### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 799 [OPPTS-42196; FRL-5760-3] RIN2070-AB07 Proposed Test Rulefor In Vitro Dermal Absorption Rate TestingofCertain Chemicals ofInterest toOccupational Safety and Health Administration AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule.
SUMMARY: EPA is proposing a test rule under section 4(a) ofthe Toxic Substances Control Act (TSCA) to require manufacturers, importers, and processors of47chemical substances of interest tothe Occupational Safety and Health Administration (OSHA)to conduct invitro dermal absorption rate testing. These chemicals, and others,

were designated for invitrodermal absorption rate testing in the 31st, 32nd, and 35th Reports oftheTSCA Section 4(e) Interagency Testing Committee (ITC)tothe EPAAdministrator. The dermal absorption rate data obtained under this testingprogram would be used to support OSHA's development of "skin designations" for the chemical substances included in thisproposed rule. Skin designations areused by OSHA toprovide specific guidance to employers concerning whether changes should be made to processes involving chemical substances in order to reduce the hazard ofsystemic toxicity from dermal absorption ofthese chemicals. Changes to aprocess might include changes in engineering controls or changes in the use ofor type ofpersonal protective equipment. Skin designations alert industrial hygienists, employers, and workers to potential adverse health effects resulting from dermal exposure to chemicals in the workplace. Persons who export or intend to export any chemical substance included in the final rule based on this proposed rule will be subject to the export notification requirements in TSCA section 12(b)(1).
DATES: Comments, identified by docket control number OPPTS-42196, mustbe received byEPA on or before August 9, 1999. Your request to present oral
comments must be in writing and must be received byEPA on or before July 9, 1999.
ADDRESSES: Comments may be submitted by mail, electronically, or in person. Follow the detailed instructions for each method as provided in Unit I.C. ofthe "SUPPLEMENTARY INFORMATION" section ofthis preamble. To ensure proper receipt by EPA, your comments must identify docket control number OPPTS-42196 in the subject line on the first page ofyour response. FOR FURTHER INFORMATION CONTACT: For generalinformation:Christine Augustyniak, Associate Director, Environmental Assistance Division (7408),Office ofPollution Prevention and Toxics, Environmental Protection Agency, 401 M St., SW., Washington, DC20460; telephone number: (202) 554-1404;TDD: (202) 554-0551; e-mail address: TSCA-Hotline@epa.gov.

Fortechnicalinformation:Keith Cronin, Project Manager, Chemical Control Division (7405), Office of Pollution Prevention and Toxics, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; telephone number: (202) 260-8157; fax number: (202) 260-1096; e-mail address: cronin.keith @epa.gov. SUPPLEMENTARY INFORMATION:

I. General Information

A. Does ThisActionApply To Me?

You may be affected by this action, if
you manufacture (defined by statute to include import) or process any ofthe chemical substances that are listed in Table 2 ofthis unit. Use ofthe term "manufacture" in this preamble will encompass "import," unless otherwise stated. In addition, as described in Unit VI. ofthispreamble, once the Agency issues the final rule, any person who exports, or intends to export, one of these chemical substances will be subject to the export notification requirements in 40 CFR part 707, subpart D. The export notification requirements do not apply until the Agency issues a final test rule, and then, only apply to exports ofthe chemical substances that are contained in the final test rule. Therefore, entities potentially affected by this proposed rule mayinclude, but are not limited to:

TABLE 

### 1
.- ENTITIES POTENTIALLY AFFECTED BY THE PROPOSED TESTING REQUIREMENTS
Type of entity SIC NAICS Examples ofpotentially affected entities

Chemical manufacturers 28, 2911 325, 32411 Persons who manufacture (defined by statute to include import) one or more of the

and importers subject chemical substances

Chemical processors 28, 2911 325, 32411 Persons who process one or more ofthe subject chemical substances.

This listing is not intended to be exhaustive, butrather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in Table 1 ofthis unit could also be affected. The Standard Industrial Classification (SIC) codes and the North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. To determine whether you or your business is affected by this action, you should carefully examine the applicability provisions in Unit V.C. of this preamble entitled "Would I Be Required To Test Under This Rule?" and consult the proposed regulatory text in §799.5115. Ifyou have any questions regarding the applicability ofthis action
to a particular entity, consult the technical person listed in "FOR FURTHER INFORMATION CONTACT"
atthe beginning ofthe preamble.

Ifyou are an entity identified in Table 1 ofthis unit, you would only be subject
to the testing requirements contained in this proposed rule if you manufacture or process any ofthe 47 chemical substances that are listed in Table 2 of this unit. TABLE 2.-LIST OF CHEMICAL SUBSTANCES PROPOSED FOR TESTING

CAS No. Chemical substance

60-29-7 74-96-4 75-05-8 75-15-0 75-35-4 77-73-6 77-78-1 78-59-1 78-83-1 78-87-5 78-92-2 79-20-9 79-46-9 91-20-3 Ethyl ether Ethyl bromide Acetonitrile Carbon disulfide Vinylidene chloride Dicyclopentadiene Dimethyl sulfate Isophorone Isobutyl alcohol Propylene dichloride sec-Butyl alcohol Methylacetate 2-Nitropropane Naphthalene 

## 31074

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

TABLE 2.-LIST OF CHEMICAL SUBSTANCES PROPOSED FOR TESTING

### Continued

CAS No. Chemical substance

92-52-4 Biphenyl 95-49-8 o-Chlorotoluene 95-50-1 o-Dichlorobenzene 97-77-8 Disulfiram 98-29-3 tert-Butylcatechol 99-99-0 p-Nitrotoluene 100-00-5 p-Nitrochlorobenzene 100-01-6 p-Nitroaniline 100-44-7 Benzyl chloride 106-42-3 p-Xylene 106-46-7 p-Dichlorobenzene 107-06-2 Ethylene dichloride 107-31-3 Methyl formate 108-03-2 1 -Nitropropane 108-90-7 Chlorobenzene 108-93-0 Cyclohexanol 109-66-0 Pentane 109-99-9 Tetrahydrofuran 110-12-3 Methyl isoamyl ketone 111-84-2 Nonane 120-80-9 Catechol 121-69-7 Dimethylaniline 122-39-4 Diphenylamine 123-42-2 Diacetone alcohol 126-99-8 beta-Chloroprene 127-19-5 Dimethyl acetamide 142-82-5 n-Heptane 150-76-5 p-Methoxyphenol 528-29-0 o-Dinitrobenzene 628-63-7 n-Amyl acetate 768-52-5 N-Isopropylaniline 25013-15-4 Vinyl toluene 34590-94-8 Dipropylene glycol methyl ether

B. How CanI GetAdditional InformationorCopiesofThisDocument

orOtherDocuments?
1.Electronically.You may obtain electronic copies ofthis document and other documents from the EPA Internet EPA Home Page at http://www.epa.gov/

•On the Home Page select "Law and Regulations" and then look up the entry for this document under "Federal Register Environmental Documents." You can also go directly to the Federal Register listings at http://www.epa.gov/ fedrgstr/.

2. Inperson

. The official record for this proposed rule, which includes the public version, has been established under docket control number OPPTS42196. The official record consists ofthe documents referenced in this preamble (see Unit VIII. ofthispreamble), as well

as the public comments that will be received during the comment period, and other information related to this rulemaking, including information claimed as Confidential Business Information (CBI). This official record includes the documents that are physically located in the docket, as well

as all documents that arereferenced in those documents. The public version of the offical record does not include any information claimed as CBI. The public version ofthe official record, which includes printed, paper versions ofany electronic comments that may be submitted as described in Unit I.C. and D. ofthis preamble, is available for inspection in the TSCA Nonconfidential Information Center, Rm. NE B-607, 401 M St., SW., Washington, DC. The Center is open from 12 noon to 4p.m., Monday through Friday, excluding legal holidays. The telephone number ofthe Center is (202) 260-7099.

C.How andTo Whom DoI Submit Comments?

You may submit comments through the mail, in person, or electronically. To

ensure proper receipt by EPA, your comments must identify docket control number OPPTS-42196 in the subject line on the first page ofyour response. 1.By mail.Submit comments to: Document Control Office (7407),Office ofPollution Prevention and Toxics, Environmental Protection Agency, 401 M St., SW., East Tower, Rm. G-099, Washington, DC 20460.

2. Inpersonorby courier. Deliver
comments to: Document Control Office, Office ofPollution Prevention and Toxics, Environmental Protection Agency, 401 M St., SW., East Tower, Rm. G-099, Washington, DC. The telephone number for the OPPT Document Control Office is (202) 260- 7093.

3. Electronically.Submit your comments electronically by e-mail to: oppt.ncic@epa.gov, or you may mail or deliver your computer disk to the addresses identified in Units I.C.1. or 2. ofthis preamble. Do not submit any information electronically that you consider to be CBI. Submit comments as

an ASCII file, avoiding the use ofspecial characters and any form ofencryption. Comments will also be accepted on standard disks in WordPerfect 5.1/6.1 or ASCII file format. All copies of electronic comments must be identified by docket control number OPPTS42196. Electronic comments may be filed online at many Federal Depository Libraries.

D.How ShouldIHandleCBI Information ThatI Want To SubmitTo TheAgency?

Do not submit any information electronically that you consider to be CBI. You may claim information that you submit in response to this document as CBI by marking any part or all ofthat information as CBI. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFRpart 2. In addition to one complete version of the comments that include any information claimed as CBI, acopy of the comments that does not contain the information claimed as CBImust be submitted forinclusion in the public version ofthe official record. Information not marked confidential willbe included in the public version ofthe official record byEPA without prior notice. Ifyou have any questions about CBI or the procedures for claiming CBI, consultthe technical person identified in "FORFURTHER INFORMATION CONTACT"at the beginning ofthispreamble.

E. Can IRequestAn OpportunityTo PresentOralComments To TheAgency?

You may submit a request for an opportunity to present oral comments. Thisrequest must be in writing. If such

arequest is received on or before July 9, 1999, EPA will hold apublic meeting

on thisproposed rule in Washington, DC. This written request must be submitted to the address provided in UnitI.C. ofthispreamble. If such a request is received, EPA will announce the scheduling ofthe public meeting in

a subsequent Federal Register document. Ifapublic meeting is announced, and if you are interested in attending or presenting oral and/or written comments at the public meeting, you should follow the instructions provided in the subsequent Federal Register document announcing the public meeting.

F. WhatShouldI Consider asIPrepare My CommentsForEPA ?

We invite you to provide yourviews

on the various options we propose, new approaches we have notconsidered, the potential impacts ofthe various options (includingpossible unintended consequences), and any data or information that you would like the Agency to consider during the development ofthe final rule. You may find the following suggestions helpful forpreparing your comments: oExplain your views as clearly as possible. 

### oDescribe any assumptions thatyou used. oProvide copies of any technical 

### information and/or data you used that support your views. olfyou estimate potential burden or costs, explain how you arrived at the estimate. oProvide specific examples to illustrate your concerns. *Offer alternative ways to improve the rule or collection activity. 

### 31075

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

oMake sure to submit your comments by the deadline in this document. eAt the beginning ofyour comments, be sure to properly identify the document you are commenting on. To ensure proper receipt byEPA, your comments must identify the docket control number assigned to this action in the subject line on the first page of your response. You may also provide the name, date, and Federal Register citation.

G.Are ThereIssues On WhichEPA Is Particularly InterestedIn Receiving Comment?

EPA invites comment on any aspect of this proposed rule. EPA is particularly interested in specific comments on the approach discussed in Unit V.C. ofthis preamble, entitled "Would IBe Required To Test Under This Rule?"

II. Authority

This document proposes a testrule under TSCA section 4(a) (15 U.S.C 2603(a)) that would require an in vitro dermal absorption rate test for 47 ofthe chemical substances designated by the ITC for this testing.

Section 2(b)(1) ofTSCA (15 U.S.C. 2601(b)(1)) states that it is the policy of the United States that "adequate data should be developed with respect to the effect ofchemical substances and mixtures on health and the environment and that the development ofsuch data should be the responsibility ofthose who manufacture and those who process such chemical substances and mixtures [.]" To implement this policy, TSCA section 4(a) mandates that EPA require by rule that manufacturers and processors ofchemical substances and mixtures conduct testing if the Administrator finds that:

(1)(A)(i) the manufacture, distribution in
commerce, processing, use, or disposal ofa chemical substance or mixture, or thatany combination ofsuch activities, may present

an unreasonable risk ofinjurytohealth or the environment,

(ii)there are insufficient dataand experience upon which the effects ofsuch manufacture, distribution in commerce, processing, use, ordisposal ofsuch substance

or mixture or ofany combination ofsuch activities on health orthe environment can reasonably be determined or predicted, and

(iii)testing ofsuch substanceor mixture with respect to such effects is necessary to develop such data; or

(B)(i)achemical substance or mixture is or will beproduced in substantial quantities, and (I) itenters or may reasonably be anticipated to enter the environment in substantial quantities or (II) there is or may be significant or substantial human exposure to such substance or mixture, (ii)there are insufficient data and experience upon which the effects ofthe manufacture, distribution in commerce, processing, use, or disposalofsuch substance

or mixture or ofany combination ofsuch activities on health or theenvironment can reasonably be determined or predicted, and

(iii)testing ofsuch substance ormixture with respect to such effects is necessary to develop such data [.]

IfEPA makes these findings for a chemical substance or mixture, the Administrator must require by rule that testing be conducted on that chemical substance or mixture. The purpose of the testing would be to develop data about the substance or mixture's 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 ofthe substance or mixture, or any combination of such activities, does or does not present an unreasonable risk ofinjury to health or the environment.

Once the Administrator has made a finding under TSCA section 4(a)(1)(A)(i) (i.e., a finding that a chemical substance may present an unreasonable risk of injury to health or the environment) or

afinding under TSCA section 4(a)(1)(B)(i) (i.e., a findingthat a chemical substance is or will be produced in substantial quantities and either itmay enter the environment in substantial quantities or there may be significant or substantial human exposure to the chemical substance), EPA may require any type ofhealth or environmental effects testing necessary to address unanswered questions about the effects ofthe chemical substance. EPA need not limit the scope oftesting required to the factual basis for the TSCA section 4(a)(1)(A)(i) or (B)(i) findings, as long as EPA also finds that there are insufficient data and experience upon which the effects ofthe manufacture, distribution in commerce, processing, use, or disposal ofsuch substance or mixture or ofany combination ofsuch activities on health

or the environment can reasonably be determined or predicted, and that testing is necessary to develop such data. This approach is explained in

more detail in EPA's statement ofpolicy for making findings under TSCA section 4(a)(1)(B) (frequently described as the "B" policy) in the Federal Register of May 14, 1993 (58 FR28736, 28738- 28739).

In this proposed rule, EPA intends to

use its broad TSCA section 4(a) authority to obtain dermal absorption rate data necessary to support OSHA's development of "skin designations" (see UnitIII.C. ofthis preamble) forthe 47 chemical substances included in the proposed rule. EPA has made preliminary findings for these chemicals under TSCA section 4(a)(1)(B) that: They are produced in substantial quantities; there is ormay be substantial human exposure to them; existingdata

are insufficient to determine or predict theirhealth effects; and testing is necessary to develop such data.

Under TSCA section 10(b), EPA is responsible, through an interagency committee, for collecting data and disseminating the data to other Federal agencies, such as OSHA, as the Agency is proposing in this document. EPA has used its TSCA section 4(a) authority in the pastto support regulatory programs ofother EPA offices as well as other Federal agencies needing health and/or environmental effects test data. See, e.g., the final testrule for the Office ofWater Chemicals (58 FR 59667, 59673 November 10, 1993).

III.Background

A. Why Is EPA ProposingTo Take This Action?

Under TSCA section 4(e)(1), the ITC is responsible for recommending chemical substances and mixtures to the EPA Administrator for priority testing consideration. The chemical substances and mixtures so designated by the ITC comprise a list called thePriority TestingList. OSHA nominated 658 chemical substances and mixtures for ITCreview in September 1991. The results ofthe ITC'sreview were published in the FederalRegister issues ofMay 5, 1993 (58 FR 26898, 26900) and July 16, 1993 (58 FR 38490, 38492- 38493). OSHA requested that the ITC

assess the availability ofdata relevant to dermal absorption for these chemical substances and mixtures and determine the need forfurther testing (58 FR 26898, 26900, May 5, 1993). OSHA indicated to the ITC that it needed quantitative measures ofdermal absorption to evaluate the potential hazard ofthese chemicals to workers (58 FR 38490, 38492, July 16, 1993). These quantitative measures are expressed as the dermal absorption rate for a particular chemical (59 FR 35720, 35725, July 13, 1994).

In its 31st, 32nd, and 35th ITC Reports to the EPA Administrator (58 FR 26898, May 5, 1993; 58 FR 38490, July 16, 1993; and 59 FR 67596, December 29, 1994, respectively), the ITC designated for in vitrodermal absorption rate testing a total of83 of the chemical substances nominated by OSHA. In reducing OSHA's list of658 chemicals to 83 chemicals, the ITC 

## 31076

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

grouped the nominated chemicals into categories as a means ofprioritizing the chemicals for consideration. Chemicals that were assigned to categories such as polymers, pesticides, and chloroflurocarbons were eliminated from consideration by the ITC. They

were eliminated because, among other
reasons, they are regulated under other Federal authorities or because EPA, under TSCA, does not have the authority to require the testing ofcertain chemicals (58FR 26898, 26900-26902 and 58 FR 38490, 38493). The remaining chemicals were then grouped by production volume, and literature searches were performed.

The ITCperformed searches for data relating to the chemicals on the following data bases: RTECS (Registry of Toxic Effects ofChemical Substances), TOXLINE (TOXicology information onLINE), MEDLINE (MEDlars onLINE), TOXLIT (TOXicology LITerature from special sources), CECATS (OPPT/Risk Assessment Division/Chemical Screening Branch's Existing Chemical Assessment Tracking System), TSCATS (Toxic Substances Control Act Test Submissions), and INDEX MEDICUS. The search strategy was designed to identify any toxicological tests that used the dermal route ofexposure. The information from the searches was collected and the chemicals were subcategorized based on the number of postings (58FR 38490, 38493).

The 83 chemicals designated by the ITC were identified as follows: The ITC first ascertained those chemicals having

no dermal information postings in any ofthe data bases searched, and, in its 31st ITC Report, the ITC designated this group of24 chemicals forpriority testing consideration (58 FR26898, 26900). A second group ofchemicals with limited dermal toxicity or dermal absorption data (as determined by the searches described in this unit) from which dermal absorption rate could not be estimated was then identified by the ITC, which designated this group of34 chemicals in its 32nd ITC Report (Ref. 1) (58 FR 38490, 38492, 38494). Another 25 chemicals were designated in the 35th ITC Report, after the ITCreviewed the dermal data of63 high production volume chemicals with slightly larger information bases (59 FR 67596, 67598). These data were insufficient to estimate dermal absorption rate because dermal absorption rate could notbe calculated

on the basis ofthe dermal absorption data which were available to the ITC.

The ITCthen reviewed data from TSCA section 8(a) and 8(d) rules which

were promulgated by EPA for these 83 chemical substances included in the 31st, 32nd, and 35th ITC Reports (40 CFR 712.30(e) (58 FR 68311, December 27, 1993; 59 FR 5956, February 9, 1994; 60 FR 34879, July 5, 1995)). These rules required the reporting to EPA ofcertain production, use and exposure-related information, and unpublished health and safety data concerning these 83 chemicals.

In reviewing the available data relating to these 83 chemicals, the ITC determined that the dermal absorption
rate data for methyl methacrylate (Ref. 2), diethyl phthalate (Ref.3), and cyclohexanone (Ref.4) would meet OSHA's data needs for the chemicals (59 FR 35720, 35722, July 13, 1994; 60 FR42982, 42985, August 17, 1995). Accordingly, the ITC withdrew its designation for these 3 chemicals: Methyl methacrylate and diethyl phthalate in the 34th ITC Report (59 FR 35720, 35725, July 13, 1994), and cyclohexanone in the 36th ITC Report (60 FR42982, 42987, August 17, 1995).

Eighty ofthe chemical substances nominated by OSHA are thus currently designated by the ITC for in vitro dermal absorption rate testing under TSCA. In the Federal Register notices containing the 3 1st, 32nd, and 35th ITCReports, EPA additionally solicited proposals for TSCA section 4 enforceable consent agreements (ECAs)for dermal absorption rate testing ofthe 80 chemical substances. EPA received no proposals for ECAs for dermal absorption rate testing in response to these solicitations.

On April 3, 1996 (61 FR 14773), EPA again solicited interested parties to submit proposals for ECAs. On June 26, 1996, EPA received aproposal for the development ofan ECA for tert-butyl alcohol from the ARCO Chemical Company (ARCO). On March 26, 1998, EPA received a study entitled "[14C]-tButyl Alcohol: Topical Application: Dermal Absorption Study in the Male Rat," from ARCO (Ref.5). This study

was reviewed and found acceptable as

ameans of determining the dermal absorption rate for tert-butylalcohol (Ref.6). Accordingly, this action does
not propose testing oftert-butylalcohol.

In this action, EPA is proposing in vitro dermal absorption rate testing of47 chemical substances ofinterest to OSHA. These chemical substances are listed in Table 2 ofUnit I.A. ofthis preamble, entitled "List ofChemical Substances Proposed for Testing," and in Table 2 of§799.5115(i) ofthe proposed regulatory text, entitled "Required Testing: Chemical Substances Designated for In Vitro Dermal Absorption Rate Testing." EPA has selected these 47 chemicals for testing because the Agency believes that the production volumes ofthese chemicals are higher than the production volumes ofthe 32 chemicals remaining outofthe 80 chemicals currently designated by the ITC. Testing ofthe latter chemicals for dermal absorption rate willbe addressed at a laterdate.

B. How Was the Test Standard DevelopedForEPA 's Use in This ProposedRule?

In the solicitations discussed in Unit III.A. ofthis preamble, EPA referenced

an in vitrodermal absorption rate test protocol forreview bypotential submitters in developing their proposed protocols (Ref.7). The draft protocol

was developed by a group ofscientists from EPA in conjunction with ITC member and liaison agencies (Consumer Product Safety Commission (CPSC), Department ofDefense (DoD), Food and DrugAdministration (FDA), National Institute forOccupational Safety and Health (NIOSH), and OSHA) and consisted ofthe methods ofBronaugh and Collier (Ref.7). EPA received public comments on the proposed protocol and entered them, along with the protocol itself,into the dockets for the 31st, 32nd, and 35th ITC Reports, as appropriate (docket control numbers OPPTS-41038, OPPTS-41039, and OPPTS-41042, respectively). In addition, the Chemical Manufacturers Association (CMA) submitted a proposed protocol outlining an alternative method (Ref. 8). Scientists from EPA and other Federal agencies represented on the ITC (including OSHA)reviewed the public comments and the CMA proposal. Based on their review ofthe Bronaugh and Collier protocol, public comments, and the CMAproposal, EPA and ITC scientists developed the in vitro dermal absorption rate test method which is the
test standard used in this proposed rule.

C.How Will The DataDeveloped Under This TestRule Be Used?

This proposed rule would require the development ofquantitative measures of dermal absorption rate to assist in evaluating the potential contribution of dermal absorption ofthe chemical substances proposed for testingto total exposures to workers from chemicals in the workplace. The dermal absorption
rate data obtained under this testing program would be used to support OSHA's development of "skin designations" for the chemical substances included in this proposed rule.

OSHA assigns a skin designation to a chemical if it determines that cutaneous exposure (through the skin, eyes, and

mucous membranes) to the chemical mayresult in systemic toxicity. Skin 

### 31077

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

designations are used by OSHA to provide specific guidance to employers concerning whether changes should be made to processes involving chemical substances in order to reduce the hazard ofsystemic toxicity from dermal absorption ofthese chemicals. Changes
to aprocess might include changes in engineering controls or changes in the

use or type ofpersonal protective equipment. Skin designations alert industrial hygienists, employers, and workers to potential adverse health effects resulting from dermal exposure to chemicals in the workplace.

The information that would be developed under this testrule would
not only support OSHA's activities, but also would support chemical risk
assessment activities at EPA as well as at other Federal agencies. Inparticular, these data would provide input for chemical risk assessments involving environmental exposure scenarios which include intentional or incidental skin contact.
IV. EPA Findings

A. WhatIs The BasisForEPA'sProposal To Test These ChemicalSubstances?

As indicated in Unit II. ofthis preamble, in order to develop a rule under TSCA section 4(a) requiring the testing ofchemical substances or mixtures, EPA must make certain findings for those chemicals regarding either: 1. Hazard (TSCA section 4(a)(1)(A)(i));

or2. Production and either chemical release or human exposure (TSCA section 4(a)(1)(B)(i)). EPA is proposing to require testing of the chemical substances included in this test rule based on its findings under TSCA section 4(a)(1)(B)(i) relating to "substantial" production and "substantial human exposure," as well

as findings under TSCA sections 4(a)(1)(B)(ii) and (iii). In EPA's "B" policy, discussed in Unit II. ofthispreamble, "substantial" production ofachemical substance or mixture is generally interpreted to be aggregate production (includingimport) volume equaling or exceeding one million pounds (lbs)per year ofthat chemical substance or mixture (58FR 28736, 28746, May 14, 1993). The "B" policy sets out the numeric threshold for "substantial human exposure" of workers to achemical substance or mixture of 1,000workers annually being exposed to that chemical substance or mixture. Id. SeeEPA's "B" policy (58 FR28736, May 14, 1993) for further discussion on how EPA makes decisions under TSCA section 4(a)(1)(B)(i).

EPA has found preliminarily that, under TSCA section 4(a)(1)(B)(i), each of the 47 chemical substances proposed for dermal absorption rate testing is produced in "substantial quantities" and there is or may be "substantial human exposure" to each chemical substance. In addition, under TSCA section 4(a)(1)(B)(ii), EPAbelieves that there are insufficient data and experience to reasonably determine or predict the effects ofthe manufacturing, processing, or use ofthese chemical substances, or ofany combination of such activities, on human health. In particular, as discussed in Unit IV.D. of this preamble, EPA has determined that there are insufficient datarelating to dermal absorption rate resulting from human exposure to these chemicals. EPA also finds that testing the substances identified in this document is necessary to develop such data (TSCA section 4(a)(1)(B)(iii)). EPA has not identified any "additional factors" as discussed in the "B" policy (58 FR 28736, 28746, May 14, 1993) to cause the Agency to use decisionmaking criteria other than those described in the policy.

The specific chemical substances included in this proposed testrule are listed in Table 2 ofUnit I.A. ofthis preamble, and in §799.5115(i) ofthe proposed regulatory text.

B. Are These ChemicalSubstances ProducedinSubstantialQuantities?

Each ofthe chemical substances included in this proposal is produced in

an amount equal to or greater than one million lbs per year (Ref.9), based on information gathered pursuant to the 1994 TSCA section 8(a) Inventory Update Rule (40CFR part 710) and contained in the TSCA Chemical Update System. Their production volumes range from over one million to well over one billion lbs annually. Assuming the continued accuracy of these figures, EPA believes that these annual production volumes are "substantial" as that term is used with reference to production in TSCA section 4(a)(1)(B)(i). See 58 FR28736, 28746, May 14, 1993.

C.Are aSubstantialNumberOfWorkers Exposed To These Chemicals?

EPA finds that the manufacturing, processing, and use ofthe chemical substances included in this document result or mayresult in exposure ofa substantial number ofworkers. Table 3, entitled "Exposure Information for Chemical Substances Included in This Proposed Test Rule," in Unit IV.C.of thispreamble contains an estimate of the actual and potential worker exposure to these chemical substances (Ref. 10). These chemical substances are used in awide variety ofapplications as industrial solvents, which result in potential exposures ofworkers as described in the exposure support document forthis proposed rule (Ref. 10). EPA believes that the exposure to each chemical substance of 1,000 workers or more (Table 3 ofthis unit) is or may be "substantial" as that term is used with reference to "human exposure" in TSCA section 4(a)(1)(B)(i). See 58 FR 28376, 28746, May 14, 1993.

TABLE 3.-EXPOSURE INFORMATION FOR CHEMICAL SUBSTANCES INCLUDED IN THIS PROPOSED TEST RULE

CAS No. Chemical name Number of workersexposed1

Ethyl ether Ethyl bromide Acetonitrile Carbon disulfide Vinylidene chloride Dicyclopentadiene Dimethyl sulfate Isophorone Isobutyl alcohol Propylene dichloride sec-Butyl alcohol Methyl acetate 2-Nitropropane Naphthalene Biphenyl 272,746 12,285 31,341 45,761 2,679 6,247 10,482 47,097 256,975 2,944 126,200 20,455 9,817 112,695 32,000 

## 31078

60-29-7 74-96-4 75-05-8 75-15-0 75-35-4 77-73-6 77-78-1 78-59-1 78-83-1 78-87-5 78-92-2 79-20-9 79-46-9 91-20-3 92-52-4

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules 

## 31079

TABLE 3.-EXPOSURE INFORMATION FOR CHEMICAL SUBSTANCES INCLUDED IN THIS PROPOSED TEST 

### RULE-Continued

CAS No. Chemical name Number of workersexposed1

95-49-8 o-Chlorotoluene 11,617 95-50-1 o-Dichlorobenzene 92,248 97-77-8 Disulfiram 53,525 98-29-3 tert-Butylcatechol 27,528 99-99-0 p-Nitrotoluene 4,354 100-00-5 p-Nitrochlorobenzene 2,949 100-01-6 p-Nitroaniline 1,448 100-44-7 Benzyl chloride 41,075 106-42-3 p-Xylene 20,367 106-46-7 p-Dichlorobenzene 33,980 107-06-2 Ethylene dichloride 83,245 107-31-3 Methyl formate 7,739 108-03-2 1 -Nitropropane 21,535 108-90-7 Chlorobenzene 18,049 108-93-0 Cyclohexanol 112,366 109-66-0 Pentane 38,464 109-99-9 Tetrahydrofuran 356,041 110-12-3 Methyl isoamyl ketone 18,835 111-84-2 Nonane 7,277 120-80-9 Catechol 13,517 121-69-7 Dimethylaniline 30,479 122-39-4 Diphenylamine 155,673 123-42-2 Diacetone alcohol 264,660 126-99-8 beta-Chloroprene 17,752 127-19-5 Dimethyl acetamide 28,944 142-82-5 n-Heptane 449,487 150-76-5 p-Methoxyphenol 250,088 528-29-0 o-Dinitrobenzene 1,358 628-63-7 n-Amyl acetate 265,435 768-52-5 N-Isopropylaniline >1,0002 25013-15-4 Vinyl toluene 25,353 34590-94-8 Dipropylene glycol methyl ether 210,735

1National Occupational Exposure Survey (NOES) conducted by the NIOSH (1981-1983), unless otherwise indicated. These data are the most recent availableto the Agency (Ref. 10).

2Not listed in NOES data base. The exposure analysis forthis chemical is attached to Reference 10.

D.Do SufficientDataExistForThese ChemicalSubstances?

As discussed in thispreamble, dermal absorption rate is an important factor in ascertaining the effects ofthe 47 chemicals in this proposed rule on human health. EPA has determined that there are no dermal absorption rate data for the chemicals in thisproposed rule and, therefore, existing data are insufficient to reasonably determine or predict the human health effects relating
to dermal absorption rate that result from manufacturing, processing, oruse ofthe subject chemical substances. This finding is based on the review and analysis ofrelevant databy the ITC (which included EPA participation), as described in Unit III.A. ofthispreamble.

E. Is TestingNecessaryForThese ChemicalSubstances?

EPA believes that the proposed testing ofthe 47 subject chemical substances is necessary to develop dermal absorption
rate data. This testing is needed to determine ifthe manufacturing, processing, or use ofthese chemical substances presents an unreasonable risk ofinjury to human health. V. Proposed Rule

A. How Would the StudiesProposed UnderThis TestRule Be Conducted?

EPA is proposing specific testing and reporting requirements for the chemical substances specified in Table 2 in §799.5115(i) ofthe proposed regulatory
text according to the in vitro dermal absorption rate test standard set forth at §799.5115(h) ofthe proposed regulatory
text.

The test standard that would be required under this rule was developed

as described in Unit III.B. ofthis preamble. This standard describes the procedures for measuring apermeability
constant (Kp) and a short-term absorption rate for chemicals in liquid form. Measurement ofshort-term absorption rates is only required when

a Kp cannot be obtained using this test standard. For most chemicals, a Kp is useful in estimating skin permeation. However, for "harsh" chemicals, i.e., those that may damage the skin more severely with prolonged contact, itis

more appropriate to obtain a short-term absorption rate measurement.

This test standard utilizes established in vitro diffusion cell techniques that allow absorption rate studies to be conducted using human skin (see the proposed regulatory text at §799.5115(h)). The in vitro approach

was chosen forpractical considerations because it is efficient in terms oflabor and materials and can be performed easily by avariety oflaboratories. In addition, in vitro diffusion cell studies

are necessary for measuring a Kp (Ref. 7).The in vitrodermal absorption rate test standard allows use ofcadaver skin and static diffusion cells to maintain the viability ofthe skin, thus more closely simulating in vivo conditions. This test method also requires the use of radiolabelled chemical substances unless the test sponsor can demonstrate that alternative, non-radiolabelled methods provide sensitivity sufficient to detect the parent chemical (and its major metabolites in those cases in which skin viability is maintained). The first six parameters that are discussed (choice ofmembrane, preparation of membrane, diffusion cell design, temperature, testinghydrophobic chemicals, and vehicle) are similar for determination ofeither ofthe two percutaneous absorption rate values. In

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

contrast, the remaining two parameters (i.e., dose and study duration) are different for the two percutaneous absorption rate values.

Testing under this proposed rule must be conducted in accordance with TSCA Good Laboratory Practice (GLP) Standards (40CFRpart 792).

B. WhatSubstancesWouldBe Tested UnderThisRule?

EPA is proposing that the chemical substances listed in Table 2 in §799.5115(i) ofthe proposed regulatory
text be tested at a purity ofat least 99%.

C. WouldIBeRequiredTo Test Under ThisRule?

Under TSCA section 4(a)(1)(B), EPA has made preliminary findings that there are insufficient data and experience to reasonably determine or predict health effects resulting from the manufacturing, processing, oruse ofthe chemical substances listed in this proposed rule. As a result,under TSCA section 4(b)(3)(B), manufacturers and processors ofthese substances would be subject to the rule with regard to those listed chemicals which they manufacture orprocess. 1. WouldIbe subjectto this rule?You would be subject to this rule and may be required to test if you manufacture (which is defined by statute to include import) or process, or intend to manufacture orprocess, one or more 

### chemical substances listed in this proposed rule during the timeperiod discussed in Unit V.C.2. ofthis preamble, entitled "When would my manufacturing orprocessing (ormy intent to do so) cause me tobe subject to this rule?" However, ifyou do not know or cannot reasonably ascertain that you manufacture orprocess a listed test substance (basedon all information in your possession or control, aswell as allinformation that areasonable person similarly situated might be expected to possess, control, orknow, or could obtain without unreasonable burden), you would not be subject totherule.

2. When wouldmy manufacturingor processing(ormy intenttodo so) cause
me to be subjectto thisrule?You would be subject to this rule ifyou manufacture orprocess, orintend to manufacture orprocess, a substance listed in therule at any time from the effective date ofthe finaltest rule to the end ofthetest data reimbursement period.

The term reimbursement periodis defined at40 CFR791.3(h) and may vary in length foreach substance tobe tested under afinal TSCA section 4(a) test rule, dependingon what testing is required and when testing is completed. SeeUnit V.C.4. ofthis preamble, entitled "How do thereimbursement procedures work?" 3. WouldIbe requiredtotest if Iwere subjectto the rule?Itdepends on the nature ofyour activities. All persons who would be subject to this TSCA section 4(a) testrule, which incorporates EPA's generic procedures applicable to TSCA section 4(a) test rules (contained within 40 CFR part 790), would fall into one oftwo groups, designated here as Tier 1 and Tier 2. Persons in Tier 1 (those who would have to initially comply with the rule)
must either: Submit to EPA letters of intent to conduct testing, conduct this testing, and submit the test data to EPA

or apply to and obtain from EPA exemptions from testing.Persons in Tier 2 (those who would not have to initially comply with the rule) need not take any action unless they are notified by EPA that they are required to do so, as described in Unit V.C.3.d. ofthis preamble, entitled "What would my obligations be ifI were in Tier 2?" Note that persons in Tier 1who obtain exemptions and persons in Tier 2 would nonetheless be subject to providing reimbursement to persons who do actually conduct the testing, as described in Unit V.C.4. ofthis preamble, entitled "How do the reimbursement procedures work?"

a. Who would be in TierI and Tier 2?All persons subject to this rule would be considered to be in Tier 1 unless they fallwithin Tier 2. The following table describes who is in Tier 1 and Tier 2.

TABLE 

### 4.- PERSONS SUBJECT TO THE RULE: PERSONS IN TIER 1 AND TIER 

### 2

Tier 1 (Persons initially requiredto comply)

*Persons that manufacture (as defined at TSCA section 3(7)),

or intend to manufacture, a test rule substance who are not listed under Tier2 Tier 2 (Persons not initiallyrequired to comply)

*Persons that manufacture (as defined atTSCA section 3(7)) or intend to manufacture a test rulesubstance solely as one or more of thefollowing: -As a byproduct (as defined at 40 CFR 791.3(c)); -As an impurity (as defined at40 CFR 790.3); -As a naturally occurring substance (as defined at 40 CFR 710.4(b)); -As a non-isolated intermediate (as defined at40 CFR 704.3); -As a component of a Class 2 substance (as described at 40 CFR

720.45(a)(1 )(i)); -In amounts of less than 500 kilograms (kg) (1,100 Ibs) annually (as described at 40 CFR 790.42(a)(4)); or -In small quantities solely for research and development (as described at 40

CFR 790.42(a)(5)). *Persons that process (as defined at TSCA section 3(10)) or intend to process

a test rule substance (see 40 CFR 790.42(a)(2))

b. When would it be appropriate for

aperson in Tier] toapply foran exemption ratherthan to submitaletter ofintentto conducttesting?You may apply for an exemption if you believe that the required testing willbe performed by another person (or a consortium ofpersons formed under TSCA section 4(b)(3)(A)) in Tier 1. You

can find procedures relating to exemptions in 40 CFR 790.80 through 790.99, and in the proposed regulatory text at §799.5115(c)(2), (c)(5), and (c)(7). In this rule, EPA would not require equivalence data (i.e., data demonstrating that your substance is equivalent to the substance actually being tested) as a condition for approval ofyour exemption. EPA is interested in evaluating the effects attributable to each listed substance itself and has specified almost pure substances for testing. c. WhatwouldhappenifIwere in Tier ] andIsubmittedan exemption application ?EPA believes that requiring the collection ofduplicative data is unnecessarily burdensome. As aresult, ifEPA has received aletter ofintent to test from another source or has received (or expects to receive) the test data that would be required under this rule, the Agency would conditionally approve your exemption application under 40 CFR 790.87. The Agency would 

## 31080

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

terminate conditional exemptions, if a problem occurs with the initiation, conduct, or completion ofthe required testing or the submission ofthe required data to EPA. EPA may then require you to submit a notice ofintent to test or an exemption application. See 40 CFR 790.93 and the proposed regulatory text at §799.5115(c)(6). Persons in Tier 1 who obtain exemptions and persons in Tier 2 would nonetheless be subject to providing reimbursement to persons who do actually conduct the testing, as described in Unit V.C.4. ofthis preamble, entitled "How do the reimbursement procedures work?."

d. Whatwouldmy obligationsbe ifI

were in Tier2?Ifyou are in Tier 2, you would be subject to the rule and you would be responsible for providing reimbursement to persons in Tier 1, as described in Unit V.C.4. ofthis preamble. You are considered to have

an automatic conditional exemption. You would not need to take any action unless you are notified byEPA that you

are required to do so.

Ifaproblem occurs with the initiation, conduct, or completion ofthe required testing, or the submission of the required data to EPA, the Agency may require you to submit a notice of intent to test or an exemption application. See 40 CFR 790.93 and the proposed regulatory text at §799.5115(c)(6).

In addition, you would need to submit anotice ofintent to test or an exemption application if:

i. No manufacturer in Tier 1has notified EPA ofits intent to conduct testing and

ii. EPA has published a Federal Register document directing all persons in Tier 2 to submit to EPA letters of intent to conduct testing or exemption applications. See40 CFR 790.48(b) and the proposed regulatory text at §799.5115(c)(4) and (c)(5). The Agency would conditionally approve an exemption application under 40 CFR 790.87, ifEPA has received a letter ofintent to test orhas received (or expects to receive) the test data required under thisrule.

e. How didEPA decidewho wouldbe in TierI and Tier2 andwho would be excluded from the rule?Under 40 CFR 790.2, EPA may establish procedures applying to specific test rules that differ from the generic procedures governing TSCA section 4(a) test rules in 40 CFR part 790. For purposes ofthis proposed rule, EPA is proposing to set forth certain requirements that differ from those under40 CFR part 790.

Under 40 CFRpart 790, in TSCA section 4(a) test rules EPA traditionally has treated the following persons as being in Tier 2. (These rules are found at40 CFRpart 799, subparts B and D).

oProcessors (40CFR 790.42(a)(2)); oManufacturers ofless than 500 kg (1,100 lbs) per year ("small-volume manufacturers") (40CFR 790.42(a)(4)); and

*Manufacturers ofsmall quantities for research and development ("R&D manufacturers") (40CFR 790.42(a)(5)).

EPA has historically placed processors in Tier 2because the Agency "expected that, in most cases, testing will be performed bythe manufacturers and that part ofthe cost oftesting will be passed on to processors through the pricing mechanism, thereby enabling them to share in the costs oftesting" (50 FR20652, 20654, May 17, 1985). In addition, "[t]here are so many processors that itwould be difficult to include them all in the technical decisions about the tests and in the financial decisions about how to allocate the costs" (48 FR 31786, 31789, July 11, 1983).

EPA has historically placed smallvolume manufacturers and R&D manufacturers in Tier 2because this type ofmanufacturing "normally represents a smallpercentage ofthe overall production volume [and] test sponsors are not expected to expend the administrative resources to recover the smallproportional amounts ofthe testing costs from these manufacturers" (55 FR 18881, May 7, 1990).

In this proposed test rule, EPA has reconfigured the tiers in 40 CFR 790.42. EPA has added the following persons to Tier 2: Byproduct manufacturers; impurity manufacturers; manufacturers ofnaturally occurring substances; manufacturers ofnon-isolated intermediates; and manufacturers of components ofClass 2 substances. The Agency took administrative burden and complexity into account in determining who was to be in Tier 1 in thisproposed rule. EPAbelieves that those persons in Tier 1who would conduct testing under this rule, when finalized, would generally be large chemical manufacturers who, in the experience of the Agency, have traditionally conducted testing or participated in testing consortia under previous TSCA section 4(a) test rules.

The Agency also believes that byproduct manufacturers, impurity manufacturers, manufacturers of naturally occurring substances, manufacturers ofnon-isolated intermediates, and manufacturers of components ofClass 2 substances have
not themselves historically participated in testing or contributed to reimbursement ofthose persons who have conducted testing. EPA understands that these may include persons for whom the marginal transaction costs involved in negotiating and administering testing arrangements

are deemed likelyto raise the expense and burden oftesting to alevel that is disproportional to the additional benefits ofincluding these persons in Tier 1. Therefore, EPA does not believe that the likelihood ofthe persons proposed to be added to Tier 2 actually doing the testing is sufficiently high to justify burdening these persons with Tier 1requirements (e.g., submitting requests for exemptions). Nevertheless, thesepersons, along with all other persons in Tier 2, would be subject to providing reimbursement to persons who do actually conduct the testing, as described in Unit V.C.4. ofthis preamble, entitled "How do the reimbursement procedures work?" Section 4(b)(3)(B) ofTSCA requires all manufacturers and processors ofa chemical substance to test that chemical substance ifEPA has made findings for that chemical substance, and therefore issued a TSCA section 4(a) test rule requiring testing. However, practicality
mustbe afactor in determining who is subject to aparticular testrule. Thus, persons who do notknow or cannot reasonably ascertain that they are manufacturing or processing the substances subject to this proposed rule, e.g., manufacturers or processors ofthe substances as trace contaminants who

are not aware ofthese activities, would
notbe subject to the rule. SeeUnit V.C.1 ofthis preamble and §799.5115(b)(2) of the proposed regulatory text.

EPA is soliciting comment on who should be included in Tier 1 and Tier 2. The Agency may define these categories differently in response to comments received. EPA is also soliciting comment on who should not be subject to the rule. The latter persons

are described at Unit V.C.1 ofthis preamble and §799.5115(b)(2) ofthe proposed regulatory text.

f. ShouldEPAprioritizewhich
personsin Tier2 wouldbe requiredto perform testing?EPAis considering subdividing Tier 2 to enable the Agency
to prioritize which persons in Tier 2 would be required to perform testing,if needed. This would involve subdividing Tier 2 into:

i. Tier2A. Those who manufacture, or intend to manufacture, a testrule substance solely as one or more ofthe following: A byproduct; an impurity; a naturally occurring substance; a nonisolated intermediate; a component ofa Class 2 substance; in amounts less than 1,100 lbs. annually; or in small quantities solely for research and development. 

## 31081

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

ii. Tier2B. Those who process, or intend to process, a test rule substance. Ifthe Agency needed testing from persons in Tier 2, EPA would seek testing from persons in Tier 2A before proceeding to Tier 2B. EPA believes that, if the Agency were to subdivide Tier 2, persons in Tier 2A should be required to submit letters ofintent to test or exemption applications before processors are called upon because testing costs are traditionally passed by manufacturers alongto processors.

EPA is soliciting comment on whether this subtiering scheme should be applied in the final rule.

4. How do the reimbursement procedureswork?In the past, persons subject to test rules have independently worked out among themselves their respective financial contributions to those persons who have actually conducted the testing.However, if persons are unable to agree privately on reimbursement, they may take advantage ofEPA'sreimbursement procedures at40 CFR part 791, promulgated under the authority of TSCA section 4(c). These procedures include: The opportunity for ahearing with the American Arbitration Association; publication byEPA ofa Federal Register document concerning the request for ahearing; and the appointment ofahearing officer to propose an order for fair and equitable reimbursement. The hearing officer may base his orher proposed order on the production volume formula set out at 40 CFR 791.48, but is not obligated to do

so. Under thisproposed rule, amounts manufactured as impurities would be included in production volume (40CFR 791.48(b)), subject to the discretion of the hearing officer (40 CFR 791.40(a)). The hearing officer's proposed order may become the Agency's final order, which is reviewable in Federal court (40 CFR 791.60).

D. WhatAre theReporting RequirementsProposedUnderThis Test Rule?

You would be required to submit interim progress reports for each test every 6 months, beginning 6 months after the effective date ofthe final rule. You would berequired to submit a final report for a specific test by the deadline indicated as the number ofmonths after the effective date that would be shown in Table 2 in §799.5115(i) ofthe proposed regulatory text.

E. Would ThereBe Sufficient Test Facilities andPersonnelTo Undertake the Testingin This TestRule?

EPA has conducted a study to assess the availability oftest facilities and personnel to handle the additional demand for testing services created by TSCA section 4(a) test rules and has found that test facilities and personnel would adequately accommodate the testing specified in this proposed rule (Ref. 11).

F.MightEPA Seek FurtherTestingof the Chemicalsin This ProposedTest Rule?

IfEPA determines that it needs additional data regarding any ofthe chemical substances included in this proposed rule, the Agency might seek further health and/or environmental effects testing for these chemicals. Should the Agency decide to seek such additional testing, EPA would initiate a separate action for thispurpose. 

### VI. Export Notification

Any person who exports, or intends to export, one ofthe chemical substances contained in thisproposed rule in any form will be subject to the export notification requirements in TSCA section 12(b)(1) and 40 CFRpart 707, subpart D,but only afterthe final rule is issued and only ifthe chemical is contained in the final rule. However, notification ofexport would generally
not be required for articles, as provided by 40 CFR 707.60(b).

VII. Materials in the Official Record

The official record for this proposed rule has been established under docket control number OPPTS-42196. The following is a listingofthe documents that have already been placed in the official record for this proposed rule:

A. SupportingDocumentation
1. Federal Register documents:

a. Notice containing the 31st ITC Report to the EPA Administrator (58 FR 26898, May 5, 1993 (FRL-4583-4)).

b. Notice containing the TSCA section 4(a)(1)(B) Final Statement ofPolicy (58 FR28736, May 14, 1993 (FRL-4059-9)).

c. Notice containing the 32nd ITC Report to the EPA Administrator (58 FR 38490, July 16, 1993 (FRL-4630-2)).

d. TSCA Sections 8(a) and 8(d) Final Rules for Chemicals Contained in the 31st ITCReport to the EPA Administrator (58 FR 68311, December 27, 1993 (FRL-4644-1)).

e. TSCA Sections 8(a) and 8(d) Final Rules for Chemicals Contained in the 32nd ITCReport to the EPA Administrator (59 FR 5956, February 9, 1994 (FRL-4745-5)).

f.Notice containing the 34th ITC Report to the EPA Administrator (59 FR 35720, July 13, 1994 (FRL-4870-4)).

g. Notice containing the 35th ITC Report to the EPA Administrator (59 FR 67596, December 29, 1994 (FRL-4923- 2)).

h. TSCA Sections 8(a) and 8(d) Final Rules for Chemicals Contained in the 35th ITC Report to the EPA Administrator (60 FR 34879, July 5, 1995 (FRL-4954-9)).

i. Notice containing the 36th ITC Report to the EPA Administrator (60 FR 42982, August 17, 1995 (FRL-4965-6)).

j. Small Business Size Standards; Final Rule, issued by the Small Business Administration (SBA) (61 FR 3280, January 31, 1996).

k. Notice containing EPA's Solicitation ofInterested Parties for Proposals for Enforceable Consent Agreements for Testing of80 Chemicals ofInterest to OSHA (61 FR 14773, April 3, 1996 (FRL-5359-3)).

2. Correspondence:

a. ARCO Chemical Company. Letter to Charles M. Auer, USEPA. Proposal for Development ofECA for Tert-Butyl Alcohol (June 26, 1996).

b. ARCO Chemical Company. Letter to Keith Cronin, USEPA. Letter transmitting a Dermal Absorption Rate Study in the Male Rat for Tert-Butyl Alcohol (March 23, 1998).

3. Other support documentation: EPA. "EPA Interim Guidance for Implementing the Small Business Regulatory Enforcement Fairness Act and Related Provisions ofthe Regulatory Flexibility Act." EPA SBREFA Task Force (February 5, 1997).

B. References
1. ITC.Chemicals Under Consideration for the 32nd ITCReport; Summary ofSkin Absorption Data on OSHA Tier 2 Chemicals (September 22, 1993).

2. Zeneca. Methyl Methacrylate: In Vitro Absorption through Human Epidermis. Zeneca Central Toxicology Report No. CTL/P/4025 provided by the Methacrylate Producers Association, Washington, D.C. (1993). 3. Scott, R.C., Dugard, P.H., Ramsey, J.D., and Rhodes, C.In Vitro Absorption ofSome o-Phthalate Diesters through Human and Rat Skin. Environmental HealthPerspectives.74:223-227 (1987).

4. Mraz, J., Galova, E., Nohova, H., and Vitkova, D. Uptake, Metabolism and Elimination ofCyclohexanone in Humans. International Archivesof Occupational EnvironmentalHealth. 66:203-208 (1994).

5. ARCO Chemical Company. [1 4C]-tButyl Alcohol: Topical Application: Dermal Absorption Study in the Male Rat. HuntingtonLife Sciences(January 7, 1998).

6. OSHA. Review of [14C]-t-Butyl Alcohol: Topical Application: Dermal Absorption Study in the Male Rat. (June 24, 1998). 

## 31082

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

7. Bronaugh, R.L., and Collier, S.W. Protocol for In Vitro Percutaneous Absorption Studies. In Vitro Percutaneous Absorption:Principles, Fundamentals,andApplications.R.L. Bronaugh and H.I. Maibach, Eds. CRC Press, Boca Raton, FL. pp. 237-241 (1991).

8. Chemical Manufacturers Association (CMA). Letter to Charles M. Auer, USEPA. (October21, 1994).

9. EPA. Economic Impact Analysis and Small Entity Impact Analysis of Proposed TSCA Section 4(a) Test Rule for 47 Chemicals Targeted forIn Vitro Dermal Absorption Rate Testing. OPPT/ EETD/EPAB, Washington, DC (May 5, 1999).

10. EPA. CEB Support to the OSHA Chemicals Test Rule-Number of Workers Exposed and TRIRelease Data. OPPT/EETD/CEB, Washington, DC (March 1998).

11. EPA. EPA Census ofTSCA Testing Laboratories. Washington, DC (October 10, 1996).

12. EPA. Laboratory Cost Estimate for In VitroDermal Absorption Rate Testing. OPPT/EETD/EPAB, Washington, DC (April 14, 1999). 13. EPA. "Treatment of 12(b) Export Notification Unit Costs for Section 4 Test Rule Analyses." OPPT/EETD/ EPAB, Washington, DC (April 1, 1999). 14. EPA. "Economic Analysis in Support ofthe TSCA 12(b) Information Collection Request." OPPT/EETD/ EPAB, Washington, DC (October 30, 1998). 

### VIII. Regulatory Assessment Requirements

A. Executive Order12866

Under Executive Order 12866, entitled RegulatoryPlanningand Review (58 FR 51735, October4, 1993), this is not a "significant regulatory action" subject to review by the Office ofManagement and Budget (OMB), because this action is not likely to result in a rule that meets any ofthe criteria for a "significant regulatory action" provided in section 3(f) ofthe Executive Order.

EPA has prepared an economic analysis ofthe potential impact ofthis proposed rule, which is contained in a document entitled "Economic Impact Analysis and Small Entity Impact Analysis ofProposed TSCA Section 4(a) Test Rule for 47 Chemicals Targeted for In VitroDermal Absorption Rate Testing" (Ref.9). This document is available as apart ofthe public version ofthe official record for this action (instructions for accessing this document are contained in Unit I.B. of this preamble), and is briefly summarized here. The costs developed in the economic impact analysis are based on laboratory test cost estimates that have been placed in the docket for this proposed rule (Ref. 12).

While legally subject to this test rule, processors ofa subject chemical would only be required to comply with the requirements ofthe rule if they are directed to do so byEPA as described in §799.5115(c)(5) and (c)(6) ofthe proposed regulatory text. EPA would only require processors to test ifno person in Tier 1 has submitted anotice ofits intent to conduct testing, or if, under 40 CFR 790.93, aproblem occurs with the initiation, conduct, or completion ofthe required testing, or the submission ofthe required data to EPA. Because EPA has identified at least

one manufacturer in Tier 1 for each subject chemical, the Agency assumes that, for each chemical in this proposed rule, at least one such person will submit aletter ofintent to conduct the required testing and that that person will conduct such testing and will submit the test data to EPA. Because processors would not need to comply with the rule initially, the economic analysis does not address processors.

To evaluate the potential economic impact oftesting on manufacturers of the chemical substances in this proposed rule, EPA estimated the impact oftesting requirements as a percentage ofeach chemical's sale price. This measure compares the annualized testing costs per pound (based on the conservative assumption that all chemicals are produced in volumes of

one million lbs), to the price per pound for each chemical. First, annualized testing costs (includinglaboratory and administrative expenditures) are calculated by converting the total testing costs in the first year into an equivalent series ofexpenditures over 15 years using a7% discount rate. Second, annualized testing costs are divided by

one million lbs (the assumed production volume per chemical) to derive the annualized unit (perpound) testing
cost. The price impacts-testing costs as

apercentage ofeach chemical's priceare calculated by dividing the annualized unit testing cost by each unit price and multiplyingby 100. The Agency's estimated total costs oftesting (includingboth laboratory and administrative costs), annualized testing cost, price impacts, and public reporting burden hours for the chemicals are presented in the economic analysis (Ref. 9).Based on the economic analysis, the total one-time cost ofthis action, if finalized asproposed, is estimated to be $1.55 million. When this cost is annualized over 15 years using a 7% discount rate, the total annualized cost is estimated to be $170,576, with an estimated annualized cost of$3,628 per chemical. In addition, the estimated cost ofthe TSCA section 12(b)(1) export notification, which, in the final rule, would be required for the first export to

aparticular country ofachemical subject to the rule, is estimated to be $83.38 for the first time that an exporter must comply with TSCA section 12(b)(1) export notification requirements, and $19.08 for each subsequent export notification submitted by that exporter (Ref.9, 13, and 14).

The economic impacts ofthe testing, expressed as a percentage ofeach chemical's sale price, range from 0.09%
to 3.3%, with an average impact of 0.64%. EPA estimates that 5 ofthe 35 chemicals forwhich price data are available will experience an adverse impact of 1% or greater under the assumption that production volumes for these chemicals are one million lbs. In fact, these chemicals are all manufactured or imported in excess of 10 million lbs, reducing the estimated impact by a factor of 10 to less than 1%. For the remaining 12 chemicals without price data, EPA estimates that with annualized testing costs of$3,628 per chemical and one million lbs production volumes each, an economic impact of 1% or greater would occur only at a sales pricebelow $0.36 per lb. Given that the average price for the other 35 chemicals is $0.97 per lb (prices range from $0.11 to $3.96 per lb), that the unavailability ofprice datafor these 12 chemicals may indicate that they are higher priced specialty chemicals, and that their production volumes are likely to be higher than the

one million lbs minimum, the likelihood ofan adverse impact is low.

B. Executive Order12898

This proposed rule does not involve special considerations of environmental-justice related issues pursuant to Executive Order 12898, entitled Federal Actions toAddress EnvironmentalJusticein Minority PopulationsandLow-Income Populations(59 FR7629, February 16, 1994).

C.Executive Order13045

Executive Order 13045, entitled ProtectionofChildren from EnvironmentalHealthRisks andSafety Risks (62 FR 19885, April 23, 1997), does not apply to thisproposed rule, because it is not "economically significant" as defined under Executive Order 12866; and does notconcern an 

## 31083

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

environmental health or safety risk that may have a disproportionate effect on children. This proposed rule would require the development ofquantitative

measures ofdermal absorption rate to assist in evaluating the potential contribution ofthe chemical substances proposed for testing to total exposures to adult workers. The public is invited, however, to submit or identify peerreviewed studies and data, ofwhich EPA may not be aware, that assess results ofearly life exposure to the 47 chemicals proposed for testing in this document.

D.RegulatoryFlexibilityAct

Pursuant to section 605(b) ofthe Regulatory Flexibility Act (RFA), 5 U.S.C. 601 etseq., the Agency hereby certifies that this rule, ifpromulgated as proposed, will nothave a significant economic impact on a substantial number ofsmall entities. The factual basis for the Agency's determination is presented in the small entity impact analysis prepared as part ofthe economic analysis for this proposed rule (Ref.9), and is briefly summarized here. The costs developed in the small entity impact analysis arebased on the laboratory test cost estimates that have been placed in the docket for this proposed rule (Ref. 12).

For the purpose ofanalyzing potential impacts on small entities, EPA used the RFA definition ofsmall entities in RFA section 601(6).Under this section, a small entity maybe a small government,

a small non-profit organization, or a smallbusiness. Because EPA does not believe that governments or non-profit organizations are likely to beburdened by testing requirements under this proposed rule, EPA's analysis presents only the estimated potential impacts on smallbusinesses.

Section 601(3) ofthe RFA establishes

as the default definition ofsmall business the definition used in section 3 ofthe Small Business Act (15 U.S.C. 632) under which the SBA establishes smallbusiness size standards (13 CFR 121.201). For this proposed rule, EPA has analyzed the potential small business impacts using the size standards established under the RFA section 601(3) definition.

In addition, in analyzing potential impacts, the RFA recognizes that itmay be appropriate at times forFederal agencies to use an alternate definition of smallbusiness. As such, RFA section 601(3) also provides that an agency may establish a different definition ofsmall business after consultation with the SBA Office ofAdvocacy and after notice and an opportunity forpublic comment. Even though the Agency has used the default SBA definition ofsmall business to conduct its analysis ofpotential small entity impacts for this proposed rule, EPA does not believe that the SBA size standards are generally the best size standards to use in assessing potential small entity impacts with regard to TSCA section 4(a) test rules.

The SBA size standards, which are primarily intended to define whether a business entity is eligible for Federal government programs and preferences reserved for small businesses (13 CFR 121.101), "seek to ensure that aconcern that meets a specific size standard is not dominant in its field ofoperation" (13 CFR 121.102(b)). See section 632(a)(1) of the Small Business Act. The SBA size standard is generally based on the number ofemployees an entity in a particular industrial sector may have. For example, in the chemical manufacturing industrial sector (i.e., SIC 28 and SIC 29), approximately 98% of the industries would be classified as smallbusinesses under the default SBA definition. The SBA size standard for 75% ofthis industry sector is 500 employees, and the size standards for 23% ofthis industry sector are 750, 1,000, or 1,500 employees. As a result, when assessing the potential impacts of
test rules on chemical manufacturers, EPA believes that a standard based on total annual sales may provide amore appropriate means tojudge the ability of

achemical manufacturing firm to support chemical testing without significant costs or burdens.

EPA is currently determining what level ofannual sales would provide the
most appropriate size cutoffwith regard
to various segments ofthe chemical industry usually impacted byTSCA section 4(a) test rules, buthas not yet reached adetermination. As stated in this unit, therefore, the factual basis for the RFA determination for this proposed rule is based on an analysis using the default SBA size standards. Although EPA is not proposing to establish an alternate small business definition in the small entity impact analysis conducted for this proposed rule, the analysis includes the results of calculations using a size standard based

on total annual sales. EPA is interested in receiving comments on whether the Agency should consider establishing an alternate small business definition to

use in the small entity impact analyses for future TSCA section 4(a) test rules, and what size cutoffmay be appropriate.

Based on the Agency's estimated total
costs for this proposed rule, which are summarized in Unit VIII.A. ofthis preamble, EPA estimates that the annualized cost for the testing in this proposed rule willbe $3,628 per chemical. As discussed previously, EPA

was unable to obtain any price information on 12 ofthe 47 chemicals in thisproposed test rule. Nevertheless, EPA provides an estimate ofthe price of these chemicals in the economic analysis, and concludes that the total
cost oftesting these 47 chemicals as proposed, will not result in a significant impact on the chemical manufacturers subject to the proposed rule,regardless oftheir size. EPA identified atotal of 102 ultimate corporate entities (UCEs) that would be potentially impacted by the proposed test rule. None ofthese manufacturers would experience a significant impact as aresult ofthe rule.

In addition, the estimated cost ofthe TSCA section 12(b)(1) export notification, which, as aresult ofthe final rule, would be required for the first export to a particular country ofa chemical subject to the rule, is estimated to be $83.38 for the first time that an exporter must comply with TSCA section 12(b)(1) export notification requirements, and $19.08 for each subsequent export notification submitted by that exporter (Ref.9, 13, and 14). EPA has concluded that the
costs ofTSCA section 12(b)(1) export notification would have a negligible impact on exporters ofthe chemicals in the final rule, regardless ofthe size of the exporter.

The Agency has also examined the standard practices that industry uses in carrying out chemical testing in response to test rules, such as this one. Based on that examination, EPA believes that: 1. Small businesses donot perform the testing themselves, nor do they participate in the organization ofthe testing effort, because health effects testing ofchemical substances is generally carried outby consortia ofthe large manufacturers or importers ofthe chemical substances;

2. A small business would experience onlyvery minor costs, if any, in securing an exemption from testing requirements, because exemption request requirements, described generally at 40 CFR 790.80 through 790.99 and the proposed regulatory text at §799.5115(c)(2), (c)(5), and (c)(7), are minimal and EPA does not charge afee for filing such a request; and

3. Small businesses are unlikely to be affected by the reimbursement requirements because under the reimbursement provisions described in 40 CFRpart 791, manufacturers and importers with a significant share of production or importation are the entities that will likely pay the highest share oftesting costs, and the marginal 

## 31084

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

benefit ofsecuring reimbursement from small contributors may not be worth the
cost.

Information relating to this determination has been included in the public version ofthe official record for the proposed rule. This information will also be provided to the SBA Chief Counsel for Advocacy upon request. Any comments regarding the impacts that this action may impose on small entities, orregarding whether the Agency should consider establishing an alternate definition ofsmallbusiness to be used for analytical purposes for future test rules and what size cutoff may be appropriate, should be submitted to the Agency in the manner specified in Unit I.C. ofthis preamble.

E. PaperworkReductionAct

Pursuant to the Paperwork Reduction Act (PRA) (44U.S.C. 3501 etseq.), an Agency may not conduct or sponsor, and aperson is not required to respond to, acollection ofinformation that is subject to approval under the PRA, unless it displays a currently valid OMB control number. The OMB control numbers forEPA's regulations, after appearing in the preamble ofthe final rule, are listed in 40 CFRpart 9, and included on the related collection instrument. The information collection activities related to chemical testing under TSCA section 4(a) have already been approved under OMB control number 2070-0033 (EPA ICR# 1139), and the information collection activities related to export notification under TSCA section 12(b)(1) are already approved under OMB control number 2070-0030 (EPA ICR# 0795). Since this proposed rule does not contain any new information collection activities, additional review and approval ofthese activities by OMBunder the PRA is not necessary.

Although the information collection activities contained in thisproposed rule have already been approved by OMB, the total burden hours currently approved for the information collection activities related to chemical testing in general include an average burden estimate to cover future test rules. As described in the information collection instrument for chemical testing, the Agency's total burden estimate specifically accounts for the potential issuance ofapproximately 7 final test rules during the approval period, with

an estimated burden ofless than 20,000 burden hours each. EPAbelieves that the existing approval includes a sufficientburden hour allocation to

cover the estimated burden related to this proposed rule, iffinalized as proposed. When the final rule is issued, EPA will verify that the approved burden hours will cover the estimated burden for the final rule, orrequest that the total approved burden hour allocation be increased accordingly.

The standard chemical testing program involves the submission of letters ofintent to test (orexemption applications), study plans, semi-annual progress reports, and test results. For this proposed rule, EPA estimates that the information collection activities related to chemical testing would result in 105.4 burden hours for each chemical, for a total estimated burden increase of4,954 hours (Ref.9). The estimated burden ofthe information collection activities related to export notification is 0.5-1.5 burden hours for each chemical/country combination (Ref.9). In estimating the totalburden hours approved for the information collection activities related to export notification, the Agency has included sufficient burden hours to accommodate any export notifications that may be required bythe Agency's issuance of final chemical testrules (Ref.9, 13, and 14). As such, EPA does not expect to need to request an increase in the total burden hours approved by OMB for export notifications.

As defined bythe PRA and 5 CFR 1320.3(b), burdenmeans the total time, effort, or financial resources expended by persons to generate, maintain, retain,

or disclose or provide information to or for aFederal agency. This includes the time needed to review instructions; develop, acquire, install, and utilize technology and systems for the purposes ofcollecting, validating, and verifying information, processing and maintaining information, and disclosing and providing information; adjust the existing ways to comply with any previously applicable instructions and requirements; train personnel to be able
to respond to acollection of information; search data sources; complete and review the collection of information; and transmit or otherwise disclose the information.

Comments are requested on the Agency's need for this information, the accuracy ofthe provided burden estimates, and any suggested methods for minimizing respondent burden, including through the use ofautomated collection techniques. Send comments to EPA as part ofyour overall comments

on this proposed action in the manner specified in Unit I.C. ofthis preamble. In the final rule, the Agency will address any comments received regarding the information collection requirements contained in this proposal. F. UnfundedMandatesReform Act
Pursuant to TitleII ofthe Unfunded Mandates Reform Act of 1995 (UMRA), Pub. L. 104-4, EPA has determined that thisproposed rule does not contain a Federal mandate that mayresult in expenditures of$100 million or more for State, local, and tribal governments, in the aggregate, or the private sector in any 1 year. It is estimated that the total one-time cost ofthe rule, which is summarized in Unit VIII.A. ofthis preamble, is $1.55 million, with the total annualized cost estimated to be $170,576, and the estimated annual cost per chemical to be $3,628. In addition, EPA has determined that this proposed rule does not significantly or uniquely affect small governments. Accordingly, today's proposed rule is not subject to the requirements ofUMRA sections 202, 203, 204,or 205.

G. Executive Order12875

Under Executive Order 12875, entitled Enhancingthe IntergovernmentalPartnership(58 FR 58093, October 28, 1993), EPA may not issue a regulation that is not required by
statute and that creates a mandate upon
a State, local, or tribal government, unless the Federal government provides the funds necessary to pay the direct compliance costs incurred bythose governments, orEPA consults with those governments. IfEPA complies by consulting, Executive Order 12875 requires EPA to provide to OMB a description ofthe extent ofEPA's prior consultation with representatives of affected State, local, and tribal governments, the nature oftheir
concerns, any written communications from the governments, and a statement supporting the need to issue the regulation. In addition, Executive Order 12875 requires EPA to develop an effective process permitting elected officials and other representatives of State, local, and tribal governments "to provide meaningful and timely input in the development ofregulatory proposals containing significant unfunded mandates."

EPA does not believe the today's proposed rule under TSCA section 4(a)
creates aFederal mandate on State, local, or tribal governments, and thus, EPA does notbelieve that the requirements ofsection 1(a) of Executive Order 12875 apply to this rule. The Agency does not know ofany State, local, or tribal governments that would be subject to the requirements of the rule if it were promulgated as proposed. In the history ofthe TSCA section 4(a) testingprogram, the Agency has never received a letter ofintent to 

## 31085

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

test or an exemption application from a State, local, or tribal government. EPA is requesting comment on whether any State, local, or tribal government would be subject to the requirements ofthe proposed rule. If, on the basis ofthese comments, EPA determines that the rule would create aFederal mandate, the Agency will consult with representatives ofaffected State, local,

or tribal governments in accordance with the Executive Order prior to promulgating the final rule.

H. Executive Order13084

Under Executive Order 13084, entitled Consultationand Coordination with IndianTribalGovernments(63 FR 27655, May 19, 1998), EPA has determined that this proposed rule does not significantly or uniquely affect the communities ofIndian tribal governments. This determination is based on the Agency's beliefthat, as a practical matter, the burden ofchemical testing under TSCA section 4(a) rules has traditionally fallen on large, private
sector manufacturers rather than on tribal governments. Accordingly, the requirements ofsection 3(b) of Executive Order 13084 do not apply to this proposed rule.

I.NationalTechnology Transferand AdvancementAct

Section 12(d) ofthe National Technology Transfer and Advancement Act of 1995 (NTTAA) (15 U.S.C. 272 note), directs EPA to use voluntary

consensus standards in its regulatory activities unless to do so would be inconsistent with applicable law or otherwise impractical. Voluntary

consensus standards are technical standards (e.g., materials specifications,
test methods, sampling procedures, and business practices) that are developed or adopted by voluntary consensus standards bodies. The NTTAA directs EPA to provide Congress, through OMB, explanations when the Agency decides
not to use available and applicable voluntary consensus standards.

Ifthe Agency has made findings under TSCA section 4(a),EPA is required byTSCA section 4(b) to include specific standards for the development ofdata in test rules. The testing that would be required under this rule would be conducted according
to the enforceable in vitro dermal absorption rate test standard proposed in this document. This test standard was developed byEPA in conjunction with ITC member and liaison agencies (CPSC, DoD, FDA, NIOSH, and OSHA). It was based on the methods ofBronaugh and Collier (Bronaugh, R.L., and Collier, S.W., Protocol for In Vitro Percutaneous Absorption Studies, In Vitro Percutaneous Absorption:Principles, Fundamentals,andApplications.R.L. Bronaugh and H.I. Maibach, Eds. CRC Press, Boca Raton, FL. pp. 237-241 (1991)) (Ref.7), and modified in response to public comments. The group ofscientists that developed this
test standard did so based on their experience with the methodologies available for conducting this type of testing. As aresult oftheir collective expertise in these methodologies, they considered the method developed for this testing program to be an effective and efficient method for testing a large number ofchemicals to determine an in vitro dermal absorption rate using human cadaver skin.

EPA is not aware ofany potentially applicable voluntary consensus standards which needed to be considered in lieu ofthe in vitrodermal absorption rate test standard included in this proposed rule. The Agency invites
comment on the potential use of voluntary consensus standards in this proposed rule, and, specifically, invites the public to identify potentially applicable voluntary consensus standard(s) and to explain why such standard(s) should be used here.
List of Subjects in 40 CFRPart799

Environmental protection, Chemicals, Hazardous substances, Reporting and recordkeeping requirements, Laboratories.

Dated: June 1,1999.

Susan H. Wayland,
ActingAssistantAdministratorfor Prevention,PesticidesandToxicSubstances.

Therefore, it is proposed that 40 CFR chapter 1,subchapter R, be amended as follows: 

### PART799-[AMENDED]

1. The authority citation for part 799 would continue to read as follows:

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

2. By adding §799.5115 to subpart D
to read as follows: 

### §799.5115 Chemicaltesting requirements forcertain chemicals of interesttothe OccupationalSafety and Health Administration.

(a) Whatsubstanceswill be tested underthissection?Table 2 in paragraph (i) ofthis section identifies the chemical substances that must be tested under this section. The purity ofeach test substance mustbe 99% or greater unless otherwise specified in this section.

(b)Am Isubjectto thissection? (1) If you manufacture (includingimport) or intend to manufacture, orprocess or intend to process, any chemical substance listed in Table 2 ofparagraph (i) ofthis section at any time from the effective date specified in Table 2 of paragraph (i) ofthis section to the end ofthe test datareimbursement period as defined in 40 CFR 791.3(h), you are subject to this section with respect to that chemical substance.

(2) Ifyou do notknow or cannot reasonably ascertain that you manufacture or process achemical substance listed in Table 2 ofparagraph (i) ofthis section during the time period described in paragraph (b)(1) ofthis section (based on allinformation in your possession or control, as well as all information that areasonable person similarly situated might be expected to possess, control, or know, or could obtain without unreasonable burden), you are not subject to this section with respect to that chemical substance. (c)If lam subjectto thissection,when
mustIcomply with it?(1)(i) Persons subject to this section are divided into
two groups, as set forth in Table 1 of thisparagraph: Tier 1 (persons initially required to comply) and Tier 2 (persons
notinitially required to comply). Ifyou

are subject to this section, you must determine ifyou fall within Tier 1 or Tier 2, based on Table 1 ofthis paragraph. 

## 31086

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

TABLE 1.- PERSONS SUBJECT TO THE RULE: PERSONS INTIER 1 AND TIER 2

Persons initially required to comply with this section (Tier 1)

*Persons not otherwise specified in column 2 of this

table that manufacture (as defined at TSCA section 3(7)) or intend to manufacture a chemical substance included in this section. Persons not initiallyrequired to complywith this section (Tier 2)

+*Persons that manufacture (as defined at TSCA section 3(7)) or intend to manufacturea chemical substance included in this section solely as one or more ofthe following: -As a byproduct (asdefined at 40 CFR 791.3(c)); -As an impurity (as defined at 40 CFR 790.3); -As a naturally occurring substance (asdefined at 40 CFR 710.4(b)); -As a non-isolated intermediate (as defined at 40 CFR 704.3); -As a component ofa Class 2 substance (asdescribed at40 CFR 720.45(a)(1)(i)); -In amounts of lessthan 500 kilograms (kg) (1,100 Ibs) annually (as described at40

CFR 790.42(a)(4)); or -For research and development (as described at 40 CFR 790.42(a)(5)). *Persons that process (as defined at TSCA section 3(10)) or intend to process a

chemical substance included in this section (see 40 CFR 790.42(a)(2)).

(ii) Table 1 ofparagraph (c)(1)(i) of this section expands the list ofpersons specified in §790.42(a)(2), (a)(4), and (a)(5) ofthis chapter, who, while legally subject to this section, must comply with the requirements ofthis section only if directed to do so byEPA under the circumstances set forth in paragraphs (c)(4) and (c)(5) ofthis section.

(2) Ifyou are in Tier 1 with respect to a chemical substance listed in Table 2 ofparagraph (i) ofthis section, you will be required to comply with this section with regard to that chemical substance, as described in paragraph (d) ofthis section, no later than 30 days after the effective date specified in Table 2 ofparagraph (i) ofthis section for that chemical substance. Sections 790.45(a) and 790.80(b)(1) ofthis chapter do not apply to this section.

(3) Ifyou are in Tier 2 with respect to a chemical substance listed in Table 2 ofparagraph (i) ofthis section, you are considered to have an automatic conditional exemption and you willbe required to comply with this section with regard to that chemical substance only if directed to do so byEPA under paragraphs (c)(5) or (c)(6) ofthis section.

(4) Ifno person in Tier 1has notified EPA ofits intent to conduct one or more ofthe tests required by this section on any chemical substance listed in Table 2 ofparagraph (i) ofthis section within 30 days after the effective date in Table 2 ofparagraph (i)ofthis section, EPA will publish a Federal Register document that will specify the test and the chemical substance for which no letter ofintent has been submitted. Section 790.48(b)(2) ofthis chapter does
not apply to this section.

(5) Ifyou are in Tier 2 with respect to a chemical substance listed in Table 2 ofparagraph (i) ofthis section, and if you manufacture orprocess this chemical as ofthe effective date specified in Table 2 ofparagraph (i) of this section, or within 30 days after publication ofthe Federal Register document described in paragraph (c)(4) ofthis section, you must do the following: Foreach test on that chemical specified in the Federal Register document described in paragraph (c)(4) ofthis section, either notify EPA byletter ofyourintent to test

or submitto EPA an exemption application. You must comply within 30 days after the date ofpublication ofthe Federal Register document described in paragraph (c)(4) ofthis section. Sections 790.48(b)(3), and 790.80(a)(2) and (b)(1) ofthis chapter do not apply to this section.

(6) Ifaproblem occurs with the initiation, conduct, or completion ofthe required testing or the submission ofthe required data with respect to a chemical substance listed in Table 2 ofparagraph (i) ofthis section, under the procedures in 40 CFR 790.93 and 790.97, EPA will terminate alltesting exemptions with respect to that substance and may notify persons in Tier 1 and Tier 2 that they

are required to submit letters ofintent
to test or exemption applications within

a specified period oftime. A notification will be given by certified letter orby publication ofa Federal Register document. (7) Ifyou are required to comply with this section, but your manufacturing or processing ofachemical substance listed in Table 2 ofparagraph (i) ofthis section begins after the applicable compliance date referred to in paragraphs (c)(2), (c)(5) or (c)(6) ofthis section, you must comply by submitting

aletter ofintent to test or an exemption application as ofthe day you begin manufacturing or processing. Sections 790.45(d)(1) and (d)(2), and 790.80(b)(2) and (b)(3) ofthis chapter do not apply
to this section. (d) WhatmustIdo to comply with thissection?(1) To comply with this section you must either: (i) Submit to EPA aletter ofintent to test, conduct the testing specified in Table 2 ofparagraph (i) ofthis section, and submit the test data to EPA; or

(ii) Apply to and obtain from EPA an exemption from testing.

(2) You must also comply with the procedures governing testrule requirements in part 790 ofthis chapter, including the submission ofletters of intent to test or exemption applications, the conduct oftesting, and the submission ofdata; part 792 ofthis chapter; and this section.

(e)Ifldo notcomply with thissection, when will I be consideredin violation of it?You will be considered in violation ofthis section as of 1 day after the date by which you arerequired to comply with this section. Sections 790.45(e) and (f) ofthis chapter do not apply to this section.

(f) How areEPA 's datareimbursement proceduresaffected forpurposesofthis section?Ifpersons subject to this section

are unable to agree on the amount or method ofreimbursement for test data development for one or more chemical substances included in this section, any person may request ahearing as described in 40 CFRpart 791. In the determination offair reimbursement shares under this section, if the hearing officer chooses to use a formula based

on production volume, the total production volume amount willinclude
amounts ofa chemical substance produced as an impurity. (g) Who must comply with the export notificationrequirements? Any person who exports, or intends to export, a chemical substance listed in Table 2 of paragraph (i) ofthis section is subject to part 707, subpart D, ofthis chapter. (h) What teststandardmustIfollow? The chemical substances identified by Chemical Abstract Service (CAS) registry number and chemical name in Table 2 ofparagraph (i) ofthis section
mustbe tested as follows: 

## 31087

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

(1)Applicability.This in vitrodermal absorption rate test standard must be used for all testing conducted under this section.

(2) Source.The source used to develop this test standard is the "Protocol for In Vitro Percutaneous Absorption Studies," (Referenced in paragraph (h)(8)(i)(A)ofthis section).

(3) Purpose.In the assessment and evaluation ofthe characteristics of a chemical substance or mixture (test substance), determination ofthe rate of absorption ofthe chemical substance where dermal exposure to the chemical substance in the workplace may result in systemic toxicity is important. This
test standard is designed to develop data

on the rate at which chemicals are absorbed through the skin so that the body burden ofchemical resulting from dermal exposure in the workplace can be better evaluated.

(4)Principlesofthe testmethod.This
test standard describes procedures for measuring apermeability constant (Kp) and a short-term in vitro absorption rate for chemical substances in liquid form. The test standard utilizes in vitro diffusion cell techniques which allow absorption studies to be conducted with human skin. In vitro diffusion studies

are necessary for measuring a Kp. This test standard specifies the use of cadaver skin and static diffusion cells to maintain the viability ofthe skin, thus,

more closely simulating in vivo conditions. It also requires the use of radiolabeled test chemicals unless it can be demonstrated that procedures utilizing a non-radiolabeled test substance are able to measure the substance with a sensitivity equivalent to the radiolabeled method.

(5) Testprocedure-(i)Choiceof membrane-(A) Skin selection.Human cadaver skin mustbe used in alltesting conducted under this test standard. The
most accurate absorption-rate data for regulatory concerns related to human health would be obtained with live human skin. Because this test standard requires the use ofstatic diffusion cells, maintenance ofskin viability is not necessary. However, the time elapsed between death and harvest ofthe tissue
must be reported.

(B) Numberofsamples.Data from a total ofat least six samples obtained from at least three human subjects must be averaged to allow for biological variation among subjects.

(C)Anatomicalregion.In order to minimize the variability in skin absorption measurements for these tests, samples ofhuman skin must be obtained from the abdominal region of human subjects ofknown source and disease state. Variability in skin permeation is well known to occur in different anatomical regions. The trunk and its extremities have reasonably similar barrier properties (lessthan 2- fold differences). Enhanced absorption

can be observed in regions ofthe face (4- fold) and the scrotum (20-fold). Small differences in regional absorption may not be significant compared to intersubject variability (D) Validationofhuman skin barrier. Barrier properties ofhuman skin must be pretested with a standard compound such as tritiated water prior to conducting an experiment with the test chemical because barrier alteration can result from surgery or topical scrubbing,

as discussed in the reference in paragraph (h)(8)(i)(B) ofthis section. (ii) Preparation ofmembrane.Full thickness skin must not be used. Because chemicals are taken up by blood vessels directly beneath the epidermis in vivo, this in vitro test standard must be conducted using a membrane with most ofthe dermis removed. This is particularly important for hydrophobic chemicals that diffuse slowly through the dermis. A suitable membrane must be prepared from skin with a dermatome at a thickness of200
to 500 millimeters (mm).The microtomed skin samples can be stored frozen for up to 2 weeks, ifnecessary, provided that they are frozen quickly and the barrier properties ofthe samples

are confirmed.

(iii)Diffusioncell design. Static diffusion cells mustbe used in these studies. The testing laboratory must verify that the difference in the concentration ofthe test compound

across the skin membrane does not decrease by more than 10% during the experiment. This will ensure that the
test compound concentration in the receptor fluid does not alter the penetration rate. Concentration ofthe
neat liquid must be taken as the density ofthe compound. (iv) Temperature.Skin must be maintained at a physiological temperature of320 Celsius. (v) Testinghydrophobicchemicals. Chemicals with water solubility less than about 10milligrams/liter do not freely partition from skin into aqueous receptor fluid. To increase the water solubility ofsuch hydrophobic chemicals, polyethoxyoleate (polyethylene glycol (PEG)20 oleyl ether) must be added to the receptor fluid at a concentration of6%. To

ensure that an increase in concentration ofthe chemical in the receptor fluid does not alter penetration rate, the concentration difference across the membrane must not decrease by more than 10% during the experiment. (vi) Vehicle.Ifthe test chemical is a liquid at room temperature and does not damage the skin during the determination ofKp, it mustbe applied neat. Ifthe chemical cannot be applied
neatbecause it is a solid atroom temperature or because itdamages the skin when applied neat, it must be dissolved in water. Ifthe concentration ofa hydrophobic chemical in water is
nothigh enough so that a steady-state absorption can be obtained, the chemical must be dissolved in isopropyl myristate. A sufficient volume ofliquid
mustbe used to completely coverthe skin and provide the amount oftest chemical needed as described in paragraph (h)(5)(vii) ofthis section. (vii) Dose--(A) Kp. An "infinite dose" ofthe test chemical must be applied to the skin to achieve the steady-state rate ofabsorption necessary for calculation ofa Kp. The actual concentration required to give an undepletable reservoir on the surface ofthe skin depends on the rate ofpenetration ofthe
test chemical. Preliminary studies may be necessary to determine this concentration. The diffusion cell tops mustbe covered with a stopper or with parafilm 7 to ensure that significant evaporation ofthe vehicle or test chemical does not occur. The skin barrier integrity must be verified atthe end ofthe experiment bymeasuring the absorption of a standard compound such as tritiated water, as discussed in the reference inparagraph (h)(8)(i)(B) of this section.

(B) Short-term absorptionrate.Shortterm absorption rates mustbe determined for alltest chemicals. The dose oftest chemical applied to the skin mustbe sufficient to completely cover the exposed skin surface. A minimum of four to six diffusion cells must be setup using skin from a single subject and two to three ofthese shall be terminated at 10 and 60 minutes. Skin absorption at each sampling timeis the sum ofthe receptor-fluid levels and the absorbed chemical that remains in the skin, as discussed in the reference in paragraph (h)(8)(i)(C)ofthis section. Unabsorbed chemical must be removed from the skin surface by washing gently with soap and water. This procedure mustbe repeated with skin from two additional subjects. In order to ensure reliable short-term absorption rates, the diffusion cell tops must be covered with

a stopper or with parafilm 7 to prevent evaporation ofthe test chemical.

(viii)Study duration-(A)Kp. This in vitrodermal absorption rate test must be performed until at least four absorption
measurements are obtained during the steady state absorption portion ofthe procedure. A preliminary study may be 

## 31088

### Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

useful to establish time points for sampling.The required absorption
measurements can be accomplished in

an hour or two with fast-penetrating chemicals but require 24 hours or longer for slow-penetrating chemicals. Unabsorbed material need not be removed from the surface ofthe skin.

(B) Short-term exposurerate.The test chemical must be applied to skin for durations of at least 10 and 60 minutes. At the end ofthe study, the unabsorbed material mustbe removed from the surface ofthe skin with soap and water and the amount absorbed into the skin and receptor fluid must be determined,

as discussed in the reference in paragraph (h)(8)(i)(C)ofthis section.

(6)Results--(i)Kp. The Kp must be calculated by dividing the steady-state
rate ofpenetration (measured in micrograms x hr -1x centimeters (cm) -2) by the concentration ofthe test chemical (measured in micrograms x cm -3) applied to the skin. For example, ifthe steady-state rate is 1 microgram x hr -1x cm -2 and the concentration applied to the skin is 1,000 micrograms x cm -3, then the Kp value is calculated to be 0.001 cm x hr-.

(ii) Short-term exposurerate.The
rates ofpenetration (micrograms x hr-1

x cm -2 ) must be determined from the total amount oftest chemical found in the receptor fluid and skin after the 10- and 60-minute exposures.

(7) Test reports.In addition to compliance with the TSCA Good Laboratory Practice (GLP) Standards at 40 CFRpart 792, the following specific information must be collected and reported underparagraph (i) ofthis section:

(i) Test systemsand testmethods. (A) A description ofthe date, time, and location ofthe test, the name(s) ofthe person(s) conducting the test, the location ofrecords pertaining to the test,

as well as a GLP statement. These
statements mustbe certified by the signatures ofthe individuals performing the work and their supervisors. (B) A description ofthe source, identity, and purity ofthe test chemical and the source, identity, and handling ofthe test skin. There must be a detailed description ofthe test procedure and all materials, devices used and doses tested, as well as a detailed description and illustration offlow-cell design. There must also be a description ofthe skin preparation method including
measurements ofthe skin membrane thickness. (C) A description ofthe analytical techniques to be used, including their accuracy, precision, and detection limits (inparticular for non-radiolabeled tests), and, if aradiolabel is used, there must be adescription ofthe radiolabel (e.g., type, location of,and radiochemical purity ofthe label). (D)All data must be clearly identified

asto dose and specimen. Derived values (means, permeability coefficient, graphs, charts, etc.) are not sufficient. (ii) Conductofstudy. Datamust be collected and reported on the following: (A) Monitoring oftesting parameters. (B) Temperature ofchamber. (C) Receptor fluid pH. (D)Barrier property validation. (E)Analysis ofreceptor fluid for radioactivity or test chemical. (iii)Results.The Kp or short-term absorption rate must be presented. In addition, allraw data from each individual diffusion cell mustbe maintained to support the calculations ofKp and short-term exposure rates. When radiolabeled compounds are used, a fullbalance ofthe radioactivity
must be presented, including cell rinsing and stability ofthe test substance in the donor compartment.

(8) References.(i) Forbackground information on this test standard, the following references should be consulted. These references are available at the TSCA Nonconfidential Information Center, Rm. NE B-607, Environmental Protection Agency, 401 M St., SW., Washington, DC, 12 noon to 4 p.m., Monday through Friday, except legal holidays. (A) Bronaugh, R.L., and Collier, S.W. Protocol forIn Vitro Percutaneous Absorption Studies. In Vitro Percutaneous Absorption:Principles, Fundamental,andApplications.R.L. Bronaugh and H.I. Maibach, Eds. CRC Press, Boca Raton, FL. pp. 237-241 (1991).

(B) Bronaugh, R.L., Stewart, R.F., and Simon, M. Methods forIn Vitro Percutaneous Absorption VII: Use of Excised Human Skin. Journalof Pharmaceutical Sciences.Vol. 75, pp. 1094-1097 (1986).

(C) Bronaugh, R.L., Stewart, R.F., and Storm, J.E. Extent ofCutaneous Metabolism during Percutaneous Absorption ofXenobiotics. Toxicology and Applied Pharmacology.Vol. 99, pp. 534-543 (1989).

(ii) Two additional documents consulted in developing this test standard are:

(A)Walker, J.D., Whittaker, C. and McDougal, J.N. Role ofthe TSCA Interagency Testing Committee in Meeting the U.S. Government Data Needs: Designating Chemicals for Percutaneous Absorption Rate Testing. Dermatoxicology.F. Marzulli and H. Maibach, Eds. Taylor &Francis, Washington, DC.pp. 371-381 (1996). (B) Bronaugh, R.L. Stewart, R.F. Methods for In Vitro Percutaneous Absorption Studies IV: The FlowThrough Diffusion Cell. Journalof Pharmaceutical Sciences.Vol. 74,pp. 64-67 (1985).

(i) Reportingrequirements.The reports submitted under this section
must include the information specified in paragraph (h)(7) ofthis section. Interim progress reports for each test mustbe submitted every 6 months, beginning 6 months after the effective date ofany specific test listed in Table 2 ofthisparagraph. A final report for a specific test must be submitted bythe deadline indicated as the number of months after the effective date shown in Table 2 ofthis paragraph.

TABLE 2.-REQUIRED TESTING: CHEMICAL SUBSTANCES DESIGNATED FOR IN VITRO DERMAL ABSORPTION RATE TESTING

Deadline for final Number of Interim (6 CAS No. Chemical name report month) reports re- Effective date quired

Ethyl ether Ethyl bromide Acetonitrile Carbon disulfide Vinylidene chloride Dicyclopentadiene Dimethyl sulfate Isophorone Isobutyl alcohol Propylene dichloride sec-Butyl alcohol 

## 31089

60-29-7 74-96-4 75-05-8 75-15-0 75-35-4 77-73-6 77-78-1 78-59-1 78-83-1 78-87-5 78-92-2

## 31090 Federal Register/Vol. 64, No. 110/Wednesday, June 9, 1999/Proposed Rules

TABLE 2.-REQUIRED TESTING: CHEMICAL SUBSTANCES DESIGNATED FOR INVITRO DERMAL ABSORPTION RATE TESTING-Continued

Deadline for final Number of Interim (6 CAS No. Chemical name report month) reports re- Effective date quired

79-20-9 Methyl acetate 9 1 79-46-9 2-Nitropropane 9 1 91-20-3 Naphthalene 9 1 92-52-4 Biphenyl 9 1 95-49-8 o-Chlorotoluene 9 1 95-50-1 o-Dichlorobenzene 9 1 97-77-8 Disulfiram 9 1 98-29-3 tert-Butylcatechol 9 1 99-99-0 p-Nitrotoluene 9 1 100-00-5 p-Nitrochlorobenzene 9 1 100-01-6 p-Nitroaniline 9 1 100-44-7 Benzyl chloride 9 1 106-42-3 p-Xylene 9 1 106-46-7 p-Dichlorobenzene 9 1 107-06-2 Ethylene dichloride 9 1 107-31-3 Methyl formate 9 1 108-03-2 1 -Nitropropane 9 1 108-90-7 Chlorobenzene 9 1 108-93-0 Cyclohexanol 9 1 109-66-0 Pentane 9 1 109-99-9 Tetrahydrofuran 9 1 110-12-3 Methyl isoamyl ketone 9 1 111-84-2 Nonane 9 1 120-80-9 Catechol 9 1 121-69-7 Dimethylaniline 9 1 122-39-4 Diphenylamine 9 1 123-42-2 Diacetone alcohol 9 1 126-99-8 beta-Chloroprene 9 1 127-19-5 Dimethyl acetamide 9 1 142-82-5 n-Heptane 9 1 150-76-5 p-Methoxyphenol 9 1 528-29-0 o-Dinitrobenzene 9 1 628-63-7 n-Amyl acetate 9 1 768-52-5 N-Isopropylaniline 9 1 25013-15-4 Vinyltoluene 9 1 34590-94-8 Dipropylene glycol methyl ether 9 1

[ERDoc. 99 14640 Filed 6 8 99; 8:45 am]

BILLING CODE 6560-50-F