61654 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

businesses. However, EPA expects to receive few SNUNs for the substances. Therefore. EPA believes that thenumber ofsmall businesses affected by this rule would not be substantidl, even ifall of the SNUN submitters were small firms.

C.PaperworkReductionAct.

The information collection requirements contained in this rule have been approved by OMB under the provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.), and have been assigned OMB control number 2070-0012.

Public reporting burden for this collection ofinformation is estimated to vary from 30 to 170 hours per response, with an average of 100 hours per response, including time for reviewing instructions, searching existing data

sources, gathering and maintaining the data needed, and completing and reviewing the collection ofinformation.

Send comments regarding theburden estimate or any other aspect ofthis collection ofinformation, including suggestions for reducing this burden, to Chief,Information Policy Branch, (2131), U.S. Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; and to the Office of Management and Budget, Paperwork Reduction Project (2070-0012), Washington, DC 20503.

List ofSubjects in 40 CFR Part 721

Environmental protection, Chemicals, Hazardous materials, Reporting and " recordkeeping requirements, Significant

new uses,

Dated: November 15, 1993. Victor J. Kimm, ActingAssistantAdministrator for Prevention, PesticidesandToxicSubstances. Therefore, it is proposed that 40 CFR part 721 be amended as follows:

PART 721--AMENDED]

1.The authority citation forpart 721 would continue to read as follows:

Authority: 15 U.S.C. 2604, 2607, and 2625(c)

2. By adding new §721.340 to subpart Eto read as follows: §721.340 Acrylate esters.

(a) Chemicalsubstancesand significantnew uses subjectto reporting. (1)Chemical substances falling within the acrylate ester category definition and not on the TSCA Inventory as of [Insert proposed date ofthis rule] are subject to reporting under this section for the significant new uses described in paragraph (a)(2) ofthis section. The acrylate ester category shall include any ester ofan acrylate, as defined in paragraph (b)(3)(i) ofthis section

aving: (i)A measured number-average molecular weight of 1,000 amu (anuis the unified atomic mass unit referenced
to the mass ofCarbon 12) or less.

(ii) A measured number-average molecular weight ofover 1,000 amu and containing more than 2 percentby weight ofany acrylate ester with a molecular weight of 500 amu or less.

(2)The significant new uses are: (i)Protectionin the workplace. Requirements as specified in §721.63(a)(1), (a)(2)(i), (a)(2)(iii), (a)(2)(iv), (a)(3). (a)(4), (a)(5)(xi). (a)(6)(i), (a)(6)(ii). (a)(6)(iv). (b) (concentration set at 0.1 percent), and (c).

(ii) Hazardcommunication program. Requirements as specified in §721.72(a), (b), (c), (d), (e) (concentration set at 0.1 percent), (0, (h)(1)(i}(A}, (h)(1)(i)(B), (h)(1)(i)(C), (h)(1)(iii)(A}, (h)(1)(vi), (h)(2)(i)(B), (h)(2)(i)(C), and (h)(2)(i)(D).

(iii) Industrial, commercial,and

consumeractivities.Requirements as specified in §721.80(o).

(b) Specific requirements. The provisions ofsubpart A ofthispart apply to this section except as modified by this paragraph.

(1)Recordkeepingrequirements. Recordkeeping requirements as specified in §721.125(a) through (i)are applicable to manufacturers, importers, and processors of these substances.

(2) Limitationsorrevocationof certainnotificationrequirements.The provisions of§ 721.185 apply to this section.

(3)Definitions.(i) Acrylate means those chemical substances (including combinations ofchemical substances that are not mixtures) whose structures contain one or more covalently bound substructures which are described as terminal or pendant acrylate groups. Such chemical substances are considered to contain a functional acrylate moiety. The functional nature of these chemical substances is attributed to the conjugated carbon to carbon double bond present in the acrylate. Functional acrylate substructures may be produced from several types ofreactions. Regardless of the synthetic route,the unsaturated bond ofthe acrylate group(s) remains present and unreacted. Functional acrylate substructures are typically but
not always produced from reactions between mono- orpolyhydric alcohols and acrylic acid in which the -OH radical(s) from the alcohol combines with the -COOH radical ofthe acrylic acid to form acrylate esters. This reaction mechanism ensures that the double bond remains intact. The substructures produced from the possible chemical reaction types are diagramed below; the free valence is the location ofcovalent linkage to the rest ofthe molecule:

-0-(-C--O)CH=CH 2 Acrylate Group (2-Propenoate Group) (ii) [Reserved] [FR Doc. 93-28611 Filed 11-19-93; 8:45 am)

BILiNG CODE W60-"

40 CFR Part 799 [OPPTS-42150, FRL 4010-2]

RIN No.2070-AS07
Acetophenone, Phenol, N,NDimethylaniline, Ethyl Acetate, and 2,6- Dimethylphenol; Proposed Test Rule, Notice of Opportunityto Initiate Negotiations forTSCA Section 4 Testing Consent Agreements

AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule.

SUMMARY: EPA is proposing atest rule under section 4(a) ofthe Toxic Substances Control Act (TSCA) that would require manufacturers and
processors offive chemicals (acetophenone, phenol, NNdimethylaniline, ethyl acetate, and 2,6- dimethylphenol) to conduct testing for certain chemical fate, health and environmental effects. Thisrule would require that testing be conducted to develop data with respect to chemical fate and health and environmental effects for which there is an insufficiency ofdata and experience and which are relevant to a determination that the manufacture, distribution in
commerce, processing, use, or disposal ofsuch chemicals, or that any combination ofsuch activities, does or does not present an unreasonable risk of injury to health or the environment. In addition to the proposed test rule, EPA has negotiated a testing consent agreement development program under TSCA section 4 to allow the Agency to make greater use ofenforceable consent agreements (ECAs). Therefore, EPA is soliciting interested parties for participation in ormonitoring of consent agreement negotiations for the chemicals that are proposed for testing in this rulemaking. EPA is also inviting manufacturers and/or processors of chemical substances who wish to participate in consent agreement negotiations forthe chemicals proposed fortesting to develop and submit testing consent agreement proposals to EPA.Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

DATES: Written comments on the proposed rule mustbe received byEPA

on or before January 21, 1994. Ifpersons request an opportunity to submit oral
comments by January 6, 1994, EPA will hold apublic meeting on this proposed rule inWashington, DC. For further information on arranging to speak at the meeting see Unit VII ofthis preamble. Written ECA testing proposals mustbe received by January 21, 1994. Written notice of interest in being designated an "interested party" to the consent agreement negotiations forthe chemicals proposed for testing in this r-lemaking must bereceived by January 21, 1994. Those submitting written testing proposals will be considered "interested parties" and do not have to submit separate written notice of interest in being designated. EPA will

contact all "interested parties" and advise them ofmeeting dates. ADDRESSES: Submit written comments, identified by the document control number (OPPTS-42150) and the chemical-specific docket number, in triplicate to: TSCA Nonconfidential Information Center (7407), Office of Pollution Prevention and Toxics, Environmental Protection Agency, East Tower, Rm. G-99, 401 M St., SW., Washington, DC, 20460. A public version ofthe administrative record supporting this action, without confidential business information (CBI), is available for inspection at the above address in Room G-102, from 8 a.m. to 12 noon, and I p.m. to 4 p.m., Monday through Friday, except legal holidays.
FOR FURTHER INFORMATION CONTACT: Susan B. Hazen, Director, Environmental Assistance Division (7408), Office ofPollution Prevention and Toxics, Rm. E-543B, 401 M St., SW.,.Washington, DC 20460, (202) 554- 1404, TDD (202) 554-0551. SUPPLEMENTARY INFORMATION: This notice proposes a test rule under TSCA section 4(a)(1)(A) and (B) to require certain health, environmental, and chemical fate tests for acetophenone (CAS No. 98-86-2), phenol (CAS No. 108-95-2), N,N-dimethylanilne (CAS No. 121-69-7), ethyl acetate (CAS No. 141-78-6), and 2,6-dimethylphenol (CAS No. 576-26-1).

I. Introduction

A. ITCRecommendation

At the request ofEPA, the ITC reviewed a subset ofchemicals included

on EPA's Integrated Risk Information System (IRIS) data base for which theAgency believed there is inadequate data. EPA brought these chemicals to the ITCto fosterinteragency coordination and cooperation on testing needs. The ITC designated six chemicals included in IRIS [acrylic acid (addressed in a separate rulemaking at 57 FR 7656, March 4, 1992), acetophenone, phenol, NNdimethylaniline, ethyl acetate, and 2,6- dimethylphenol] for priority consideration as candidates for chemical fate, health effects and environmental effects testing.

IRISis an electronic database, prepared and maintained by EPA, containing both cancer and non-cancer chronic health hazard information on specific chemicals. IRIS provides hazard identification and dose-response
assessment information. This information, when combined with specific exposure information, can be used to help characterize the public health risks posed by a chemical in a particular situation (Ref. 7).

In addition, asother agencies brought theirtesting needs andconcerns forthe chemicals to bear onthe ITC deliberations, the ITC's testing recommendations expanded to include additional endpoints such as mutagenicity and neurotoxicity testing.

Besides health effects data, theITC also recommended additional data to bettercharacterize the environmental effects and chemical fate oftwo ofthese chemicals. The reasons forthese particular testing recommendations by the ITC are further discussed in the Federal Register ofMarch 6, 1991 (56 FR 9534), and in the chemical-specific sections of thisnotice.

B. TestRule Development UnderTSCA

Under section 4(a) ofTSCA, EPA shall, by rule, require testing ofa chemical to develop appropriate test data ifthe Administrator makes certain findings as described in TSCA section 4(a)(1)(A) or (B). Discussions ofthe statutory section 4 findings are provided in EPA's first and second proposed test rules, which were published in the Federal Register ofJuly 18, 1980 (45 FR 48510) and June 5, 1981 (46 FR 30300). EPA also proposed its policy for making findings under TSCA section 4(a)(l)(B) in the Federal Register ofJuly 15, 1991 (55 FR 32294) and finalized thispolicy in the Federal Register ofMay 14, 1993 (58FR 28736). This is referred to in this
test rule as the "B policy." For further discussion ofEPA's interpretation ofits authority under sections 4(a)(l)(A) and (B) of TSCA, see Unit III ofthis preamble. In evaluating the ITC's testing recommendations forthese chemicals, EPA considered the information

rovided by the ITC, theon-line IRIS data base, and supplemental information developed by EPA. In developing the testing requirements for this rule, EPA has also considered the
statusofacetophenone and phenol under the Clean Air Act Amendments of 1990 (Ref.51). These considerations have influenced the proposed testing and routes of administration selected. From this evaluation, EPA is proposing health effects testing for five ofthese chemicals, and chemical fate and environmental effects testing for two of these chemicals under TSCA section 4(a)(1)(A) and/or (B). Either finding alone is sufficient to support atest rule. EPA has entered into an enforceable testing Consent Order for the sixth chemical--acrylic acid.

EPA did not require reporting for these chemicals under sections 8(a) or 8(d) ofTSCA becausb production, use and exposure information and toxicity data for these chemical substances are available in the general literature and EPA expects that any unpublished studies will be submitted in response to the proposed rule. Where less is known about the toxicity and exposures to the chemical, section 8(a) and 8(d) information is needed and routinely required before EPA proposes a section 4 test rule.

This action constitutes EPA's
response to the ITC asrequired by TSCA section 4(e)(1)(B).

H. Proposed Testing and Reporting Requirements

A. Test Standardsand Reporting Requirements

EPA is proposing that health effects, environmental effects, and/or chemical fate testing be contlucted on acetophenone, phenol, NNdimethylaniline, ethyl acetate, and 2,6- dimethylphenol according to the specific test guidelines set forth in §799.4450.

Data developed under the final rule

must be reported in accordance with TSCA Good Laboratory Practice (GLP) Standards, 40 CFR part 792.

As required by section 4(b)(1) of TSCA, EPA is proposing specific testing and reporting requirements for each of the proposed tests for the five IRIS chemicals as specified in the following Table 1: 6165561656 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

TABLE 1.-TESTING AND REPORTING FOR FIVE IRIS CHEMICALS

Mini. Deadline for mum Final Re- Chemical Name (CAS Test (Route of Administration) Guideline Per- Docket No. No.) cent Purity (months)

Acetophenone (98-86-

2).

Phenol (108-95-2)

........

N,N-Dlmethylanline

(121-69-7).

Ethyl Acetate (141-78-

6). Health effects testing:

Subchronic toxicity, Inhalation

................. Toxicokinetics2, Oral

................................ Toxicokinetics2, Inhalation

...................... Neurotoxicity, Acute and Subchronic, Inhalation. Neurotoxicity, Subchronic, Inhalation

...... Reproductive toxicity, Gavage

................. Developmental toxicity, Inhalation

........... Salmonella assay .................................... In vitro gene mutation assay

................... In vivocytogenetics assay

......................

..... ............................................................. Health effects testing:

Subchronic toxicity. Inhalation

................. Toxicokinetics2, Oral

................................ Toxicokinetics2, Inhalation

....................... Neurotoxcity, Acute and Subchronic, Inhalation. Neurotoxicity, Subchronic, Inhalation

...... Reproductive toxicity, Inhalation

.............. Developmental neurotoxicity, Gavage

.....

Health effects testing:

Subchronlc toxicity, Inhalation

................. Toxlcokinetics2, Oral

................................ Toxicokinetics2, Inhalation

....................... Neurotoxclty, Acute and Subchronlc, Inhalation. Neurotoxicity, Subchronic, Inhalation

...... Reproductive toxicity, Gavage

................. Developmental toxicity, Gavage

.............. In vivo cytogenetics assay

...................... Environmental Effects Testing:. Algal test

.................................................. Daphnid acute test

.................................. Mysid shrimp acute test

.......................... Fathead minnow life stage test...... Sheepshead minnow life stage test

........ Daphnid chronic test

........................... Mysid shrimp chronic test

........................ Chemical Fate Testing:.

Activated sludge testing

.......................... Anaerobic biodegradation testing

............



### I Health effects testing: § 798.2450

OECD 417
OECD 417 § 798.6050 and 798.6200

§ 798.6400
§ 798.4700
§ 798.4900
§ 798.5265
§ 798.5300

§ 798.5385 or 798.5395

§ 798.2450

OECD 417

OECD 417
§ 798.6050 and 798.6200 § 798.6400 § 798.4700

§ 795.250

§ 798.2450

OECD 417

OECD 417 § 798.6050 and 798.6200

§ 798.6400 § 798.4700 § 798.4900 § 798.5385 or 798.5395

§ 797.1050 § 797.1300 § 797.1930 § 797.1600 § 797.1600 § 797.1330 § 797.1950

§ 796.3340 § 796.3140 .......... . . . . ...... 142150/42151

. . . . .............. . 142150/42152

42150/42153

.......... 42150/42141AFederal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

TABLE 1.-TESTING AND REPORTING FOR FIVE IRIS CHEMICALS-Continued

Mini- Deadline for mum FnaRe Chemical Name (CAS Test (Route of Administration) Guideline Per- Docket No. No.) Per- 

### ~portl oke o No.) cent (months) Purity
Reproductive toxicity, Gavage

................. § 798.4700 99.0 29 Developmental toxicity. Gavage

.............. § 798.4900 99.0 12 In vitro gene mutation assay

................... § 798.5300 99.0 10 2,6-Dimethylphenol

................................................. ................ 42150/42154

(576-26-11. Health effects testing: Toxicokinetics2, Oral

................................ OECD 417 99.0 15 Toxicokinetics2, Inhalation

....................... OECD 417 99.0 15 Neurotoxicity, Acute and Subchronic, § 798.6050 and 798.6200 99.0 21

Gavage. Neurotoxicity, Subchronic, Gavage

......... § 798.6400 99.0 21 Reproductive toxicity, Gavage

................. § 798.4700 99.0 29 Developmental toxicity, Gavage

.............. § 798.4900 99.0 12
In vitro gene mutation assay

................... § 798.5300 99.0 10
In vivo cytogenetics assay

...................... § 798.5385 or 798.5395 99.0 14
Environmental Effects Testing:. Algal test

................................................. § 797.1050 99.0 12 Fathead minnow life stage test

............... § 797.1600 99.0 12 Daphnid chronic test

................................ § 797.1330 99.0 18 Chemical Fate Testing:. River die-away testing

............................. (incorporated by reference) 99.0 12

Anaerobic biodegradation testing

............ § 796.3140 99.0 12 Aqueous photolysis testing

...................... § 795.70 99.0 12

I Figure indicates the reporting deadline in months calculated from the effective date of the final rule or from the date of test sponsor notification by certified letter to initiate test where such notification is specified.

2 The toxicokinetics (pharmacokinetics and metabolism) guideline was developed by the European Organization for Economic Cooperation and Development (OECD) and is proposed to be incorporated by reference inthis rule.

All oftheguidelines referenced in Table I are intended to be used as currently published in Title 40 ofthe Code ofFederal Regulations, except for the neurotoxicity test guidelines, which

are modified in the codified section of this rule. The neurotoxicity guideline modifications specify the duration and frequency ofexposure and specify that lower exposure levels shall show a graded neurotoxic response or no neurotoxicity. Exceptions also are the toxicokinetics and biodegradation in natural surface water guidelines, which

are proposed to be incorporated by reference and are available in the docket forthisrule.

B. InterimMutagenicityTestingPolicy

The proposed health effects testing in this rule reflects EPA's current thinking in the area ofmutagenicity testing, both

as an endpoint and as it leads to oncogenicity testing. The science of mutagenicity testing has undergone considerable change since EPA first required mutagenicity testing in a section 4 test rule (50 FR 20662, May 17, 1985). This new information, particularly data from EPA's Gene-tox Program related to the ability ofshort
term tests to predict mutagenicity (Ref. 105), the National Toxicology Program's study ofthe ability of shortterm tests to predict carcinogenic potential (Ref. 90), and expert meetings, such as the 1987 Williamsburg conference, has led EPA
to revise theTSCA section 4 mutagenicity testing scheme. This includes how EPA requires additional mutagenicity testing based on results from lower-tier mutagenicity tests and also how itrequires oncogenicity testing based on mutagenicity testresults. EPA believes the flexibility and opportunity
to apply professional scientific judgment offered by the new approach afford considerable advantages over the prior scheme. EPA's rationale forthese changes is discussed in the technical literature (Ref. 19) and will notbe discussedhere. For purposes ofthisrule, in which only Tier Itesting is being proposed, the changes are relatively minor.First, Tier I is redefined as a battery oftwo invitro
tests and one in vivotest. There is no longer a distinction as to gene mutations

or chromosomal aberrations in Tier I, and the previously utilized in vitro cytogenetics test wouldbe eliminated. The purpose ofTier Itesting, however, continues to be to determine intrinsic mutagenic potential.

Subsequent mutagenicity testing, including Tier II testing, is notbeing proposed atthis time.The test guidelines for several ofthe Tier IItests

are stillundergoing refinement. Thus, rather than delaying the Agency's response to the ITC until all ofthe details ofthe mutagenicity testing scheme have been completed, EPAhas decided to propose only TierI ofthe

new mutagenicity testing scheme at this time. Ifappropriate, further mutagenicity testing, including triggers
to oncogenicity testing, will be 6165761658 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

addressed in a subsequent rulemaking after review ofthe Tier Iresults.

C. Persons Requiredto Test

Because ofthe findings in Unit IMof this preamble, EPA is proposing that persons who manufacture (including import) orprocess, or who intend to manufacture orprocess, acetophenone, phenol. NN-dimethylaniline, ethyl acetate, or 2,6-dimethylphenol, other than as an impurity, at any time from the effective date ofthe final testrule to the end ofthe reimbursement period, be subject to the testing requirements in thisrule. Byproduct manufacturers and importers ofacetophenone, phenol, N,N-dimethylaniline, ethyl acetate, and/

or 2.6-dimethylphenol are considered manufacturers under thisrule. As explained in 40 CFR 790.42, manufacturers ofthese substances would be required to submit letters of intent to conduct testing or exemption applications. However, small quantity manufacturers, research and development manufacturers and processors would not berequired to submit letters ofintent or exemption applications unless directed to do so in

a subsequent notice as described in §790.48(b).

EPA has specified relatively pure substances fortesting (99 percent, or higher). EPA is notproposing to require submission ofequivalence data as a condition for exemption from testing. since EPA is interested in evaluating the effects attributable to the substances themselves. III, Findings

EPA interprets TSCA section 4(a) to

mean that EPA's authority to require testing underTSCA section 4(a)(1)(A) and (B)is related to the "data insufficiency" and "testing is necessary" findings under TSCA section 4(a)(1)(A)(ii) and (iii) and (B)(ii) and (iii). Thus, once the Administrator has made a finding under TSCA section 4(a)(1)(A)(i) that a chemical may present

an unreasonable risk, orunder TSCA section 4(a)(1)(B)(i) that a chemical is or will be produced in substantial quantities and may either bereleased to the environment in substantial quantities or that there may be substantial or significant human
exposure to the chemical, the Administrator may require any type of testing necessary to address unanswered questions about the effects ofthe chemical. EPA neednot limit the scope oftesting required to the factual bases for the section 4(a)(1)(A)(i) or (B)(i) findings. For a more detailed discussion of this interpretation, seeEPA's final "B-policy" rule (58 FR 28736, May 14, 1993).

The proposed chemical fate, health and environmental effects testing is based on the authority of section 4(a)(1)(A) and (B) ofTSCA. EPA finds that available data indicate that three of the chemicals may present an unreasonable risk ofinjury to human health or the environment; all five of these chemicals are produced in substantial quantities; there is or may be significant or substantial human
exposure to all five of these chemicals; there is or may be substantial environmental release ofone ofthese chemicals; there are insufficient data and experience to determine or predict the effects from manufacturing, distribution, processing, use, and disposal ofall ofthese chemicals; and testing is necessary to develop these data.

As noted earlier, a general discussion ofthe statutory section 4 findings is provided in EPA's first and second proposed test rules, which were published in the Federal Register of July 18, 1980 (45 FR 48510) and June 5, 1981 (46FR 30300). in EPA's final "B" policy, published in the Federal Register ofMay 4, 1993 (58 FR 28736), and in Unit II. C. ofthis preamble.

A. Acetophenone

EPA is proposing testing of acetophenone under the authority of section 4(a)1)(B) ofTSCA.

1. Substantialquantities produced finding.EPA believes that acetophenone is or will be produced in substantial quantities. According to records available to EPA, acetophenone production exceeds 1 million pounds
per year; actual production volumes are CBI. EPA believes thatproduction of 1 million pounds or greater constitutes substantial production under TSCA section 4(a)(1)(B)(i).

2. Substantial human exposure finding.EPA believes that there is or may be substantial human exposure to acetophenone. This assessment is based

on a National Occupational Exposure Survey (NOES) which indicates that 39,880 workers were potentially exposed to acetophenone in various industrial applications (Refs. 70 and 109). Ofthese workers, 97 percent were potentially exposed during the use of trade name products containing acetophenone. As explained in EPA's "B" policy, EPA believes that the potential exposure of39,880 workers to acetophenone constitutes substantial human exposure under section 4(a)(1)(B) ofTSCA. Acetophenone is used as a perfume base in the fragrance industry, as a process solvent for gums, resins, and dyestuffs, as an intermediate for the synthesis ofpharmaceuticals, in corrosion inhibitors, in rubber chemicals, in flavorings, as a polymerization catalyst, and as a photoinitiator (Refs. 14 and 81). The use ofacetophenone as a fragrance in soaps and detergents also gives rise to widespread consumer exposure. EPA estimates an exposure ofindividual persons up to 3,783 mg/yr from use of hand soaps (Ref. 96).

EPA also believes that there is or may be general population exposure to acetophenone. Acetophenone has been detected in U.S. drinking water supplies. In a survey of 10 U.S. cities between 1969 and 1972, acetophenone

was found in Philadelphia's drinking water, on 7different occasions, at a concentration of approximately 1.0 pgg/ L (Refs. 54 and 89). This may result in the exposure ofmillions ofpeople. For the reasons set forth in EPA's "B" policy, EPA believes that the potential exposure of100,000 or more people in the general population to acetophenone constitutes substantial human exposure under TSCA section 4(a)(1)(B)(i).

3. Insufficientdataandexperience finding.EPAbelieves that there are insufficient data and experience to determine or predict the effects on human health orthe environment from manufacturing, processing, distribution,
use, and/or disposal ofacetophenone. EPA believes that available studies are insufficient and other data are lacking to sufficiently evaluate the effects of acetophenone.

Inhalation data to assess the subchronic effects ofexposure to acetophenone do not adequately address the concentration-response relationship for the portal-of-entry effects via the inhalation route. The primary study cited as providing the baseline RfC (for inhalation) indicated ano observed effect level (NOEL) of0.007 mg/m3 and

a lowest observed effect level (LOEL) of 0.07 mg/m3 based on congestion of cardiac vessels, liver dystrophy and changes in the ratios ofblood proteins and muscle chronaxie (Ref. 49). This study exposed groups of 15 white male
rats continuously to acetophenone vapor at 0, 0.007. or0.07 Mg/ m3 for 70 days. While a NOEL and LOEL were reported, this study is inadequate because only one sex ofanimals was examined, only five animals per group
were used to study cholinesterase activity, and serum protein levels and the number ofanimals which underwent histopathological examination were unreported (Ref. 51).

Another inhalation study reported a specific pattern ofdegeneration ofthe olfactory bulb in groups of fourWistarFederal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

rats continuously exposed to acetophenone vapors from 1 week to 3 months (Ref. 78). However, other parameters oftoxicity were not evaluated in this study.

EPA is also aware of two oral subchronird.;tudies. These studies failed
to identify ddverse effects in groups of five male and five female albino rats fed diets containing acetophenone at levels of0.003, 0.05, 0.125, or 0.2 percent for 30 days (Ref. 85) or in groups of 10 male and 10 female Osborne-Mendel rats fed diets containing 1,000, 2,500, or 10,000
ppm acetophenone for 17 weeks (Ref. 40). These studies were judged adequate

to predict oral toxicity, but only marginally so, because no LOAEL was established (Ref. 51).

Developmental toxicity data on acetophenone are limited to a study that reported no effects on length of gestation or postnatal development in the offspring ofrats exposed dermally at 0.48 mg/kg on days 10

- 15 ofgestation (Ref. 57). The data are insufficient because key study parameters were not reported, apparently only a single dose

was administered, and the critical period oforganogenesis may have been missed.

Available mutagenicity data in Salmonella(Ames testing) are insufficient because only three strains of the test organism were used, rather than the usual four or five that EPA considers
necessary to establish a negative
response in this assay. EPA's mutagenicity testing scheme (described in more detail in Unit II.B. ofthis preamble) also includes in vitrogene mutation and in viva cytogenetics in the lowest tier. As neither study is available for acetophenone, additional mutagenicity testing is necessary to

assess acetophenone's mutagenic potential.

Available in vitroand in viva pharmacokinetics and metabolism studies are inadequate because quantitative data on acetophenone's
rates ofabsorption, distribution, and excretion are lacking in these studies (Refs. 33, 58, 60, 91, 92, 84 and 55).

Finally, no data were found for reproductive effects or neurotoxicity.

4. Testingis necessaryto develop data finding.EPA believes that testing of acetophenone is necessary to develop data for subchronic effects, neurotoxicity, pharmacokinetics and metabolism, reproductive effects, developmental effects and mutagenic effects. EPAbelieves that these testing data are needed to determine if the manufacturing, processing, distribution,

use, or disposal ofacetophenone or any combination of such activities does or does not present an unreasonable risk of injury to human health.

B. Phenol

EPA is proposing testing ofphenol under the authority ofsection 4(a)(1)(A) and 4(a)(1)(B) ofTSCA.

1. Unreasonble riskofinjury to humanhealthorenvironment finding. EPA believes that the manufacture, processing, distribution in commerce, use, or disposal, or any combination of such activities for phenol may present

an unreasonable risk ofinjury tohealth

orthe environment. This finding is based on several studies that indicate that phenol is neurotoxic. After 20 exposures byinhalation to 100-2.00 mg/ m3, hind limb paralysis was reported for guinea pigs (Ref.23). Continuous
exposure to phenol vapors at 100 mg/m3 for 15 days affected the performance of
rats in a test assessing central nervous system (CNS) effects (Ref. 18). A developmental toxicity screening test with a single gavage dose of100, 333, 667 or 1,000 mg/kg given togroups of 12-13 Sprague-Dawley rats on day 11 of gestation (Ref.53), produced a syndrome ofeffects Involving the limbs, tail, and urogenital system, which provides evidence ofdevelopmental neurotoxicity. The limb effects consisted ofparalysis andlorpalsy. Although the effect is not evident in newborns, limb function matures postnatally and requires aweek to 10 days foreffects to appear. This delayed effect was seen in 21.4 percent and 27.3 percent ofthe litters at 667 and 1,000 mg/kg, respectively.

As discussed further below, over 320,000 workers may be exposed to phenol in numerous industrial settings, and the wide variety ofuses ofphenol
may result in more widespread worker and consumer exposure. Furthermore, phenol isproduced andreleased into the environment in substantial quantities which may result in general population exposures. Because of these
concerns, EPA believes that phenol may present an unreasonable risk ofinjury to health.

2.,Substantialquantities produced finding.EPA believes thatphenol is or will be produced in substantial quantities. EPA records indicate that phenol is produced in excess of I million pounds per year. In 1989, 13 facilities were listed as manufacturing this compound (Ref. 86). EPA estimates the annual production for 1989 tobe 3,512,000,000 pounds for 10 manufacturers at 11 sites. As explained in the "B" policy, EPAbelieves that production of Imillion pounds or greater ofphenol constitutes substantial production under section 4(a)(1)(B)(i) of TSCA.

3. Substantial human exposure finding.EPA believes that here is or will be substantial human exposure to phenol. This assessment is based on worker, general population and

consumer exposure to phenol. The NOES conducted during 1981-1983 by NJOSH estimated that 320,914 workers

were potentially exposed to phenol in 35 different industrial categories (Refs. 70 and 109). For the reasons set forth in the "B" policy, EPA believes that the potential exposure of 341,516 workers
to phenol is sufficient to qualify as substantial human exposure under section 4(a)(1)(B)(i) ofTSCA.

Phenol is used in a variety of commercial applications including phenolic resins

- 38 percent; synthesis ofbisphenol A

- 23 percent; synthesis of caprolactam

- 17 percent; synthesis of alkylphenols

- 4 percent; synthesis of aniline

- 3 percent; miscellaneous uses

- 5 percent; exports

- 6 percent (Ref. 16). The miscellaneous uses of phenol include: (1) The synthesis of adipic acid, salicylic acid, phenolphthalein, pentachlorophenol, acetophenetidine, picric acid, and pharmaceuticals; (2) as

a selective solvent for refining lubricating oils, germicidal paints, laboratory reagent, dyes and indicators, slimicide,biocide, and (3) as a general disinfectant (Ref. 81). Many of these are

uses that can lead to worker and

consumer exposure.

In a compilation of air monitoring data collected between 1970 and 1987, the mean concentration ofphenol in suburban and urban areas wasreported

as 0.015 and 6.883 ppb, respectively (Ref. 83). The concentration of phenol in the air ofPortland, OR, during seven rain events in 1984 was 56 to 105 ppt, while the concentration of phenol in the rain ranged from 75 to 1,200 ppt (Ref. 61). It has also been detected In U.S. drinking water supplies (Refs. 29 and 69).

Phenol is used in numerous consumer products indicating a potential for
exposure to consumers (Ref. 100).

4. Release to environmentin substantial quantities finding EPA believes that phenol is released to the environment in substantial quantities. Over I million pounds of phenol is released into the environment each year. The Toxics Release Inventory (TRI) for 1987, indicates that 8,100,731 pounds of phenol was released to the air, 402,579 pounds to water, and 1,098,624 pounds
to land (Ref, 93). For 1988, the TRI indicates that 10,155,101 pounds was released to air, 262,127 pounds to water, and 2,162,250 pounds to land (Ref. 93).
As explained in EPA's "B" policy, EPA . ...... .... ...... ... .. . . .. ... . . . . .. I I II!1 1II

'[I III

Ill HIr[]lll I I 6165961660 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

believes that 1million pounds ofrelease
to the environment each year is a sufficiently large amount ofrelease for making a finding ofsubstantial environmental release under section 4(a)(1)(B) ofTSCA.

Phenol was detected in 738 samples obtained from 33 industries and publicly owned treatment works (POTWs) at a maximum concentration range of 7.5 ppb to 530 ppm (Refl 82). Data from the STORET database indicate that phenol was found in42.1 percent ofindustrial effluent samples obtained from 1980-83, at a median concentration of 10 ppb (Ref.87). The STORET database also indicates that phenol was found in 13 percent of ambient surface water samples, and 9 percent of sediment samples (Ref. 87), and also in groundwater samples (Ref. 88). Phenol was detected in 4 percent of 86 samples obtained during the National Urban RunoffProgram of1982, at concentrations ranging from 3to 10 ppb (Ref. 17).

5. Insufficientdataandexperience finding.EPA believes that there are insufficient data and experience to determine or predict the effects on human health or the environment from manufacturing, processing, distribution,
use, and/or disposal ofphenol. EPA believes that there are insufficient data and experience to reasonably determine

or predict the potential subchronic effects, neurotoxicity, pharmacokinetics and metabolism, reproductive toxicity, and developmental neurotoxicity from the manufacturing, processing, distribution, use, and/or disposal of phenol. Although anumber of studies describe the metabolism and pharmacokinetics ofphenol (Refs. 13, 20, 22, 52, 62, 65, and 66), the information isinsufficient to make comparisons and assumptions that would allow full use oftheexisting database for regulatory purposes. The Chemical Manufacturers Association's Phenol Panel is conducting pharmacokinetic studies and has consulted EPA on study design (Refs. 113, 114, and 115).

A number ofsubchronic and chronic
tests have been conducted with phenol by the oral and inhalation routes (Refs. 6, 21, 23, 27, 67, and 80). None ofthese studies are adequate to characterize portal-of-entry effects via the inhalation
route. Several ofthe inhalation subchronic studies did not use controls and tested too few animals of unspecified sex (Ref. 23). A one-doselevel study determined a NOEL of 19 mg/m3 (Ref. 80), but the design ofthis study did not include establishing an effect level for phenol. In addition, the inforoation available shows phenol to be more toxic by inhalation exposure than by oral exposure, thereby precluding a high degree ofreliance on conclusions based onroute-to-route extrapolation. For these reasons, EPA is proposing torequire testing to develop data on the effects ofphenol bythe inhalation route.

Anger and Johnson (1985), summarizing known neurotoxic effects ofa number ofchemicals, indicate
motor and mental disturbances for phenol (Ref. 2). EPA hasinsufficient information to evaluate these effects. Deichmann et al. (1944) reported hindlimb paralysis in guinea pigs after 20 exposures by inhalation to 100-200 mg/

m3phenol (Ref.23). Inaddition, Dalin andKristoffersson (1974) found that continuous exposure tophenol vapors at 100 mg/m3 for 15 days adversely affected the performance ofrats in a test assessing CNS effects (Ref. 18). Furthermore, Kavlock (1990) noted neurologically significant effects in the pups ofdams exposed tophenol in a screening test for developmental effects (Ref. 53). However, these studies did not extend long enough to adequately characterize these effects. Furthermore, the Deichmann etal. study (Ref. 23) did
notinclude control animals, and the Dalin andKristoffersson study (Ref. 18) did not establish a NOAEL for the observed CNS effects.

The Kavlock study (Ref. 53) also supports concern fordevelopmental neurotoxicity. When pregnant rats were given a single gavage dose ofphenol, their offspring showed developmental toxicity affecting the limbs, tail, and urogenital systems. This study was a screening test, designed to help identify substances which may need additional developmental toxicity testing, and was not adequate to characterize these effects, In order to address the inadequacy of the data developed by these studies, EPA proposes to require both neurotoxicity and developmental neurotoxicity testing forphenol.

No additional testing for developmental effects is being proposed because NTP studies (Refs. 71 and 112)

are adequate forthis endpoint. Although these studies were conducted by the oral route, EPA expectsthat additional reproductive effects testing, which will be conducted bythe inhalation route, will be an adequate complement to the existing database.

EPAbelieves a reproductive effects study on phenol by Holler and Pursell (1938) isinadequate for risk assessment purposes because the experimental methodology and testresults reporting

areinadequate and unreliable (Ref.44). EPA is proposing to require reproductive effects testing. The inhalation route was selected because information indicates that animals are

more sensitive to phenol when exposed by the inhalation route.

6. Testingisnecessaryto developdata findings.EPAbelieves that the testing of phenol isnecessary to develop data for oral and inhalation pharmacokinetics and metabolism, inhalation subchronic effects, reproductive effects, developmental neurotoxicity, and neurotoxicity. EPA believes that these testing data areneeded to determine if the manufacture, distribution in

commerce, processing, use, or disposal ofphenol, or any combination ofsuch activities, does or does not present an unreasonable risk of injury to health or the environment.

C.N,N-Dimethylaniline

EPA is proposing testing ofN,Ndimethylaniline under the authority of sections 4(a)(1)(A) and 4(a)(1)(B) of TSCA.

1. Unreasonable risk ofinjuryto healthortheenvironment finding EPA believes that the manufacture, processing, distribution in commerce, use, or disposal, or any combination of such activities for NN-dimethylaniline,
may present an unreasonable risk of injury tohealth or the environment.

a.Evidenceof potential foradverse humanhealtheffects. The health portion ofthis assessment is based on N,N-dimethylaniline's toxicity in subchronic (13-week), chronic, oncogenicity, and mutagenicity studies.

A 2-year chronic toxicityoncogenicity gavage study in groups of 50 male and 50 female F344/N rats treated with 3 or 30 mg/kg 5days per week and similarly sized groups of B6C3F1 mice treated with 15 or 30 mg/ kg 5 days perweek reported some evidence ofcarcinogenicity in male rats (sarcomas and osteosarcomas of the spleen) and equivocal evidence of carcinogenicity in female mice (squamous cell papillomas of the forestomach) (Ret 72). Mutagenicity data were negative for reverse mutation in four strains ofSalmonella,but were positive for forward mutation in mouse lymphoma L5178Y cells and for sister chromatid exchange and chromosomal aberrations in Chinese hamster ovary cells (Ref. 72).

A 13-week gavage study (that included comprehensive histopathological examination) in groups of10 malh and 10 female F344/ N rats and B6C3F1 mice treated with 31.25, 62,5, 125, 250, or 500 mg/kg for 5 days per week identified the erythrocytes and the spleen as the most sensitive targets in both species (Refs. I and 72). Compound-related clinicalFederal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

signs included lethargy in rats and mice and cyanosis in rats. The National Toxicology Program (NTP) study identified therat as more sensitive than the mouse to the noncarcinogenic effects ofN,N-dimethylaniline on erythrocytes and the spleen; these effects were seen in rats even at the lowest dose level tested, while an NOAEL of 31.25 mg/kg was seen for the mice (Ref. 72). An inhalation study reported altered muscle chronaxie and evidence ofhemolytic anemia in the high dose group of rats continuously exposed for 100 days to 0.04 or 0.3 mg/

m3 (Ref. 64). Anger and Johnson (1985), summarizing known neurotoxic effects of NN-dimethylaniline, indicate vision disturbances and central nervous system depression (Ref.2).

As discussed further elsewhere in this preamble, over 28.000 workers maybe exposed to NN-dimethylaniline in various industrial settings and there is also evidence ofgeneral population
exposure.

b.Evidence of potential environmentaltoxicity.This assessment is based on probabilistic dilution modelling indicating that NNdimethylaniline is present in the environment at levels within a factor of 100 of itsknown acute toxicity to environmental organisms. EPA believes that there may be an unreasonable risk ofinjury to the environment from chronic effects when acute toxicity is observed at levels within a factor of100 ofpredicted stream concentrations. Specifically, EPA has determined a concentration ofconcern of300 ppb (based on .N,N-dimethylaniline's * predicted chronic toxicity to daphnids) and has estimated that this concentration is exceeded 144 to 198 days ofthe year in receiving streams (Ref. 108).

Furthermore, NN-dimethylaniline, which is produced in substantial quantities, has been detected in soiland
water. According to the TRI, 147,692 pounds ofNN-dimethylaniline were released to the environment in 1987 (Ref.93). For 1988, the TRI indicates that 119,122 pounds were released (Ref. 93). The TRI also indicates that some of these releases would be to the marine or estuarine environment (Ref. 116).

From these concerns. EPA believes that NN-dimethylaniline may present

an unreasonable risk of injury to health and the environment.

2. Substantialquantities produced finding.EPA believes that NNdimethylaniline is or will be produced in substantial quailtities. EPA records indicate that domestic production of NN-dimethylaniline in 1979 was 13.7 million pounds (Ref. 1021. Information oncurrent production volumes is CBI, but production is substantial (1million pounds or greater). For the reasons set forth above, EPAbelieves that production of 1million pounds or more per year ofN,N-dimethylaniline is substantial production under section 4{a)(lJ)(Bi) ofTSCA.

3. Substantial human exposure finding.EPA believes that there is or may be substantial human exposure to N,N-dimethylaniline. This assessment is based on an NOES survey which estimated that27,895 workers were potentially exposed to NNdimethylaniline in9 different industrial classifications [Refs. 70 and 109). Of these workers, 39 percent were potentially exposed during the use of trade name products containing this compound. NN-Dimethylaniline is used in dyes. as a synthetic intermediate for vanillin, pharmaceuticals, and other compounds, and as a sclvent, stabilizer. and polymerization catalyst (Refs. 59, 81 and 99). For the reasons set forth in the "B" policy,EPA believes that the potential exposure of28,048 workers to N,N-dimethylaniline constitutes substantial human exposure under TSCA section4(a)(1(B)(i).

Furthermore, there is ormay be general population exposure to NN dimethylaniline. N,N-Dimethylaniline

was detected in 8 samples obtained from three industries and POTWs at a maximum concentration of 3.1 ppm (Ref. 82). According to the TRL 129,829 pounds ofN,N-dimethylaniline was released to the air, 17,613 pounds to water, and 250 pounds to land in 1987 (Ref.93). For 1988, the TRI indicates that 98,905 pounds was released to.air, 19,967 pounds to water, and 250 pounds to land (Ref.93). NNDimethylaniline was detected in soil samples obtained near thebank of the Buffalo River, NY, at concentrations of 10 to 40 ppm (Ref. 68). NNDimethylaniline was reported as being detected (no levels given) in water from Lake Ontario (Ref. 39).

4. Insufficientdataand experience finding.EPA believes that there are insufficient data and experience to determine orpredict the effects on human health or the environment from manufacturing, processing, distribution,
use, and/or disposal ofNNdimethylaniline. EPAbelieves that available studies are insufficient and other data are lacking to sufficiently evaluate the effects ofNNdimethylaniline.

Data assessing the potential subchronic effects ofinhalation
exposure toNNdimethylaniine were not found in the literature. Available oral data areinadequate toestimate inhalation riskbecause the dose levels selected did not give a NOAEL (forrats) and there are no data on comparative pharmacokinetics or portal-of-entry effects (Refs. 1and 72). The only inhalation study report available was a briefabstract that indicated altered muscle chronaxie and evidence of hemolytic anemia in the high dose group (0.3 mg/m3 ofrats continuously exposed for 100 days to 0.04 or0.3 mg/ m3) (Ref. 64). This study cannot be used forrisk assessment because itwas reported in limited detail and histopathologic effects were not examined. Anger and Johnson (1985), summarizing known neurotoxic effects of a number ofchemicals, cited visual disturbances and CNS depression for N,N-dimethylaniline (Ref. 2). EPA has insufficient information to evaluate these observations.

Developmental toxicity testing for N,N-dimethylaniline is limited to a screening study in 50 CD-i albino mice treated with NN-dimethylaniline in

corn oil at 365 mg per kgper day on gestation days 7 to 14; maternal mortality, butno effects on body weight

orviability ofthe neonatal offspring,

was reported (Ref. 77). Although the test results are negative, EPA considers this test inadequate forrisk assessment purposes because the exposure period didnot cover the fullperiod ofmajor organogenesis (days 6 to 15 forthe mouse), nor were sufficient dose groups used (only one versus the three required by EPA). EPA also specifies that two animal species be tested for a definitive developmental toxicity assessment. Therefore, developmental toxicity by gavage isproposed fortwo species, a rat and a non-rodent.

The available (negative) Salmonellal Ames data are adequate, as are the (positive) data in mouse lymphoma L51784 cells (Ref. 72). Available data also include positive results for sister chromatid exchange and chromosomal aberrations in Chinese hamster ovary cells (Ref.72). Given these data, EPA believes that gene mutation data are adequate but that the chromosomal toxicity ofNN-dimethylaniline is insufficiently characterized.

Although numerous metabolism studies have been conducted forNNdimethylaniline, these are inadequate because quantitative pharnacokinetics data forabsorption, distribution, or excretion are lacking (Refs. 5, 10, 11. 25, 26, 28, 37, 38, 41,43, 45, 46. 47, 56, 73, 74, 75, 76, 79,95 and 106).

No reproductive effects data were found for NN-dimethylaniline.

Environmental effects data forN,Ndimethylaniline are limited.Algal toxicity data include a toxicity testin 6166161662 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

bluegreen algae (Ref. 9) and a study on energy metabolism enzymes in marine algae (Ref.4). The study by Batterton et al. (Ref. 9) is inadequate because the Agency needs data for a sensitive species ofgreen algae such as Selenastrum capricornutum. Blue-green algae are not an acceptable substitute for green algae. The study by Armstrong et al. (Ref.4) is inadequate because a rigorous measurement ofgrowth inhibition such as a 96-hour EC50 value

was not determined. The Agency believes that the 96-hour EC50 Value for growth will be a more sensitive measure ofeffects on energy metabolism enzymes and will have more relevance in an environmental risk assessment. Acute aquatic toxicity studies are available for a ciliated protozoan and several species offish (Ref. 3). While the acute toxicity studies for fish appear adequate, no chronic toxicity data for fish were found, nor were any relevant data found forthe acute or chronic effects ofNN-dimethylaniline on aquatic invertebrates. The toxicity data for the ciliated protozoan are of unknown utility because little is known about how representative protozoa are
as surrogate species for other aquatic invertebrates.

EPA found no data to determine anaerobic biodegradation or the biodegradation of NN-dimethylaniline in systems which simulate in situ wastewater treatment.

5. Testingisnecessaryto develop data finding.EPA believes that testing of N,N-dimethylaniline is necessary to develop data for subchronic effects, neurotoxicity, pharmacokinetics and metabolism, reproductive effects, developmental effects, mutagenic effects, algal toxicity, daphnid acute and chronic toxicity, mysid shrimp acute and chronic toxicity, fathead minnow chronic toxicity, sheepshead minnow chronic toxicity, anaerobic biodegradation, and activated sludge biodegradation. EPA believes that this testing is needed to determine ifthe manufacturing, processing, distribution,
use, ordisposal ofNN-dimethylaniline

or any combination ofsuch activities does or does not present an unreasonable risk ofinjury to health or the environment.

D. EthylAcetate

EPA is proposing testing ofethyl acetate under the authority ofsections 4(a)(1)(A) and 4(a)(1)(B) ofTSCA.

1. Unreasonable riskofinjuryto healthorthe environment.EPA believes that the manufacture, processing, distribution in commerce, use, or disposal, or any combination ofsuch activities for ethyl acetate may present an unreasonable risk ofinjury to health

or the environment.

a.Evidenceof potential foradverse humanhealtheffects. This finding is based on ethyl acetate's neurotoxic effects, as outlined and supported in previous rule-making for the testing of this chemical [citefinalmulti-substance rule for the testingofneurotoxicity]. 1. Substantialquanitities produced finding..EPA believes that ethyl acetate is or will be produced in substantial quantities. In 1988, 254.2 million pounds ofethyl acetate was produced in the United States (Ref. 103). EPA estimates the annual U.S. production for 1989 to be 292 million pounds forthree manufacturers at five production sites (Ref.101). For the reasons set forth in the "B" policy, EPAbelieves that production ofImillion pounds or greater ofethyl acetate constitutes substantial production under section 4(a)(1)(B)(i) ofTSCA.

2. Substantialhumanexposure finding.EPA believes that there is or will be substantial human exposure to ethyl acetate. The NOES survey estimated that 419,180 workers were potentially exposed to ethyl acetate (Refs. 70 and 109). Ofthese workers, 87 percent were potentially exposed during the use oftrade name products containing this compound. Potential exposure to ethyl acetate was associated with 34 different industrial classifications (Ref. 70). Ethyl acetate has the following uses: coatings-41 percent; exports-36 percent; solvents13 percent; plastics-8 percent; chemical synthesis-2 percent (Ref. 15). Inaddition, ethyl acetate is used as a solvent in numerous consumer applications. For the reasons explained in the "B" policy, EPAbelieves that the potential exposure of419,180 workers to ethyl acetate is substantial human exposure under TSCA section 4(a){1)(B)(i).

Ethyl acetate is found in numerous
consumer products including lacquers, varnishes, coatings, detergents and soaps. EPA estimates the highest exposure levels occur by the dermal (4,680 mg/yr from use oflatex paints) and inhalation (901 mg/yr from use of lacquer thinner) routes (Ref. 98).

There may also be widespread general population exposure. Ethyl acetate was detected in 66 samples obtained from 17 industries and POTWs at a maximum concentration of 7.7 ppm (Ref. 82). In a compilation ofair monitoring data collected between 1970 and 1987, the median concentration ofethyl acetate in urban sites was 0.733 ppb (Ref. 83). Ethyl acetate was also detected in industrialized and urban sites in Virginia and West Virginia at concentrations ranging from <0.012 to 1.9 ppb (Ref.30). The STORET database indicates that ethyl acetate has also been detected in groundwater (Ref.88).

3.Insufficientdataandexperience finding.EPA believes that there are insufficient data and experience to determine or predict the effects on human health or the environment from manufacturing, processing, distribution.
use, and/or disposal ofethyl acetate. Under section 4(a)(1)(B)(ii), EPA believes thatthere are insufficient data and experience to determine or predict the potential reproductive toxicity, developmental toxicity, and mutagenicity from the manufacturing, processing, distribution, use, and/or disposal ofethyl acetate.

EPA is proposing to test ethyl acetate forreproductive effects and developmental toxicity. EPA found no data for these effects.

EPA is also proposing mutagenicity testing for ethyl acetate. Ethyl acetate

was negative for induction ofreverse mutation in Salmonellawhen tested with and without metabolic activation (Refs. 24 and 50). Positive results were observed for mitotic aneuploidy but negative results were observed for point mutations and recombinations in yeast (Ref. 107).

In mammalian test systems, a positive response was reported for chromosomal aberrations in Chinese hamster fibroblasts in vitro (Ref.50); however, these results do not support a concern
or a finding for chromosomal effects under TSCA section 4 (a)(1)(A) because, in a more definitive in vivo test system,

a negative response was reported for micronucleus formation in Chinese hamsters (Ref. 8).

EPA considers the existing Salmonelladata (negative) on ethyl acetate to be acceptable. However, these data in bacteria alone are insufficient to adequately characterize the gene mutation effects ofethyl acetate, and EPA is proposing an invitro gene mutation assay for ethyl acetate in mammalian cells in culture.

4. Testing isnecessaryto develop data finding.EPA believes that the testing of ethyl acetate is necessary to develop data forreproductive effects, developmental toxicity, and mutagenicity. EPAbelieves that this testing is needed to determine ifthe manufacture, distribution in commerce, processing, use, ordisposal ofethyl acetate, or any combination of such activities, does or does not present an unreasonable risk ofinjury to health or the environment.Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

E.2,6-Dimethylphenol

EPA is proposing to test 2,6- dimethylphenol under the authority of sections 4(a){1)[A) and (B)ofTSCA.

1. Unreasonable riskofinjuryto humanhealthandenvironment finding. EPA believes that the manufacture, processing, distribution in commerce, use, ordisposal, or anycombination of such activities for 2,6-dimethylphnol
may present an unreasonable risk of injurytohealth or the environment.

a.Evidenceof potential foradverse humanhealtheffects.This assessment is based on 2,6-dimethylphenol's toxicity in an 8-month rat gavage study, thatshowed histopathological changes in the liver, spleen, and kidneys and changes in body weight, bloodpressure and levels ofprotein sulfhydryl groups inblood serum and internal organs in 53 male rats treated with 6 mg/kg/day (Refs. 63 and 104). Effects werenot seen in rats dosedwith 0.06 mg/kgfday.In another study, increased relative liver and spleen weights, decreased body. weight gain and marked atrophy and parenchymatous dystrophy of livercells

were observed in 10 male albinorats treated by gavage with 29.5 mg/kglday for 10 weeks (Ref.63).

b. Evidence of potential for environmentaltoxicity.This assessment is based on probabilistic dilution modelling indicating that 2,6- dimethylphenol ispresent in the environment at levels within a factor of 100 ofits known acute toxicityto environmental organisms (Ref. 106). EPAbelieves that there maybe an unreasonable riskofinjuryto the environment from chronic effects when
acutetoxicity is observed at levels within a factor of 100ofpredicted
stream concentrations. Specifically, EPA has preliminarily determined a concentration ofconcern of 100 ppb (based on 2,6-dimethylphenol's predicted chronic toxicityto daphnids) and has estimated that this concentration is exceeded 260.days of the year inreceiving streams (Ref. 108).

As discussed further below, over 1,900 workers may beexposed to 2,6- dimethyiphenol in avariety of commercial applications. Furthermore, 2,6-dimethylphenol. which is produced in substantial quantities, has been detected in air, rain, wastewater, and groundwater samples,which may indicate general population and environmental exposures (Refs. 34, 36, 42,61. 81 and 83). Because ofthese
concerns, EPA believes that 2,6- dimethylphenol may presentan unreasonable risk ofinjury to health and the environment. 2. Suhstantialquantities produced finding.EPA believes that 2,6- dimethylphenol is orwillbe produced in substantial quantities. Information available to EPA indicates that in 1977, from 2 to20million pounds of2,6- dimethyiphenol wasproduced at six different facilities inthe United States (Ref. 94). There were two facilities that manufactured 2,6-dimethylphenol in the United States in 1989 (Ref.86). EPA estimates production in 1989 to have been 130 million pounds (Ref. 101). For the reasons set forth in the "B" policy, EPA believes that production of 1 million pounds or greater of2,6- dimethylphenol constitutes substantial production under section 4(a)(1)(B)(i) of TSCA.

3. Substantial humanexposure finding. EPAbelieves that there is or may be substantialhuman exposure to 2,6-dimethylphenol. EPA findsthat 2,6- dimethylphenol is used in a variety of commercial applications, many of which can lead to worker exposure. The NOES survey estimated that 1.941 workers were potentially exposed to 2,6- dimethylphenol (Refs. 70 and 109). Of these workers, 95 percentwere potentially exposed duringtheuse of trade name productscontaining this chemical. 2,6-Dimethylphenol isused primarily in the production of poly(phenylene oxide)resins (Ref. 31). 2,6-Dimethylphenol isalso used in the manufacture oftetramethylbisphenol A, 2,6-dimethylaniline, bis(4-hydroxy-2,5-. dimethylphenyl)methane, dyes, pharmaceuticals and fragrances, and as

a mixture withother xylenols, in disinfectants, solvents, pharmaceuticals, insecticides, fungicides, plasticizers, rubber chemicals, lubricant and gasoline additives, and wetting agents (Ref. 81). As explained in the "B"policy, EPA believes that the potential exposure of 1,941 workers to 2,6-dimethylphenol is substantialhuman exposure under section 4(a)(1)(B)(i) ofTSCA.

Furthermore, general population
exposure to 2,6-dimethylphenol is also indicated. 2,6-Dimethylphenol was detected in 64 samples obtained from 33 industries and POTWs at a maximum concentration of2,895 ppm (Ref.81). Monitoring data indicate trace quantities of 2,6-dimothylphenol inair andrain (Refs. 61 and83). 2,6- Dimethylphanol was detected in shale oil wastewater in the range 0.75 to 1.7 tig/L (Ref.42) and at 12 mgfL inthe
wastewater from the gasification ofcoal (Ref. 34). In addition' it was detected in groundwater samples from a wood preserving facility in Florida ata concentration of0.90 mg/L,while the concentration of2,6-dimethylphenol in groundwater 330 meters from the site

was0.29 mg/L (Ref.36).

4. Insufficientdataandexperience finding.EPAbelieves that there are insufficient data and experience to determine orpredict theeffects on human health or theenvironment from manufacturing, processing, distribution,

use, and/or disposal of 2,6- dimethylphenol.This assessment is based onthe following information. EPA has adequate negative data evaluating the gbne mutation effects of 2,6-dimethylphenol in Salmonella(Refs. 24 and 32). However, EPA has nodata evaluating thischemical's potential as a gene toxicant in mammalian cells or as

a chromosomaltoxin. EPAfound no data for neurotoxicity, pharmacokinetics and metabolism, reproductive effects, or developmental toxicity.

For environmental effects, acute aquatic toxicity studies are available for
green algae, duckweed, daphnids, sea urchins, fathead minnows andAtlantic cod (Ref. 3). The study for green algae is inadequate because It lacks a rigorous
measurement ofgrowth inhibition as a 96-hourEC50 value. The effect measured was inhibition ofchlorophyll synthesis and the lowest-observed-effect concentration (LOEC was the only effective concentration reported. The Agency believes that the 96-hour EC5O value forgrowth will be a more sensitiveeffect than inhibition of chlorophyll synthesis and will be more relevant in an environmental risk
assessment. While fish and invertebrate
acutetoxicity data are adequate, EPA foundno available data foraquatic invertebrate chronic toxicity. An available 8-day study onfathead minnows for 2,-dimethylphenol is of
too short duration to beconsidered a chronic effects study, nordidit evaluate sensitive life stages, and, thus,this study is inadequate (Ref. 3).

Available chemical fate screening data for 2,6-dimethylphanol indicate that it
may undergo substantial degradation under aerobic conditions; however, EPA found no available data to determine or reliably predict the half-life for the removal of2,6-dimethylphenol by this
process (Ref. 12).,Data on the anaerobic degradation of2,6-dimethylphenol are likewise limited. One screening study indicates that 2i6-dimethylphenol may not degrade under anaerobic conditions; another studyindicated that this chemical undergoes anaerobic biodegradation in ground water and laboratory digestors (Refs. 12 and 35). These (contradictory) dataere insufficient to adequately characterize thisremoval process. EPA alsobelieves that the aqueous photolysis of2,6- dimethylphenol is inadequately 6166361664 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

characterized, with no data available which simulates this process under natural conditions (Ref. 12).

5. Testingnecessaryto develp data finding.EPA believes that testing of 26- dimethylphenol is necessary to develop data for neurotoxicity, pharmacokinetics and metabolism, reproductive effects, developmental effects, mutagenic effects, algal toxicity, fathead minnow chronic toxicity, daphnid chronic toxicity, aerobic biodegradation, anaerobic biodegradation, and aqueous. photolysis. EPA believes that these testing data are needed to determine if the manufacturing, processing. distribution, use, or disposal of 2,6- dimethylphenol or any combination of such activities, does or does notpresent

an unreasonable risk of injuryto health

or the environment.

IV. Issues for Comment

In addition to any relevant, general comments on the chemicals and ,proposed testing in this rulemaking, EPA would appreciate comments on the following specific issues:

1. EPA is proposing subchronic testing ofacetophenone by the inhalation route ofexposure. EPA is soliciting comment on the feasibility of inhalation testing given acetophenone's known irritant properties. Ifinhalation testing is not feasible, should EPA require subchronic testing by the oral route given the, atbest, marginally acceptable nature ofthe existing oral studies?

2. In thisrule, EPA is only proposing to require first tier mutagenicity testing
atthis time. Forpurposes of this rulemaking, EPA solicits comments on the appropriateness ofthese tests and its decision to defer higher tier mutagenicity testing and oncogenicity testing pending the receipt of first tier results.



### a.EPA is also soliciting comments on the proposed toxicokinetics and biodegradation in natural surface water guidelines, which are proposed to be incorporated by reference.

V. Economic Analysis ofthe Proposed Rule

EPA has prepared an economic analysis that evaluates the potential for significant economic impacts as aresult ofthe testing proposed in this notice (Ref. 101). Total costs oftesting, including both laboratory costs and administrative costs, are as follows: acetophnone--$1.3 to 2.0 million; phenol-$1.5 to 2.4 million; NNdimethylaniline-$1.4 to 2.2 million; ethyl acetate-$0.8 to 1.2 million; and 2,6-dimethylphenol--$1.2 to 1.7 million. Total costs oftesting for each chemical have been annualized and compared with annual revenues as an indication ofpotential economic impact. Annualized costs, calculated

over 15 years using a 7 percent discount rate, represent the equivalent constant costs which would have to be recouped each year ofthe payback period to finance the testing expenditure in the first year.

On the basis ofthese calculations, EPA believes that forphenol, ethyl
acetate and 2,6-dimethylphenol there is

no potential for adverse economic impact. Because these three chemicals have relatively largeproduction volumes, the annualized costs oftesting, expressed as apercentage of annual
revenue, are very small-ranging from 0.2- to 0.13 percent. Costs oftesting are therefore found to be insignificant relative to revenues for these three chemicals.

For theremaining two chemicalsacetophenone and NNdimethylaniline-there may be some potential for adverse economic impacts due to the proposed testing. Because these two chemicals are produced in smaller quantities than the other three chemicals subject to this proposed rule,
costs of testing as apercentage of

revenues are higher-ranging from approximately 2- to 4 percent. Costs of testing may therefore be significant relative to revenues for acetophenone and NN-dimethylaniline.

VI. Availability ofTest Facilities and Personnel

EPA believes that test facilities and personnel are available to perform the testing specified in thisproposed rule. (Ref. 111).

VII. Public Meeting

Ifrequested, EPA will hold a public meeting in Washington, DC after the close ofthe public comment period. Persons who wish to attend orto present comments at the meeting should
contact Mary Louise Hewlett, Chemical Testing Branch (202) 260-8162 by January 6, 1994. The meeting willbe open to the public,but active participation will be limitedto those who requested to comment and EPA representatives. Participants are requested to submit copies of their statements by the meeting date. These
statements and a transcript of the meeting will become part ofEPA's rulemaking record.

VIII. Comments Containing Confidential Business Information

All comments willbe placed inthe public file unless they are clearly labeled as Confidential Business Information (CBI) when they are submitted. While apartofthe record, CBI comments will be treated in accordance with 40 CFRpart 2. A sanitized version ofall CBI comments must be submitted to EPA for inclusion in the public file.

It is the responsibility ofthe commenter to complywith 40 CFRpart. 2 in orderthat all materials claimed as confidential may be properly protected. This includes, but is not limited to, clearly indicating on the face ofthe
comment (aswell as on any associated correspondence) that information claimed as CBI is included, and marking "CONFIDENTIAL", "TSCA CBI" or similar designation on the face of each document or attachment in the
comment which contains information claimed as CBI. Should information be put into the public file because of failure to clearly designate its confidential status on the face ofthe comment, EPA willpresume any such information which has been in the public file for more than 30 days to be in the public domain.

IX. Rulemaking Record

EPA has established arecord forthis rulemaking (docket number OPPTS42150). Thisrecord contains the basic information considered by EPA in developing this proposal and appropriate Federal Register notices. EPA will supplement thisrecord as necessary.

A public version ofthe record, from which all information claimed as CBI hasbeen deleted, is available for inspection in the TSCA Noncynfidential Information Center, alsoknown as the TSCA Public Docket Office, East Tower, Rm. G-102,401 M St., SW., Washington, DC. 20460, from 8 a.m. to
noon, and Ip.m. to 4 p.m., Monday through Friday, except legal holidays.

The record includes the following information:

A. SupportingDocumentation (1)Notice containing the ITC designation.

(2) Federal Register notices pertaining
to this rule consisting of:

(a) "Twenty-seventh Report ofthe Interagency Testing Committee to the Administrator; receipt ofreport and request for comments regarding priority list ofchemicals." (March 6, 1991, 56 FR 9534). (b)Notice offinal rule on EPA's TSCA Good Laboratory Practice Standards (54 FR 34034, August 17, 1989).

(c)Notice of finalrule on data reimbursement policy andprocedures (48 FR 31786,July 11,1983).Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

(d) Notice ofproposed test rule on chloromethane and chlorinated benzenes (45 FR 48524, July 18, 1980).

(e) Notice ofproposed test rule on dichloromethane, nitrobenzene and 1,1,1 trichloroethane (46 FR 30300, June 5, 1981).

(f) Notice of final test rule on the C9 aromatic hydrocarbon fraction (50 FR 20662, May 17, 1985).

(g) Notice ofproposed TSCA section 4(a)(1)(B) statement ofpolicy (56 FR 32294, July 15, 1991).

(h) Notice of final TSCA section 4(a)(1)(B) statement ofpolicy (58 FR 28736, May 14, 1993).

(i) Notice ofproposed test rule on glycidol and its derivatives category (56 FR 57144, November 7, 1991).



### (j)

Notice oftesting consent order for acrylic acid (57 FR 7656, March 4, 1992).

(3) TSCA test guidelines cited as test standards for this rule.

(4) Communications consisting of: (a) Written letters. (b)Contact reports oftelephone conversations

(c) Meeting summaries.

B. References

(1)Abdo, K., Wolfe, M., and Hiles, R. "Subchronic toxicity of NN-dimethylaniline for F344 rats and B6C3F1 mice." Federal Proceedings. 43(3): 1698 (1984). (2)Anger, W.K., and Johnson, B.L. "Chemicals Affecting Behavior." Neurotoxicityof IndustrialandCommercial Chemicals.J.L. O'Donoghue, ed. Boca Raton, FL: CRC Press (1985).

(3)AQUIRE. Aquatic Toxicity Information Retrieval Data Base. Duluth, MN: U.S. Environmental Protection Agency, Environmental Research Laboratory (1990).

(4)Armstrong, J.E., Fehler, S.W.,and Calder, J.A. "Effects ofpetroleum hydrocarbons on the growth and energetics of marine microalgae." Biological Monitoringof MarinePollutants. pp. 449-466 (1981). (5)Arrhenius, E."Effects on hepatic microsomal N- and Coxygenation ofaromatic amines by in viva corticosteroid or aminofluorene treatment, diet, or stress." Cancer Research.28(20): 264-273 (1968). (6) Baker, E.L., Landrigan, P.J., Bertozzi, P.E.,Field, P.H., Basteyns, B.J., and Skinner, H.G."Phenol poisoning due to contaminated drinking water." Archives ofEnvironmental Health.83: 89-94 (1978).

(7)Barnes, D.G., and Dourson, M. "Reference dose (RfD): Description and use in health riskassessments." Regulatory ToxicologyandPharmacology. 8: 471-486. (1988).

(8)Basler, A. "Aneuploidy-inducing chemicals in yeast evaluated by the micronucleus test." MutationResearch. 174: 1113.(1986).

(9)Batterton, K., Winters, K., and Van Ballen, C. "Anilines: Selective toxicity to blue-green algae." Science. 199(4333): 1068- 1070 (1978).

(10) Beije, B., and Arrhenius, E. "Influence of cysteine deficiency on the inhibition of hepatic microsomal detoxication by methyl mercury in two rat strains." ChemicoBiological Interactions. 21(2-3): 167-178 (1978).

(11) Bickel. M.H., Willi, P., and Gigon, P.L. "Species and substrate differences ofliver microsomal N-dealkylation and Noxidation oftertiary amines and N-dealkylation ofNoxides." Xenobiotica. 1(4-5): 533-534 (1971).

(12) BIODEG. (Database). Syracuse, NY: Syracuse Research Corporation (1990).

(13) Capel, I.D.; French, M.R., Milluburn, P., Smith, R.L., and Williams, R.T. "The fate of [14C]phenol in various species." Xenobiotica.2: 25-34 (1972).

(14) Chemcyclopedia. Kuney, J.H., Ed. Vol. 8. Washington, DC: American Chemical Society. pp. 43,278 (1989).

(15) CMR. "Ethyl Acetate Chemical Profile." Chemical MarketingReporter. March 31, 1986.

(16) CMR. "Phenol Chemical Profile." ChemicalMarketingReporter.September 14, 1987.

(17) Cole, R.H., Frederickj, R.E., Healy, R.P., and Rolan, R.G. "Preliminary findings ofthe priority pollutant monitoring project of the nationwide urban runoffprogram," Journalofthe WaterPollutionControl Federation. 56: 898-908 (1984). (18) Dalin, N.M.; and Kristofferson, R. "Physiological effects of sublethal concentrations ofinhaled phenol in the rat." AnnalesZoologicaFennici.11: 193-199 (1974).

(19) Dearfield, K.L., Auletta, A.E., Cimino, M.C.,and Moore, M.M. "Considerations in the U.S. Environmental Protection Agency's testing approach for mutagenicity." Mutation Research.258: 259-283 (1991).

(20) Deichmann, W.B. "Phenol studies. V. The distribution, detoxification, and excretion ofphenol in the mammalian body." Archives of Biochemistry.3: 345-355 (1944). (21) Deichmann, W.B., and Oesper, P. "Ingestion ofphenol. Effects on the albino rat." Industrial Medicine.9: 296 (1940). (22) Deichmann, W.B., and M.L. Keplinger. "Phenols and phenolic compounds." In: Patty'sIndustrial Hygieneand Toxicology. Clayton, G.D., and Clayton, F.E., eds. Vol. 2A, 3rd revised edition. New York, NY: John Wiley Sons. pp. 2576-2584 (1981).

(23) Deichmann, W.B., Kitzmiller, K.V., and Witherup, S. "Phenol studies. VII. Chronic phenol poisoning with special reference to the effects upon experimental animals ofthe inhalation ofphenol vapor." American Journal ofClinical Pathology.14: 273-277 (1944).

(24) Department of Health and Human Services. Letter from Beth Anderson to Andrea Blaschka. Research Triangle Park, N.C.,National Institute ofEnviromental Health Sciences (November 12, 1991).

(25) Devereux, T.R., and Fouts, J.R. "NOxidation and demethylation ofNNdimethylaniline by rabbit liver and lung microsomes. Effects of age and metals." Chemico-BiologicalInteractions. 8: 91-105 (1974).

(26) Devereux, T.R., Diliberto, J.J.' and Fouts, J.R. "Cytochrome P-450 monooxygenase, epoxide hydrolase and flavin monooxygenase activities in Clara cells and alveolar type IIcell isolated from rabbit." Cellular BiologyandToxicology. 1(2): 57-65 (1985).

(27) Dow Chemical Co. "The toxicity of phenol." Biochemical Research Laboratory. Unpublished Report dated 04/12/45 (1945).

(28) Elson, L.A., Gouulden, F., and Warren, F.L. "The metabolism of aromatic amines." BiochemicalJournal.40: 29 (1946).

(29) EPA. Ambient water quality document for phenol. EPA 440/5-80-066. U.S. Environmental Protection Agency. p. C-3 (1980).

(30) Erickson, M.D., and Pellizzari, E.D. "Analysis oforganic airpollutants in the Kanawha Valley, WV and the Shenandoah Valley, VA." EPA-903/9-78-007 (1978).

(31) Fiege, H., and Bayer, A.G. "Cresols and xylenols." In: Ullmann'sEncyclopediaof IndustrialChemistry. 5th edition. A8: 25-59 (1987).

(32) Florin, I., Rutberg, L., Curvall, M., and Enzell, C.R. "Screening oftobacco smoke constituents for mutagenicity using the Ames test." Toxicology. 15(3): 219-232 (1980).

(33) Fraser, I.M., Peters, M.A.S., and Hardinge, M.G. "Purification and some characteristics ofan alpha, beta-unstaturated ketone reductase from dog erythrocytes and human liver." Molecular Pharmacology. 3: 233-247 (1967).

(34) Giabbi, M.F., Cross, W.H., Chain, E.S.K., and Dewalle, F.B. "Characterization of major and minor pollutants in waste waters from coal gasification processes." International JournalofEnvironmental AnalyticalChemistry.20: 113-129 (1985).

(35) Godsy, E.M., Goerlitz, D.F., and Ehrlich, G.G. "Methanogenesis ofphenolic compounds by a bacterial consortium from a contaminated aquifer in St. Louis Park, Minnesota." Bulletinof Environmental Contamination and Toxicology. 30: 261-268. (1983).

(36) Goerlitz, D.F., Troutman, D.E., Godsy, E.M., and Franks, B.J. "Migration ofwoodpreserving chemicals in contaminated groundwater in a sand aquifer at Pensacola, Florida." EnvironmentalScience and Technology. 19(10): 955-961 (1985).

(37) Gorrod, J.W., and Gooderham, N.J. "The in vitrometabolism ofNNdimethylaniline by guinea pig and rabbit tissue preparations." European Journalof DrugMetabolismandPharmacokinetics. 6(3): 195-206 (1981).

(38) Gorrod, J.W., Temple, D.J., and Beckett, A.H. "The N and alpha-C-oxidation ,f NN-dialkylanilines by rabbit liver microsomes in vitro." Xenobiotica.9(1): 17- 25 (1979).

(39) Great Lakes Water Quality Board. "An inventory ofchemical substances identified in the Great Lakes ecosystem." Report to the Great Lakes Water Quality Board, Windsor Ontario, Canada. 1: 16 (1983).

(40) Hagan, E.C., Hansen, W.H., Fitzhugh, D.G., et al. "Food flavorings and compounds ofrelated structure. II. Subacute and chronic toxicity." Foodand CosmeticsToxicology. 5(2): 141-157 (1967).

(41) Hamill, S., and Cooper, D.Y. "The role ofcytochrome P-450 in the dual pathways of N-demethylation ofNN-dimethylaniline by hepatic microsomes." Xenobiotica. 14(1-2): 139-149 (1984).

(42) Hawthorne, S.B., and Sievers, R.E. "Emission of organic air pollutants from 61665

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shale oil wastewaters." Environmental Scienceand Technology.18(6): 483-490 (1984).

(43) Heinza, E., Hlavica, P., Kiese, M., and Lipowsli, G. "N-Oxygenation ofarylamines in microsomes prepared from corpora lutea and other tissues ofthe pig." Biochemical Pharmacology. 19(3): 641-690 (1970). (44) Heller, V.G., and Pursell, L. "Phenolcontaminated waters and their physiological action." JournalofPharmacology and Experimental Therapeutics. 63: 99-207 (1938).

(45) Hildebrandt, H. "Ober das biologische Verhalten von Phenylalkylaminen und Phenylalkylammoniumbasen." Beitroegezur ChemischenPhysiologieundPathologie. 9: 470 (1907).

(46) Hlavica, P., and Kehl, M. "Effect of carbon monoxide on the N-oxidation ofN,- dimethylaniline." HoppeSeyler'sZeitschrift fdr PhysiologischeChemie.355(12): 1508-

1514 (1974).

(47) Hlavica, P., and Kehl, M. "Comparative studies on the N-oxidation of aniline and NN-dimethylaniline by rabbit liver microsomes." Xenobiotica.6(11): 679- 690 (1976).

(48) House Committee on Interstate and Foreign Commerce. Legislative Historyof the Toxic SubstancesControl Act. (December 1976).

(49) Imasheva, N.B. "Threshold concentrations ofacetophenone during shortand long-term inhalation." In: AICE Survey of USSR AirPollutionLiterature, Vol. VIII, M.Y. Nuttonson, Ed. American Institute ofCrop Ecology, Silver Spring, MD. pp. 79-:93. (1971).

(50) Ishidate, M., Sofuni, T., and Yoshikawa, K. "Primary mutagenicity screening offood additives currently used in Japan." FoodandChemical Toxicology.22: 263 (1984).

(51) Jarabek, A.M. "Draft 27th report." Memorandum from Amnie M. Jarabek to Letty Tahan. USEPA. Environmental Criteria and Assessment Office, Research Triangle Park, North Carolina (November 20, 1990).

(52) Kao, J., Bridges, J.W., and Faulkner, J.K. "Metabolism of ["1Ciphenol by sheep, pig and rat." Xenobiotica.9: 141-147 (1979).

(53) Kavlock, R.J. "Structure-activity relationship in the developmental toxicity of substituted phenols: Invivaeffects," Teratology. 41: 43-59 (1990). (54) Keith, L.H., Garrison, A.W.. Allen, F.R., Carter, M.H., Floyd, T.L., Pope, J.D., and Thurston. A.D., Jr. "Identification of organic compounds in drinkingwater from thirteen U.S. cities." In: IdentificationandAnalysisof Organic Pollutants in Water.Keith. L.H., ad. Ann Arbor Press. pp. 329-373 (1976)

(55) Kiese, M., and Lank, W. "Hydroacetophenones. Urinary metabolites ofethylbenzene and acetophenone in the rabbit." Xenobiotica.4(6): 337-343 (1974).

(56) Kiese, M.,and Renner, G. "Urinary metabolites ofNN-dimethylaniline produced by dogs." Naunyn Schmiedebergs Archives of Pharmacology. 283:143-150 (1974). (57) Lagno, Z.Y., and Babbitizina, G.Z. "The skin resorptive action of acetophenone." Tr. Ufim. Nausch-Issled. Inst. Gig. Prof. Sabol. AirPollutionandIndustrial Hygiene. 5: 90-94 (1969) (58) Lande, S.S., Durkln, P.R..Christopher. D.H.. Howard, P.H., and Saxena, J. "Investigation of selected potential environmental contaminants: ketonic solvents." EPA-,60/2-76--003. Washington, DC: U.S. EPA. Office ofToxic Substances. (1976).

(59) Lawrence. F.R., and Marshall, W.J. "Aniline" In: Ullmann'sEncyclopediaof IndustrialChemistry.5th edition. Vol. A2. Gerhartz, W.,ad. Weinheim, Germany: VCH Publishers. pp. 309-310(1985).

. (60) Leibman, K.C. "Reduction ofketones in liver cytosol." Xenobiotica,1(1)7 97-104 (1971).

(61) Leuenberger, C., Ligocki, M.P., and Pankow, J.F. "Trace organic compounds in rain. 4. Identities, concentrations, and scavenging mechanisms for phenols in urban air and rain." Environmental Science and Technology.19:1053-1058 (1985).

(62) Liao, T.F., and Oehme, F.W. "Tissue distribution and plasma protein binding of [14Clphenol in rats." ToxicologyandApplied Pharmacology. 57: 220-225 (1981). (63) Maazik, I.K. "Standards for dimethylphenol isomers in water bodies." GigienaISanitaria. (Hygieneand Sanitation). 11: 28-35 (1968).

(64) Markosyan, T.M. "Comparative toxicity ofmonomethylaniline and dimethylaniline in chronic experimental exposure." Chemical Abstracts. 71: 11369u (1969).

(65) Mehta, R., Hirom, P.C., and Millburn, P. "The influence of dose on the pattern of conjugation ofphenol and 1-naphthol in nonhuman primates." Xenobiotica.8(7): 445-452 (1978).

(66)Miller, J.J., Powell, G.M., Olavesen, A.H., and Curtis, C.G. "The toxicity of dimethoxyphenol and related compounds in the cat." Toxicology and Applied Pharmacology. 38:47-57 (1976). (67)NCI (National Cancer Institute), Bioassasy ofphenol for possible carcinogenicity in F344 rats and B6C3P1 mice. NIH Publication No. 80-1759 (1980).

168) Nelson, C.R., and Hites, R.A. "Aromatic amines in and near the Buffalo River." EnvironmentalScienceand Technology. 14(9):1147-1149 (1980).

(69) Nicola, R.M., Branchflower, R., and Douglas, P. "Chemical contaminants in bottomfish," Journalof Environmental Health.49(6): 342-347 (1987).

(70) NIOSH (National Institute for Occupational Safety and Health). National Occupational Exposure Survey (NOES) (1990).

(71) NTP (National Toxicology program). Teratologic evaluation ofphenol in CD rats. Prepared by Research Triangle Institute, Research Triangle Park, NC. NTIS PB83- 247726. (uly 29, 1983).

(72) NTP (National Toxicology Program). Toxicology and carcinogenesis studies of N,N-dimethylaniline in F344/N rats and B6C3F1 mice. NTP Technical Report No. 350. U.S. Department ofHealth and Human Services, Public Health Service, National Institute ofHealth, Research Triangle Park, NC. (1989).

(73) Odenbro, A., and Arrhentus, E. "Effect oftriethyl lead chloride on hepatic microsomal N-oxygenation and Coxygenation of NN-dimethylaniline in rats." Toxicology andApplied PharmacoloSy. 7443): 357-363 (1984).

(74) Ohmiya, Y., and Mehendale, H.M. "N Oxidation ofNN-dimethylaniline in the rabbit and rat lung." Biochemical Pharmacology. 32(7): 1281-1285 (1983). (75) Olsson, U., Belje, B., Wachtmeister, C.A., and Arrhenius, E. "Effects of dimethylnitrosoamine on metabolism of Ndimethylaniline by rat liver microsomes. A comparative study oftreatment in vivc in isolated liver perfusion and in the microsomal system." Chemico-Biological Interactions. 45(2): 191-201 (1983). (76) Olsson, U., Onflet, A.,and Beije B. "Dietary selenium deficiency causes decreased N-oxygenation ofNNdimethylanihne and increased mutagenicily ofdimethylnitrosoamine in the isolaied rat liver/cell culture system." Mutation Research.126(1): 73-80 (1984).

(77) Piccirillo, V.J., McCall, D.L., Luntebhick,
C., Plankenhom, L.J., and Sexsmith. C. Screening ofpriority chemicals for reproductive hazards. NTIS PB 83-2576000.
p. 108 (1983).

(78) Pinching, A.J., and Doving, K.B. "Selective degeneration in the rat olfactory bulb following exposure to different odors." BrainResearch.82(2): 195-204 (1974).

(79) Rane, A. "N-Oxidation of a tertiary amine (N,N-dimethylaniline) by human feta! liver microsomes." ClinicalPharmacology andTherapeutics.15(1): 32-38 (1974).

(80) Sandage, C "Tolerance criteria for continuous inhalation exposure to toxic material." ASD TechnicalReport61519 I). Kansas City, MO: Midwest Research Institute
pp. 1-29 (1961).

(81) Sax, N.I., and l4wis, R.J. Haweley's CondensedChemicalDictionary. 11th edition. New York, NY: Van Nostrand Reinhold Company. pp. 9-10, 411, 421, 896- 897, 1244 (1987).

(82) Shackelford, W.M., Cline, D.M., Fass, L., and Kurth, G."An evaluation of automated spectrum matching for survey identification of wastewater components by
gas chromatography mass spectrometry." Analytica ChemicaActa. 146: 15-27 [supplemental data) (1983).

(83) Shah, J.J., and Heyerdahl, E.K. National ambient volatile organic compGunds (VOCS) database update. EPA/600-3-88 010 p. 48 (1988).

(84) Smith, J.N., Smithies, R.H., and Williams, R.T. "Studies in detoxication 5b. The metabolism ofalkylbenzenes. Stereochemical aspects ofthe biological hydroxylation ofethylbenzene to methylphenylcarbinol." Biochemical Jourrma 56: 320-324 (1954).

(85) Smyth, H.F. "Acute and sub-acute toxicity ofacetophenone." Report 9-42. Mellon Institute of Ind.Res. (1946).

(86) SRI (SRI International). Directory of Chemical Producers. Menlo Park, CA: SRI International. pp. 844-845, 1063 (1989).

(87)Staples, C., Wener, A., and Hoogheem• T. "Assessment ofpriority pollutant concentrations in the United States usiy STORET database." Environmental Toxicology and Chemistry. 4: 131-142 (1985).

(88) STORET. STORET Date Base retrieval 3/19/90. Washington, DC: U.S. EPA. (1990). 58, No. 223 / Monday, November 22, 1,993 / Proposed Rules 

### 61666 Federal Register / Vol.

### Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

(89) Suffet, I.H, Brenner, L., and Cairo, P.R. "Gas chromatography-mass spectrometry identification oftrace organics in Philadelphia, Pennsylvania, USA drinking
waters during a two year period." Water Research. 14: 853-867 (1980).

(90) Tennant, R.W., Margolin, B.H., Shelby, M.D., Zeiger, E.,Haseman, J.K., Spalding, J., Caspary, W., Resnick, M., Stasiewicz, S., Anderson, B.. and Minor, R. "Prediction of chemical carcinogenicity in rodents from in vitrogenetic toxicity assays." Science. 236: 933-941. (1987).

(91) Thierfelder, K., and Daiber, K."Zur kenntis des Verhaltens fettaromatischer Ketone in Tierk6rper." HoppeSeyler's Zeitschrift furPhysiologieChemie. 130: 380- 396 (1923).

(92) Thierfelder, K., and Klenk, E. "Zur kenntis des Verhaltens des Acetophenons und Benzols in Tierk6rper." Hoppe Seyler's Zeitschriftfir PhysiologieChemie. 141: 29- 32 (1924).

(93) TRI (Toxics Release Inventory). Database retrieval 3/16/90. U.S. EPA. (1990).

(94) TSCAPP. Computer printout ofnon- confidential production data from TSCA inventory. Washington, DC: OTS, CID,U.S. EPA. Online 3/15/90 (1990).

(95) Uehleke, H., Reiner, 0., and Hellmer, K.H. "Perinatal development oftertiary amine N-oxidation and NADPH cytochrome

c reduction in rat liver microsomes." Research Communicationsin Chemical PathologyandPharmacology. 2(6): 793-805 (1971).

(96) USEPA. U.S. Enviromental Protection Agency. "27th ITC list exposure report
- acetophenone." Washington, DC, Office of Toxic Substances, USEPA (October 23, 1991).

(97) USEPA. U.S. Enviromental Protection Agency. "27th ITC list exposure report

- 2,6- dimethylphenol." Washington, DC, Office of Toxic Substances, USEPA (November 7, 1991).

(98) USEPA. U.S. Enviromental Protection Agency. "27th ITC list exposure report
- ethyl acetate." Washington, DC, Office ofToxic Substances, USEPA (October 23, 1991).

(99) USEPA. U.S. Enviromental Protection Agency. "27th ITC list exposure report

- NNdimethylaniline." Washington, DC, Office of Toxic Substances, USEPA (November 7, 1991).

(100) USEPA. U.S. Enviromental Protection Agency. "27th ITClist exposure report

- phenol." Washington, DC, Office ofToxic Substances, USEPA (October 23, 1991).

(101) USEPA. U.S. Environmental Protection Agency. Economic impact evaluation ofproposed test rule for IRIS chemicals (group I).Prepared by Dan Axelrad, Regulatory Impacts Branch, Economics and Technology Division, USEPA (March, 1992).

(102) U.S. ITC (U.S. International Trade Commission). Synthetic Organic Chemicals.. U.S. Production and Sales, 1979. Washington, DC: U.S. Goverment Printing Office. Publication No. 1099. p. 43 (1980).

(103) U.S. ITC(U.S. International Trade Commission). Synthetic Organic Chemicals. U.S. Production and Sales 1988. Washington, DC. U.S. Government Printing Office. Publication No. 2219. pp. 3-12, 15-4, and 15--6 (1989). (104) Veldre, I.A., and Janes, H.J. "Toxicological studies ofshale oils, some of their components and commercial products." EnvironmentalHealthPerspectives. 30: 141- 146 (1979).

(105) Waters, M.D., and Auletta, A. "The gene-tox program: genetic activity evaluation."

,. Chem:Inf. Comput.Sci.21: 35-38 (1981).

(106) Ziegler, D.M., and Gold, M.S. "Oxidative metabolism of tertiary amine drugs by human and liver tissue." Xenobiotica.1: 325-326 (1971).

(107) Zimmermann, F.K., Mayer, V.W., Sqheel, I.,and Resnik, M.A. "Acetone, methyl ethyl ketone, ethyl acetate, acetonitrile and otherpolar aprotic solvents

are strong inducers ofaneuploidy in Saccharomycescerevisiae."Mutation Research. 149: 339-351 (1985).

(108) USEPA. U.S. Environmental Protection Agency. "PDM estimates for NNdimethylaniline and 2,6-dimethylphenol." Memorandum from Sidney Abel toJohn Schaeffer. Washington, DC, Office of Pollution Prevention and Toxics, USEPA (October 8, 1991).

(109) U. S. Department ofHealth and Human Services. NIOSH (National Institute for Occupational Safety and Health). National Occupational Exposure Survey Field Guideline. DHHS (NIOSH) Publication No. 88-106 (1988).

(110) USEPA. Chemicalsin Commerce InformationsSystems Search(CICIS).Office ofToxic Substances. USEPA. (1977).

(111) Booz, Allen, Hamilton., Inc., Bethesda, MD. "EPA census ofthe toxicological testing industry." Prepared for the Office of Policy Analysis OTS, USEPA, Washington, DC (June 1990).

(112) NTP (National Toxicology Program). Teratologic evaluation ofphenol in CD mice. Prepared by Research Triangle Institute, Research Triangle Park, NC. NTIS PB85- 104461 (July 29, 1983).

(113) USEPA. Memorandum from Andrea Blaschka and John Schaeffer to the Workgroup scheduling a meeting with the Phenol Panel to discuss pharmacokinetic testing for phenol. CMA's Phenol Panel
comments to the ITCReport and a protocol for pharmacokinetic testing for phenol are attached. Washington, DC, Office ofPollution Prevention and Toxics, USEPA (April 24, 1991).

(114) USEPA. Memorandum from Andrea Blaschka and John Schaeffer to the Workgroup summarizing the results ofthe meeting with the Phenol Panel on 4/24/91 and a request for comments on pharmacokinetic protocols. Washington, DC, Office ofPollution Prevention and Toxics, USEPA (May 9, 1991).

(115) USEPA. Memorandum from Andrea Blaschka to the Workgroup summarizing the meeting held on 11/7/91 and requesting
comments on further testing. Washington, DC, Office ofPollution Prevention and Toxics, USEPA (November 22, 1991).

(116) USEPA. Discharge ofNN,- dimethylaniline and 2,6-dimethylphenol to saline surface waters. Memorandum from Sid Abel, Exposure Evaluation Division toJohn Schaeffer, Chemical Testing Branch. Washington, DC, Office ofToxic Substances, USEPA (April 15, 1992). (117) Elliger, C.A., Henika, P.R., and MacGregor, J.T. "Mutagenicity of flavones, chromones and acetophenones inSalmonella typhimurium:New structure-activity relationships." Mutation Research.135:77- 86 (1984).

X. Regulatory Assessment Requirements

A. Executive Order12291

Under Executive Order 12291, EPA
mustjudge whether a rule is "major" and therefore subject-to the requirement of a Regulatory Impact Analysis. EPA has determined that this proposed test rule would not be major because it does

not meet any of the criteria set forth in section 1(b) ofthe Order; i.e., it would
not have an annual effect on the
economy ofat least $100 million, would

not cause a major increase in prices, and would not have a significant adverse effect on competition or the ability ofU. S. enterprises to compete with foreign enterprises.

This proposed rule was submitted to the Office ofManagement and Budget (OMB) for review as required by Executive Order 12291. Any written
comments from OMB to EPA, and any EPA response to those comments, are included in the rulemaking record.

B.RegulatoryFlexibility Act

Under the Regulatory Flexibility Act (5 U.S.C. 601 et seq.) EPA is certifying that this test rule, ifpromulgated, would

not have a significant impact on a substantial number ofsmall businesses because: (1)They would not be expected to perform testing themselves,

or to participate in the organization of the testing effort; (2) they would experience only very minor costs, ifany, in securing exemption from testing requirements; and (3) they are unlikely

to be affected by reimbursement. requirements.

C. Paperwork ReductionAct

OMB has approved the information collection requirements contained in this rule under the provisions ofthe Paperwork Reduction Act of 1980, 44 U.S.C. 3501 et seq., and has assigned

OMB Control number 2070-0033.

Public reporting burden for this collection ofinformation is estimated to
average 10,100 hours per response, including time for reviewing instructions, searching existing data

sources, gathering andmaintaining the data needed, and completing and reviewing the collection ofinformation. The total public reporting burden is estimated to be 222,000 hours for all
responses. Send comments regarding the burden estimate or any other aspect of this collection ofinformation, 61667

### 61668 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

including suggestions for reducing this burden, to Chief, Information Policy Branch, 2131, U.S. Environmental Protection Agency, 401 M St., SW.. Washington, DC 20460; and to the Office ofManagement and Budget, Paperwork Reduction Project (2070- 0033), Washington DC 20503. The final rule will respond to any 0MB or public
comments on the information collection requirements contained in thisproposal

List ofSubjects in 40 CFR Part 799

Environmental protection, Chemicals, Hazardous substances, Reporting and recordkeeping requirements, Testing, Incorporation by reference.

Dated: November 15, 1993.

VictorJ.Kimm, ActingAssistant Administrator for Prevention, Pesticides andToxicSubstances.
Therefore, it is proposed that 40 CFR, chapter I, subchapter R, part 799 be amended asfollows:

PART 799--[AMENDED]

a. The authority citation forpart 799 would continue to read as follows:

Authority: 15 U.S.C. 2601, 2603, 2611, 2625.

b. By adding § 799.4450 to subpart B
toreadas follows:
§799.4450 Designated IRIS chemicals.

(a)Identificationoftestsubstances. (1)The IRIS chemicals subject to this
test guideline were designated in the Twenty-Seventh ITC report. These chemicals include acetophenone (CAS No. 98-86-2), phenol (CAS No. 108-95- 2), NN-dimethylaniline (CAS No. 121- 69-7), ethyl acetate (CASNo. 141-78- 6), and 2,6-dimethylphenol (CAS No. 576-26-1).

(2) Acetophenone, phenol, NNdimethylaniline, ethyl acetate, and 2,6- dimethylphenol ofat least 99 percent purity shall be used as the test substance.

(b)Personsrequired to submitstudy plans,conducttests andsubmitdata. All persons who manufacture (includin import)or process orintend to manufacture or process acetophenone, phenol, NN-dimethylaniline, ethyl acetate, and 2,6-dimethylphenol other than as an impurity, afterJanuary 5, 1994, to the end ofthe reimbursement period shall submit letters ofintent to conduct testing, submit study plans, conduct tests, and submit data, or submit exemption applications as specified inthis section, subpart A of this part and parts 790 and 792 ofthis chapter for single-phase rulemaking, for the substances they manufacture subjec * to exclusions contained in §790.42(a)(2), (a)(4) and (a)(5). These sections provide that processors, persons who manufacture less than 500

g(1,100 lbs) annually, orpersons who manufacture small quantities ofthe chemical solely forresearch and development as defined in § 790.42(a)(5) shall not berequired to submit study plans, conduct tests and submit data, or submit exemption applications as specified in this section unless directed
to do so in a subsequentnotice as set forth in § 790.48(b).

(c)Healtheffects -41) Subchronic toxicity

- (i) Requiredtesting. Subchronic toxicitytesting shall be conducted by inhalation with acetophenone, phenol, andNNdimethylaniline in accordance with § 798.2450 ofthis chapter.

(ii) Reportingrequirements. (A) The required subchronic toxicity test shall be completed and the final reports submitted to EPA within 18 months of the effective date in paragraph (f)ofthis section.

(B)Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in Raragraph (f) ofthis section until the nal report is submitted. (2) Pharmacokinetics and metabolism-(i)Requiredtesting.(A) Pharmacokinetics and metabolism studies shall be conducted with acetophenone, phenol, NNdimethylaniline, and 2,6- dimethylphenol by the oral route of administration in accordance with OECD testguideline 417 "Toxicokinetics", which is incorporated

- by reference. Copies ofthis guideline

are available in the TSCA Nonconfidential Information Center, East Tower, Rm. G-102, 401 M St., SW., Washington, DC 20460. This guideline is also available forpublic inspection at the Office ofthe Federal Register, 800 North Capital St., Suite 700, Washington, DC. This incorporation by reference was approved bythe Director ofthe Federal Register in accordance with 5 U.S.C. 552(a) and 1CFR part 51.
g This guideline is incorporated as it exists on the date ofapproval and a notice ofany changes to the guideline will be published in the Federal Register.

(B)Pharmacokinetics and metabolism studies shallbe conductedwith acetophenone, phenol,NNdimethylaniline, and 2,6- dimethylphenol by the inhalation route ofadministration In accordance with OECDtest guideline 417 "Toxicokinetics", which isincorporated by reference. Copies ofthis guideline t are available in the TSCA Nonconfidential Information Center, East Tower, Rm. G-102,401 M St., SW., Washington, DC 20460. This guideline is available for public inspection at the Office ofthe Federal Register, 800 North Capital St., Suite 700, Washington, DC. This incorporation by reference was approved by the Director ofthe Federal Register in accordance with 5U.S.C. 552(a) and 1CFRpart 51. This guideline is incorporated as it exists onthe date ofapproval and anotice ofany changes
to the guideline'will be published in the Federal Register. (ii) Reportingrequirements.

### (A)The required pharmacokinetics and metabolism studies shall be completed and the final reports submitted to EPA within 15 months aftefthe effective date inparagraph (f)ofthis section.

(B)Progress reports shallbe submitted
to EPA every 6 monthsbeginning 6 months after the effective date in paragraph (f)ofthis section until the final reportis submitted.

(3) Neurotoxicity(Inhalation)-i) Requiredtesting-(A)Functional observational battery.(1)Functional observational battery tests shallbe conducted with acetophenone, phenol, and N,N-dimethylaniline in accordance with § 798.6050 ofthis chapter except for the provisions in paragraphs (d)(4)(ii), (d)(5), and (d)(6) of§ 798.6050.

(2)For the purpose ofparagraph (c)(3)(i)(A) ofthis section, the following provisions also apply:

(i)Lowerdoses.Either the data from the lower doses shall show graded dosedependent effects orthere shallbe no neurotoxic (behavioral) effects at any dose tested. (ii)Durationand frequencyof
exposure.For the acutetesting, animals shallbe exposed for 6 hours per day for I day. For the subchronic testing, animals shall be exposed for6 hours per day 5 consecutive days per week for a 90-day period.

(iii)Routeofexposure.Animals shall be exposed to acetophenone, phenol, and NN-dimethylaniline by inhalation administration.

(B)Motoractivity.(1) Motor activity testing shall be conducted with acetophenone, phenol, andNNdimethylaniline in accordance with §798.6200 ofthis chapter except forthe

rovisions in paragraphs (d)(4)(ii), d)(5), and (d)(6) of § 798.6200.

(2)Forthe purpose ofparagraph (c)(3)(i)(B) ofthis section, the following provisions also apply: I) Lower doses.Either the data from the lower doses shall show graded dosedependent effects orthere shallbe no neurotoxic (behavioral) effects at any dose tested.Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

(i) Duration and frequencyof exposure. For the acute testing, animals shall be treated for 6 hours per day for
I day. For the subchronic testing, animals shall be exposed 6 hours per day 5 consecutive days per week for a 90-day period.

(iii) Route ofexposure.Animals shall be exposed to acetophenone, phenol, and NN-dimethylaniline by inhalation administration.

(C) Neuropathology.(1) Neuropathology testing shall be conducted with acetophenone, phenol, and NN-dimethylaniline in accordance with § 798.6400 ofthis chapter except for the provisions in paragraphs (d)(4}(ii), (d)(5), (d)(6) and (d)(8)(iv)(C) of§ 798.6400.

(2)For the purpose ofparagraph (c)(3)(i)(C) ofthis section, the following provisions also apply:

(i) Lower doses. Either the data from the lower doses shall show graded dosedependent effects or there shall be no neurotoxic (behavioral) effects at any dose tested.

(i) Duration and frequencyof
exposure.For the acute testing, animals shall be exposed for 6 hours per day for 1 day. For the subchronic testing, animals shall be exposed for 6 hours per day 5 consecutive days per week for a 90-day period.

(iii) Route ofexposure.Animals shall be exposed to acetophenone, phenol, and NN-dimethylaniline by inhalation administration.

(iv) Clearing andembedding.After dehydration, tissue specimens shall be cleared with xylene and embedded in

wax orplastic medium, except forthe sural nerve, which should be embedded in plastic. Multiple tissue specimens (e.g. brain, cord, ganglia) maybe embedded together in one single block forsectioning. All tissue blocks shall be labelled to provide unequivocal identification. Plastic embedding should follow the method described by Spencer, et al., in § 798.6400(f) ofthis chapter, or an equivalent method.

(ii) Reportingrequirements.(A) The functional observational battery, motor activity, and neuropathology testing with acetophenone, phenol, and N,Ndimethylaniline shall be completed and the final reports submitted to EPA within 21 months of the effective date in paragraph (f) ofthis section. B Progress reports shall be submitted
every 6 months beginning 6 months after the effective date in paragraph (f) ofthis section until the final report is submitted.

(4) Neurotoxicity(Gavage)-(i) Requiredtesting-(A)Functional observational battery.(1) A functional observational battery test shall be conducted with 2,6-dimethylphenol in accordance with S798.6050 ofthis chapter except forthe provisions in paragraphs (d)(4)(ii), (d)(5), and (d)(6) of §798.6050.

(2)For the purpose ofparagraph (c)(4)(i)(A) ofthis section the following provisions also apply:

(i) Lowerdoses.Either the data from the lower doses shall show graded dosedependent effects or there shall beno neurotoxic (behavioral) effects at any dose tested.

(iijDurationand frequencyof
exposure.For the acute testing, animals shall be treated once. For the subchronic testing, animals shall betreated 5 consecutive days per week for a 90-day period.

(iii) Route ofexposure.Animals shall be exposed to 2,6-dimethylphenol by gavage administration.

(B) Motoractivity.(1)Motor activity testing shall be conducted with 2,6- dimethylphenol in accordance with §798.6200 ofthis chapter except for the provisions in paragraphs (d)(4)(ii), (d)(5), and (d)[6) of 

### §798.6200.

(2)For the purpose ofparagraph (c)(4)(i)(B) ofthis section, the following provisions also apply:

01)Lowerdoses.Either the data from the lower doses shall show graded dosedependent effects orthere shall be no neurotoxic (behavioral) effects at any dose tested.

(ii)Duration and frequencyof exposure. Forthe acute testing, animals shall betreated once. For the subchronic testing, animals shall be treated 5 consecutive days per week for a 90-day period.

(iiN) Routeofexposure.Animals shall be exposed to2,6-dimethylphenol by gavage administration.

(C)Neuropathology. (1) Neuropathology testing shall be conducted with 2,6-dimethylphenol in accordance with §798.6400 ofthis chapter except forthe provisions in paragraphs (d)(4)(ii), (d)(5), (d)(6) and (d)(8)(iv)(C) of§ 798.6400.

(2)For the purpose ofparagraph (c)(4)(i)(C) ofthis section, the following provisions also apply:

(i)Lowerdoses.Eitherthe data from the lower doses shall show graded dosedependent effects or there shallbe no neurotoxic (behavioral) effects at any dose tested.

(iijDuration and frequencyof
exposure.For the acute testing, animals shall be treated once. For the subchronic testing animals shall be treated 5 consecutive days per week for a 90-day period.

(iii)Routeofexposure.Animals shall be exposed to 2,6-dimethylphenol by gavage administration. (iv) Clearing andembedding.After dehydration, tissue specimens shall be cleared with xylene and embedded in

wax or plasticmedium, except for the sural nerve, which should be embedded in plastic. Multiple tissue specimens (e.g. brain, cord, ganglia) may be embedded together in one single block for sectioning. All tissueblocks shall be labelled to provide unequivocal identification. Plastic embedding should follow the method described by Spencer, et al., in paragraph 

### (0 of §798.6400 of this chapter, or an equivalent method.

(ii) Reportingrequirements.(A) The functional observational battery, motor activity, and neuropathology testing with 2,6-dimethylphenol shall be completed and the final reports submitted to EPA within 21 months of the effective date in paragraph 

### (f)ofthis section.

(B)Progress reports shall be submitted every 6 months beginning 6 months after the effective date in paragraph 

### (f) ofthis section until the final report is submitted,

(5)Reproductivetoxicity-(i) Requiredtesting.Reproductive toxicity testing shall be conducted with acetophenone, NN-dimethylaniline, ethyl acetate, and 2,6-dimethylphenol by gavage, and phenol by inhalation in accordance with 

### §798.4700 of this chapter.

(ii) Reportingrequirements.(A) The reproductive toxicity tests shall be completed and the final reports submitted to EPA within 29 months of the effective date in paragraph 

### (0 ofthis section.

(B)Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph 

### (f0 ofthis section. (6) Developmentaltoxicity--(i) Requiredtesting.Developmental toxicity testing in two species, a rat and

a non-rodent, shall be conducted with acetophenone by inhalation, and NNdimethylaniline, ethyl acetate, and 2,6- dimethylphenol by gavage in accordance with §798.4900 ofthis chapter.

(ii) Reportingrequirements. (A)The developmental toxicity testing shall be completed and the final reports submitted to EPA within 12 months of the effective date in paragraph (f)ofthis section.

(B)Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph 

### (f)ofthis section until the final report is submitted.

(7)Developmentalneurotoxicity-(i) Requiredtesting.Developmental neurotoxicity testing in the rat shall be 6166961670 Federal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

conducted with phenol by gavage administration in accordance with §795.250 ofthis chapter.

(ii)Reportingrequirements.(A) The developmental toxicity testing shall be completed and the final report submitted to EPA within 21 months of the effective date in paragraph (f) ofthis section.

(B)Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph (f)ofthis section until the final report is submitted.

(8) Mutageniceffects-gene mutation--(i)Requiredtesting. (A) Gene mutation assays in the Salmonella typhimuriumhistidine reversion system shall be conducted with acetophenone in accordance with §798.5265 ofthis chapter.

(B)Gene mutation assays in somatic cells in culture shall be conducted with acetophenone, ethyl acetate, and 2,6- dimethylphenol in accordance with §798.5300 of this chapter.

(ii) Reportingrequirements. Mutagenic effects-gene mutation tests shall be conducted and the final reports submitted to EPA as follows:

(A] Gene mutation in Salmonella,9 months after the effective date in paragraph (f)ofthis section.

(B) Gene mutation in somatic cells in culture, 10 months after the effective date in paragraph (f)ofthis section.

(9) Mutageniceffects-chromosomal aberrations

- (i)Required testing.In vivacytogenetic assays shall be conducted by gavage with acetophenone, NN-dimethylaniline, and 2,6-dimethylphenol in accordance with § §798.5385 or 798.5395 ofthis chapter.

(ii)Reportingrequirements.(A) Mutagenic effects

- In vivo cytogenetics testing shall be completed and the final reports submitted to EPA within 14 months after the effective date in paragraph (f) ofthis section.

(B} Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph (f)ofthis section.

(d) Environmental effects -(1) Algal toxicitytesting

- (i)Requiredtesting. Algal toxicity testing shall be conducted with NN-dimethylaniline and 2,6- dimethylphenol in accordance with §797.1050 of this chapter.

(ii) Reportingrequirements.(A) The algal toxicity testfor NNdimethylaniline and 2,6- dimethylphenol shallbe completed and the final reports submitted to EPA within 12 months ofthe effective date in paragraph (f)ofthis section.

(B)Progress reports shall be submitted to EPA every 6 months beginning 6 months after the effective date in paragraph (f) ofthis section until the final report is submitted.

(2) Invertebrateacutetoxicity

- (i) Requiredtesting.(A) Daphnid acute toxicity tests shall be conducted with N,N-dimethyaniline and 2,6- dimethylphenol in accordance with §797.1300 ofthis chapter.

(B)Mysid shrimp acute toxicity tests shall be conducted with NNdimethylaniline in accordance with §797.1930 ofthis chapter.

(ii)Reportingrequirements.(A) Invertebrate acute toxicity testing shall be conducted and the final reports submitted to EPA within 12 months after the effective date in paragraph (f) ofthis section.

(B) Progress-reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph (f)ofthis section until the final report Is submitted.

(3)Invertebratechronictoxicity testing-(i) Required testing. (A) Daphnid chronic toxicity tests shall be conducted with N,N-dimethylaniline and 2,6-dimethylphenol in accordance with §797.1330 ofthis chapter. (B) Mysid shrimp chronic toxicity
tests shall be conducted with NNdimethylaniline in accordance with §797.1950 ofthis chapter.

(ii)Reportingrequirements.(A) -Invertebrate chronic toxicity testing shallbe conducted and the final reports submitted to EPA within 24 months after the effective date in paragraph (f) ofthis section.

. (B) Progress reports shall be submitted
to EPA every 6 months beginning 6

- months after the effective date in paragraph (f)ofthis section until the final report is submitted.

(4)Fish chronictoxicity-(i) Required testing.Fish early life stage toxicity tests shallbe conducted with fathead minnows with NN-dimethylaniline and 2,6-dimethylphenol, and sheepshead minnows with NN-dimethylaniline, in accordance with §797.1600 ofthis chapter.

(ii) Reportingrequirements.(A)Fish early life stage toxicity tests shall be completed and the final reports submitted to EPA within 12 months of the effective date in paragraph () ofthis section.

(B) Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph (f) ofthis section until the final report is submitted.

(e) Chemical fate-(I) Biodegradation in naturalsurfacewaters-(i) Required testing.(A) Biodegradation testing in natural surface waters shall be conducted with 2,6-dimethylphenol. (B)The testing shall be conducted in accordance with the test procedure specified in the American Society for Testing and Materials (ASTM) test method, entitled "Standard Test Method forBiodegradation By a Shake-Flask DieAway Method, Designation: E1279- 89," published in the Annual Book of ASTM Standards, March 1989, Philadelphia, Pa., which is incorporated by reference. Copies ofthis test method

are available in theTSCA Nonconfidential Information Center, East Tower, Rm. G-102, 401 M St., SW., Washington, DC 20460. This test method is also available for inspection at the Office ofthe Federal Register, 800 North Capital St., Suite 700, Washington, DC. This incorporation by reference was approved by the Director ofthe Federal Register in accordance with 5U.S.C. 552(a) and 1CFR part 51. This method is incorporated as it exists

on the date ofapproval and a notice of any changes to the method will be published in the Federal Register. (ii)Reportingrequirements.(A) The biodegradation test in natural surface
waters shall be completed and the final reports submitted to EPA within 12 months ofthe effective date in

-paragraph (f)ofthis section. (B Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph (f)ofthis section until the final report is submitted.

(2) Biodegradation in activated sludge

- (i)Requiredtesting.Biodegradation testing in activated sludge shallbe conducted withN,N-dimethylaniline in accordance with §796.3340 ofthis chapter.

(ii)Reportingrequirements. (A)The biodegradation testin activated sludge shall be completed and the final report submitted to EPA within 12 months of the effective date in paragraph (f) ofthis section.

(B)Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date in paragraph (f)of this section until the final report is submitted.

(3) Anaerobicbiodegradation

- (i) Requiredtesting.Anaerobic biodegradation testing shallbe conducted with NN-dimethylaniline and 2,6-dimethylphenol in accordance with §796.3140 ofthis chapter. (ii)Reportingrequirements. (A)The required anaerobic biodegradation testing shall be completed and the final report submitted to EPA within 12 months ofthe effective date in paragraph () ofthis section. (B) Progress reports shall be submitted
to EPA every 6 months beginning 6 months after the effective date inFederal Register / Vol. 58, No. 223 / Monday, November 22, 1993 / Proposed Rules

paragraph (f) ofthis section until the final report is submitted,

(4) Photolysis-(i) Requiredtesting. Aqueous photolysistesting shall be conducted on 2,6-dimethylphenol in accordance with §795.70 ofthis chapter.

(ii) Reportingrequirements.(A) The required aqueous photolysis testing shall be completed andthe final report submitted to EPA within 12 months of the effective date in paragraph (f)ofthis section.

(B)Progress reports shall be submitted to EPA every 6 months beginning 6 months after the effective date in paragraph (0 ofthis section until the final report is submitted.

(f)Effective date.This testguideline is effective (44days after publication of the final rule in the Federal Register).
[FR Doc. 93-28614 Filed 11-19-.3; 8:45 am]

BILLNG CODE 6560-0-F

FEDERAL COMMUNICATIONS

COMMISSION

47 CFR Part 73 [MM Docket No.93-279, RM-8368]

Radio Broadcasting Services; Cal-NevAr], NV

AGENCY: Federal Communications Commission.

ACTION: Proposed rule.

SUMMARY: The Commission requests comments on a petition filed by Richard W. Myers seeking the allotment of Channel 285A to Cal-Nev-Ari, Nevada,

as its first local aural transmission service. Channel 285A can be allotted to Cal-Nev-Ari in compliance with the Commission's minimum distance separation requirements with a site restriction of 2.6 kilometers (1.6 miles) southeast, at coordinates North Latitude 35-17-12 and West Longitude 114-51- 57, to avoid a short-spacing to Station KJUL, Channel 282C, North Las Vegas, Nevada. The petitioner is requested to provide further information to demonstrate that Cal-Nev-Ari is a community for allotment purposes. Concurrence bythe Mexican Government is required because CalNev-Ari is located within 320 kilometers (199 miles) ofthe U.S.- Mexican border. DATES: Comments must be filed on or before January 3, 1994, and reply comments on or before January 18. 1994. ADDRESSES: Federal Communications Commission, Washington, DC 20554. In addition to filing comments with the FCC, interested parties should serve the petitioner, or its counsel or consultant,

as follows: Peter Tannenwald, Esq., Kathleen L. Franco, Esq., Arent Fox Kintner Plotkin &Kahn, 1050 Connecticut Avenue NW., Washington, DC 20036-5339 (Counsel to petitioner).

FOR FURTHER INFORMATION CONTACT: Leslie K. Shapiro, Mass Media Bureau, (202) 634-6530.
SUPPLEMENTARY INFORMATION: This is a synopsis ofthe Commission's Notice of Proposed Rule Making, MM Docket No. 93-279, adopted October 20, 1993, and released November 12, 1993. The full text ofthisCommission decision is available for inspection and copying during normal business hours in the FCC Reference Center (room 239), 1919 M Street NW., Washington, DC. The complete text ofthis decision may also be purchased from the Commission's copy contractor, International Transcription Services, Inc., (202) 857- 3800, 2100 M Street NW., suite 140, Washington, DC 20037.

Provisions ofthe Regulatory FlexibilityAct of 1980 do notapply to thisproceeding.

Members ofthe public should note that from the time aNotice of Proposed Rule Making is issued untilthe matter is no longer subjectto Commission consideration or court review, all ex partecontacts are prohibited in Commission proceedings, such as this one, which involve channel allotments. See 47 CFR 1.1204(b) for rules governing permissible expartecontacts.

For information regarding proper filing procedures for comments, see 47 CFR 1.415 and 1.420.
List ofSubjects in47 CFRPart 73

Radio broadcasting. -Federal Communications Commission. VictoriaM. McCauley,
AssistantChief, AllocationsBranch,Policy and Rules Division, MassMediaBureau. [FR Doc. 93-28546 Filed 11-19-93; 8:45 am]

BILLING CODE 6712-01-M

DEPARTMENT OF COMMERCE

National Oceanic and Atmospheric Administration

50 CFR Part 651

[Docket No. 931076-3276; I.D. 100193A]

RIN 0648-AD33

Northeast Multlspecles Fishery; Correction

AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration .(NOAA), Commerce. ACTION: Proposed rule; request for comments; correction.

SUMMARY: This document corrects a proposed rule published on October 27, 1993 (58 FR 57774), whichis related to Amendment 5to the Fishery Management Plan for the Northeast Multispecies Fishery (FMP). This document corrects Figure 2 ofthe proposed ruleto depict Closed Areas properly. EFFECTIVE DATES: November 22, 1993.

FOR FURTHER INFORMATION CONTACT: John G.Terrill, Fishery PolicyAnalyst, Northeast Regional Office, 508-281- 9252.

. The publication on October 27, 1993, ofthe proposed rule,which was the subject of FR Doc. 93-26251, is corrected as follows:

On page 57801, inFigure 2: Closed Areas, "Closed Area I" should read "Closed Area II". and "Closed Area II" should read "Closed Area I". A corrected Figure 2appears below.

Dated: November 16, 1993. Samuel W. McKeen, ActingAssistant Administrator forFisheries, National Marine Fisheries Service.

BIUNG CODE 3510-22-4 61671