Forty-Sixth Report of the TSCA Interagency Testing Committee to the Administrator; Receipt of Report and Request for Comments

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice.

SUMMARY:

The Toxic Substances Control Act (TSCA) Interagency Testing Committee (ITC) transmitted its Forty-Sixth Report to the Administrator of the EPA on May 25, 2000. In the 46^th Report, which is included with this notice, the ITC: Solicits information on uses, exposures, ecological effects, environmental fate, and health effects on 3 classes of structurally related chemicals (4 polychlorophenols and polychlorobenzenethiols, 8 chlorotrifluoromethylphenoxy benzenes, and 50 perfluorinated chemicals) that have potential to persist and bioconcentrate; requests more detailed exposure and use information be included in the TSCA Electronic Hazard and Safety Data Reporting Form; adds 8 nonylphenol polyethoxylate degradation products to the Priority Testing List; and removes 4 alkylphenols and 15 alkylphenol ethoxylates from the Priority Testing List.--

EPA invites interested persons to submit written comments on the Report.

DATES:

Comments, identified by docket control number OPPTS-41054, must be received on or before January 2, 2001.

ADDRESSES:

Comments may be submitted by mail, electronically, or in person. Please follow the detailed instructions for each method as provided in Unit I. of the SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA, it is imperative that you identify docket control number OPPTS-41054 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

For general information contact: Barbara Cunningham, Acting Director, Environmental Assistance Division (7408), Office of Pollution Prevention and Toxics, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (202) 554-1404; e-mail address: TSCA-Hotline@epa.gov. -

For technical information contact: John D. Walker, ITC Executive Director (7401), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number:(202) 260-1825; fax: (202) 260-7895; e-mail address: walker.johnd@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?-

This notice is directed to the public in general. It may, however, be of particular interest to you if you manufacture (defined by statute to include import) and/or process TSCA-covered chemicals and you may be identified by the North American Industrial Classification System (NAICS) codes 325 and 32411. Because this notice is directed to the general public and other entities may also be interested , the Agency has not attempted to describe all the specific entities that may be interested in this action. If you have any questions regarding the applicability of this action to a particular entity, consult the technical person listed under FOR FURTHER INFORMATION CONTACT.

B. How Can I Get Additional Information, Including Copies of this Document or Other Related Documents?-

1. Electronically. You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/. To access this document, on the Home Page select “Laws and Regulations,” “Regulations and Proposed Rules,” and then look up the entry for this document under the “Federal Register—Environmental Documents.” You can also go directly to the Federal Register listings at http://www.epa.gov/fedrgstr/.-

You may also access additional information about the ITC and the TSCA testing program through the web site for the Office of Pollution Prevention and Toxics (OPPT) at http://www.epa.gov/opptintr/,, or go directly to the ITC Home Page at http://www.epa.gov/opptintr/itc/.-

2. In person. The Agency has established an official record for this action under docket control number OPPTS-41054. The official record consists of the documents specifically referenced in this action, any public comments received during an applicable comment period, and other information related to this action, including any information claimed as Confidential Business Information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period, is available for inspection in the TSCA Nonconfidential Information Center, North East Mall Rm. B-607, Waterside Mall, 401 M St., SW., Washington, DC. The Center is open from noon to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Center is (202) 260-7099.

C. How and to Whom Do I Submit Comments?-

You may submit comments through the mail, in person, or electronically. To ensure proper receipt by EPA, it is imperative that you identify docket control number OPPTS-41054 in the subject line on the first page of your response. -

1. By mail. Submit your comments to: Document Control Office (7407), Office of Pollution Prevention and Toxics (OPPT), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.-

2. In person or by courier. Deliver your comments to: OPPT Document Control Office (DCO) in East Tower Rm. G-099, Waterside Mall, 401 M St., SW., Washington, DC. The DCO is open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for the DCO is (202) 260-7093. -

3. Electronically. You may submit your comments electronically by e-mail to: oppt.ncic@epa.gov, or mail your computer disk to the address identified above. Do not submit any information electronically that you consider to be CBI. Electronic comments must be submitted as an ASCII file avoiding the use of special characters and any form of encryption. Comments and data will also be accepted on standard disks in WordPerfect 6.1/8.0 or ASCII file format. All comments in electronic form must be identified by docket control number OPPTS-41054. Electronic comments may also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI Information That I Want to Submit to the Agency?-

Do not submit any information electronically that you consider to be CBI. You may claim information that you submit to EPA in response to this document as CBI by marking any part or all of that information as CBI. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. In addition to one complete version of the comment that includes any information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public version of the official record. Information not marked confidential will be included in the public version of the official record without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the technical person listed under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?-

We invite you to provide your views and comments on the ITC 46^th Report. You may find the following suggestions helpful for preparing your comments:-

1. Explain your views as clearly as possible.-

2. Describe any assumptions that you used.-

3. Provide copies of any technical information and/or data you used that support your views.--

4. Provide specific examples to illustrate your concerns.--

5. Make sure to submit your comments by the deadline in this notice.-

6. To ensure proper receipt by EPA, be sure to 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.

II. Background-

The Toxic Substances Control Act (TSCA) (15 U.S.C. 2601 et seq.) authorizes the Administrator of the EPA to promulgate regulations under TSCA section 4(a) requiring testing of chemicals and chemical groups in order to develop data relevant to determining the risks that such chemicals and chemical groups may present to health or the environment. Section 4(e) of TSCA established the ITC to recommend chemicals and chemical groups to the Administrator of the EPA for priority testing consideration. Section 4(e) of TSCA directs the ITC to revise the TSCA section 4(e) Priority Testing List at least every 6 months. -

1. The ITC's 46^thReport. The 46^th Report was received by the EPA Administrator on May 25, 2000, and is included in this notice. In the 46^th Report, the ITC:-

i. Solicits information on uses, exposures, ecological effects, environmental fate, and health effects on 3 classes of structurally related chemicals (4 polychlorophenols and polychlorobenzenethiols, 8 chlorotrifluoromethylphenoxy benzenes, and 50 perfluorinated chemicals) that have potential to persist and bioconcentrate.-

ii. Requests more detailed exposure and use information be included in the TSCA Electronic Hazard and Safety Data Reporting Form.-

2. Status of the Priority Testing List. The current TSCA section 4(e) Priority Testing List as of May 2000 can be found in Table 1 of the 46^th ITC Report which is included in this notice. In the 46^th ITC Report, the ITC added 8 nonylphenol polyethoxylate degradation products and removed 4 alkylphenols and 15 alkylphenol ethoxylates from the Priority Testing List.

List of Subjects-

• Environmental protection
• Chemicals
• Hazardous substances

Forty-Sixth Report of the TSCA Interagency Testing Committee to the Administrator, U.S. Environmental Protection Agency

Table of Contents

Summary

I. Background

II. TSCA Section 8 Reporting

A. TSCA Section 8 Rules

B. ITC's Use of TSCA Section 8 and “Other Information”

C. Promoting More Efficient Use of Information Submission Resources

D. Request to Promulgate a TSCA Section 8(d) Rule

III. ITC's Activities During This Reporting Period (November 1999 to April 2000): Information Solicitations

A. Polychlorophenols and Polychlorobenzenethiols

B. Chlorotrifluoromethylphenoxy Benzenes

C. Perfluorinated Chemicals

IV. Revisions to the TSCA Section 4(e) Priority Testing List

A. Chemicals Added to the Priority Testing List: Nonylphenol Polyethoxylate Degradation Products

B. Chemicals Removed from the Priority Testing List: Alkylphenols and Alkylphenol Ethoxylates

V. References

VI. The TSCA Interagency Testing Committee

Summary

This is the 46^th Report of the TSCA Interagency Testing Committee (ITC) to the Administrator of the U.S. Environmental Protection Agency (USEPA). The ITC described Degradation Effects Bioconcentration Information Testing Strategies (DEBITS) in its 45^th Report as strategies to test for the availability of degradation, ecological or human health effects, and bioconcentration information for chemicals with potential to persist, bioconcentrate, and cause ecological or health effects. The ITC implemented DEBITS to identify three classes of structurally related chemicals that have potential to persist and bioconcentrate. These three classes (and number of chemicals associated with each class in parentheses) include polychlorophenols and polychlorobenzenethiols (4), chlorotrifluoromethylphenoxy benzenes (8), and perfluorinated chemicals (50). In this Report the ITC is:

1. Soliciting uses, exposures, ecological effects, environmental fate, and health effects information on these three classes.

2. Requesting more detailed exposure and use information be included in the TSCA Electronic Hazard and Safety Data Reporting Form.

3. Adding 8 nonylphenol polyethoxylate degradation products to the Priority Testing List.

4. Removing 4 alkylphenols and 15 alkylphenol ethoxylates from the Priority Testing List.

The revised TSCA section 4(e) Priority Testing List follows as Table 1.

I. Background

The ITC was established by section 4(e) of the Toxic Substances Control Act (TSCA) “to make recommendations to the Administrator respecting the chemical substances and mixtures to which the Administrator should give priority consideration for the promulgation of a rule for testing under section 4(a)....At least every six months..., the Committee shall make such revisions to the Priority Testing List as it determines to be necessary and transmit them to the Administrator together with the Committee's reasons for the revisions” (Public Law 94-469, 90 Stat. 2003 et seq., 15 U.S.C. 2601 et seq.). Since its creation in 1976, the ITC has submitted 45 semi-annual (May and November) Reports to the EPA Administrator transmitting the Priority Testing List and its revisions. ITC Reports are available from the ITC's web site (http://www.epa.gov/opptintr/itc) within a few days of submission to the Administrator and from http://www.epa.gov/fedrgstr after publication in the Federal Register. The ITC meets monthly and produces its revisions to the Priority Testing List with administrative and technical support from the ITC staff, ITC members, and their U.S. Government organizations and contract support provided by EPA. ITC members and staff are listed at the end of this Report.

II. TSCA Section 8 Reporting

A. TSCA Section 8 Rules

Following receipt of the ITC's Report by the EPA Administrator and addition of chemicals to the Priority Testing List, the EPA's Office of Pollution Prevention and Toxics (OPPT) promulgates TSCA section 8(a) Preliminary Assessment Information Reporting (PAIR) and TSCA section 8(d) Health and Safety Data (HaSD) rules for chemicals added to the Priority Testing List. These rules require producers and importers of chemicals recommended by the ITC to submit production and exposure reports under TSCA section 8(a) and producers, importers, and processors of chemicals recommended by the ITC to submit unpublished health and safety studies under TSCA section 8(d). These rules are automatically promulgated by OPPT unless requested not to do so by the ITC.

B. ITC's Use of TSCA Section 8 and “Other Information”

The ITC reviews the TSCA section 8(a) PAIR reports, TSCA section 8(d) HaSD studies and “other information” that becomes available after the ITC adds chemicals to the Priority Testing List. “Other information” includes TSCA section 4(a) and 4(d) studies, TSCA section 8(c) submissions, TSCA section 8(e) “substantial risk” notices, “For Your Information” (FYI) submissions, ITC voluntary submissions, unpublished data submitted to and from U.S. Government organizations represented on the ITC, published papers, as well as use, exposure, effects, and persistence data that are voluntarily submitted to the ITC by manufacturers, importers, processors, and users of chemicals recommended by the ITC. The ITC reviews this information and determines if data needs should be revised, if chemicals should be removed from the Priority Testing List or if recommendations should be changed to designations.

C. Promoting More Efficient Use of Information Submission Resources

The Voluntary Information Submissions Innovative Online Network (VISION) is accessible through the world wide web (http://www.epa.gov/opptintr/itc/vision.htm). VISION includes the Voluntary Information Submissions Policy (VISP) and links to the TSCA Electronic HaSD Reporting Form (http://www.epa.gov/opptintr/.er/hasd.htm). The VISP provides examples of data needed by ITC member U.S. Government organizations, examples of studies that should not be submitted, the milestones for submitting information, guidelines for using the TSCA Electronic HaSD Reporting Form and instructions for electronically submitting full studies. The TSCA Electronic HaSD Reporting Form is used to provide electronic information on ITC voluntary submissions, TSCA section 8(d) studies (to meet data needs of the ITC member U.S. Government organizations), FYI submissions, and TSCA section 8(e) studies.

In its 45^th Report, the ITC stated that use and exposure information should be submitted through VISION using section 3.2 of the TSCA Electronic HaSD Reporting Form (Confidential Business Information (CBI) should NOT be submitted on the TSCA Electronic HaSD Reporting Form). Since then the ITC Director has received numerous requests to provide more details on the type of use and exposure information needed by the ITC. In response to these requests, the ITC asked EPA to include the following use and exposure information in section 3.2 of the TSCA Electronic HaSD Reporting Form:

• Manufacturing or processing procedures (batch, continuous, closed, open, etc.).
• Product (raw-material, site-limited intermediate, end-use, etc.).
• Type of end use (consumer product, industrial product, consumer and industrial product).
• Percent of chemical in end-use product.
• Average concentrations in air, water and soil within the borders of manufacturing and processing facilities.
• Number of people likely to be exposed during chemical manufacturing and average exposure concentrations.
• Number of people likely to be exposed during chemical processing and average exposure concentrations.
• Number of people likely to be exposed during chemical use and average exposure concentrations.

D. Request to Promulgate a TSCA Section 8(d) Rule

The ITC encourages producers, importers, processors, and users of its recommended chemicals to use VISION to voluntarily provide electronic information and establish a dialogue with the ITC to discuss needed data. If the ITC does not receive voluntary electronic information submissions to meet its data needs, then it will ask the EPA to promulgate a TSCA section 8(d) HaSD rule to determine if there are unpublished data to meet those needs. The ITC strongly encourages those companies that must respond to a TSCA section 8(d) rule to provide data by using the TSCA Electronic HaSD Reporting Form.

III. ITC's Activities During This Reporting Period (November 1999 to April 2000): Information Solicitations

In its 45^th Report, the ITC discussed its strategies to screen chemicals for persistence and bioconcentration potential (http://www.epa.gov/opptintr/itc). These strategies are referred to as Degradation Effects Bioconcentration Information Testing Strategies (DEBITS). DEBITS provides a means to prioritize chemicals based on degradation, ecological or human health effects, and bioconcentration information. Briefly the ITC screened 12,557 chemicals and used criteria to identify 435 chemicals with potential to persist and bioconcentrate (see Figure 1 in 45^th Report).

Since the 45^th Report was delivered to the EPA Administrator on November 30, 1999, the ITC used DEBITS to further prioritize these 435 chemicals. The ITC used DEBITS to identify a subset of 112 chemicals with bioconcentration factors (BCFs) >250. These and structurally related chemicals with BCF <250 were placed in chemical classes and screened for the existence of ecological effects, health effects, and environmental fate data. A BCF of 250 has been used by the EPA as a lower “threshold” to identify substances with potential to bioconcentrate. From these 112 chemicals, the ITC reviewed 42 chemicals which had BCF >250 and production/importation volumes between 100,000 and 1,000,000 pounds reported in response to the 1986, 1990, 1994, or 1998 EPA Inventory Update Rules. The ITC is interested in identifying structurally related classes of chemicals for testing which have a suspicion of toxicity but lack adequate screening data. The ITC is also interested in utilizing Structure Activity Relationships (SARs) to predict the toxicity of untested chemicals in these structural classes. Although High Production Volume (HPV) chemicals with production/importation volumes >1,000,000 pounds are expected to have screening data developed as part of the EPA's HPV Chemical Challenge (http://www.epa.gov/opptintr/chemrtk/volchall.htm) and OECD SIDS (http://www.oecd.org/) programs, they were included in groups of structurally related chemicals in order to provide additional opportunities to develop SARs. In a few instances, stucturally related chemicals not previously identified by DEBITS were also included in a chemical class, if there were data useful for establishing SARs.

In this reporting period, three classes of chemicals:

1. Polychlorophenols and polychlorobenzenethiols.

2. Chlorotrifluoromethylphenoxy benzenes.

3. Perfluorinated chemicals have emerged from DEBITS as classes of specific interest.

The ITC is seeking information on uses, exposures, health effects, and ecological effects from the manufacturers, importers, and processors of those chemicals in order to determine whether any of them should be added to the Priority Testing List. It is requested that solicited information be electronically submitted before August 29, 2000, consistent with the 90-day milestone of the VISP (http://www.epa.gov/opptintr/itc/visp.htm) for submitting data through the TSCA Electronic HaSD Reporting Form. DEBITS will continue to be implemented in the future to prioritize chemicals with potential to persist and bioconcentrate.

A. Polychlorophenols and Polychlorobenzenethiols

1. Background. Polychlorophenols and polychlorobenzenethiols includes pentachlorothiophenol (Chemical Abstract Service (CAS) number (No.) 133-49-3) and tetrachloropyrocatechol (CAS No. 1198-55-6). Pentachlorothiophenol is one of the 42 chemicals with BCF >250 and production/importation volume between 100,000 and 1,000,000 pounds. Tetrachloropyrocatechol is one of the 435 chemicals that satisfy the DEBITS production/importation, persistence, and bioconcentration potential criteria described by the ITC in its 45^th Report. The ITC used available data for 2 structurally related chemicals, pentachlorophenol (CAS No. 87-86-5) and hexachlorobenzene (CAS No. 118-74-1), to evaluate suspicion of potential ecological and health effects of pentachlorothiophenol and tetrachloropyrocatechol.

Pentachlorothiophenol meets the DEBITS criteria; it has an ultimate predicted aerobic biodegradation rate of >2-3 months and an estimated log octanol-water partition coefficient of 5.91, and an estimated BCF of 7,066.There are limited health effects data on pentachlorothiophenol except mild eye irritation in the standard Draize test and an intraperitoneal LD₅₀ of 100 milligram/kilogram (mg/kg) in mice. The ITC has no ecological effects data on pentachlorothiophenol. However, pentachlorothiophenol is a metabolite of hexachlorobenzene and pentachlorophenol. It is formed as a result of glutathione conjugation (Hahn et al, 1988, 1989; Linko et al, 1986; Mehendale et al, 1975; Rozman et al, 1977). It has been detected in the urine of human populations exposed to hexachlorobenzene (To-Figueras et al., 1992, 1997). The carcinogenicity, reproductive effects, and development toxicities of pentachlorophenol and hexachlorobenzene are well known (ATSDR, 1996; Chhabra et al., 1999). The ITC believes pentachlorothiophenol may present a suspicion of toxicity given the metabolic relationship and structural similarity to hexachlorobenzene and pentachlorophenol.

Tetrachloropyrocatechol also meets the DEBITS criteria; it has an ultimate predicted aerobic biodegradation rate of >2-3 months and an estimated log octanol-water partition coefficient of 4.29, and a measured BCF of 316-5,011.There is very little known about the health effects of tetrachloropyrocatechol, except for severe eye irritation in the Draize tests and an oral LD₅₀ in mice of 318 mg/kg. However, tetrachloropyrocatechol is a metabolite of pentachlorophenol. A fathead minnow LC₅₀ value of 1 mg/Liter (L) (highly toxic) from 96-hour flow-through tests has been reported (Russom et al., 1997) and six TSCA section 8(d) studies were submitted where tetrachloropyrocatechol was a component of the test substance, biologically treated bleached kraft mill effluent. It is predicted to inhibit cellular respiration as an uncoupler of oxidative phosphorylation. The ITC believes tetrachloropyrocatechol may present a suspicion of toxicity given the metabolic relationship and structural similarity to pentachlorophenol.

Information Profiles for pentachlorothiophenol and tetrachloropyrocatechol are posted on the ITC's web site (http://www.epa.gov/opptintr/itc).

2. Information needs. The ITC needs more information on uses and data on exposures, environmental releases, pharmacokinetics, subchronic toxicity, reproductive and developmental effects, carcinogenicity, and ecological effects for pentachlorothiophenol and tetrachloropyrocatechol. The ITC also needs mutagenicity data for pentachlorothiophenol. If the information is not voluntarily obtained, the ITC will consider adding these chemicals to the Priority Testing List in its next Report to the EPA Administrator so that final TSCA section 8(a) and 8(d) rules are promulgated by EPA.

B. Chlorotrifluoromethylphenoxy Benzenes

1. Background. The chlorotrifluoromethylphenoxy benzenes is a structural class of eight chemicals that satisfy the DEBITS persistence and bioconcentration potential and production/importation criteria described by the ITC in its 45^th Report (Table 2). Four of the chlorotrifluoromethylphenoxy benzenes are among the 42 chemicals with BCF >250 and production/importation volume between 100,000 and 1,000,000 pounds; p-toluidine, 5-chloro-.alpha.,.alpha.,.alpha.-trifluoro-2-nitro-N-phenyl (CAS No. 1806-24-2) has a production/importation volume <100,000 pounds.

One member of the class, lactofen (CAS No. 77501-63-4) is a well-studied herbicide, considered to be a probable human carcinogen by the USEPA. Lactofen or 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitro-2-ethoxy-1-methyl-2-oxo ethyl ester was found to increase the incidence of liver tumors in CD-1 mice and hepatic neoplastic nodules and preneoplastic focii in Sprague-Dawley rats (PPG Industries, 1985a,b). On the basis of these findings, the USEPA concluded that lactofen met the critieria of a category B2 probable human carcinogen (http://ace.orst.edu/cgi-bin/mfs/01/pips/lactofen.htm). A number of other hepatic, renal, and hematologic effects have been reported in CD-1 mice, Sprague-Dawley rats, and beagle dogs after repeated dosing. Lactofen caused developmental effects in a 2-generation reproductive study using CD rats (PPG Industries, 1983) and when fed to pregnant Sprague-Dawley rats (PPG Industries, 1982). Lactofen was administered in the diet for all these studies. Mixed results have been obtained in genotoxicity testing. As a result of the oncogenicity and other adverse health effects associated with lactofen, there is a heightened concern for potential toxicity of the other seven chlorotrifluoromethylphenoxy benzenes which have not been as extensively investigated.

Six chlorotrifluoromethylphenoxy benzenes had fish LC₅₀ values; all were less than or equivalent to about 1 mg/L; chemicals with LC₅₀ values <1 mg/L are considered “highly toxic” to aquatic organisms. Four chlorotrifluoromethylphenoxy benzenes had a nitro group on the benzene ring (Table 2). Estimates from the EPA's Cancer Expert System (Lai et al.,1996; Woo et al., 1995, 1998) suggested that chlorotrifluoromethylphenoxy benzenes with a nitro group on the benzene ring might have higher carcinogenicity potential than chlorotrifluoromethylphenoxy benzenes with no nitro group on the benzene ring. Data are needed to validate these suggestions. In addition, the ITC has determined that health effects data are indexed in TOXLINE or the Registry of Toxic Effects of Chemical Substances (RTECS) for three chlorotrifluoromethylphenoxy benzenes: Phenol, 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitro- (CAS No. 42874-63-5); phenol, 3-(2-chloro-4-(trifluoromethyl)phenoxy)-, acetate (CAS No. 50594-77-9); and benzoic acid, 3-(2-chloro-4-(trifluoromethyl)phenoxy)- (CAS No. 63734-62-3). For the latter 2 chlorotrifluoromethylphenoxy benzenes acute and genetoxicity studies were submitted to the EPA as a result of a TSCA section 8(d) rule that was promulgated for the chlorotrifluoromethylphenoxy benzenes (CAS No. 42874-96-4, 50594-77-9, and 63734-62-3) that were previously added to the Priority Testing List in the ITC's 29^th Report published in the Federal Register of December 30, 1991 (56 FR 67424) (FRL-4007-6) as trifluoromethyl diaryl ethers and then removed from the Priority Testing List in the 41^st Report published in the Federal Register of April 9, 1998 (63 FR 17658) (FRL-5773-5). TOXLINE, RTECS, and TSCA section 8(d) studies for phenol, 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitro- (CAS No. 42874-63-5); phenol, 3-(2-chloro-4-(trifluoromethyl)phenoxy)-, acetate (CAS No. 50594-77-9); and benzoic acid, 3-(2-chloro-4-(trifluoromethyl)phenoxy)- (CAS No. 63734-62-3) have been considered by the ITC. An Information Profile for 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitro- is posted on the ITC's web site (http://www.epa.gov/opptintr/itc).

2. Information needs. The ITC needs information on uses, exposures, environmental releases, ecological effects, pharmacokinetics, subchronic toxicity, reproductive and developmental effects, mutagenicity, and carcinogenicity for four chlorotrifluoromethylphenoxy benzenes, except lactofen and the three HPV chemicals (Table 2). If the information is not voluntarily obtained, the ITC will consider adding these chemicals to the Priority Testing List in its next Report to the EPA Administrator, so that final TSCA section 8(a) and 8(d) rules are promulgated by EPA.

C. Perfluorinated Chemicals

1. Background. The ITC is interested in 50 perfluorinated chemicals, because:

i. The carbon-fluorine bond is highly stable and likely to persist.

ii. There is potential for long-range atmospheric transport, persistence, bioconcentration, and bioaccumulation.

iii. There are few publicly available data on ecological effects, health effects, wildlife exposures, or human exposures.

Forty-eight perfluorinated chemicals were assigned to 10 structural classes while two did not fit any structural class. Thirty-eight perfluorinated chemicals satisfy the DEBITS persistence (ultimate biodegradation >2-3 months) and bioconcentration potential (log octanol-water partition coefficient 3-6) and production/importation criteria described by the ITC in its 45^th Report. An additional 12 (identified by an asterisk in Tables 3, 4, 7, 10, and 11) were selected from TSCA section 8(e) submissions because they were structurally related to the 38 perfluorinated chemicals and may be useful in developing SARs. The 12 structurally related perfluorinated chemicals from TSCA section 8(e) submissions include chemicals that:

i. Are present in human and animal blood.

ii. Are pesticide active ingredients.

iii. Cause tumors and developmental toxicity in animal studies.

iv. Are metabolites of the 38 perfluorinated chemicals that satisfy the DEBITS criteria.

Estimated BCFs and Henry's Law Constants (HLCs) for perfluorinated chemicals were based on associated or non-hydrolyzed chemical structures. Estimated BCFs for the 50 perfluorinated chemicals range from 3 to 26,000. HLCs ranged from 10³ to 10^-10 atm m³/mole. Approximately half of the perfluorinated chemicals had estimated HLCs >^10-2 atm m³/mole, suggesting they could evaporate and be susceptible to long-range transport. The perfluoroalkyl iodides are likely to undergo rapid photolysis in the atmosphere, leading to possibly long-lived degradation products. Estimated BCFs and HLCs for perfluorinated chemicals are listed in Tables 3-13. Information Profiles for non-HPV perfluorinated chemicals for which there were publicly available toxicity data are posted on the ITC's web site (http://www.epa.gov/opptintr/itc). The ITC is continuing to evaluate information on uses, exposures, environmental fate, ecological effects, and health effects of perfluorinated chemicals.

2. Information needs. The ITC needs measured BCFs, HLCs, and bioaccumulation data for most of the perfluorinated chemicals. Information on uses, exposures, health effects, and ecological effects is needed for perfluoroalkyl acids and salts, perfluoroalkyl sulfonamides, perfluorinated quaternary ammonium chemicals, perfluoroalkanes, fluoroalkyl ethers, fluoroalkyl iodides, gamma, omega-perfluoroalkyl alcohols, perfluoroalkyl sulfonyl fluorides, perfluoroglycol acid fluorides, perfluoroalkyl carboxylic acid fluorides, 1-hexene, 3,3,4,4,5,5,6,6,6-nonafluoro- (CAS No. 19430-93-4), and perfluoroalkyl (C4-C10) ethyl mercaptan (CAS No. 68140-20-5). For the perfluoroalkyl iodides, the ITC needs information on possible long-lived atmospheric degradation products. ITC is not soliciting information on two perfluoroalkyl sulfonamides that are in the EPA's HPV Challenge Program, 1-octanesulfonamide, 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8- heptadecafluoro-N-(2-hydroxyethyl)-N-ethyl- (CAS No. 1691-99-2) and 1-octanesulfonamide, 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-N-(2-hydroxyethyl)-N-methyl- (CAS No. 24448-09-7) and the pesticides, lithium perfluorooctane sulfonate (LPOS) or 1-octanesulfonic acid, 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-, lithium salt (CAS No. 29457-72-5) (see http://www.epa.gov/opprd001/factsheets/factsht2.htm) and Sulfuramid or 1-octanesulfonamide, -ethyl-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro- (CAS No. 4151-50-2) (see http://www.epa.gov/opp).

IV. Revisions to the TSCA Section 4(e) Priority Testing List

A. Chemicals Added to the Priority Testing List: Nonylphenol Polyethoxylate Degradation Products

1. Recommendation. Add 8 nonylphenol polyethoxylate degradation products to the Priority Testing List to obtain information to meet U.S. Government data needs.

2. Rationale for recommendation. Alkylphenols, polyalkylphenols, alkylphenol ethoxylates, and alkylphenol polyethoxylates were recommended in the ITC's 37^th (61 FR 4188, February 2, 1996) (FRL-4991-6), 39^th (62 FR 8578, February 25, 1997) (FRL-5580-9), and 41^st Reports. Nonylphenol polyethoxylates were recommended in the ITC's 39^th Report. Recent studies have measured nonylphenol polyethoxylate degradation products in wastewater effluents and surrounding aquatic systems (Bennett and Metcalfe, 2000; Hale et al., 2000). Some of these products can cause neuroendocrine-mediated effects in fish at low parts per billion (ppb) concentrations. One nonlylphenol polyethoxylate degradation product, branched 4-nonylphenol (mixed isomers) (CAS No. 84852-15-3) was previously recommended in the ITC's 37^th Report. As a result of these findings and to meet U.S. Government data needs for these chemicals, the ITC is adding 8 nonlylphenol polyethoxylate degradation products to the Priority Testing List (Table 14).

3. Supporting information. Recent studies have documented that nonylphenol polyethoxylate degradation products can act as in vitro and in vivo estrogen agonists in fish and amphibians (Jobling and Sumpter, 1993; Jobling et al., 1996; Kloas et al., 1999). While most of these studies were conducted with nonylphenol and octylphenol, there is evidence to suggest that nonylphenol polyethoxylate degradation products (short-chain ethoxylates and carboxylates) can also act to disrupt neuroendocrine function.

i. Effects. Exposure of male fathead minnows to nonylphenol at 1.1 ppb caused an increase in the number and size of sertoli cells and germ cell syncytia (Miles-Richardson et al., 1999). In the same study, exposure of fathead minnows to 5.5 ppb nonylphenol polyethoxylate consisting of primarily 7-11 carbon ethoxylate chains, no changes in number and size of sertoli cells and germ cell syncytia were detected, but shorter carbon ethoxylate chains (1-4 carbons) were not tested. In the same laboratory, exposure of fathead minnows to 0.05 ppb nonylphenol caused significant increases in plasma vitellogenin and estradiol (Giesy et al., 2000).

Exposure of male rainbow trout to 30 ppb octylphenol, nonylphenol, 4-nonylphenoxy acetic acid (NP1EC), and 4-nonylphenol diethoxylate (NP2EO) caused increases in serum vitellogenin and inhibition in testicular growth (Jobling et al., 1996). Octylphenol was the most potent followed by nonylphenol, NP2EO, and NP1EC. A lowest-observed-effect-concentration (LOEC) was not determined for NP2EO or NP1EC, but the 30 ppb exposure concentrations for NP1EC and NP2EO are well below total concentrations of carboxylates and ethoxylates reported for many of the effluents in the midwestern United States that are discussed below. Exposure of female rainbow trout to 1 ppb nonylphenol and NP2EO and 10 ppb NP1EC reduced growth (Ashfield et al., 1998).

ii. Environmental concentrations. Despite data suggesting that nonylphenolpolyethoxylate metabolites may biodegrade (Staples et al., 1999), recent studies demonstrated that nonylphenol polyethoxylate effluent and effluent dominated stream concentrations may exceed LOEC concentrations reported in the literature. Barber et al. (1999) estimated nonylphenol polyethoxylate degradation products in seven midwest sewage treatment plant effluents and in one effluent-dominated stream (Des Plaines River, IL) approximately 100 killometers (km) downstream of the major nonylphenol polyethoxylate sources. Generally effluents had nonylphenol polyethoxylate degradation product concentrations greater than 50 ppb with NPE2C the predominant form in most effluents and in the effluent dominated stream. Nonylphenol concentrations in the Des Plaines River slightly exceeded 1 ppb. Naylor et al. (1996) and Field and Reed (1996) estimated nonylphenol, total nonylphenol ethoxylate, and NP1EC-NP4EC (4-nonylphenoxy triethoxy acetic acid) concentrations in 15 pulp and paper mill and 6 sewage treatment plant effluents to the Fox River, WI. Total nonylphenol ethoxylate typically exceeded 50 ppb in all effluents, while nonylphenol concentrations were generally greater than 1 ppb. The nonylphenol carboxylates concentrations were always greater than 15 and 140 ppb in the pulp and paper mill and sewage treatment effluents, respectively. Nonylphenol and total nonylphenol ethoxylate Fox River concentrations near Green Bay were 0.582 and 2.78 ppb, respectively, while the total nonylphenol carboxylate concentration was 13.5 ppb. Nonylphenol carboxylates were shown to persist for considerable distances downstream. In addition to these existing data, EPA is sponsoring ongoing programs to sample sediment and fish in the midwestern United States.

4. Information needs. Data are needed to determine the LOECs (in comparison to estradiol) of branched 4-nonylphenol (mixed isomers), 4-nonylphenol ethoxylate (NP1EO), 4-nonylphenol diethoxylate (NP2EO), 4-nonylphenol triethoxylate (NP3EO), 4-nonylphenol tetraethoxylate (NP4EO), 4-nonylphenoxy acetic acid (NP1EC), 4-nonylphenoxy diethoxy acetic acid (NP2EC), 4-nonylphenoxy triethoxy acetic acid (NP3EC), and 4-nonylphenoxy tetraethoxy acetic acid (NP4EC) causing neuroendocrine effects in aquatic organisms. Data are also needed to determine whether nonylphenol polyethoxylate degradation products have the potential to interfere with growth and metamorphosis of amphibians (e.g., tadpoles).

B. Chemicals Removed From the Priority Testing List: Alkylphenols and Alkylphenol Ethoxylates

1. Background. In this Report, the ITC is removing 4 alkylphenols (APs) and 15 alkylphenol ethoxylates (APEs) from the Priority Testing List. The 4 APs were added to the Priority Testing List in the ITC's 37^th Report; the 15 APEs were added to the Priority Testing List in the ITC's 39^th Report. Submission of TSCA section 8(d) studies for APs added to the Priority Testing List in the ITC's 37^th Report were required by a TSCA section 8(d) HaSD rule (61 FR 7421, February 28, 1996) (FRL-4991-6). TSCA section 8(d) and FYI studies for APEs added to the Priority Testing List in the ITC's 39^th Report were voluntarily submitted in response to information solicitations discussed in the ITC's^39th Report.

2. Removal rationale. The APs and APEs being removed from the Priority Testing List are listed in Table 15. Three APs and 13 APEs are being removed because no domestic production or importation volumes were reported to the USEPA in response to any of the 1986, 1990, 1994, and 1998 Information Update Rules (IURs) or the 2000 PAIR rule. Production/importation volumes were reported for one AP and two APEs in the 1990 IUR but not in the subsequent 1994 and 1998 IURs or the 2000 PAIR rule. These three chemicals are also being removed because of insufficient production.

V. References

1. Ashfield, L.A., Pottinger, T.G., and Sumpter, J.P. 1998. Exposure of female juvenile rainbow trout to alkylphenolic compounds results in modification to growth and ovosomatic index. Environmental Toxicology and Chemistry 17:679-686.

2. Agency for Toxic Substances and Disease Registry (ATSDR). 1996. Toxicological Profile for Hexachlorobenzene. ATSDR. Atlanta, Georgia.

3. Barber, L.B., Brown, G.K., and Zaugg, S.D. 1999. Potential endocrine disrupting chemicals in treated municipal wastewater and river water, Upper Midwest, USA. In: Keith, L., Jones-Lepp, T., and Needham, L. (Eds) Analysis of Environmental Endocrine Disruptors, American Chemical Society Symposium Series No. 747. American Chemical Society. Washington, DC.

4. Bennet, E.R. and Metcalfe, C.D. 2000. Distribution of degradation products of alkylphenol ethoxylates near sewage treatment plants in the Lower Great Lakes, North America. Environmental Toxicology and Chemistry 19:784-792.

5. Chhabra, R.S., Maronpot, R.M., Bucher, J.R., Haseman, J.K., Toft, J.D., and Hejtmancik, M.R. 1999. Toxicology and carcinogenesis studies of pentachlorophenol in rats. Toxicological Science 48:14-20.

6. Field, J. F. and Reed, R. L. 1996. Nonylphenol polyethoxy carboxylate metabolites of nonionic surfactants in paper mill effluents, municipal sewage treatment plant effluents and river waters. Environmental Science and Technology 30:3544-3550.

7. Giesy, J.P., Pierens S.L., Miles-Richardson S., Kramer, V.J., Snyder, S.S., Nichols, K.M., Snyder, E., Villenueve, D.A., and Giesy, J.P. 2000. Effects of 4-Nonylphenol on Fecundity and Biomarkers of Estrogenicity in Fathead Minnows (Pimephales promelas). Environmental Toxicology and Chemistry 19:1368-1377.

8. Hahn, M.E, Gasiewicz, T.A, Linko, P., and Goldstein, J.A. 1988. The role of the Ah locus in hexachlorobenzene-induced porphyria: Studies in congenic C57BL/6J mice. Biochemical Journal 254:245-254.

9. Hahn, M.E, Goldstein, J.A, Linko, P., and Gasiewicz, T.A. 1989. Interaction of hexachlorobenzene with the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro and in vivo. Archives of Biochemistry and Biophysics 270:344-355.

10. Hale, R.C., Smith, C.L., De Fur, P.O., Harvey, E., Bush, E.O., La Guardia, M.J., and Vadas, G.G. 2000. Nonylphenols in sediments and effluents associated with diverse wastewater outfalls. Environmental Toxicology and Chemistry 19:946-952.

11. Jobling, S. and Sumpter, J. P. 1993. Detergent compounds in sewage treatment plant effluents are weakly oestrogenic to fish: an in vitro study using rainbow trout hepatocytes. Aquatic Toxicology 27:361-372.

12. Jobling, S., Sheahan, D., Osborne, J.A., Matthiessen, P., and Sumpter, J.P. 1996. Inhibition of testicular growth in rainbow trout (Oncorhynchus mykiss) exposed to estrogenic alkylphenolic compounds. Environmental Toxicology and Chemistry 15:194-202.

13. Kloas, W., Lutz, I., and Einspanier, R. 1999. Amphibians as a model to study endocrine disruptors: II. Estrogenic activity of environmental chemicals in vitro and in vivo. Science of the Total Environment 225:59-68.

14. Lai, D.Y., Woo, Y.T., Argus, M.F., and Arcos, J.C.1996. Cancer risk reduction through mechanism-based molecular design of chemicals. pp. 62-73. In: S.C. DeVito and R.L. Garrett, (Eds) Designing Safer Chemicals, ACS Symposium Series No. 640, American Chemical Society, Washington, DC.

15. Linko, P., Yeowell, H.N., Gasiewicz, T.A., and Goldstein, J.A.1986. Induction of cytochrome P-450 isozymes by hexachlorobenzene in rats and aromatic hydrocarbon (Ah)-responsive mice. Journal of Biochemical Toxicology 1:95-107.

16. Mehendale, H.M., Fields, M., and Matthews, H.B. 1975. Metabolism and effects of hexachlorobenzene on hepatic microsomal enzymes in the rat. Journal of Agriculture and Food Chemistry 23:261-265.

17. Miles-Richardson, S.R., Pierens, S.L., Nichols, K.M., Kramer, V.J., Snyder, E.M., Snyder, S.A., Render, J.A., Fitzgerald, S.D., and Giesy, J.P. 1999. Effects of waterborne exposure to 4-nonylphenol and nonylphenol ethoxylate on secondary sex characteristics and gonads of fathead minnows (Pimephales promelas). Environmental Research A80:S122-S137.

18. Naylor, C.G., Williams, J. B., Varineau, P. T., Webb, D. A., and Sanders, D. F. 1996. Nonylphenol ethoxylates in an industrial river. 4^th CEISO World Surfactants Congress, Volume 4.

19. PPG Industries. 1982. MRID No. 00117566. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

20. PPG Industries. 1983. MRID No. 00132885. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

21. PPG Industries. 1985a. MRID No. 00150343, 00150366. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

22. PPG Industries. 1985b. MRID No. 00132883, 00150329. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

23. Rozman, K., Mueller W., Coulston, F., and Korte, F. 1977. Long-term feeding study of hexachlorobenzene in rhesus monkeys. Chemosphere 6:81-84.

24. Russom, C.L., Bradbury, S.P., Braiders, S.J., Hammermeister, D.E., and Drummond, R.A. 1997. Predicting modes of toxic action from chemical structure: Acute toxicity in the fathead minnow (Pimephales Promelas). Environmental Toxicology and Chemistry 16:948-967.

25. Staples, C.A., Williams, J.B., Blessing, R.L., and Varineau, P.T. 1999. Measuring the biodegradability of nonylphenol ether carboxylates, octylphenol ether carboxylates and nonylphenol. Chemosphere 38:2029-2039.

26. Woo, Y.T., Lai, D.Y., Argus, M.F., and Arcos, J.C. 1995. Development of structure-activity relationship rules for predicting carcinogenic potential of chemicals. Toxicology Letters 79:219-228.

27. Woo, Y.T., Lai, D.Y., Argus, M.F., and Arcos, J.C. 1998. An integrative approach of combining mechanistically complementary short-term predictive tests as a basis for assessing the carcinogenic potential of chemicals. Journal of Environmental Science and Health C16:101-122.

VI. TSCA Interagency Testing Committee

Statutory Organizations and Their Representatives

Council on Environmental Quality

Department of Commerce

   National Institute of Standards and Technology

    Robert Huie, Member

    Barbara C. Levin, Alternate

   National Oceanographic and Atmospheric Administration

    Nancy Foster, Member

    Teri Rowles, Alternate

Environmental Protection Agency

  Paul Campanella, Member

  David R. Williams, Alternate

National Cancer Institute

  Victor Fung, Alternate

National Institute of Environmental Health Sciences

  Scott Masten, Member

  William Eastin, Alternate

National Institute for Occupational Safety and Health

  Albert E. Munson, Member

  Mark Toraason, Alternate

National Science Foundation

  A. Frederick Thompson, Member

  Marge Cavanaugh, Alternate

Occupational Safety and Health Administration

  Val H. Schaeffer, Member, Chair

  Lyn Penniman, Alternate

Liaison Organizations and Their Representatives

Agency for Toxic Substances and Disease Registry

  William Cibulas, Member

Consumer Product Safety Commission

  Jacqueline Ferrante, Member

  Treye Thomas, Alternate

Department of Agriculture

  Clifford P. Rice, Member

Department of Defense

  Barbara Larcom, Member

  Kenneth Still, Alternate

  Jose Centeno, Alternate

Department of the Interior

  Barnett A. Rattner, Member, Vice Chair

Food and Drug Administration

  Ronald Lorentzen, Member

  Raju Kammula, Alternate

  David Hatten, Alternate

National Library of Medicine

  Vera W. Hudson, Member

National Toxicology Program

  NIEHS, FDA, and NIOSH Members

Counsel

  Scott Sherlock, Office of Pollution Prevention and Toxics, EPA

Technical Support Contractor

  Syracuse Research Corporation

ITC Staff

  John D. Walker, Executive Director

  Norma S. L. Williams, Executive Assistant

TSCA Interagency Testing Committee, Office of Pollution Prevention and Toxics (7401), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (202) 260-1825; fax number: (202) 260-7895; e-mail address: williams.norma@epa.gov; url: http://www.epa.gov/opptintr/itc.