Federal Register / Vol. 65, No. 233 / Monday, December 4, 2000 / Notices 75727

Non-Asbestiform) changes on the

agenda from number seven to number

six; and Estrogens, Steroidal changes

from number five to number seven for

review. Summary data and the revised,

preliminary order for review of the

nominations are listed in the table

below:

SUMMARY DATA FOR NOMINATIONS TO BE REVIEWED AT THE MEETING OF THE NTP BOARD OF SCIENTIFIC COUNSELORS’

REPORT ON CARCINOGENS SUBCOMMITTEE—DECEMBER 13, 14, & 15, 2000

Nomination to be reviewed/cas number Primary uses or exposures To be reviewed for Tentative

review order

Broad Spectrum UV Radiation and UVA, UVB

and UVC.

Solar and artificial sources of ultraviolet radiation Listing in the 10th Report.1

Chloramphenicol/(56–75–7) ................................... Used widely as an antibiotic since the 1950s ....... Listing in the 10th Report.5

Estrogens, Sterodial ............................................... Estrogens are widely used in post-menopausal

therapy and in oral contraceptives for women.

Listing in the 10th Report.7

Metallic Nickel & Nickel Alloys ............................... Widely used in commercial applications for over

100 years.

Listing in the 10th Report.4

Methyleugenol/(93–15–2) ....................................... Flavoring agent used in jellies, baked goods,

nonalcholoic beverages, chewing gum, candy,

and ice cream. Also used as a fragrance for

many perfumes, lotions, detergents and soaps.

Listing in the 10th Report.3

Talc/(14807–96–6) (Asbestiform and (NonAsbestiform).Asbestiform talc (i.e. talc containing Asbestiform

fibers) occurs in various geological settings

around the world. Occupational exposure occurs during mining, milling and processing.

Non-asbestiform talc (i.e. talc not containing

asbestiform fibers) occurs in various geological

settings around the world. Occupational exposure occurs during mining, milling and processing. Exposure to general population occurs

through use of products such as cosmetics.

Listing in the 10th Report.6

Trichloroethylene (TCE)/(79–01–6) ........................ Trichloroethylene is widely used as a solvent with

80–90% used worldwide for degreasing metals.

Upgrade to Known ......... 2

Wood Dust .............................................................. It is estimated that at least two million people are

routinely exposed occupationally to wood dust

worldwide. Non-occupational exposure also occurs. The highest exposures have generally

been reported in wood furniture and cabinet

manufacturer, especially during machine sanding and similar operations.

Listing in the 10th Report.8

The RoC Subcommittee will provide

separate recommendations for each of

the agents, substances, mixtures or

exposure circumstance listed in the

table above. This includes separate

recommendations for Broad Spectrum

UV Radiation and for UVA, for UVB,

and for UVC; for Metallic Nickel and for

Nickel Alloys, and for Talc Asbestiform

and for Talc Non-Asbestiform.

The agenda and a roster of

Subcommittee members is available on

the NTP web homepage at http://ntpserver.niehs.nih.gov/ and upon request

from Dr. Wolfe (Dr. Mary S. Wolfe, P.O.

Box 12233, A3–07, Research Triangle

Park, NC 27709 (telephone 919/541–

3971; FAX 919/541–0295; email

wolfe@niehs.nih.gov). Summary

minutes for the previous meeting are

available on the NTP web homepage

and upon request from Dr. Wolfe.

Dated: November 21, 2000.

Samuel H. Wilson,

Deputy Director, National Institute of

Environmental Health Services.

[FR Doc. 00–30712 Filed 12–1–00; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Public Health Service

National Toxicology Program; Request

for Comments on Substances

Nominated to the National Toxicology

Program (NTP) for Toxicological

Studies and on the Testing

Recommendations Made by the NTP

Interagency Committee for Chemical

Evaluation and Coordination (ICCEC)

Summary

The National Toxicology Program

(NTP) routinely solicits, accepts and

reviews for consideration nominations

for toxicological studies to be

undertaken by the Program on

substances of potential human health

concern. Nominations are solicited

widely from Federal agencies, the

public, and other interested parties and

those received undergo several levels of

review before toxicological studies are

designed and implemented. The NTP

Interagency Committee for Chemical

Evaluation and Coordination (ICCEC)

serves as the first level of review for

NTP nominations. At the October 27,

2000 ICCEC meeting, 18 new

nominations were reviewed and testing

recommendations were made. As part of

an effort to inform the public and to

obtain input for consideration when

selecting chemicals for evaluation, the

NTP routinely seeks public comment on

(1) substances nominated to the Program

for toxicological studies and (2) the

testing recommendations made by the

ICCEC. This announcement provides

brief background information about the

nomination of substances for NTP

study; presents the ICCEC’s testing

recommendations from the October 27,

2000 meeting; solicits public comment

on those nominations and

recommendations; and requests the

submission of additional relevant

information for consideration by the

NTP in its subsequent evaluation of the

nominations.

Background

The NTP actively seeks to identify

and select for study chemicals and

agents with the highest potential for

75728 Federal Register / Vol. 65, No. 233 / Monday, December 4, 2000 / Notices

adversely impacting public health. The

nomination process is open to all

interested parties and substances

selected for study generally fall into two

broad overlapping categories: (1) Those

substances of greatest concern for public

or occupational health based on the

extent of human exposure and suspicion

of toxicity; and (2) substances for which

toxicological data gaps exist and

additional studies would aid in

assessing potential human health risks

by facilitating cross-species

extrapolation and evaluation of doseresponse relationships. Particular

assistance is also sought for the

nomination of studies that permit the

testing of hypotheses to enhance the

predictive ability of future NTP studies,

address mechanisms of toxicity, or fill

significant gaps in the knowledge of the

toxicity of chemicals or classes of

chemicals. Substances may be studied

for a variety of health-related effects,

including but not limited to

reproductive and developmental

toxicity, genotoxicity, immunotoxicity,

metabolism and disposition, as well as

carcinogenicity. Selections for NTP

testing also consider legislative

mandates that require responsible

manufacturers to evaluate their own

chemicals or agents for health and

environmental effects. The possible

human health consequences of

anticipated or known human exposure,

however, remain the over-riding factor

in the decision to study a particular

chemical or agent.

The review and selection of

substances nominated for study is a

multi-level process. A broad range of

concerns are addressed during this

process through the participation of

representatives from Federal agencies,

the NTP Board of Scientific

Counselors—an external scientific

advisory body, the NTP Executive

Committee—the NTP Federal

interagency policy body, and a public

comment period. This process is

described in further detail in a March 2,

2000 Federal Register Announcement

(Volume 65, Number 42, pages 11329–

11331). As a result of this multi-step

evaluative process for NTP nominations,

the Program receives appropriate

direction and guidance to ensure that

it’s testing program addresses

toxicological concerns relative to all

areas of public health, and furthermore,

that there is balance among the types of

substances selected for study (e.g.,

industrial chemicals, consumer

products, therapeutic agents, etc.). As

such, it must be recognized that for any

given committee review, the substances

being considered for new testing do not

necessarily reflect the overall balance of

substances historically or currently

being evaluated by NTP in it’s testing

program. For further information on

NTP studies (previous or in progress)

visit the NTP web page at the URL listed

at the end of this announcement.

Nominated Substances and ICCEC

Review

The NTP Interagency Committee for

Chemical Evaluation and Coordination

(ICCEC) is composed of representatives

from the Agency for Toxic Substances

and Disease Registry, Consumer Product

Safety Commission, Department of

Defense, Environmental Protection

Agency, Food and Drug

Administration’s National Center for

Toxicological Research, National Cancer

Institute, National Institute of

Environmental Health Sciences,

National Institute for Occupational

Safety and Health, National Library of

Medicine, and the Occupational Safety

and Health Administration. As part of

the review and selection process for

nominations, the ICCEC meets once or

twice annually to review and evaluate

the nominations and to make testing

recommendations with respect to both

specific types of studies and testing

priorities. At its meeting on October 27,

2000, the ICCEC reviewed 18 new

nominations for NTP studies. For 15 of

these nominations, pharmacokinetic,

toxicity, and/or carcinogenicity studies

were recommended. A testing

recommendation for three nominations

was deferred pending receipt of (1)

additional information or data from the

nominator or other organizations on

related studies completed, anticipated

or in progress, or (2) additional

information on production, exposure,

use patterns, and regulatory needs. The

nominated substances with CAS

numbers, nomination source, types of

studies recommended, study rationale

and other information are given in the

attached tables.

Request for Comment

Interested parties are encouraged to

provide comments or supplementary

information on the nominated

substances and recommendations

identified in this announcement. The

NTP would welcome receiving

toxicology and carcinogenesis

information from completed, ongoing,

or planned studies, as well as

information on current production

levels, human exposure, use patterns,

environmental occurrence, or public

health concerns for any of the

substances listed in the attached tables.

Comments or information should be

sent to Dr. Scott Masten at the address

given below within 60 days of the

publication date of this announcement.

Persons responding to this request are

asked to include their name, affiliation,

mailing address, phone, fax, e-mail

address and sponsoring organization (if

any) with the submission. An electronic

copy of this announcement as well as

further information on the NTP and the

NTP Chemical Nomination and

Selection Process can be accessed

through the NTP web site. The URL for

the NTP homepage is http://ntpserver.niehs.nih.gov.

Contact may be made by mail to Dr.

Scott Masten, NIEHS/NTP, P. O. Box

12233, Research Triangle Park, North

Carolina 27709; by telephone at (919)

541–5710; by FAX at (919) 558–7067; or

by email to masten@niehs.nih.gov.

Dated: November 20, 2000.

Samuel H. Wilson,

Deputy Director, National Institute of

Environmental Health Sciences.

Attachment—Substances Nominated to

the NTP for Study and Testing

Recommendations Made by the ICCEC

on October 27, 2000

TABLE 1.—SUBSTANCES RECOMMENDED FOR TESTING

Substance [CAS Number] Nominated by ICCEC recommendations Study rationale; other information

Aluminum complexes

found in drinking water,

Aluminum fluoride,

[7784–18–1], Aluminum

citrate, [31142–56–0].

Environmental Protection

Agency; National Institute of Environmental

Health Sciences.

Long-term drinking water studies to address pharmacokinetics, neurotoxicity,

bone development, and reproduction

and developmental toxicity.

Drinking water contaminants with a high

health research priority; known

neurotoxicity of aluminum; need for better understanding of pharmacokinetics

and toxicity of aluminum species occurring in drinking water.

—Consider testing in transgenic animal

models of neurodegenerative disease.

Federal Register / Vol. 65, No. 233 / Monday, December 4, 2000 / Notices 75729

TABLE 1.—SUBSTANCES RECOMMENDED FOR TESTING—Continued

Substance [CAS Number] Nominated by ICCEC recommendations Study rationale; other information

Bilberry fruit extract,

[84082–34–8].

National Cancer Institute —In vitro and in vivo genotoxicity testing .. Widespread human exposure through use

as a dietary supplement; lack of toxicity

information.

Black cohosh, [84776–26–

1].

National Cancer Institute;

National Institute of

Environmental Health

Sciences.

—Subchronic toxicity testing in young and

aged female animals.

Widespread human exposure through use

as a dietary supplement; reported estrogenic activity; inadequate toxicity information.

—Two-generation reproductive and developmental toxicity study.

Blue-Green algae (dietary

supplements and selected toxins).

National Cancer Institute —Subchronic toxicity and neurotoxicity

studies of commercial blue-green algae

dietary supplements.

Widespread human exposure through

drinking water and via contamination of

algal dietary supplements; demonstrated acute toxicity but only limited

chronic toxicity information available.

—Consider testing specific cyanobacterial

toxins pending results of Blue-Green

algae dietary supplement and

microcystin-LR studies.

Cefuroxime, [55268–75–2] Food and Drug Administration.—Genotoxicity testing (Syrian hamster

embryo in vitro cell transformation

assay; in vivo micronucleus assay).

Prescription drug with widespread and potentially long-term use; lack of chronic

toxicity data for any member of this

class of drugs.

Clarithromycin, [81103–11–

9].

Food and Drug Administration.—Genotoxicity testing (Syrian hamster

embryo in vitro cell transformation

assay; in vivo micronucleus assay).

Prescription drug with widespread and potentially long-term use; numerous

known toxicities in short-term studies;

lack of chronic toxicity data.

D&C Red No. 27, [13473–

26–2] and D&C Red No.

28, [18472–87–2].

Food and Drug Administration.—In vitro percutaneous absorption testing Approved colorings for drugs and cosmetics that can lead to DNA damage;

lack of sufficient data on long-term

phototoxicity or photocarcinogenicity.

—Photocarcinogenicity testing dependent

on results of absorption studies.

N,N-Dimethyl-p-toluidine,

[99–97–8].

National Cancer Institute —Subchronic toxicity testing pending review of industry test plans and/or data

developed under EPA’s High Production

Volume Chemical Challenge Program.

High production volume chemical with potential for widespread human exposure

and limited chronic toxicity or carcinogenicity data; genotoxic; suspicion of

carcinogenicity.

Lemon Oil, [8008–56–8]

and Lime Oil, [8008–26–

2].

Food and Drug Administration.—Photogenotoxicity testing ....................... Widespread consumer exposure as a fragrance component; known phototoxicity;

long-term toxicity unknown.

—Photocarcinogenicity testing dependent

on results of phototogenotoxicity studies.

Local anesthetics that metabolize to 2,6-xylidine or

o-toluidine, Bupivacaine,

[38396–39–3],

Prilocaine, [721–50–6].

Private Individual; National Institute of Environmental Health

Sciences.

—Short-term in vitro/in vivo mechanistic

studies to evaluate carcinogenic metabolite formation and genotoxicity of

representative local anesthetic compounds.

Widespread clinical use and human exposure; potentially metabolized to carcinogenic and neurotoxic intermediates; little

available quantitative metabolism or

genotoxicity data.

Microcystin-LR, [101043–

37–2].

National Institute of Environmental Health

Sciences.

—Toxicokinetic, subchronic, reproductive

toxicity, chronic toxicity and carcinogenicity studies including doses relevant

to environmental concentrations in

drinking water.

Cyanobacteria and their toxins are drinking water contaminants with a high

health research priority; many have high

acute toxicity and known hepatotoxicity

and hepatocarcinogenicity.

—Consider carcinogenicity testing in Japanese Medaka fish model.

Organotins occurring in

drinking water,

Monomethyltin trichloride, [993–16–8],

Dimethyltin dichloride,

[753–73–1], Monobutyltin

trichloride, [1118–46–3],

Dibutyltin dichloride,

[683–18–1].

Environmental Protection

Agency; National Institute of Environmental

Health Sciences.

—Long-term single chemical and binary

mixture drinking water studies to address pharmacokinetics, neurotoxicity,

immunotoxicity, and reproductive and

developmental toxicity.

Drinking water contaminants with a high

health research priority; numerous

organotins have demonstrated a broad

spectrum of toxicity; chronic toxicity information on organotin species primarily

found in drinking water is limited.

—Consider testing in transgenic animal

models of neurodegenerative disease.

All-trans-retinyl palmitate,

[79–81–2].

Food and Drug Administration.—Phototoxicity and photocarcinogenicity

testing.

Widespread use in cosmetic products;

known biochemical and histological cutaneous alterations; other retinoids

known to enhance photocarcinogenesis.

75730 Federal Register / Vol. 65, No. 233 / Monday, December 4, 2000 / Notices

TABLE 1.—SUBSTANCES RECOMMENDED FOR TESTING—Continued

Substance [CAS Number] Nominated by ICCEC recommendations Study rationale; other information

S-Adenosylmethionine,

[29908–03–0].

National Cancer Institute —In vitro genotoxicity testing (Syrian hamster embryo cell transformation and

DNA alkylation assays).

Widespread exogenous human exposure

through use as a dietary supplement;

limited toxicity data available.

—Subchronic toxicity testing dependent

on results of genotoxicity studies.

Senna ................................ Food and Drug ............... —Carcinogenicity testing in p53 ................ Data needed to complete safety

[8013–11–4] ....................... Administration ................. transgenic mouse model ............................ evaluation of stimulant laxatives;

transgenic studies will complement

manufacturer sponsored carcinogenicity

studies.

TABLE 2.—SUBSTANCES FOR WHICH A TESTING RECOMMENDATION IS DEFERRED PENDING RECEIPT AND CONSIDERATION

OF ADDITIONAL INFORMATION

Substance [CAS Number] Nominated by Nominated for Nomination rationale Additional information needed

1,3-Dichloropropane,

[142–28–9], 2,2-

Dichloropropane,

[594–20–7], 1,1-

Dichloropropene,

[563–58–6].

Environmental Protection Agency;

National Institute

of Environmental

Health Sciences.

—Short-term comprehensive drinking water toxicity

studies.

Drinking water contaminants with

high health research priority;

very limited toxicity data; known

toxicity and carcinogenicity of

structurally similar compounds.

Additional drinking water occurrence data; production volumes;

potential sources of drinking

water contamination; anticipated

regulatory value of additional

toxicity data.

—Pharmacokinetics

—Medaka studies ....

—Testing in human

bladder cell transformation model.

Hydergine, [8067–24–

1].

National Cancer Institute.—Genotoxicity testing.Ergot alkaloid prescription drug

with recent increase in ‘‘off

label’’ and dietary supplement

use in healthy individuals; lack

of available information on toxicity and carcinogenicity.

Dietary supplement sales and use

information; regulatory agency

information needs.

Yohimbe bark extract,

[85117–22–2], Yohimbine, [146–48–5].

National Cancer Institute.—Micronucleus

assay.

Significant human exposure

through use as a dietary supplement; suspicion of carcinogenicity of yohimbine based on

structural similarity to reserpine.

Dietary supplement use levels and

patterns; regulatory agency

informaiton needs.

[FR Doc. 00–30715 Filed 12–1–00; 8:45 am]

BILLING CODE 4140–00–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Substance Abuse and Mental Health

Services Administration

Agency Information Collection

Activities: Submission for OMB

Review; Comment Request

Periodically, the Substance Abuse and

Mental Health Services Administration

(SAMHSA) will publish a list of

information collection requests under

OMB review, in compliance with the

Paperwork Reduction Act (44 U.S.C.

Chapter 35). To request a copy of these

documents, call the SAMHSA Reports

Clearance Officer on (301) 443–7978.

Treatment Improvement Protocols

(TIPs) Evaluation Project—Prospective

Study—New—Since 1993, SAMHSA’s

Center for Substance Abuse Treatment

has published 37 Treatment

Improvement Protocols, which provide

administrative and clinical practice

guidance to the substance abuse

treatment field. This is the third of three

major studies and is designed to assess

readers’ use of TIPs and the impact of

TIPs on changing substance abuse

treatment practices.

The Prospective Study seeks to

determine the most cost effective level

of support needed by substance abuse

treatment providers to implement in

practice the information contained in

TIPs. Specifically, this study will

examine the use of TIP # 35,

‘‘Enhancing Motivation for Change in

Substance Abuse Treatment,’’ by

treatment professionals in four different

areas of the country. The study will use

a pretest/post-test experimental design

in which treatment facilities will be

randomly assigned to one of four

conditions: (1) The control group

(which will receive the TIP and no

additional support); (2) a TIP-plus

curriculum group; (3) a TIP-plus

curriculum and training group; and (4)

a TIP-plus curriculum, training, and

ongoing support group.

Data will be collected at baseline and

follow-up. Measures will include

providers’ awareness of TIP 35, their

knowledge of the content contained in

this TIP, their attitudes toward the TIP

and its content, and their use of this TIP

and its impact on practices within their

facilities. Burden for State substance

abuse (SSA) agency directors in the four

areas of the country chosen will consist

of information gathering by telephone.

Burden for other respondents will

consist of completing the pretest and

post-test questionnaires. The total

estimated burden for this project, to be

completed in a 1-year period, is

summarized below.