Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

[OPTS-41023; FRL-3109-7]

Nineteenth Report of the Interagency

Testing Committee to the

Administrator; Receipt and Request

for Comments Regarding Priority List

of Chemicals

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: The Interagency Testing

Committee (ITC), established under

section 4(e) of the Toxic Substances

Control Act (TSCA), transmitted its

Nineteenth Report to the Administrator

of EPA on October 31, 1986. This report,

which revises and updates the

Committee's priority list of chemicals,

adds four chemicals to the list for

priority consideration by EPA in the

promulgation of test rules under section

4(a) of the Act. The new chemicals are

isopropanol, C.I. Disperse Blue 79,

methyl tert-butyl ether, and methyl ethyl

ketoxime. These chemicals are not

designated for response Within 12

months. One substance previously

recommended with intent to designate,

tributyl phosphate (51 FR 18368), is now

designated for response within 12

months. The Nineteenth Report is

included in this notice. The Agency

invites interested persons to submit

written comments on the Report, and to

attend a Focus Meeting to help narrow

and focus the issues raised by the ITC's

recommendations. Members of the

public are also invited to inform EPA if

they wish to be notified of subsequent

public meetings on these chemicals. ITC

also notes the removal of five chemicals

from the priority list because EPA has

responded to the ITC's previous

recommendations for testing of the

chemicals.

DATES: Written comments should be

submitted by December 15, 1986. Focus

Meetings will be held on December 16

and 17, 1986.

ADDRESSES: Send written submissions

to: TSCA Public Information Office (TS793), Office of Pesticides and Toxic

Substances, Environmental Protection

Agency, Rm. NE G-404, 401 M St., SW.,

Washington, DC 20460.

Submissions should bear the document

control number (OPTS-41023).

The public 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. to 4

p.m. Monday through Friday, except

legal holidays. Focus Meetings will be

held at EPA Headquarters, Rm. 103 NE

Mall, 401 M St., SW., Washington, DC.

Persons planning to attend the Focus

Meetings and/or seeking to be informed

of subsequent 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:

Edward A. Klein, Director, TSCA

Assistance Office (TS-799), Office of

Toxic Substances, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC. 20460, (202-554-1404).

SUPPLEMENTARY INFORMATION: EPA has

received the Report of the TSCA

Interagency Testing Committee to the

Administrator.

I. Background

TSCA (Pub. L. 94-469, 90 Stat. 2003 et

seq; 15 U.S.C. 2601 et seq.) authorizes

the Administrator of EPA to promulgate

regulations under section 4(a) requiring

testing of chemical 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) of TSCA established an

Interagency Testing Committee to make

recommendations to the Administrator

of EPA of chemical substances and

mixtures to be given priority

consideration in proposing test rules

under section 4(a). Section 4(e) directs

the Committee to revise its list of

recommendations at least every 6

months as necessary. The ITC may

"designate" up to 50 substances and

mixtures at any one time for priority

consideration by the Agency. 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 Nineteenth

Report was received by the

Administrator on October 31, 1986, and

follows this Notice. The Report adds

four 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

relating to the human and environmental

exposure to these chemicals. A notice is

published elsewhere in today's Federal

Register adding the substances

recommended in the ITC's Nineteenth

Report to the TSCA section 8(d) Health

and Safety Data Reporting Rule (40 CFR

Part 716). The section 8(d) rule requires

the reporting of unpublished health and

safety studies on the listed chemicals.

These chemicals will also 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 of production 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 ITC recommendations.

The Focus Meetings will be held on

December 16 and 17, 1986 at EPA

Headquarters, Rm. 103 NE Mall, 401 M

St., SW., Washington, DC. This meeting

is intended to supplement and expand

upon written comments submitted in

response to this notice. The schedule for

the Focus Meetings is as follows:

December 16, 10 a.m.-isopropanol; 1

p.m.-C.I. Disperse Blue 79. December

17, 10 a.m.-methyl tert-butyl ether; 1

p.m.-methyl ethyl ketoxime.

Persons wishing to attend this meeting

or subsequent meetings on these

chemicals should call the TSCA

Assistance Office at the toll free number

listed above at least one week in

advance.

All written submissions should bear

the identifying docket number (OPTS41023).

III. Status of List

In addition to adding the four

recommendationsto the priority list, the

ITC's Nineteenth Report notes the

removal of five chemicals from the list

since the last ITC report because EPA

has responded to the Committee's prior

recommendations for testing of the

chemicals. Subsequent to the ITC's

preparation of its Eighteenth Report,

EPA responded to the ITC's

recommendations for six additional

chemicals. The five chemicals removed

and the dates of publication in the

Federal Register of EPA's responses to

the ITC for these chemicals are:

methylcyclopentane, May 15, 1986 (51 FR

17854); tetrabromobisphenol A, May 15,

1986 (51 FR 17872); triethylene glycol

monomethyl ether, May 15, 1986

(51 FR 17883); triethylene glycol

monobutyl ether, May 15, 1986

(51 FR 17883); triethylene glycol

monobutyl ether, May 15, 1986 (51 FR

17883). The report also notes that

tributyl phosphate, which was originally

recommended with intent to designate

(51 FR 18368, May 19, 1986), has now

41417
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

been designated for response within 12

months by the ITC.

The current list contains three

designated substances. two chemicals

recommended with intent-to-designate,

and four recommended substances.

Authority: 15 U.S.C. 2603.

Dated: November 6. 1986.

J. Merenda,

Director, Existing Chemical Assessment

Division.

Nineteenth Report of the TSCA

Interagency Testing Committee to the

Administrator, Environmental Protection

Agency

Summary

Section 4 of the Toxic Substances

Control Act of 1976 (TSCA, Public Law

94-469) provides for the testing of

chemicals in commerce that may present

an unreasonable risk of injury to health

or the environment. It also provides for

the establishment of a Committee (ITC),

composed of representatives from eight

designated Federal agencies, to

recommend chemical substances and

mixtures (chemicals) to which the

Administrator of the U.S. Environmental

Protection Agency (EPA) should give

priority consideration for the

promulgation of testing rules.

Section 4(e](1)(A) of TSCA directs the

Committee to recommend to the EPA

Administrator chemicals to which the

Administrator should give priority

consideration for the promulgation of

testing rules pursuant to section 4(a).

The Committee is required to designate

those chemicals, from among its

recommendations, to which the

Administrator should respond within 12

months by either initiating a rulemaking

proceeding under section 4(a) or

publishing the Administrator's reason

for not initiating such a proceeding. At

least every 6 months, the Committee

makes those revisions in the TSCA

section 4(e) Priority List that it

determines to be necessary and

transmits them to the EPA

Administrator.

As a result of its deliberations, the

Committee is revising the TSCA section

4(e) Priority List by the addition of four

chemicals, and is noting the removal of

five as a result of responses by EPA.

The Committee also is designating one

chemical that had been recommended

with intent-to-designate in the

eighteenth report.

The Priority List is divided into three

parts: Part A contains those

recommended chemicals and groups

designated for priority consideration

and response by the EPA Administrator

within 12 months. Part B contains

chemicals and groups recommended

with intent-to-designate. This category

was established by the Committee in its

seventeenth report (50 FR 47603;

November 19, 1985) to take advantage of

rules promulgating automatic reporting

requirements for nondesignated ITC

recommendations under the section 8(a)

Preliminary Assessment rule and the

TSCA section 8(d) Health and Safety

Data Reporting rule. Information

received following recommendation

with intent-to-designate may influence

the Committee to either designate or not

designate the chemical or group of

chemicals in a subsequent report to the

Administrator. Part C contains

chemicals and groups of chemicals that

have been recommended for priority

consideration by EPW without being

designated for response within 12

months. The changes to the Priority List

are presented, together with the types of

testing recommended, in the following

Table 1:

TABLE 1.-ADDITIONS TO THE SECTION 4(e)

PRIORITY LIST, NOVEMBER 1986

Chemical/Group Recommended Studies

A. Designated for

Response Within

12 Months

Tributyl phosphate'

(CAS No. 126-

73-8)

B. Recommended

With Intent-IoDesignate

Isopropanol I (CAS

No. 67-63-0).

Methyl tert-butyl

ether 3 (CAS No.

1634-04-4).

C. Recommended

Without Being

Designated for

Response Within

12 Months

C.I. Disperse Blue

79 4 (CAS No.

3956-55-6).

Health Effects: Chronic Toxicity including oncogenic, neurotoxic, renal, reproductive and developmental effects.

Cherical Fate: Persistence in anaerobic soils and sediments.

Ecological Effects: Chronic effects on

aquatic and terrestrial plants; chron- ic effects on daphnids and/or other

aquatic invertebrates; acute and

chronic effects on benthic organisms and soil invertebrates, if

found persistent under anaerobic

conditions.

Health Effects: Genotoxicity. including

tests for mutagenicity in mammalian

systems and clastogenicity;. chronic

toxicity including oncogenicly.

Health Effects: Chronic inhalation toxicity including neurotoxic, hematologic and ocogenic effects.

Chemical Fate: Monitoring at representative gasoline terminals and

service stations.

Health Effects: Subchronic toxicity adsorption and chemical disposition.

Chemical Fate: Solubility in water, bio.

degradation under aerobic and anaerobic conditions and the identification, of arty relatively persistent

biodegradation intermediates.

Ecological Effects: Acute toxicity to

fish, aquatic invertebrates, algae

and benthic organisms (including

filter leeders); bioconcentration in

fish; chronic effects on aquatic and

bent'ic biota, if the. acute studies

show toxicity at low mg/L concentration or it the dye does bioconcenrater

TABLE 1.-ADDITIONS TO THE SECTION 4(e)

PRIORITY LIST, NOVEMBER 1986-Continued

Chemical/Group Recommended Studies

Methyl ethyl Health Effects: Chronic toxicity with

ketoxime 5 (CAS special emphasis on hematopoietic

No. 96-29-7). and oncogenic effects.

CA Index Names (9CI):

ePhospnonc acid. tributyl ester (tributyl phosphate was recommended with intent-to-designate by the Committee in

the eighteenth report (51 FR 18368)).

r2-Propanol. 3 Propane. 2-methoxy-2-methyl- 4 Acetamide, N-[5-[bis[2-(acetyloxytethyllaminol-2-[(2-

bromo-4,6-dinitrophenyl)azo]-4-ethoxypnenyl]- 5 2-Butanone oxime.

TSCA Interagency Testing Committee

Statutory Member Agencies and Their

Representatives

Council on Environmental Quality

Harvey Doerksen. Member

Department of Commerce

Patrick D. Cosslett. Member

Environmental Protection Agency

John D. Walker, Member and Vice

Chairperson

Laurence S. Rosenstein, Alternate

National Cancer Institute

Richard Adamson, Member

Elizabeth K. Weisburger. Alternate

National Institute of Environmental Health

Sciences

James K. Selkirk, Member

National Institute for Occupational Safety

and Health

Rodger L. Tatken, Member and

Chairperson

National Science Foundation

Rodger W. Baler, Member

Jarvis L. Moyers, Alternate

Occupational Safety and Health

Administration

Joseph Jarvis, Member'

Stephen Mallinger. Alternate

Liaison Agencies and Their Representatives

Consumer Product Safety Commission

Lakshmi C. Mishra

Department of Agriculture

Richard M. Parry, Jr.

Elise A. B. Brown

Department of Defense

Edmund Cummings

Department of the Interior

Ronald Eisler 2

Food and Drug Administration

Arnold Borsetti

National Library of Medicine

Vera Hudson

National Toxicology Program

Dorothy Canter

Committee Staff

Robert H. Brink, Executive Secretary

Norma Williams, ITC Coordinator

Support Staff

Alan Carpien-Office of the General Counsel,

EPA

The Committee acknowledges and is

grateful for the assistance and support

I Appointed on August 11, 1986.

2 Appointed on July 11. 1986.

41418
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

given the ITC by the staff of Dynamac

Corporation (technical support

contractor) and personnel of the EPA

Office of Toxic 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 1976 (TSCA, Public Law

94-469). The specific mandate of the

Committee is to recommend to the

Administrator of the 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

environment. TSCA specifies that the

Committee's recommendations shall be

in the form of a Priority List, which is to

be published in the Federal Register.

The Committee is directed by section

4(e)(1)(A) of TSCA 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 for not initiating such a

proceeding. There is no statutory time

limit for EPA response regarding

chemicals that ITC has recommended

but not designated for response 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 of this report. The Committee's

chemical review procedures and priority

recommendations are described in

previous reports (Refs. 1 through 3).

1.2 Committee's previous reports.

Eighteen previous reports to the EPA

Administrator have been issued by the

Committee and published in the

FEDERAL REGISTER (Refs. I through 3).

Ninety-three entries (chemicals and

groups of chemicals) were recommended

for priority consideration by the EPA

Administrator and designated for

response within 12 months. In addition,

five chemicals and one group of

chemicals were recommended without

being so designated.

1.3 Committee's activities during

this reporting period. Between April 1,

1986, and September 30, 1986, the

Committee continued to review

chemicals from its fourth and fifth

scoring exercises, and from nominations

by Member Agencies, Liaision Agencies

and State Agencies.

The Committee contacted chemical

manufacturers and trade associations to

request information that would be of

value in its deliberations. Most of those

contacted provided unpublished

information on current production,

exposure, uses, and effects of chemicals

under study by the Committee.

During this reporting period, the

Committee reviewed available

information on 26 chemicals and 7 large

classes of chemicals. Four chemicals

were selected for addition to the section

4(e) Priority List, and five were deferred

indefinitely. The remaining chemicals

are still under study.

On August 7, 1986, the ITC published

an Intent-to-Designate notice (51 FR

28431) that listed hexamethylenediamine

and described additional information

needed by the ITC to reach a more

informed decision on whether or not to

designate hexamethylenediamine in a

subsequent report to the EPA

Administrator. The Committee

requested information on

biodegradation in aerobic ponds and

under both aerobic and anaerobic

conditions in disposal wells, in the

presence of other waste constituents

typical of hexamethylenediamine

production. A deadline of October 6,

1986 was provided for receipt of

relevant information.

1.4 The TSCA section 4(e) Priority

List. Section 4(e)(1)(B) of TSCA directs

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 four chemicals:

isopropanol, methyl tert-butyl ether, C.I.

Disperse Blue 79, and methyl ethyl

ketoxime. None of these chemicals is

designated for response within 12

months but the Committee intends to

designate isopropanol and methyl tertbutyl ether unless information received

following recommendation influences

the Committee to withhold designation.

In addition, the Committee is

designating for response within 12

months one chemical that wes

recommended with intent-to-designate

in the eighteenth report. The designated

chemical is tributyl phosphate. The

testing recommended. for these

chemicals and the rationales for the

recommendations are presented in

Chapter 2 of this report.

Five chemicals are being removed

from the Priority List because the EPA

Administrator has responded to the

Committee's prior recommendations for

testing them. They are listed in the

following Table 2 with citations to EPA

responses:

TABLE 2-REMOVALS FROM THE TSCA SECTION 4(e) PRIORITY LIST APRIL 1, 1986

THROUGH SEPTEMBER 30, 1986

EPA Responses

Chemical/Group Federal

Register Publication Date Citation

Methyl cyclopentane . 51 FR 17854..... May 15, 1986.

Tetrabromobisphenol A.. 51 FR 17872 May 15, 1986.

Tnethylene glycol 51 FR 17883 .May 15, 1986.

monomethyl ether.

Triethylene glycol 51 FR 17883 .May 15, 1986.

monoethyl ether.

Triethylene glycol 51 FR 17883 .May 15, 1986.

monobuyl ether.

Removal of 87 entries was noted in

previous reports (Ref. 1 through 3). To

date, 92 chemicals and groups of

chemicals have been removed from the

Priority List.

With the four recommendations and

five removals noted in this report, nine

entries now appear on the section 4(e)

Priority List. The Priority List is divided

in the following Table 3 into three parts;

namely, A. Chemicals and Groups of

Chemicals Designated for Response

Within 12 Months, B. Chemicals and

Groups of Chemicals Recommended

with Intent-to-Designate, and C.

Chemicals and Groups of Chemicals

Recommended Without Being

Designated for Response Within 12

Months. Table 3 follows:

TABLE 3.-THE TSCA-SECTION 4(e) PRIORITY

LIST, NOVEMBER 1986

A. Chemicals and Groups of Chemicals

Recommended and Designated for Response Within 12 Months

Entry and date of designation:

1. Cyclohexane .. .......... .....................

2. 2.6-Oiatert-butylphenol ...............

3. Tributyl phosphate ...................

B. Chemicals and Groups of Chemicals

Recommended with Intent-to-Designate

Entry and date of recommendation:

1. Isopropanol ........................

2. MethyL fe/1-butyl ether ......................

C. Chemicals and Groups of Chemicals

Recommended Without Being Designated for Response Within 12 Months:

1. 3,4.eichlorobenzotrifluonde ...............

2. Diisodecyl phenyl phosphite ............

3. C.I. Disperse Blue 79 .........................

4. Methyl ethyl ketoxime ........................

May 1986. May 1986.

Nov. 1986.

Nov. 1986.

Nov. 1986.

May 1984,

Nov. 1985.

Nov. 1988.

Nov. 1986.

References

(1) Sixteenth Report of the TSCA

Interagency Testing Committee to the

Administrator. Environmental Protection

Agency. TSCA Interagency Testing

Committee. May 21, 1985, 50 FR 20930-20939.

41419
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

Includes references to Reports 1 through 15

and annotative list of removals.

(2) Seventeenth Report of the TSCA

Interagency Testing Committee to the

Administrator, Environmental Protection

Agency. TSCA Interagency Testing

Committee, November 19, 1985, 50 FR 47603-

47612.

(3) Eighteenth Report of the TSCA

Interagency Testing Committee to the

Administrator, Environmental Protection

Agency. TSCA Interagency Testing

Committee, May 19, 1986, 51 FR 18368-18375.

Chapter 2-Recommendations of the

Committee

2.1 Chemicals recommended for

priority consideration by the EPA

Administrator. As provided by section

4(e)(1)(B) of TSCA, the Committee is

adding the following chemical

substances to the section 4(e) Priority

List: isopropanol, methyl tert-butyl

ether, C.I. Disperse Blue 79, and methyl

ethyl ketoxime. The recommendation of

these chemicals is being 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. In

addition, the Committee is designating

for response within 12 months one

chemical substance that was

recommended with intent-to-designate

in the eighteenth report. The designated

chemical is tributyl phosphate.

2.2 Chemicals designated for response

within 12 months-2.2.a Tribulyl

phosphate. In the eighteenth report to

the Administrator of EPA (51 FR 18368),

tributyl phosphate was recommended

with intent-to-designate. The rationale

for that recommendation appears in the

eighteenth report. Information reviewed

by the Committee in response to the

eighteenth report included any public

comments on the Committee's

recommendations; production volume,

use, exposure and release information

reported by manufacturers of tributyl

phosphate under the TSCA section 8(a)

Preliminary Assessment rule; health and

safety studies submitted under the

TSCA section 8(d) Health and Safety

Data Report rule; and any unpublished

and published data available to the

Committee. Health effects information

included acute toxicity studies and skin

and eye irritation studies (Ref. 1, Dow

Chemical Co., 1986; Ref. 2, Eastman

Kodak Co., 1986; Ref. 3, FMC Corp,, 1986;

and RefL 6, Stauffer Chemical Co., 1986),

mutagenicity (Ames test) data (Ref. 3,

FMG Corp., 1986) and delayed

neurotoxicity studies (Ref. 5, Monsanto

Co., 1986). Chemical fate information

included chemical and physical

properties, biological oxygen demand,

(BOD) data and- monitoring reports (Ref.

2, Eastman Kodak Co., 1986; Ref. 3, FMC

Corp., 1986; Ref. 4. Glyco, Inc., 1986; and

Ref. 5 Monsanto Co., 1986). Ecological

effects information included acute

toxicity values with aquatic

invertebrates and fish (Ref. 5, Monsanto

Co., 1986).

After reviewing the information, the

Committee concluded that data are still

lacking on chronic toxicity, chemical

fate and ecological effects. For these

reasons and for the reasons previously

presented (51 FR 18368) the Committee

is now designating tributyl phosphate

for response within 12 months and

recommending that it be tested for the

following:

1. Health effects. Chronic toxicity

including oncogenic, neurotoxic, renal,

reproductive and developmental effects.

2. Chemical Fate. Persistence in

anaerobic soils and sediments.

3. Ecological Effects. Chronic effects

on aquatic and terrestrial plants; chronic

effects on daphnids and/or other

aquatic invertebrates; acute and chronic

effects on benthic organisms and soil

invertebrates, if found persistent under

anaerobic conditions.

References

(1) Dow Chemical Co., Midland, MI. Letter

from R.L. Hagerman to Document Control

Officer, U.S. EPA. August 15, 1986.

(2) Eastman Kodak Co.. Rochester, N.Y.

Letter from R. Hays Bell to U.S. EPA. August

11, 1986.

(3) FMC Corp., Philadelphia, PA. Letter

from Ann S. Keller to U.S. EPA. August 8.

1986.

(4) Glyco, Inc.. Norwalk, CT. Letter from

Michael J. Reale to U.S. EPA. August 8, 1986.

(5) Monsanto Co.. St. Louis, MO. Letter

from J.R. Condray to Document Control

Officer, Office of Pesticides and Toxic

Substances, U.S. EPA. August 15, 1986.

(6) Stauffer Chemical Co., Westport, CT.

Letter from Stauffer Chemical Co. to

Document Control Office. Office of ToxicSubstances, U.S. EPA. August 12, 1986.

(7) Union Carbide Corp., Danbury, CT.

Letter from D.L. Heywood to U.S. EPA.

August 11, 1986.

2.3 Chemicals recommended with

intent-to-designate-2.3.a IsopropanolSummary of recommended studies. It is

recommended that isopropanol be tested

for the following:

1. Health Effects. Genotoxicity

studies, including tests for mutagenicity

in mammalian systems and for

clastogenicity Chronic toxicity,

including oncogenicity.

Physical and Chemical Information

CAS Number: 67-63-0

Synonyms: 2-propanol (9 CI);

dimethylcarbinol;' isopropyl alcohol

Acronym: IPA

Structural Formula:

OHI

CH 3 -- CH -CH 3

Empirical Formula: C31I0

Molecular Weight: 60.11

Melting Point: -87.8°C (Ref. 29, Mellan,

1977)

Boiling Point: 82.3°C (Ref. 29, Mellan,

1977)

Vapor Pressure: 33.0 mmHg at 20°C (Ref.

29, Mellan, 1977), 44.0 mmHg at 25°C

(Ref. 7, Browning, 1965), 105.6

mmHg at 40°C (Ref. 18, Hatch, 1961)

Solubility in Water: Miscible with water,

insoluble in salt solutions (Ref. 56,

Windholz, 1983)

Solubility in Organic Solvents: Miscible

with ethanol, ether, and chloroform

(Ref. 56, Windholz, 1983)

Specific Gravity: 0.79 at 20/20'C (Ref. 29

Mellan, 1977)

Log Octanol/Water Partition

Coefficient: (log P): 0.Z (estimated;

Ref. 27, Leo et al., 1971)

Description of Chemical: colorless liquid

Rationale for Recommendations

I. Exposure information-A.

Production/use/disposal/en vironmental

release. The annual production

capacities of four domestic producers of

isopropanol -as of January 1, 1985,

totaled 2.5 billion pounds (Ref. 46, SRI,

1985). The 1985 U.S. production of

isopropanol was reported to be 1.12

billion pounds, giving it the ranking of 50

among the top 50 chemicals for that year

(Ref. 9, C&EN, 1986). The 1984 U.S.

production of isopropanol was reported

to be 1.39 billion pounds (Ref. 54, USITC,

1985), up from the 1983 production of

1.21 billion pounds (Ref. 53, USITC,

1984) but down from the 1980 production

of 1.21 billion pounds (Ref. 52, US1TC,

1981).

Imports of isopropanol in 1985 totaled

136.2 million pounds (Ref. 49, USDOC,

1986a). Exports in 1985 accounted for

178.4 million pounds. (Ref. 50, USDOC,

1986b).

Most isopropanol produced in the

United States is manufactured by the

indirect hydration process. In this twostep process,, propylene reacts first with

sulfuric acid; the products are then

hydrolyzed to isopropanol and sulfuric

acid (Ref. 45. SRI, 1980).

Isopropanol has a large number of

uses. The percentage breakdown of

isopropanol demand for 1984 was

estimated to be the following:

production of acetone (24 percent),

coatings and related solvents (15

percent), other solvents (11 percentl.

41420
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

pharmaceuticals (11 percent), household

and personal products (11 percent),

chemical process solvents (9 percent),

chemical intermediates (7 percent), and

gasoline additives (4 percent). Exports

account for the other 8 percent (Ref. 12,

CMR, 1984).

It has been estimated that 50 percent

of commercial isopropanol is ultimately

released to the environment. An

additional 1.5 percent is estimated to be

lost during production (Dorigan et al.,

1976, cited in Ref. 51, USEPA, 1979).

B. Evidence for human and

environmental exposure. The National

Occupational Hazard Survey (NOHS),

conducted by the National Institute for

Occupational Safety and Health

(NIOSH) from 1972 to 1974, estimated

that 5,483,862 workers in 357,173 plants

were potentially exposed to isopropanol

in the workplace (Ref. 32, NIOSH,

1976a). These estimates were derived -

from observations of the manufacture

and use of the compound, of trade name

products knowri to contain the

compound, and of generic products

suspected to contain the compound (19,

40, and 42 percent of the total estimate,

respectively).

NIOSH conducted a second

workplace survey, the National

Occupational Exposure Survey (NOES),

from 1980 to 1983 (Ref. 34, NIOSH, 1984).

Preliminary data from NOES indicated

that 1,857,962 workers, including

1,186,141 women, in 43,616 plants were

potentially exposed to the compound in

the workplace in 1980. Unlike NOHS,

the NOES estimates were based only on

observations of the use and manufacture

of the compound, per se.

The American Conference of

Governmental Industrial Hygienists

(ACGIH) has established a threshold

limit value (TLV) of 400 parts per million

(ppm) as an 8-hour time-weighted

average with a 15-minute short-term

exposure limit of 500 ppm (Ref. 2,

ACGIH, 1986b). The TLV was set on the

basis of eye, nose, and throat irritation

(Ref. 1, ACGIH, 1986a). The permissible

exposure limit (PEL) for the workplace

adopted by the Occupational Safety and

Health Administration is also 400 ppm

(Ref. 40, OSHA, 1983).

General dilution/ventilation and the

use of personal protective equipment

have been recommended as effective

controls to reduce occupational

exposure to isopropanol in a number of

operations (Ref. 35, NIOSH/OSHA,

1978).

Isopropanol is a constituent of some

commercial food flavors (Ref. 47,

Stanley, 1939; Ref. 41, Pendleton, 1970).

For this use and its use as an adjuvant,

the Food and Drug Administration

permits the use of only the minimum

quantity of isopropanol necessary to

produce the desired effect. No residues

of the chemical may remain in foods

marked with isopropanol-derived color

additives (Ref. 15, FDA, 1986).

Isopropanol has been detected in

trace quantities in fish meal (Ref. 21,

lida et al., 1978), white bread (Wideblatt

and Kohn, 1960, cited in Ref. 16,

Fenaroli, 1975), enzyme-inactivated beef

(Wick, 1965, cited in Ref. 16, Fenaroli,

1975), and pressure-cooked pork liver

(Mussinan and Walradt, 1974, cited in

Ref. 16, Fenaroli, 1975).

Isopropanol was identified in

leachates from a Southington, CT,

landfill site in 1982-83 at concentrations

ranging from 3.9 to 8.8 mg/L (Ref. 43,

Sawhney and Kozloski, 1984). Levels of

isopropanol ranging fromn 2.3 to 21.3

ug/L have been measured at a municipal

effluent in a river in Oklahoma, and

levels ranging from 10 to 2,000 ug/L have

been found in a well in South Carolina

near an industrial impoundment area

(Ref. 48, STORET, 1986).

II. Chemical fate information.

Although very large amounts of

isopropanol are released to air and

water, most of the releases are widely

dispersed and isopropanol in the

environment will be rapidly

biodegraded or oxidized. Therefore,

chemical fate testing is not being

recommended at this time.

1II. Biological effects of concern to

human health-A. Metabolism and

toxicokinetics. Isopropanol

administered intravenously and orally

to normal, fasting dogs was rapidly

absorbed from the gastrointestinal tract;

distribution to the tissues occurred

within a range of 30 minutes to 1 or 2

hours (Ref. 26, Lehman et al., 1945).

Isopropanol is metabolized to acetone

in rats by alcohol dehydrogenase (ADH)

(Ref. 37, Nordmann, 1980). Rats were

intraperitoneally administered pyrazole,

an inhibitor of ADH and catalase, or

amino-1,2,4-triazole, an inhibitor of

catalase alone. Isopropanol was then

administered either intraperitoneally or

by gavage. Blood levels of isopropanol

and acetone were then monitored at

regular intervals. Animals receiving

amino-1,2,4-triazole showed no

significant difference in blood

isopropanol or acetone levels from those

observed in rats receiving only

isopropanol. In contrast, pretreatment

with pyrazole decreased isopropanol

clearance and delayed the rate of

acetone production (Ref. 38, Nordmann

et al., 1973).

When isopropanol was perfused

through rabbit liver in situ, a progressive

rise in the acetone concentration in

blood was observed (Ref. 14, Ellis, 1952).

An average of 10.2 percent of the dose

of isopropanol administered by gavage

to rabbits was isolated as the

glucuronide from the 24-hour urine

sample. Acetone (about 0.5 percent of

the dose) was also identified in expired

air from treated rabbits (Ref. 22, Kamil

et al., 1953).

Blood levels of isopropanol and

acetone in rats following inhalation

exposure to isopropanol for 4 hours, in

the test range of 500 to 8,000 ppm, were

directly related to atmospheric

concentrations of the chemical.

Increasing the exposure time to 8 hours

magnified the amount of acetone that

could be detected even 20 hours

following exposure. These results

indicate a slow conversion of the

alcohol to acetone (Ref. 24, Laham et al.,

1980).

In rats given single intraperitoneal

doses of isopropanol, the half-life of the

chemical in plasma declined with

decreasing dose level (Ref. 42, Rietbrock

and Abshagen, 1971).

B. Acute (short-term) effects. The

acute toxicity of isopropanol is

summarized in the following Table 4.

TABLE 4.-ACUTE TOXICITY OF ISOPROPANOL IN LABORATORY ANIMALS

Animal Route Effect Reference

Mouse ......................................................

Do .....................................................

Do .....................................................

Do ... ............... ..........................

Rat ...................................... ................

Do .................................................

Rat (14.day-old) ...................................

Rat (young adult) ...................................

Rat (older adult) .....................................

Rat .................................. ..................

Orl ...........................

Ih .....................

Ipr ............................

Ivn ...........................

Orn ........................... 01t ..................... .....

on ....................

Orl ...........................

Or .................... .

Orl .......................

LD . 4.8 g/kg; CNS depression ................................................................................................ Levy and Zakhan (1976. Rel. 28).

LD : 10.39 m g/L, 2-1w exposure.............................................................................................. o.

LD.: 1.28 g/kg ............................................................................................................................. Do.

LD.: 31.0 m m ol/kg (about 1.9 g/kg) ................................................................................... ChVapil at al. (1962, Ret. 10).

LD ,: 5.84 g/kg ............................................................................................................................. Smyth and Carpenter (1948, Ret. 44).

LL : 6.73 cm !'/k9 ..................................................................................................................... Lehm an and Chase (1944, Ref. 25).

LD.: 5.6 m L/kg .......................................................................................................................... Kim ura et al. (1971, Ret. 23).

LD : 6.0 ..m L/kg ............................................................................................................................ Do .

LD .: 6.8 m L/kg ............................................................................................................................ Do.

LD : 4.7 g/kg ........................................................................................................................... Levy and Zakhari (1976, Re . 28).

41421
41422Feea eierIVl51No22 FrdyNoebr1,18INocs

TABLE 4.-AcuTE TOXICITY OF ISOPROPANOL IN LABORATORY ANIMALS-Continued

Animal Route Effect Reference

Do .................................. LD,.-. 19.000 ppm (females), 8-hr exposure. Severe irritation to mucous membranes. Laham et al. (1980, Ref. 24).

Ataxia, prostration, narcosis. At levels between 20,000 and 22,000 ppm, paralysis of

hind legs was observed in both sexes during first 5 days of exposure.

Rat ........................ Ih............. Congestion of liver, lungs, and spleen was observed in rats exposed at 4,000 and

8,000 ppm.

............... 500-16,000 ppm. 4-hr exposure: At 4,000 ppm slight hypothermia was observed. At Laham et al. (1980, Ref. 24).

8,000 and 16,000 ppm. severe hypothermia recorded.

Do ........................................... p......... pr ............................ LD .: 1.87 g/kg ............................................................................................................................. Levy and Zakhari (1976, Ref. 28).

D o ..................................................... Scu .......................... LD , 5.70 g kg ............................................................................................................................. Do .

Rabbit ...................................................... O64 ........................... LD : 6.41 cm -/kg ....................................................................................................................... Lehm an and Chase (1944, Ref. 25).

D o ..................................................... O d ........................... LD o: 6.15 cm 3/kg .................................................................. ................................................. D o.

When applied to rabbit eyes, a drop of

isopropanol caused mild transitory

injury (Ref. 44, Smyth and Carpenter,

1948). Isopropanol did not produce any

adverse effects when applied dermally

to guinea pigs, dogs, and white rats

(Macht, 1922, cited in Ref. 32, NOISH,

1976a; Steele and Wilhelm, 1966, cited in

Ref. 32, NIOSH, 1976a). Similarly, the

chemical did not produce tissue

destruction when applied to intact and

abraded skin of rabbits and guinea pigs

(Ref. 36, Nixon et al., 1975).

C. Genotoxicity. In the Salmonella

microsomal assay using the spot test,

isopropanol was nonmutagenic in

strains TA98, TA100, TA1535, and

TA1537 both with and without S-9 from

Aroclor-induced rats (Ref. 17, Florin et

al., 1980). The chemical was

nonmutagenic in Salmonella strains

TA97, TA98, TA100, TA1535, and

TA1537 both with and without

metabolic activation, when tested using

a plate-incorporation modification of

this microbial assay (Ref. 39, NTP

CHEMTRACK, 1986).

Isopropanol yielded negative results

in mutagenicity tests in Neurospora

crassa (Ref. 6, Brockman et al., 1984).

Isopropanol did not enhance simian

adenovirus (SA7) transformation using

Syrian hamster embryo cells when

tested over a concentration range of 62

to 1,000 ug/mL (Ref. 19, Heidelberger et

al., 1983).

D. Oncogenicity. In inhalation studies,

C3H, ABC, and C57 mice were exposed

to isopropanol for 3 to 7 hours per day, 5

days per week for 5 to 8 months. There

was no significant increase in the

number of tumors observed. Similarly,

no increases in pulmonary tumors were

observed in the same strains of mice

received 20 to 40 weekly subcutaneous

injections of 0.025 mL isopropanol (Ref.

55, Weil et al., 1952).

In skin painting studies, no tumors

were observed when isopropanol was

painted on the clipped backs on 30

Rockland all-purpose mice 3 times per

week for 1 year (Weil, unpublished data,

cited in Ref. 33, NIOSH, 1976b).

E. Chronic (long-term) effects.

Isopropanol was administered as a 5

percent solution in tap water to male

albino rats for 9 months. The average

daily consumption of isopropanol was

1.9 mL/kg. There was no significant

differences in the death rates of the

treated animals compared to controls

given tap water. Treated animals

experienced a marked decrease in fluid

consumption compared to controls, as

well as a significant weight depression.

Both of these conditions were reversed

in the month following withdrawal of

the alcohol. Noisy breathing and

sluggishness were also noted in the

treated animals. In another test, 187

daily applications of a 50 percent

solution of isopropanol of the heads of

male rats failed to cause injury to the

skin, hair, or eyes that would

differentiate the treated from the control

animals (Ref. 5, Boughton, 1944).

White rats were administered 0.5, 1.0,

2.5, 5.0, and 10.0 percent solutions of

isopropanol in water for 27 weeks. Rats

given 10 percent isopropanol refused to

drink the fluid and died early in the

experiment. Some deaths occurred in

two of the other exposure groups, but

insufficient data were available to

determine whether the deaths were

treatment related. Food intake by the

exposed rats was equal to or greater

than that of the control rats. There was

a tendency for decreasing fluid intake

with increasing alcohol concentration.

Gross and histopathologic examination

of selected organs showed no evidence

of gross or microscopic changes (Ref. 25,

Lehman and Chase, 1944).

Three dogs were administered

isopropanol in water daily for 7 months.

The alcohol concentration was 4 percent

from the end of the first month until the

conclusion of the experiment. Tolerance

to the alcohol developed, as manifested

by an increased degree of

neuromuscular coordination at similar

blood levels in habituated versus control

animals and by increased elimination of

the alcohol. The only significant

histopathologic changes were noted in

the kidneys of the one dog that died

(Ref. 26, Lehman et al., 1945).

F. Reproductive and developmental

effects. In a three-generation

reproductive study, male and female

rats receiving 2.5 percent isopropanol

daily in drinking water exhibited no

deleterious effects on their reproductive

function and embryonic development.

Some retardation of growth was

observed in the early life of firstgeneration rats (Ref. 26, Lehman et al.,

1945).

Isopropanol was administered by

inhalation to groups of 15 pregnant

Sprague-Dawley rats for 7 hours per day

on gestation days I to 19 at doses of

3,500, 7,000 and 10,000 ppm. The highest

concentration produced maternal

narcosis and reduced weight gain and

feed intake. At 7,000 ppm isopropanol,

the only observable maternal effect was

decreased weight gain. No maternal

effects were observed at 3,500 ppm.

Following exposure to 10,000 ppm

isopropanol, there was a statistically

significant increase in resorptions and

decrease in fetal weights. Fetal weights

were also decreased at the two lower

dose levels. There was a significant

increase in malformations in the litters

of dams exposed to 7,000 and 10,000

ppm isopropanol. No teratogenic effects

were observed at the 3,5000 ppm dose

level (Ref. 31, Nelson et al., 1985; Ref. 30,

Nelson et al., 1986).

A single-generation reproduction

study is being conducted in the Wistar

rat at dose levels of 0.5, 1.0, and 2.0

percent isopropanol in drinking water.

Males will be exposed 70 days prior to

mating and females 21 days prior to

mating. Also underway is a teratology

study in female Wistar rats at does

levels of 0.5, 1.5, and 2.5 percent

isopropanol in drinking water. The high

does was selected to produce maternal

toxicity. Both studies are being

conducted at the request of the

government of the United Kingdom (Ref.

11, CMA, 1986).

G. Observations in humans.

Occupational exposure to isopropanol

was assessed in 12 workers employed in

a printing works by testing

environmental air, alveolar air, venous

blood, and urine during their work shift.

Isopropanol in environmental air ranged

41422 Federal Regzister / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

between 7 and 645 mg/m . It was

detected in alveolar air at levels ranging

between 4 and 437 mg/m . The chemical

was not detected in blood or urine.

Alveolar concentration of alcohol was

significantly corrected with its

environmental concentration (Ref. 8,

Brugnone et al., 1983).

The blood half-lives of isopropanol in

two patients suffering from acute

overdoses of the alcohol were estimated

at 155 and 187 minutes, respectively. In

both patients, acetone levels were higher than the alcohol values at the

beginning of the study and remained

elevated throughout the study (Ref. 13,

Daniel et al., 1981).

In five persons who died as a

consequence of drinking isopropanol,

deep and stubborn coma was observed

as well as varying degrees of shock and

hypothermia. Acetonuria without

glycosuria was also observed (Ref. 3,

Adelson, 1962).

In a historical prospective study of 262

men who had worked at an isopropanol

plant in Great Britain, the observed

deaths were slightly higher than

expected. There was a statistically

nonsignificant increase in deaths from

neoplasms. One person died from nasal

cancer; the authors stated that this

finding was unlikely to be due to chance

even though based on small numbers

(Ref. 4, Alderson and Rattan, 1980).

An increased incidence of cancer of

the paranasal sinuses was observed in

workers at factories manufacturing

isopropanol by the strong acid process.

The risk of laryngeal cancer may also

have been elevated in these workers

(Ref. 20, IARC, 1977).

H. Rationale for health effects

recommendations. Annual domestic

production of isopropanol is greater

than 1 billion pounds.Well over 1

million persons are estimated to be

exposed to the chemical in the

workplace. Widespread consumer

exposure results from its use in

pharmaceuticals and household

products. It -has been detected in trace

quantities in several foods. It has also

been identified in leachates from a landfill site. Although several limited

carcinogenicity studies have been

performed, insufficient data are

available to assess its long-term effects.

Therefore, the Committee recommends

chronic toxicity studies, including tests

to assess its oncogenic potential.

Additional genotoxicity studies,

including tests to assess its mutagenic

potential in mammalian systems and its

clastogenic effects, are also

recommended. The Committee is

concerned about possible reproductive

and developmental effects of

isopropanol given the teratogenic effects

observed at high doses in inhalation

studies in rats. However, the Committee

recommends deferring the chemical

from consideration for such testing

pending the outcome of relevant studies

presently being conducted at the request

of the government of the United

Kingdom.

IV. Ecological effects of concern.

There is sufficient information available

to show that isopropanol is unlikely to

persist in the environment at

concentrations that would cause

adverse ecological effects. Therefore,

ecological effects testing is not being

recommended at this time.

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(48) STORET. Storage and Retrieval for

Water Quality Data [data base]. Washington,

DC: U.S. Environmental Protection Agency

(1986).

(49] USDOC. U.S. Department of

Commerce, Bureau of the Census. "Imports

Statistics for TSUSA, No. 4280620." (1986a).

(50) USDOC. U.S. Department of

Commerce, Bureau of the Census. "Export

statistics for Schedule B, No. 4311060."

(1986b).

(51) USEPA. Chemical Hazard Information

Profile (CHIP). Revised draft report on

isopropyl alcohol. Washington. DC: U.S.

Environmental Protection Agency (November

20. 1979).

(52) USITC. United States International

Trade Commission. "Synthetic Organic

Chemicals. United States Production and

Sales, 1980," USITC Publication No. 1183, p.

263 (1981).

(53) USITC. United States International

Trade Commission. "Synthetic Organic

Chemicals. United States Production and

Sales, 1983." USITC Publication No. 1588, pp.

258. 282 (1984).

(54) USITC. United States International

Trade Commission. "Synthetic Organic

Chemicals. United States Production and

Sales, 1984," USITC Publication No. 1745, p.

256 (1985).

(55) Weil, C. S., Smyth, H. F., Jr., and Nale,

T. W. "Quest for a suspected industrial

carcinogen," Archives of Industrial Hygiene

and Occupational Medicine. 5:535--547 (1952).

(56) Windholz. M, ed. The Merck Index. An

Encyclopedia of Chemicals, Drugs, and

Biologicals. 9th Ed. (Rahway, NJ: Merck &

Co., Inc., 1983).

2.3.b Methyl tert-butyl etherSummary of recommended studies. It is

recommended that methyl tert-butyl

ether (MTBE) be tested for the following:

1. Chemical Fate. Monitoring studies

to determine typical concentrations of

MTBE at representatives sites where

MTBE-containing gasoline is

transferred, including gasoline terminals

and service stations.

2. Health Effects. Chronic inhalation

toxicity including neurotoxic,

hematologic, and oncogenic effects.

Physical and Chemical Information

CAS Number:

1634-04-4

Synonyms:

Propane, 2-methoxy-2-methyl-(9 CI);

Methyl 1,1-dimethylethyl ether; (2-

Methyl-2-propyl) methyl ether; tertButyl methyl either

Acronym:

MTBE

Structural Formula:

CH 3

CHI-O-C-CH3

CH 3

Empirical Formula:

C5H 12 0

Molecular Weight:

88.15

Melting Point:

-110°C (Ref. 16, Phillips Petroleum,

1984)

Boiling Point:

55°C (Ref. 16, Phillips Petroleum, 1984)

Vapor Pressure:

414 mmHg at 38°C (Ref. 16, Phillips

Petroleum, 1984)

Solubility in Water:

40,000 mg/L (Ref. 11, Hawley, 1981)

43,000 mg/L (Ref. 4, ARCO, 1986)

Solubility in Organic Solvents:

Very soluble in alcohol and ether (Ref.

12, HSDB, 1986)

Specific Gravity:

0.74 at 20/4°C (Ref. 16, Phillips

Petroleum, 1984)

Log Octanol/Water Partition

Coefficient: (log P):

1.30 (Ref. 13, Leo, 1982; cited in

ISHOW, 1984)

Henry's Law Constant:

4.5X10-4atm-m3/mol (Ref. 20, USEPA,

1986)

Description of Chemical:

Clear liquid, pleasant hydro-carbon

odor (Ref. 16, Phillips Petroleum,

1984)

Rationale for Recommendations

I. Exposure information-A.

Production/use. The commercial

production of MTBE uses the reaction of

isobutylene and methanol, in the

presence of a catalyst, at 30 to 100°C

and 7 to 14 atmospheres. Production has

increased dramatically since 1979 when

MTBE was approved by the EPA for use

as a blending component of unleaded

gasoline. Current production is in the

neighborhood of 2 billion pounds per

year in the United States. By 1989,

production is predicted to reach 3 billion

pounds per year (Ref. 5, CEH, 1985).

Nearly all of the MTBE produced in

the Uhited States is used as octaneI

41424
Federal Register / Vol. 51, No. 220 / Friday. November 14. 1986 / Notices

enhancing agent in some but not all

unleaded gasolines. Although it has

been approved as an additive at up to

all percent, typical concentrations in

gasoline range from 2 to 8 percent by

weight (Ref. 4, ARCO, 1986).

B. Evidence for human exposure. The

National Occupational Exposure Survey

(NOES), conducted between 1980 and

1983, indicated that 2,571 workers,

including 849 women, were potentially

exposed to MTBE in the workplace (Ref.

14, NIOSH, 1984).

Occupational exposures at

manufacturing sites are limited because

manufacturing occurs in closed systems.

However, two companies have reported

measured 8-hour time weighted average

(TWA) workplace exposures to MTBE of

1 to 3 ppm at manufacturing sites (Ref.

16, Phillips Petroleum, 1984; Ref. 4,

ARCO, 1986).

Workers involved in transportation

and loading operations of MTBEcontaining gasoline have been found to

be exposed to less than 2 ppm MTBE

(Ref. 4, ARCO, 1986). Halder et al. (Ref.

10 1986) monitored exposures of truck

drivers and terminal operators at five

gasoline distribution terminals. A total

of 183 samples were collected at the

terminals over a 12-month period.

Worker exposure to C4 and higher

hydrocarbons in gasoline vapors, on a 8-

hour TWA basis, varied from 0.4 to 80

ppm, with an overall 8-hour TWA

geometric mean of 1.4 ppm. Some of the

vapor samples were analyzed for

individuas hydrocarbon constituents.

No analyses were made for MTBE, but

C4 and C5 compounds constituted 61 to 74

percent by weight of the total gasoline

vapor samples. Similar hydrocarbon

exposures were reported in earlier

studies at terminals (Ref. 15, Phillips and

Jones, 1978; Ref. 8 Diakun, 1983).

In a survey of exposures to gasoline

vapors at a service station plaza,

Halder, et al.'(1986, Ref. 10) reported a

geometric mean 8-hour TWA exposure

of 1.0 ppm. Diakun (1983, Ref. 8),

reporting on analyses of 74 samples

obtained during self-service consumer

exposures, reported a cumulative mean

concentration of 59.9 ppm hydrocarbon

vapor during pumping, which, projected

to an 8-hour TWA exposure, is 0.28 ppm.

Tests performed in 1983 indicated that

MTBE accounts for approximately 3.3

percent of the organic vapors in the

head space above gasoline containing 10

percent MTBE (Ref. 4, ARCO, 1986). It is

not known how that study was

conducted or whether the results are

useful in estimating MTBE

concentrations in the hydrocarbon

vapors in the "breathing zone" locations

at gasoline terminals and service station

plazas. However, reports that C4 and C5

compounds make up 61 to 74 percent by

weight of the total gasoline vapors at

such sites (Ref. 10, Halder, 1986)

demonstrate, as might be expected, that

gasoline constituents with lower

molecular weights volatilize more

readily than the heavier fractions. The

available data are not sufficient to

permit a reliable estimate of the MTBE

concentration in gasoline vapors at

terminals and service stations or of

worker and consumer exposures at

those sites.

C. Environmental release. North

Carolina authorities have found MTBE

in ground water in test wells along the

Cape Fear River (Ref. 18, Taylor, 1986)

at concentrations of 0.18 to 3.0 parts per

million. This ground water

contamination is probably due to spills

during transfer of gasoline from

seagoing tankers to onshore storage

facilities. The largest environmental

release sources appear to be through

fugitive emissions at gasoline terminals

and service stations where distribution

to and dilution in the atmosphere will be

strongly dependent on local conditions.

Controls that recover gasoline vapors

emitted at filling stations are used at

less than 10 percent of the service

stations in the nation (Ref. 19, USEPA,

1984).

II. Chemical fate information-A.

Transport, Despite its relatively high

water solubility, MTBE is expected to

partition largely to air. The Henry's law

constant of 4.5X 10- 4 atmm 3

/mol

indicates that any MTBE present in

surface water will have a half-life of

about 9 hours before volatilizing.

Furthermore, most of the MTBE released

to the environment will be released

directly to air during transfer operations.

The low octanol/water partition

coefficient and relatively high water

solubility of MTBE indicate little

tendency for significant partitioning to

soils, sediments, or biota.

B. Persistence. Nearly all of the MTBE

released to the environment will

partition to the atmosphere where it will

be degraded by hydroxy radicals, with

an atmospheric half-life of about 3.5

days. The products of this oxidation are likely to include t-butyl formate (major

product). acetone, and methyl radical

(Ref. 7, Cox and Goldstone, 1981).

Persistence in ground water following

spills is unknown, but it may persist for

long periods if volatilization is

prevented, since MTBE is not likely to

be readily biodegraded or otherwise

transformed in ground water.

C. Rationale for chemical fate

recommendations. MTBE released to the

environment will partition to the

atmosphere (except at spill and leak

sites) where it will be degraded by

reaction with hydroxy radicals. Other

fate pathways are expected to be less

significant. The major concern for MTBE

involves exposures in the "breathing

zone" of workers and consumers

handling MTBE-containing gasoline

during transfer operations. In view of

this and the lack of data on exposure

concentrations, it is recommended that

appropriate monitoring studies be

conducted to evaluate the concentration

of MTBE at representative sites Where

MTBE-containing gasoline is transferred

from shipping units (e.g., tankers,

barges) into storage facilities, from

storage facilities into shipping units, and

from service station plaza pumps into

motor vehicles.

III. Biological effects of concern to

human health-A. Metabolism and

toxicokinetics. Over 90 percent of an

intraperitoneal dose of MTBE (232 mg/

kg) was excreted untransformed in rat

breath (Ref. 3, API, 1985). A fraction of

the dose was also excreted as CO 2 in

the breath and as formic acid in the

feces and urine.

B. Acute and subchronic effects. In

rats, the oral LD5o (short-term) was

reported as 3,865.9 mg/kg. Acute oral

exposure resulted in central nervous

system depression, ataxia, tremors,

labored breathing, and loss of righting

reflex. In rats exposed by inhalation,

eye irritation, irregular respiration,

incoordination and prostration were

noted The inhalation LD5o in rats was

found to be approximately 120 mg/L

(Ref. 3, Atlantic Richfield Co., cited in

API, 1985).

In tests with rabbits, MTBE was not

found to be a primary skin irritant. It

was irritating to the rabbit eye {Ref. 3,

Atlantic Richfield Co., cited in API,

1985).

A 9-day inhalation toxicity study was

conducted on fasted and unfasted rats.

Rats (20 per sex per group) were

exposed for 6 hours per day, 5 days per

week for 9 days at concentrations of 0,

100, 300, 1,000, or 3,000 ppm. No doserelated mortality was noted. Phosphorus

levels were significantly increased in

the fasted females in the 1,000 and 3,000

ppm groups. An increase in relative liver

weight in both sexes of fasted rats at

3,000 ppm was noted. The same trend

was seen in the unfasted high-does male

rats. Microscopic pathology revealed

chronic inflammation in the nasal

mucosa and trachea in the 1,000 and

3,000 ppm groups. (Ref. 3, API 1985)

In a 90-day inhalation study in rats,

MTBE was administered at 250, 500, and

1,000 ppm does levels for 6 hours per

day, 5 days per week for 3 months. The.

principal pharmacotoxic sign was

increased anesthesia with increased

41425
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

concentration. A slight decrease in body

weight was seen at 1,000 ppm. An

increase in hemoglobin levels in male

rats was noted at 1,000 ppm at the end

of the study, but this was not considered

toxicologically significant (Ref. 3, API,

1985).

C. Genotoxicity. MTBE was tested in

several in vitro systems (Atlantic

Richfield Co., cited in API, 1985).

Negative results were reported in the

Salmonella and Saccharomyces tests

with and without metabolic activation.

In the mouse lymphoma forward

mutation assay both with and without

metabolic activation, a dose-related

mutagenic effect was noted with S9

activation.

Sister chromatid exchange (SCE) and

chromosomal aberration assays

produced negative results. An increase

in SCE was observed at 0.2 and 1.0 uL/

mL in one activated sample. In an in

vitro cytrogenetic study in rats, negative

results were noted.

D. Oncogenicity. No information was

found.

E. Reproductive and development

effects. Tests to determine the

reproductive and developmental effects

of MTBE were conducted in female rats.

The animals were exposed to 0, 250,

1,000, and 2,500 ppm for 6 hours per day

during gestation days 6 to 15. Dams were sacrificed at day 20. No treatmentrelated effects were noted. In another

study, female mice were exposed to the

same concentrations but were sacrificed

at day 18 of gestation. No adverse

effects Were noted in the dams. Minor

fetal skeletal malformations were noted,

but in the absence of vertebral rib

defects these malformations were not

considered to be teratogenic (Ref. 6,

Conaway et al., 1985).

An inhalation study was conducted on the effects of MTBE on the reproduction

of rats through one generation. The

animals were exposed to 0. 250, 1,000 or

2,500 ppm MTBE for 6 hours per day, 5

days per week for 12 weeks, including

both premating and postmating periods.

Males were exposed for 6 hours during

the mating period. Female rats were

exposed for 6 hours per day, 5 days per

week for 3 weeks during premating and

daily for 6 hours during mating. After

mating, females were exposed 6 hours

daily during gestation days 0 to 20 and

lactation days 5 to 21. The study

involved two litter intervals, and

females were exposed for 5 days per

week, 6 hours per day during a 2-week

period between litter rest intervals. No

dose-related adverse effects were noted

(Ref. 3, API, 1985).

F. Chronic (long-term) effects. No

information was found.

G. Observations in humans. In viva

dissolution of gallstones by MTBE in

four patients was reported (Ref. 2, Allen

et al., 1985b). Dissolution occurred

within 4 to 7 hours after direct

instillation. Hematology and blood

chemistry profiles showed no

abnormalities. Results of both urinalysis

and 24-hour urine collection for

measurement of total protein were

normal.

The Food and Drug Administration

has classified MTBE as an

Investigational New Drug. It is currently

being used by one team of investigators

to dissolve gallstones (Ref. 22,

Wyngaarden, 1986).

H. Rationale for health effects

recommendations. Almost all MTBE

produced in the United States is used as

a gasoline enhancer in certain unleaded

blends, and the annual production is on

the rise, with a projected volume of 3

billion pounds in 1989, Consequently,

human exposure to MTBE low-level

fugitive emissions at gasoline pumps is

expected to occur. The major routes of

expose would be via the skin and

inhalation. In view of this potential

exposure and the lack of chronic health

effects information, the Committee

recommends chronic health effects

testing. Special emphasis should be

given to neurotoxic, hematologic, and

oncogenic effects.

IV. Ecological effects of concern-A.

Acute and subchronic (short-term)

effects. Using a flow-through system,

Veith et al. (1983, Ref. 21) reported a 96-

hour LC 0 with the fathead minnow of

760 mg/L MTBE. Using static systems,

Tarkpea and Svanberg (1982, Ref. 17)

found a 24-hour LCso of 1,700 to 1,800

mg/L with the bleak Alburnus alburnus,

and a 96-hour LCOo greater than 10,000

mg/L with the copepod Nitocra spinipes.

B. Chronic (long-term) effects. No

information was found.

C. Other ecological effects (biological,

behavioral, or ecosystem processes). No

information was found.

D. Bioconcontration and food-chain

transport. Using carp in a flow-through

system, Fujiwara et al. (1984, Ref. 9)

reported a bioconcentration factor of 1.5.

MTBE was rapidly eliminated from the

fish when they were transferred to fresh

water. No other information was found.

E. Rationale for ecological effects

recommendations. It does not appear

that MTBE will be toxic to biota at

concentrations likely to be found in the

environment except at spill and leaking

storage tank sites. Therefore, ecological

effects testing is not being recommended

at this time.

References

(1) Allen, M. J., Borody, T. J., Bugliosi, T. F.,

May, G. R., LaRusso, N. F., and Thistle, J. L.

"Cholelitholysis using methyl tertiary butyl

ether," Gastroenterology. 88:122-125 (1985a).

(2) Allen, M. J., Borody, T. J., Bugliosi, T. F.,

May, G. R., LaRusso, N. F., and Thistle, J. L.

"Rapid dissolution of gallstones by methyl

tertbutyl ether," The New EnglandJournal of

Medicine. 312:217-220 (1985b).

(3) API. Unpublished information on the

production, use, occupational exposure,

release, and toxicity of MTBE. Submitted by

W. F. O'Keefe, American Petroleum Institute

(March 15, 1985).

(4) ARCO. Letter from E.C. Capaldi, ARCO

Chemical Co., Newton Square. PA, to R.

Brink, Executive Secretary, TSCA

Interagency Testing Committee (July 21,

1986).

(5) CEH. Chemical Economics Handbook.

Stanford Research Institute. Menlo Park, CA:

SRI International. Section 675.1000A675.1001F (1985).

(6) Conaway, C. C., Schroeder, R. E., and

Snyder, N. K. "Teratology evaluation of

methyl tertiary butyl ether in rats and mice."

Journal of Toxicology and Environmental

Health. 16:797-809 (1985).

(7) Cox, R. A., and Goldstone, A.

"Atmospheric reactivity of oxygenated motor

fuel additives," in Physico-Chemical

Behavior of Atmospheric Pollutants, B.

Versino and H. Ott. eds. (Dordrecht, Holland:

D. Reidel Publishing Co., 1981].

(8) Diakun. R. "Characterization of

workplace exposures." Documentation of

presentation to EPA by API. Submitted by N.

K. Weaver, American Petroleum Institute.

FYI-AX-0783-0148, Supp. Sequence H (July

15, 1983].

(9] Fujiwara, Y., Kinoshita, T., Sato, H., and

Kojima, I. "Biodegradation and

bioconcentration of alkyl ethers" Yukagahu.

33(2).,111-114 [Abstract] (1984).

(10) Halder, C. A., Van Grop. C. S.,

Hatoum, N. S., and Warne, T. M. "Gasoline

vapor exposures. Part I. Characterization of

workplace exposures," American Industrial

Hygiene Association Journal. 47:164-172

(1986).

(11) Hawley, G. G. The Condensed

Chemical Dictionary, 10th ED.. pp. 671-672.

(New York: Van Nostrand Reinhold Co.,

1981).

(12) HSDB. "Hazardous Substances Data

Bank" [data base]. Bethesda, MD:

Department of Health and Human Services,

National Library of Medicine (1986).

(13) ISHOW. (1985). Information System for

Hazardous Organics in Water. [date base].

Baltimore, MD: Chemical Information

Systems, Inc. Supported by the National

Institutes of Health/U.S. Environmental

Protection Agency.

(14) NIOSH. "National Occupational

Exposure Survey (1980-1983)" [data base].

Cincinnati, OH: Department of Health and

Human Services, National Institute for

Occupational Safety and Health. (1984].

(15) Phillips, C. F., and Jones, R. K.

"Gasoline vapor exposure during bulk

handling operations," American Industrial

Hygiene Association Journal. 39:118-128

(1978].

41426
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

(16) Phillips Petroleum. Material Safety

Data Sheet and unpublished information on

the production, use, and occupational

exposure of MTBE. Submitted by J. J. Moon,

Phillips Petroleum Company (January 12,

1984).

(17) Tarkpea, M., and Svanberg, 0. "The

acute toxicity of motor fuels to brackish

water organisms," Marine Pollution Bulletin.

13(4):125-127. (1982).

(18) Taylor, T. Memorandum from T.

Taylor, North Carolina Department of Human

Resources, to R. Brink, Executive Secretary,

TSCA Interagency Testing Committee

(August 25, 1986).

(19) USEPA. "Estimation of the public

health risk from exposure to gasoline vapor

via the gasoline marketing system." Draft

Report. U.S. Environmental Protection

Agency, Office of Health and Environmental

Assessment, Office of Air Quality Planning

and Standards (June, 1984).

(20) USEPA. Memorandum from P.

Harrigan, Office of Toxic Substances, to R. H.

Brink, Interagency Testing Committee.

(October 6, 1986).

(21) Veith, G. D., Call, D. J. and Brooke, L.

T. "Structure-toxicity relationships for the

fathead minnow, Pimephales promelas:

narcotic industrial chemicals." Canadian

Journal of Fisheries and Aquatic Sciences.

40:743-748 (1983).

(22) Wyngaarden, J. B., "From the National

Institutes of Health: New nonsurgical

treatment removes gallstones." Journal of the

American Medical Association. 256:1692

(1986).

2.4 Chemicals and groups of

chemicals recommended without being

designated for response within 12

months-2.4.a CI. Disperse Blue 79-

Summary of recommended studies. It is

recommended that C.I. Disperse Blue 79

be tested for the following:

1. Chemical Fate. Solubility in water

at 25° C. biodegradation under aerobic

and anaerobic conditions and the

identification of any relatively persistent

biodegradation intermediates.

2. Health Effects. Absorption and

chemical disposition via oral route'of

administration. Subchronic toxicity (90-

day study).

3. Ecological Effects. Acute toxicity to

fish, aquatic invertebrates, algae, and

benthic organisms, including filter

feeders. bioconcentration in fish.

Chronic effects on aquatic and benthic

biota if the acute studies show toxicity

at low mg/L concentrations or if the dye

bioconcentrates.

Physical and Chemical Information

CAS Number:

3956-55--6

Synonym:

Acetamide, N-[5-[bis[2-

(acetyloxy)ethyl]amino]-2-[(2-

bromo-4,6-dinitrophenyl)azo]-4-

ethoxyphenyl](9CI)

Structural Formula:

Br

NO 2 -/ N

NO 2

OC 2 H 5

=N-HO N(CHCH 2 -O-COCH3 2

NHCOCH 3

Description of Chemical:

Blue powder with characteristic odor

(Ref. 12, Mobay Chemical, 1985)

Empirical Formula:

C24H27BrN6Olo

Molecular Weight:

639.44

Melting Point:

143 °C (estimated; Ref. 19, USEPA,

1986a)

Boiling Point:

476 °C (estimated; Ref. 19, USEPA,

1986a)

Vapor Pressure:

3.4X10 - 9 mmHg at 25 °C (estimated;

Ref. 19, USEPA, 1986a)

Solubility in Water:

5.4 mg/L (estimated; Ref. 19, USEPA,

1986a)

Solubility in Organic Solvents:

No information was found.

Specific Gravity:

No information was found

Log Octanol/Water Partition

Coefficient: (log P):

4.1 (estimated; Ref. 19, USEPA, 1986a)

Henry's Law Constant:

5.9X10- 10 atm-m3/mol (estimated; Ref.

19, USEPA, 1986a)

Log Adsorption Coefficient (log K,,)

3.6 (estimated; Ref. 19, USEPA, 1986a)

Bioconcentration Factor (fish)

757 (estimated; Ref. 19, USEPA, 1986a)

According to the Ecological and

Toxicological Association of the

Dyestuffs Manufacturing Industry (Ref.

6, ETAD, 1986), the bromoethoxy

compound described above, which has

the Colour Index (C.I.) Constitution No.

11345, is the only derivative properly

referred to as C.I. Disperse Blue 79.

However, there appear to be three other

closely related derivatives that have

been and may still be called Disperse

Blue 79. The concerns expressed in this

report for the bromoethoxy derivative

apply also to these other derivatives

which are expected to have physical

and chemical properties similar to the

bromoethoxy derivative and which have

the following structures:

where, for derivative 1, X=Br and

R=C-h3 ; for derivative 2, X=CI and

R=CH3 , and for derivative 3, X=CI and

R=C2I-.

Rationale for Recommendations

I. Exposure information-A.

Production/use/en vironmental release.

The U.S. International Trade

Commission listed the annual

production of C.I. Disperse Blue 79 at 5

to 10 million pounds per year in the

United States from 1980 through 1984

(Refs. 23 through 27, USITC, 1981-1985).

Heath (Ref. 21, USEPA, 1986c) has

estimated the current annual production

at 0.9 to 1.4 million kilograms (2 to 3

million pounds), as active colorant,

which is a large production for a dye.

Disperse Blue 79 appears to be the major

blue dye for textile use and a major

component of green, brown, and black

dyes. About 40 percent of production is

sold to users in a paste or liquid

formulation and about 60 percent as a

solid, mainly as low dusting granules

(Ref. 6, ETAD, 1986).

41427

X OR

NO 2 -/ \ -N- N=\ / N(CHZCH2-O-C0CH4)2

NO2 NHCOCH3
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

Heath (Ref. 21 USEPA, 1986c)

estimated that during the manufacture of

Disperse Blue 79, there would be

releases of 4,500 to 14,000 kilograms

(10,000 to 30,000 pounds) per year at a

total of nine sites, with an estimated 3 to

20 kilograms (7 to 45 pounds) per site per

day. Heath estimated releases of 2 to 18

kg (4.4 to 40 pounds) per site per day at

400 to 600 textile dyeing operations.

B. Evidence for human exposure.

According to the National Occupational

Exposure Survey (NOES) 1,450 workers

at 25 plants in the chemical and allied

products industry were potentially

exposed to C.I. Disperse Blue 79 in the

workplace in 1980 (Ref. 13, NIOSH,

1984). Workplace exposure limtis have

not been established for C.I. Disperse

Blue 79 by American Conference of

Governmental Industrial Hygienists

(Ref. 1, ACGIH, 1986) or the

Occupational Safety and Health

Administration (Ref. 15, OSHA, 1983).

Farris (Ref. 20, USEPA, 1986b) estimated

significant worker exposure during

manufacture and use. Occupational

exposure to this dye is expected from

inhalation of dye-containing dust

particles, swallowing inhaled particles

trapped in saliva and mucous, and from

dermal exposure during open batch

manufacture (Ref. 20, USEPA, 1986b;

Ref. 21, USEPA, 1986c). Consumer

exposures should be very low since this

is a fast dye which is relatively

insoluble in water and not likely to

leach from the fabrics.

C. Environmental exposure. No

published information was found.

However, an assessment (based on mathematical modeling) has been made

for the ITC by the Office of Toxic

Substances (Ref. 22, USEPA, 1986d). The

assessment used estimates of releases

(Ref. 21, USEPA, 1986c) and took into

consideration plant locations, receiving

stream characteristics, and the locations

of downstream drinking water treatment

plants. The assessment also assumed 50

percent removal of the dye during

passage through biological treatment

plants by adsorption to sludge solids.

Mean surface water concentrations

downstream from manufacturing plants

and fabric dyeing operations were estimated to range from 0.02 to 40 ug/L.

A high receiving stream concentration of

306 ug/L was predicted for low flow

conditions at one site. Drinking water

exposures resulting from releases during

manufacture and dyeing were calculated

and were estimated to range from 0.06 to

43 ug/kg/year. Variations are due to site

features, releases per day, and the

number of days per year that releases occur. These estimates assumed no loss

of the dye through biodegradation on

other transformation processes.

II. Chemicalfate information-A.

Transport. The low estimated vapor

pressure and Henry's law constant

indicate that volatilization of Disperse

Blue 79 will not be significant. The

estimated log K., value of 3.6 indicates

that about 50 to 60 percent of the dye

will adsorb to the organic matter of

waste treatment sludges and that about

40 to 50 percent will be released to - receiving streams.

B. Persistence. Information supplied

by ETAD (Ref. 6, 1986) indicates that in

static tests, where the disappearance of

total organic carbon (TOC) was

followed, 29 to 68 percent of the TOC

disappeared over a 2-week period in

solutions containing Disperse Blue 79.

No data were presented on the specific

features of the tests or on whether the

TOC disappearance might have been

due to some factors other than

biodegradation, such as adsorption onto

suspended and settled particulates or the walls of test vessels. In standard 5-

day biological oxygen demand (BOD)

tests, the BOD5 was 6.8 pounds 02 per

100 pounds dye (Ref. 7, ETAD, 19861,

which is about 4 percent of the

theoretical oxygen uptake for complete

oxidation. None of this biodegradation

information is sufficient to evaluate the

biodegradability of Disperse Blue 79.

Studies currently underway or planned

at the EPA Water Engineering Research

Laboratory in CincinnatL OH, and at the

Georgia Institute of Technology (Ref. 6,

ETAD, 1986) may provide useful

information on both adsorption and

biodegradation.

Azo dyes in general are relatively

resistant to biodegradation and Disperse

Blue 79 is likely to persist during

biological treatment, with a portion

adsorbing to the sludge solids and the

rest being discharged in the effluent.

Under anaerobic conditions, microbial

processes may cleave the azo bond to

form two aromatic amines. The 2-bromo4,6-dinitroaniline produced by this

reaction may be of concern by itself.

In its Fourth Report to the EPA

Administrator (44 FR 31867), the ITC

recommended and designated certain

anilines, including 2-chloro-4,6-

dinitroaniline (CAS No. 3531-19-9) and

2-bromo-4,6-dinitroaniline (CAS No.

1817-73-8). In an Advance Notice of

Proposed Rulemaking (ANPR) on January 3, 1984 f49 FR 108), the EPA

noted that there appeared to be no current production of 2-chloro-4,6-

dinitroaniline, but that the 2-bromo

compound was being produced and that

it was being considered for a battery of

chemical fate, health effects and

environmental effects testing.

The potential for Disperse Blue 79 to

be cleaved to release 2-bromo-4,6-

dinitroaniline, both in the environment

and in vivo following ingestion, needs to

be investigated If this product is formed

via microbial processes in sediments,

waste treatment facilities, and intestinal

tracts, then added emphasis should be

placed on testing of the sort described

by the EPA in the ANPR of January 3,

1984.

Other transformation processes (e.g.,

hydrolysis and photolysis) are not

expected to be major factors in the

transformation of this dye.

C. Rationale for chemical fate

recommendations. The lack of measured

values on physical and chemical

properties for C.I. Disperse Blue 79

increases the uncertainty with respect to

chemical fate predictions. At a

minimum, water solubility values at 25

°C should be obtained for any

commercially important forms of

Disperse Blue 79.

Disperse Blue 79 released to the

environment is likely to partition to both

water and sediments. In sediments, it

may degrade anaerobically and release

2-bromo-4,6-dinitroaniline. No data have

been found to substantiate or refute

these predictions. Since the dye has

widespread large use in the United

States and is likely to be released to the

environment during both manufacture

and use, it is recommended that

biodegradation studies be conducted to

determine (1) the potential for aerobic

and anaerobic biodegradation, and (2)

the identify of relatively persistent

intermediates, if any, resulting from

biodegradation.

III. Biological effects of concern to

human health-A. Metabolism and

toxicokinetics. No information was

found on the metabolism of C.l. Disperse

Blue 79. The dye is likely to split at the

azo bond into 2-bromo-4,6-dinitroaniline,

and 2-diethanolamino-4-methoxy-5-

amino-6-acetanilide by azoreductases

present in the intestinal flora. Many azo

dyes are split at the azo bond by the

intestinal flora (Ref. 4, Chung et al., 1978;

Ref. 7, Grasso and Golberg, 1968; Ref. 9,

Honohan et al., 1976; Ref. 15, Pritchard

et al., 1976; Ref. 16, Radomski, 1961; Ref

17, Roxon et al., 1967) and liver enzymes

(Ref. 5, Daniel, 1967). Studies on the

metabolism and disposition of 2-bromo4,6-dinitroaniline, (BDNA) in male F344

rats were reported by Chopade and

Matthews (1986, Ref 3). The

gastrointestinal absorption of 14CBDNA was nearly complete, and

approximately 80 percent of the

41428
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

radioactivity was cleared from most

tissues within 6 hours.

B. Acute and subchronic (short-term)

effects. The acute oral LD5o of Disperse

Blue 79 in rats was greater than 5,000 mg

per kg of body weight (Ref. 6, ETAD,

1986). It was found to be nonirritating in

primary skin irritation and eye irritation

tests (Ref. 6, ETAD, 1986).

C. Genotoxicity. Disperse Blue 79 was

found to be strongly mutagenic in the

standard Salmonella S-9 assay in four

tester strains TA1535, TA1537, TA98,

and TA100 (Ref. 11, Mishra et al., 1981).

It was also found to be negative in the

V79 mammalian cell and mouse

micronucleus assays (Ref. 6, ETAD,

1986).

D. Oncogenicity. No data were found

on oncogenicity testing of C.I. Disperse

Blue 79. 2,6-Dichloro-4-nitro-aniline, a

structural analog of 2-bromo-4,6-

dinitroaniline (one of the fragments of azo

bond cleavage of the dye), was found to

be negative in cancer bioassays in mice

(Ref. 16, Innes et al., 1969) and rats (Ref.

8, Hadidian et al., 1968).

2-Chloro-4,6-dinitroaniline and 2-

bromo-4,6-dinitroaniline (CAS No. 3531-

19-9 and 1817-73-18, respectively) were

recommended by the ITC in its Fourth

Report to the EPA Administrator for

carcinogenicity, mutagenicity,

teratogenicity, and other chronic effects

studies (see Part 1iB, above).

E. Chronic (long-term) effects. No

information was found.

F. Reproductive and developmental

effects. No information was found.

G. Observations in humans. No

information was found.

H. Rationale for health effects

recommendations. Because of the

potential bioavailability of C.I. Disperse

Blue 79 to workers from ingestion of

inhaled dye-containing dust, it is

recommended that the dye be tested for

subchronic toxicity (90-day study) and

for absorption and chemical dispositon

following the oral route of

administration. A chemical disposition

study is recommended to determine the

potential for liberation of 2-bromo-4,6-

dinitroaniline in the intestines due to

azo bond cleavage of the dye.

IV. Ecological effects of concern-A.

Acute and subchronic (short-term)

effects. Acute toxicity studies using

rainbow trout and Disperse Blue 79

formulations were reported as follows

(Ref. 6, ETAD, 1986):

Granule formulation, containing approximately

26% Disperse Blue 79, LQo=320 mg/L.

Granule formulation, containing approximately 52% Disperse Blue 79,

LCo =400 mg/L.

Liquid formulation, containing

approximately 13% Disperse Blue 79,

LCo=700 mg/L.

Without additional details, it is not

possible to evaluate the validity of these

test data. The Committee is concerned

about the reported LCso concentrations,

since the values cited are about 100

times the estimated water solubility of

Disperse Blue 79 and the test data are

only for a 48-hour exposure time,

whereas 96 hours is the minimal

exposure period for acute toxicitiy tests

in fish.

B. Chronic (long-term) effects. No

information was found.

C. Other ecological effects (biological,

behavioral or ecosystem processes). No

effects on activated sludge respiration

were observed when Disperse Blue 79

was present at concentrations up to 100

mg/L (Ref. 2, Brown et al., 1981).

D. Bioconcentration and food-chain

transport. No data were found for

Disperse Blue 79.

E. Rationale for ecological effects

recommendations. Although the

estimated concentration levels for C.I.

Disperse Blue 79 in surface waters are

relatively low, ranging from 0.02 to 306

ug/L, the lack of adequate data on

ecological effects and the nature of this

dye molecule raise concerns for

potential effects. Acute toxicity tests

should be run with fish, aquatic

invertebrates, algae, and benthic

organisms. If biodegradation studies

demonstrate the formation of 2-bromo4,6-dinitroaniline, then this

transformation product should also be

evaluated as noted in the EPA Advance

Notice of Proposed Rulemaking of

January 2, 1984 (49 FR 108). The

estimated log P value of 4.1 for Disperse

Blue 79, and an estimated

bio concentration factor in fish of 757,

indicate a potential for some sorption

and bioconcentration of the dye in

biolipids. Bioconcentration studies with

fish are recommended to confirm or

refute the prediction of Disperse Blue 79

uptake. Chronic studies with aquatic

and benthic organisms are

recommended if the results of the

studies show toxicity at low mg/L

concentrations or if the dye

bioconcentrates.

References

(1) ACGIH. American Conference of

Governmental Industrial Hygienists. "TLV's.

Threshold Limit Values and Biological

Exposure Indices for 1986-1987" (Cincinnati,

OH: ACGIH, 1986).

(2) Brown, D., Hitz, H.R., and Shcafer, L.

"The assessment of the possible inhibitory

effect of dyestuffs on the aerobic waste water

bacteria: Experience with a screening test,"

Chemosphere. 10(3):245-261 (1981).

(3) Chopade, H. M., and Matthews, H. B.

"Disposition and metabolism of 2-bromo-4,6-

dinitroaniline in the male F344 rat," Journal of

Toxicology and Environmental Health. 17:37-

50 (1986).

(4) Chung, K.-T., Fulk, G.E., and Andrews,

A.W. "The mutagencitiy of methyl orange

and metabolites produced by intestinal

anaerobes," Mutation Research. 58:375-379

[1978).

(5) Daniel. J.W. "Enzymatic reduction of

azo food colourings," Food and Cosmetics

Toxicology. 5:533-534 (1967).

(6) ETAD. Ecological and Toxiciological

Association of the Dyestuffs Manufacturing

Industry. Letter from E. A. Clarke, Executive

Secretary, ETAD, to R. H. Brink, Executive

Secretary, TSCA Interagency Testing

Committee (August 11. 1986).

(7) Grasso, P., and Golberg, L. "Problems

confronted and lessons learned in the safety

evaluation of Brown FK," Food and

Cosmetics Toxicology. 6:737-747 (1968).

(8) Hadidian, Z., Fredrickson, T. N..

Weisburger, E.K., Weisburger, J.H., Glass,

R.M., and Mantel, N. "Tests for chemical

carcinogens. Report on the activity of

derivatives of aromatic amines, nitrosamines,

quinolines, nitroalkanes, amides, epoxides,

aziridines, and purine antimetabolites,"

Journal of the National Cancer Institute.

41:985-1036 (1968).

(9) Honohan, T, Enderlin, F.E., and

Ryerson, B. A. "Absorption, metabolism, and

excretion of the azo food dyes amaranth,

sunset yellow and tartrazine after oral

administration to rats," Federation

Proceedings, Federation of American

Societies for Experimental Biology. 35(3):328

(1976).

(10) Innes, J.R.M., Ulland, B.M., Valerio,

M.G., Petrucelli, L., Fishbein, L., Hart, E.R.,

and Pallotta, A.). "Bioassay of pesticides and

industrial chemicals for tumorigenicity in

mice: A preliminary note," Journal of the

National Cancer Institute. 42:1101-1114

(1969).

(11) Mishra, N.K., Bell, S.J., Gomez, Y.P.,

and Prival, M.J. "Mutagenicity of synthetic

hair implant components: Biocompatibility

studies of leachates using Salmonella, "

Environmental Mutagenesis. 3:351 (1981).

(12) Mobay Chemical. "Material Safety

Data Sheet for Resolin Navy Blue 2 GLS 200

(C.I. Disperse Blue 79)." Mobay Chemical

Corporation, Union, NJ (March 22, 1985).

(13] NIOSH. National Institute for

Occupational Safety and Health. "National

Occupational Exposure Survey (1980-1983)"

[data base]. Cincinnati, OH: U.S. Department

of Health and Human Services (1984).

(14) OSHA. Occupational Safety and

Health Administration. "OSHA Safety and

Health Standards for General Industry," 29

CFR 1910. Subpart Z. U.S. Department of

Labor, Washington, DC (1983).

(15) Pritchard A.B., Holmes, P.A., and

Kirschman, J.C. "The fate of FD&C Red No. 2

and its metabolite, naphthionic acid, after

different routes of administration in the rat,"

Toxicology and Applied Pharmacology. 35:1-

10 [1976).

(16) Radomski, J.L. "The absorption, fate

and excretion of Citrus Red No. 2 (2,5-

dimethoxy-phenyl-azo-2-naphthol} and Ext.

D&C Red No. 14 (1-xylylazo-2-naphthol),"

The Journal of Pharmacology and

Experimental Therapeutics. 134:100-109

(1961).

41429
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

(17) Roxon, I.J., Ryan, A.,J., and Wright, S.E.

"Reduction of water soluble azo dyes by

intestinal bacteria." Foods and Cosmetics

Toxicology: 5:367-369 (1967).

(18) USCPSC. U.S. Consumer Product

Safety Commission. "Status of Benzidine

Congener Dyes Exposure and Toxicology

Testing,"Memorandum from A.I. Gerber to

P.W. Preuss, USCPSC (February 11, 1983).

(19) USEPA. "Chemical Property Estimates

for C.I. Disperse Blue 79." Memorandum from

P. Harrigan to J. Walker, Test Rules

Development Branch, EPA (June 3, 1986a).

(20) USEPA. "C.I. Disperse Blue 79."

Memorandum from R.E. Farris, Industrial

Chemistry Branch, to J.D. Walker, Test Rules

Development Branch, EPA (June 6, 1986b).

(21) USEPA. "Engineering Assessment for

Disperse Blue 79." Memorandum from G.

Heath, Chemical Engineering Branch, to J.D.

Walker, Test Rules Development Branch,

EPA (May 30, 1986c).

(22) USEPA. "Predicted Surface Water

Concentrations and Drinking Water Exposure

of C.I. Disperse Blue 79." Memorandum from

M.H. Thomas, Exposure Assessment Branch,

to J.D. Walker, Test Rules Development

Branch, EPA, (June 24, 1986d).

(23) USITC. U.S. International Trade

Commission. "Synthetic Organic Chemicals,

United States Production and Sales, 1980."

Publication No. 1183, p. 68. Washington, DC:

U.S. Government Printing Office (1981).

(24) USITC. U.S. International Trade

Commission. "Synthetic Organic Chemicals,

United States Production and Sales, 1981."

Publication No. 1292, p. 59. Washington, DC:

U.S. Government Printing Office (1982).

(25] USITC. U.S. International Trade

Commission. "Synthetic Organic Chemicals,

United States Production and Sales, 1982."

Publication No. 1422, p. 61. Washington, DC:

U.S. Government Printing Office (1983).

(26) USITC. U.S. International Trade

Commission. "Synthetic Organic Chemicals,

United States Production and Sales, 1983."

Publication No. 1548, p. 61. Washington, DC:

U.S. Government Printing Office (1984).

(27) USITC. U.S. International Trade

Commission. "Synthetic Organic Chemicals,

United States Production and Sales, 1984."

Publication No. 1745, p. 55. Washington, DC:

U.S. Government Printing Office (1985).

2.4.b Methyl Ethyl KetoximeSummary of recommended studies. It is

recommended that methyl ethyl

ketoxime (MEKO) be tested for the

following:

1. Health Effects. Chronic toxicity,

with special emphasis on hematopoietic

and oncogenic effects.

Physical and Chemical Information

CAS Number:

96-29-7

Synonyms:

2-Butanone oxime (9 CI); MEKOXIME; MEKO

Structural Formula:

CH3-C- -CH.-CH 3 II

NOH

Empirical Formula:

C4HsNO

Molecular Weight:

87.12

Melting Point:

-29.5 °C (Ref. 25, Verschueren, 1983)

Boiling Point:

152 °C (Ref. 25, Verschueren, 1983)

Vapor Pressure:

1.06 mmHg at 20 °C 7.6 mmHg at 50 'C

(Ref. 7, Kurita, 1967)

Solubility in Water:

100 g/L at unspecified temperature

(Ref. 25, Verschueren, 1983)

Solubility in Organic Solvents:

Miscible with alcohol and ether (Ref.

26, Weast, 1984)

Secific Gravity

0.923 at 20/4 °C (Ref. 25, Verschueren,

1983)

Log Octanol/Water Partition Coefficient

(log P):

0.8 (Ref. 6, Leo, 1982, cited in ISHOW,

1985)

Description of Chemical:

Clear, colorless to light-yellow liquid

at ambient conditions (Ref. 7,

Kurita, 1967; Ref. 2, Allied, 1984a)

Rationale for Recommendations

I. Exposure information-A.

Production/use/en vironmen tal release.

The public portion of the TSCA

Inventory listed on aggregate production

volume of 520,000 to 5,202,000 pounds of

MEKO in 1977 Ref. 23, USEPA, 1986a). In

1982, approximately 1.9 to 2.7 million

pounds of MEKO were produced in the

United States and in 1983, 2.0 to 2.9

million pounds were produced (Refs. 27

and 28, Zacharias, 1985, 1986; Ref. 17,

SRI,-1984). Imports of MEKO totaled 2.6

million pounds in 1984 (Ref. 21, USDOC,

1985) and 2.2 million pounds in 1985

(Ref. 22, USDOC, 1986).

MEKO is used almost exclusively as

the major antiskinning agent in alkyd

and coatings. (Ref. 4, CEH, 1981).

Antiskinning agents are added at less

than 1 percent concentration to typical

solvent-thinned paint formulations (Ref.

15, Scofield et al., 1975), prevent

oxidation of the paint while in the can

and volatilize while the coating is drying (Ref. 10, NIOSH, 1984a). Alkyd paints

containing MEKO are used in interior

semigloss and gloss paints and exterior

enamels, in auto refinishing, and in

product finishes for metal furniture,

machinery, and appliances (Ref. 16, SRI,

1982).

B. Evidence for human and

enviornmental exposure. The National

Occupational Hazard Survey (NOHS),

conducted by the Natioal Institute for

Occupational Safety and Health

(NIOSH) from 1972 to 1974, estimated

that 12,114 workers in 1,540 plants were

potentially exposed to MEKO in the

workplace in 1970 (Ref 10, NIOSH, 1976).

NIOSH conducted a second survey,

the National Occupational Exposure

Survey (NOES), from 1980 to 1983.

Preliminary data from NOES indicated

that 2,145 workers (including 209

women) in the chemical and allied

products industry were potentially

exposed to MEKO in 1980 (Ref. 11,

NIOSH. 1984b).

It has been conservatively estimated

that more than 900,000 individuals were

potentially exposed to MEKO as

professional painters in end-use

applications in 1984 (Ref. 19, Stoecklein,

1986). This estimate is exclusive of

consumers incidentally exposed during

routine painting/decorating activities.

Workplace exposure limits have not

been recommended for MEKO by the

American Conference of Governmental

Industrial Hygienists (Ref. 1, ACGIH,

1986) or established by the Occupational

Safety and Health Administration (Ref.

13, OSHA, 1983).

In a montoring study (Ref. 5,

Himmelsbach, 1984), a MEKOcontaining paint was applied by

nonpowered equipment in an interior

hall in an office building by four

painters. During a 4-hour sampling

period, the airborne concentration of

MEKO ranged from approximately 0.27

to 0.46 ppm.

There are 764 products listed in the

U.S. Consumer Product Safety

Commission's Chemicals in Products

data base that contained MEKO at

concentrations of 0.1 to 0.8 percent (Ref.

20, USCPSC, 1985). Of these, all but 16

are in the paints and coatings category,

which includes house and trim finish

products, floor paints, wood stains,

enamel finishes, yacht bottom and

marine paints, traffic paints, heavy-duty

equipment enamels, varnishes, interior

paints, and primers. Some of the

products identified in the nonpaint

category are bathroom bowl cleaners,

aluminum cleaners, adhesives, and

caulking compounds.

No information was found on general

population exposure to MEKO.

However, it appears that consumers as

well as professional painters would

potentially be exposed to MEKO via the

dermal and inhalation routes,

principally through contact with alkyd

paints (e.g., interior semigloss and gloss

paints, exterior enamels).

41430
Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

An exposure assessment (based on

mathematical modeling) has been made

for the ITC by the Office of Toxic

Substances (Ref. 24, USEPA, 1986b).

Based on this analysis, the level to

which consumers might be exposed to

MEKO was estimated. In this analysis,

two coats of a solvent-based alkyd paint

containing 1 percent MEKO were

applied by roller to most of the interior

of a house. The total exposure to MEKO

resulting from such an activity was

estimated to be 432 mg. While

consumers could be exposed to this

level on a casual basis, the exposure to

professional painters would be more

frequent. Hence, the levels to which this

group could be exposed to MEKO would

be considerably higher.

II. Chemical fate information. If

released tothe environment, it is likely

that MEKO will be photooxidized in the

atmosphere and photolyzed or

biodegraded in the aquatic environment.

Therefore, chemical fate testing is'not

being recommended at this time.

IlI. Biological effects of concern to

human health-A. Metabolism and

toxicokinetics. It is expected that MEKO

would metabolize to methyl ethyl ketone

and hydroxylamine (Ref. 3, Allied,

1984b).

A summary of an unpublished study

on tissue distribution (REF. 3, allied,

1984b), reported that pregnant female

mice were administered a single oral

(unspecified) dose of '

4C-MEKO on day

14 of gestation, and one male mouse was

administered an unspecified dose of the

compound by intratracheal instillation.

The following data were reported:

Whole body autoradiography revealed that

MEKO was rapidly absorbed from the

stomach and lungs. Widespread uptake and

distribution of the label over the entire body

of the animal were noted. The tissues with

the highest concentration of MEKO included

bone, bone marrow, liver, gallbladder, nasal

and bronchial epithelium, pancreas, seromucous and salivary glands, spleen.

intestinal wall, and thymus. Urine and bile

contained significant activity throughout the

study. Interstinal activity was minimal. This

suggests that MEKO is primarily excreted via

the kidneys ... high concentrations of

MEKO were detected in the liver of the

fetuses at 24 hours. This concentration was greater than that seen in the livers of the

mothers.

B. Acute and subchronic effects. The

acute toxicity of MEKO is summarized

in Table 5 which follows:

TABLE 5.-ACUTE ToxIcITY OF METHYL ETHYL

KETOXIME IN LABORATORY ANIMALS

Animal Route Effects Reference

Mouse. Ol. LDo: 1.0 g/kg' ................ Allied (1984b.

Ret. 3).

TABLE 5.-ACUTE TOXICITY OF MET

KETOXIME IN LABORATORY ANIP

tinued

Animal Route Effects

Mouse. lpr .......... Approx. LDso: 1 g/kg

Rat ........... Oil LC6 : 2.3 g/kg ..................

Rat Oil LD : 3.7 g/kg ..................

R at ........... IN ..........

Rat ........... I.

Rat ........... I Skn.

Rat ........... Scn.

Saturated vapors for

35 min. Agitation by

2 min and then

drowsiness by 35

min when exposed

to vapors for 35 min.

0.19. 1.45, and 4.83

rng/L of MEKO

vapors for 4 hr

produced no

mortality. The high

dose group showed

evidence of

anesthesia after

exposure.

Methemoglobin

formation was noted

for the mid- and

high-dose levels.

Minor changes were

noted in hematology

or clinical chemistry

for all groups.

Doses of 0.02. 0.2, or

2.0 mL/kg for 24 hr

produced 100

percent mortality at

2.0 mL/kg; no

mortality at lower

doses.

Methemoglobin was

noted at 0.2 and 2.0

mL/kg and a small

increase in

reticulocytes at 0.2

mL/kg. Nervous

system depression

was the predominant

sign for acute doses.

There was no effect

at 0.02 mL/kg.

LDO: 2.7 g/kg. LDo:

2.8 9/kg.

"Oral" LD reported as cited in Allied (198

In a study in which MEKO in

was applied to rat skin (Ref. 7,

1967], transient dermatitis was

Mild dermal irritation in the ra

usually disappearing within 72

exposure, has also been report

Allied, 1984b). Data obtained u

guinea pig maximization test in

that MEKO has a strong sensit

potential (Ref. 3, Allied, 1984b)

hyperemia of the eyelid and bu

conjunctiva was observed in ra

following instillation of MEKO

of the eyes of each of three rat

observed effects disappeared

hours (Ref. 7, Kurita, 1967).

The effects of MEKO on van

hematologic parameters in rats

been studied (Ref. 7, Kurita, 19

study, five male albino rats rec

subcutaneous doses of MEKO

oil (1.5 mL per kg every other d

weeks). Five control rats were

treated with olive oil alone (1.5

kg). At the end of the treatmen

the only statistically significan

THYL ETHYL <0.05) effect noted was inhibition of

MALS-Con- erythrocyte and plasma cholinesterease

activity.

In another study (Ref. 7, Kurita, 1967), Reference four groups of male albino rats each

Plzak and received MEKO in olive oil at dose

Doull (1969. levels of 0.1, 0.5, or 1.0 mL per kg body Ref. 14).

Allied (1984b. weight, respectively. The control group

Raf. 3). received olive oil only. The test material Allied (1984b,

Rel. 3). was injected subcutaneously once daily

Kurita (1967. for 4 weeks. Clinical examinations, Ra. 7), including body weight and hematologic

measurements were performed

throughout the experimental period.

Allied (1984b. After 4 weeks, the rats were sacrificed,

Rel. 3). with blood samples taken and gross and

microscopic pathological examinations

performed. Dose-related effects were

observed at the two highest doses but

not at the lowest dose level (0.1 mL per

kg per day). According to the author, the

effects associated with exposure to

MEKO included growth inhibition,

increases in the absolute and/or relative

weights of the spleen, liver, and kidneys,

decreased erythrocyte count and

Allied (1984b. hemoglobin content, secondary

Ret. 3). leukocytoses, lymphopenia, splenic

hypertrophy, impairment of clotting

function, atrophy of lymphatic tissue,

pulmonary atelectasis, pulmonary

emphysema, and bronchial pneumonia.

A statistically significant (p <0.01)

decrease in serum protein concentration

also was noted.

A summary of an unpublished study

(Ref. 3, Allied, 1984b) reported that rats

were administered MEKO by gavage at

doses of 25, 75, and 225 mg perkg per Rla. 7). day for 13 weeks. The following data

were reported: 84b). No mortality, changes in appearance or

vaseline behavior, or abnormalities in urine values

Kurita, were observed in the rats during the study.

noted. Slight to moderately lower mean body

bbit, weights and food consumption were noted at

hours of the high dose level at eight and thirteen

ed (Ref. 3, weeks in the males. All of the treated groups

Ising the from both sexes showed dose related

ndicated decreases in erythrocyte count, hematocrit

and hemoglobin values and displayed a ization moderate to market reticulocytosis. Heinz

Marked bodies, occasional siderocytes,

tlb polychromasia, basophilic stippling and

ats Howell-Jolly bodies were generally present in

into one the mid and high dose groups. Blood

s. The chemistries revealed an elevation of total

ifter 6 to 9 bilirubin and erythrocyte cholinesterase in

mid dose males and high dose males and

ous females. Alkaline phosphatase levels of high

have dose males also increased. A slight

67). In one depression in blood urea nitrogen and plasma

eived cholinesterase levels were noted in the high

olive dose level female group. in oDose related increases in the absolute and/ lay for 4 or relative weight of the spleen, liver and

similarly kidney were observed in all treatment groups.

mL per The spleens and livers appeared large and/or

t period, darkened upon necropsy. Histopathological

t (p examination revealed extramedullary

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Federal Register / Vol. 51, No. 220 / Friday, November 14, 1986 / Notices

hematopoiesis and increased amounts of

greenish-brown pigment located in

macrophages of the spleen and liver.

Kidney sections revealed an accumulation

of greenish-brown pigment in the epithelial

cells lining the proximal convoluted tubules.

These data suggest that MEKO induces a hemolytic anemia in the rat with

compensatory erythropoiesis. A NOEL (no

observable effect level) was not established

but was predicted to be less than 25 mg kg/

day.

C. Genotoxicity. This chemical has

been selected by the National

Toxicology Program for testing in the

Ames assay and is currently on test for

in vitro cytogenetics (Ref. 12, NTP, 1986).

In previously conducted assays,

however, MEKO was nonmutagenic in

both the Ames and sister chromatid

exchange assays (Ref. 3, Allied, 1984b).

In another study, MEKO was

nonmutagenic in Salmonella strains

TA98, TA100 TA1535, TA1537, and

TA1538 (Ref. 8, NCI, 1985a). MEKO has

also been tested in the mouse lymphoma

assay (Ref. 9, NCI, 1985b). Under the

conditions of the assay, MEKO

produced a positive response without

metabolic activation and a negative

response with metabolic activation.

D. Oncogenicity. No information was

found.

E. Chronic (long-term) effects. No

information was found.

F. Reproductive and developmental

effects. No information was found.

G. Observations in humans. No

information was found.

H. Rationale for health effects

recommendations. MEKO is the major

antiskinning agent in alkyd coating

resins for use in interior semigloss and

gloss paints and exterior enamels, in

auto refinishing and in product finishes

for metal furniture, machinery, and

appliances. It volatilizes while the

coating is drying and may be inhaled in

indoor settings by professional painters

and consumers. Apart from the workers

exposed to MEKO in the chemical and

allied products industry, more than

900,000 professional painters are

conservatively estimated to be exposed

to this chemical at low levels on a

continuous basis in end-use

applications. The number of consumers

exposed to MEKO through casual

painting and decorating activities is

assumed to be high, though data do not

exist to provide a precise estimate.

Although several short-term toxicity

studies have been performed, limited

data exist to evaluate its long-term

toxicologic effects, particularly on the

hematopoietic system. In addition, no

data are available that address the

oncogenic potential of this compound.

Therefore, the Committee recommends

the performance of chronic toxicity

studies with special emphasis on

potential hematopoietic and oncogenic

effects.

IV. Ecological effects of concern.

MEKO is unlikely to persist in the

environment at concentrations likely to

cause adverse ecological effects.

Therefore, ecological effects testing is

not being recommended at this time.

References

(1) ACGIH. "TLVs. Threshold Limit Values

and Biological Exposure Indices for 1986-

1987." Cincinnati, OH: American Conference

of Governmental Industrial Hygienists (1986).

(2) Allied Corporation. Product Safety Data

Sheet on methyl ethyl ketoxime (November

1984a).

(3) Allied. Allied Corporation. Letter from

J.B. Charm, Director, Corporate Product

Safety, Allied Corporation, Morristown, NJ,

to R. Jones, Document Control Assistant, EPA

(March 5, 1984b).

(4) CEH. Chemical Economics Handbook.

SRI International, Menlo Park, CA. Section

592.60011. (1981).

(5) Himmelsbach, B.F. Internal

memorandum on area monitoring for MEKO

and MEK during the use of alkyd paints from

B.F. Himmelsbach, Allied Corporation,

Morristown, NJ, to staff (April 27, 1984).

(6) ISHOW. Information System for

Hazardous Organics in Water [data base].

Baltimore, MD: Chemical Information

Systems, Inc. (19851.

(7) Kurita, H. "Experimental studies on

methyl-ethyl-ketoxime toxicity," Nagoya

Journal of Aedical Science. 29:393-418 (1967).

(8) NCI. National Cancer Institute. Letter

from 1. Olbrich, NCI, Bethesda, MD to L.

Borghi, Dynamac Corporation, Rockville, MD

(Iuly 25, 1985a).

(9) NCI. National Cancer Institute. "Mouse

Lymphoma Mutagenesis Assay with #83890

(ML-NCI #160)." Report prepared by

Microbiological Associates, Bethesda, MD.

under Contract No. No1-CP-41004 (December

11, 1985b).

(10) NIOSH. National Institute for

Occupational Safety and Health. "National

Occupational Hazard Survey (1972-1974)"

[data base]. Cincinnati, OH: U.S. Department

of Health and Human Services (1976).

(11) NIOSH. National Institute for

Occupational Safety and Health. "National

Occupational Exposure Survey (1980-1983)"

[data base]. Cincinnati. OH: U.S. Department

of Health and Human Services (1948b).

(12) NTP. "National Toxicology Program"

[data base]. Research Triangle Park, NC:

National Institute of Environmental Health

Sciences, U.S. Department of Health and

Human Services (Results Report of August 7,

1986).

(13) OSHA. "OSHA Safety and Health

Standards for General Industry." 29 CFR

1910. Subpart Z. U.S. Department of Labor,

Occupational Safety and Health

Administration. Washington, DC: U.S.

Government Printing Office (1983).

(14) Plzak, V., and Doull, 1. "A Further

Survey of Compounds for Radiation

Protection." USAF School of Aerospace

Medicine, Aerospace Medical Division

(AFSC), Brooks Air Force Base, TX (1969).

(15) Scofield, F., Levin, J., Beeland, C., and

Laird, T. "Assessment of Industrial

Hazardous Waste Practices, Paint and Allied

Products Industry, Contract Solvent

Reclaiming Operations, and Factory

Application on Coating." EPA Report No.

EPA/530/SW-119C, U.S. Environmental

Protection Agency, Office of Solid Waste

Management Programs, Washington, DC

(1975).

(16) SRI. "NPCA Data Bank Program,"

Section IV. Prepared for the National Paint

and Coatings Association, Inc., Washington,

DC. p. 77 (Menlo Park, CA: SRI International.

1982).

(17) SRI. "The U.S. Paint Industry:

Technology Trends, Markets, Raw Materials"

(Formerly "NPCA Data Bank Program").

Prepared for The National Paint and Coatings

Association, Inc., Washington, DC. pp. 173-

174 (Menlo Park, CA: SRI International, 1984).

(18) SRI. 1985 Directory of Chemical

Producers, United States. p. 717 (Menlo Park,

CA: SRI International, 1985).

(19) Stoecklein, P. Letter from P. Stoecklein,

American Painting Contractor, St. Louis, MO.

to L. Borghi, Dynamac Corporation, Rockville,

MD (September 25, 1986).

(20) USCPSC. U.S. Consumer Product

Safety Commission. Memorandum from E.W.

Leland, CPSC, to M. Wind, CPSC (October 11.

1985).

(21) USDOC. U.S. Department of

Commerce, Bureau of the Census. "U.S.

Imports for Consumption and General

Imports," Report FT246/Annual 1983.

Washington, DC: U.S. Government Printing

Office. P. 1-355 (1985).

(22) USDOC. U.S. Department of

Commerce, Bureau of the Census. "Import

statistics for TSUSA No. 4252600." 1986.

(23) USEPA. Consumer printout (CICIS):

1977 production statistics for chemicals in the

nonconfidential TSCA Chemical Substance

Inventory. U.S. Environmental Protection

Agency, Office of Pesticides and Toxic

Substances, Washington, DC (1986a).

(24) USEPA. "Consumer Exposure to

Methyl Ethyl Ketoxime." Memorandum from

M.H. Thomas, Exposure Assessment Branch,

EPA, to L. Rosenstein, Existing Chemical

Assessment Division (August 5, 1986(b).

(25) Verschueren, K. Handbook of

Environmental Data on Organic Chemicals.

2nd Ed. pp. 303-304 (New York: Van

Nostrand Reinhold Company, 1983).

(26) Weast. CRC Handbook of Chemistry

and Physics. A Ready-Reference Book of

Chemical and Physical Data, 14th Edition, p.

C-193. West Palm Beach, FL: CRC Press Inc.

(1984.

(27) Zacharias, K. Personal communication

from K. Zacharias, National Paints and

Coatings Association, to A. Prevesz, Existing

Chemical Assessment Division, EPA

(September 3, 1985).

(28) Zacharias, K. Personal communication

from K. Zacharias, National Paints and

Coatings Association, to A. Revesz, Existing

Chemical Assessment Division, EPA

(September 24, 1986).

[FR Doc. 86-25584 Filed 11-13-86; 8:45 am]

BILUNG CODE 6560-50-M

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