used as fabric softeners, and that are included in the recommended testing,

are shown in the following Table 5:

TABLE 5-ADDITIONAL ETHOXYLATED

QUATERNARY AMMONIUM COMPOUNDS
RECOMMENDED FOR TESTING IF USED
IN SUBSTANTIAL QUANTITIES IN FABRIC
SOFTENING APPLICATIONS

CAS No.

68389-88-8

68389-89-9

68413-04-7

68554-06-3

70914-09-9 Chemical name

Poly(oxy- 1,2-ethanediyl), a-[2-[bis(2-

aminoethyl)methylammonio] ethyl]

- w-hydroxy-, NN-dicoco acyl derivs., Me sulfates (salts) Poly(oxy-1,2.ethanediyl), a-[2-[bis(2-

aminoethyl)methylammonio]ethyl]- o-hydroxy-, N,N'-bis(hydrogenated tallow acyl) derivs., Me sulfates (salts) Poly[oxy(methyl-1,2-ethanediyl)], a-

(2-(bis(2-aminoethyl)methylammoniolmethylethyl-w-hydroxy-, NN-ditallow acyl denvs.. Poly(oxy-1,2-ethanediyl), a-[3-[bis(2-

aminoethyl)methylammonioj-2- hydroxypropyll-w-hydroxy-, N-coco acyl denvs., Me sulfates (salts) Poly(oxy-1,2-ethanediyl), a-[2[bis(2-

aminoethyl)methylammonio] ethyl)

- w-hydroxy-, N,N'-di-C ,-,. acyl derivs., Me sulfates (salts)

.Evidence for Exposure
i. Evidence forhumanexposure. General population exposure toPEQ may be high given itsuse in fabric softeners. Ethoxylated quaternary ammonium fabric softeners are used in detergent formulations and in products designed for addition to washing machines prior to the last deep rinse of the wash cycle.The major route of
exposure is skin contact with fabrics that have been treated with the fabric softener. Consumers who use these types-offabric softeners are likely to be exposed almost continuously-through skin contact with clothing, towels and bed linens. Procter and Gamble (Ref. 5, 1984b) estimated daily consumer exposure to a "similar compound," fromclothing to skin to be 0.07 mg active compound per kg per day for-adults and 0.14 mg active compound per kg per dayfor children, assuming EEQis deposited.

on fabrics at 0.17mg/in2
. Sherex (Ref.8, 1987) indicated that PEQ and EEQ are similar chemically and with respect to

use. Tiferefore, the exposure estimates made by Procter and Gamble for EEQ appear to be applicable to PEQ.

An assessment by the Office ofToxic Substances (Ref.1, Battin, 1988b) estimated annual consumer dermal exposure to this kind ofcompound, from exposure to softened clothing, linens, etc, at 1.08 to 2.69 g per year. Human exposure via drinking water is not expected to be significant. The ethoxylated quaternary ammonium compounds are expected to sorb strongly to sediments and other solids in surface waters and soils. Surface and ground waters used for drinking water will receive treatment (e.g., flocculation and sedimentation) that will further reduce the concentration ofdissolved ethoxylated quaternary ammonium compounds. It has been estimated that surface waters used for drinking water supplies would contain no more than 0.35 tkg/L ofthese compounds (Ref. 5, Procter and Gamble, 1984b).

2.Evidenceforenvironmental
exposure.No monitoring studies were found. An assessment by the Office of Toxic Substances (Ref.1, Battin, 1988b) estimated receiving stream concentrations of0.03 to0.25 ug/L at manufacturing sites and 0.02 to 18.5 ug/L

nearuse sites, depending upon location and stream flows. Procter and Gamble (Ref.5, 1984b) estimated that consumer

uses ofEEQ would yield raw wastewater concentrations ofabout 280 ug/L. Most (95 percent ormore) will be sorbed by sludge solids during wastewater treatment and the concentration ofEEQin treatment plant effluents was estimated at 35 ug/L.

II. ChemicalFateInformation

A. Transport

The physical and chemical properties ofthe ethoxylated quaternary ammonium compounds indicate that they will partition strongly to sludge solids and organic sediments. The estimated low vapor pressure and moderate solubility in water rule out volatilization as an important factor. The cationic nature ofthese compounds will contribute to their sorption to sludge and sediment solids which generally are negatively charged.

B. Persistence

. No published information was found

on the persistence of the ethoxylated

- quaternary ammonium fabric softeners. A summary report ofunpublished information (Ref. 5, Procter and Gamble, 1984b) showed 24 to 34 percent biodegradation after 138 days,,using EEQ at 10 and 100 ug/L in river water 

### and following carbon dioxide evolution. BOD studies using PEQ reported by Sherex (Ref.7,1984) showed 18 percent oftheoretical oxygen uptake after 5 days and 31 percent after 30 days. While this indicates that EEQ and PEQ are biodegradable under aerobic conditions in river water,it also indicates that aerobic biodegradation will be relatively slow. The Procter and Gamble report (Ref.5,1984b) noted that the river water biodegradation studies were conducted with andwithout sediment but did not provide details. These quaternary ammonium compounds are expected to partition to sediments following release to the environment and their persistence in sediments, under both aerobic and anaerobic conditions, is unknown. Also unknown is the persistence of these compounds under conditions found in estuaries and the ocean. Persistence in saline water may be different than in fresh water. Nitrilotriacetic acid,for example, was found to be resistant to biodegradation in estuarine waters (Ref. .3,Bourquin and Przybyszewski, 1977) "althoughit is readily biodegraded by acclimated.microorganisms in fresh water.
C.Rationale forChemical Fate Recommendations

EEQ, PEQ and PEQ analogs are likely to sorb strongly to waste treatment sludges and,receiving stream organic sediments and may persist forrelatively long time periods following sorption. Since they are being continuously released,to both fresh water and estuarine receiving waters and may persist forrelatively long periods oftime there may be a tendency forthese compounds to accumulate in estuarine, river and lake sediments near discharge points,with gradually increasing concentrations. There-is a need to better define the persistence of these compounds, under both aerobic and anaerobic.conditions, when sorbed to organic sediments typical ofboth freshwater and estuarine conditions. This information is needed in order to better assess the potential concentrations of these compounds in the sediments and the-potential hazard to benthic organisms. II. Biological Effects ofConcernto HIuinanHealth
A. Met abolism;andToxicokinetics
No information,was found.
&Acute andSubchronic(Short-term) Effects

Summaryreports on unpublished data from acute,oral, percutaneous, ocular, skin irritation and subchronic toxicity 18208

### Federal Register / Vol. 53, No. 98 / Friday, May 20, 1988 / Notices

studies with EEQ were submitted by Procter and Gamble (Ref. 5,1984b; Ref. 6, 1988). Data on acute oral, eye irritation, skin irritation and skin sensitization studies with PEQ were submitted by Sherex (Ref.7,1984). Data from acute oral, eye irritation and primary skin irritation studies with PEQ

were provided by Capital City Products (Ref. 4, 1987).



### The acute oral testswith EEQ and PEQwere all conducted using rats. Studies with EEQyielded a minimum lethal dose greater than 15 g/kg. Studies with a 4 percent dispersion of PEQ showed an LD 5

### ogreater than 15.38 g/kg. Minimal eye irritation was observed forEEQjnstifled in the conjunctival sac ofrabbit eyes unrinsed after treatment. PEQwas rated minimally irritating after instillation to unrinsed rabbit eyes.

Percutaneous studies with undiluted EEQ applied occluded to clipped intact and abraded backs ofrabbits at dose levels of 2gperkg for 24 hours yielded a minimum lethal does greater than 1.5 g perkg (the only dose tested, with a 14- day post-application period for mortality.

EEQ was applied occluded or on an open patch to clipped intact and abraded rabbit backs for 24 hours. Mild to moderate skin irritation was observed for up to 48hours after patch removal. PEQ was applied togauze patches and * exposed to clipped intact and abraded rabbit backs for 24 hours. The substance

was rated mildly to severely irritating following observations at 24 and 72 hours.

A skin sensitization study reported by Procter and Gamble (Ref. 5,1984b) employed 25 percent (w/v)EEQ in80:20 ethanol: Water solution applied in occluded patches to the clipped backs of guinea pigs for six hours, once a week, during a three-week induction period. The EEQtreated animals were challenged with 20 percent (w/v)EEQ in acetone for a single 6-hour occluded exposure approximately two weeks after completion ofinduction. Five out of 20 induced guinea pigs showed signs of delayed contacthypersensitivity. These studies led to the conclusion with EEQ is a mild skin sensitizer in guinea pigs. Similar studies reported by Sherex (Ref. 7.1984) concluded that PEQ isnot a skin sensitizer.

In a subchronic toxicity study (Ref.5, Procter and Gamble, 1984b) rabbits were treated topically with 2mL per kg per day ofEEQ at a dose level of300mg of active compound per kg per day, five days per week for4 weeks. Each group contained five males and five females. There were no treatment-related changes inbody weights, body weight gain, organ weights or organ to body weight ratios. It was alsoreported that there were no treatment-related clinical changes. However, animals receiving EEQ had significantly greater mean corpuscular volumes in week4 than the controls and there was an increased incidence of dermal inflammation, of diffuse distribution and associated with acanthosis, that was considered treatment-related. An increased incidence ofdermatitis was attributed to "random variation."

C. Genotoxicity

In summary reports it was stated that EEQ was tested formutagenicity in the Salmonellaassay, with and without metabolic activation, and themouse lymphoma assay (Ref.5,Procter and. Gamble 1984b) and that those tests produced negative results. No information was found for PEQ or the other ethoxylated quaternary ammonium compounds recommended in this Report.
D.Oncogenicity

No information was found.

E. Reproductive and Developmental Effects

No information was found.
F.Chronic (Long-term) Effects

No information was found.

G. Observations in Humans Little or no irritation-was observed with human volunteers in a skin irritation testwith aqueous dispersions ofEEQ using 0.3 mL ofEEQ per occludedpatch (Ref. 5,Procter and Gamble, 1984b). EEQ was tested in a single 24-hour and three 24-hour exposures over a 6-day period at concentrations up to 20 percent w/v). In another Procter and Gamble study (Ref. 5,1984b),87 volunteers received 9 exposures to 10 percent (w/v] aqueous EEQ and 205 volunteers received 9 exposures to 25 percent (w/v)aqueous EEQ (0.3mL per occluded patch) applied for a 24-hour period, 3times a week during a 3-week induction period. No skin sensitization was observed when subjects were challenged two weeks later with a single 24-hour occluded patch with the same concentration used during induction.
H. Rationale for Health Effects Recommendations

It has been estimated that fabric softeners that are applied to fabrics during the washing process are widely used in the U.S. Annual U.S. consumption of the ethoxylated quaternary ammonium type fabric softeners has been estimated at about 25 million pounds. It is quite apparent that

a significant portion ofthe population is exposed, on a nearly continuous basis,
to these chemicals in clothing, toweling and bed linens. Exposure will be primarily dermal although there may be
very low concentrations in some drinking water supplies. Dermal
exposure tests reported to date have involved only acute or short-term
exposures. EEQ was described as a mild
to severe irritant and PEQ was mildly irritating when applied to rabbit skin. EEQ was a mild skin sensitizer in some guinea pig studies.

Although exposure concentrations used in short-term studies were reported
to be several-fold higher than estimated human exposures from softened fabrics, information from these short-term, intermittent-exposure tests isnot useful in predicting what effects might occur with long-term (years) continuous
exposure. It is therefore recommended that EEQ, PEQ and commercially important analogs ofPEQ be tested for chronic toxicity to evaluate potential effects resulting from long-term dermal
exposure.
IV.Ecological Effects ofConcern

A. Acute and Subchronic (Short-term) Effects

Summary data submitted by Procter and Gamble (Ref. 5, 1984b) show EEQ toxicity to bluegills, sheepshead minnows, mysid shrimp and Daphnia
magnawater fleas, with LC5 , values ranging from 0.3 to 45 mg/L. The presence ofan anionic surfactant or the

use ofnatural surface waters with sediments mitigated the effects on bluegills and daphnia. No data were found for benthic organisms and this is a data gap ofconcern since these compounds are likely to partition to sediments following release to the environment. No data were found for PEQ or its analogs.

B. Chronic (Long-term) Effects

No information was found.

C. Other Ecological Effects (Biological, Behavioral or Ecosystem Processes)

EEQ was reported to inhibit algal growth at moderately low concentrations (Ref. 5, Procter and Gamble, 1984b). The algistatic concentrations were 1.33 mg/L for a Selenastrumsp., 0.52 mg/L for a Mycrocystis sp., and 9.4 mg/L for a Dunalielasp. No data were found for PEQ or its'analogs. 

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### Federal Register / Vol. 53, No. 98 / Friday, May 20, 1988 /. Notices.

D. Bioconcentration and Food-chain Transport

The measured log P of2.48 for EEQ indicates a potential for some bioconcentration. Procter and Gamble (Ref. 5,1984b) reported an estimated bioconcentration factor (BCF) ofA5 for EEQ, based on the log P. No information

was found for PEQ orits analogs.

E. Rationale for Ecological Effects Recommendations

Environmental fate considerations indicate that the ethoxylated quaternary ammonium compounds will sorb strongly to sludge solids and sediments. They may persist for relatively long periods oftime under those conditions and.accumulate in sediments in the vicinity of wastewater discharges. This information plus the demonstrated toxicity ofEEQ to fish, aquatic invertebrates and algae, raise concerns for benthic organisms. Acute toxicity should be determined for representative freshwater and estuarine benthic organisms andifthe ethoxylated quaternary ammonium compounds are found to be relatively persistent in the environment, chronic studies on the

same organisms may be warranted.

References

(1)Battin, A. Memorandum on exposure and release ofethoxylated quaternary ammonium compounds inliquid fabric softeners from Andrew Battin, Exposure Assessment Branch, Office ofToxic Substances, U.S. Environmental Protection Agency, to John D.Walker,Test Rules ' Development Branch. (February 2, 1988b).

(2) Battin, A. Memorandum onphysical/ chemical property estimations from Andrew Battin, Exposure Assessment Branch, Office ofToxic Substances, U.S. Environmental Protection Agency, to Robert Brink, TSCA Interagency Testing Committee (April 8, 1988c).

(3)Bourquin, A.W. and Przybyszewski, V.A. "Distribution of bacteria and nitrilotriacetate-degrading potential in an estuarine environment," Appliedand EnvironmentalMicrobiology.34:411-418 (1977). (4) Capital City Products. Letter and unpublished information from John B. Braunwarth, Operations Manager, Capital City Products Co. Janesville, WI, to Robert Brink, TSCA Interagency Testing Committee (February 18, 1987).

(5)

Procter and Gamble. Letter and unpublished information from T.W. Mooney, Manager, Technical Government Relations, The Procter and Gamble Co., Cincinnati, OH,
to Arthur Stern,TSCA Interagency Testing Committee (September 12, 1984b).

(6) Procter and Gamble. Letter from R.N. Sturm, Associate Director, Bar Soap and Household Cleaning Product Development, Procter and Gamble Co., Cincinnati, OH, to Robert Brink, TSCA Interagency Testing 'Committee (April 19, 1988).

(7) Sherex. Unpublished information submitted from Howard M. Hickman, Sherex Chemical Co., Inc., Dublin, OH, to Martin Greif,TSCA Interagency Testing Committee (January 17, 1984).

(8) Sherex. Personal communication from Howard Hickman of Sherex Chemical Co., Inc. Dublin, OH, to L. Borghi, Dynamac Corporation (January 13, 1987).
[FR Doc. 88-11254 Filed 5-19-88; 8:45 am]

BILLING CODE 6560-50-M 

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