[Federal Register Volume 67, Number 101 (Friday, May 24, 2002)]
[Notices]
[Pages 36620-36621]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-13059]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Toxicology Program (NTP); Availability of Data From 
Preliminary Studies and Proposed Study Protocols for Cancer Bioassays 
of Hexavalent Chromium in Rats and Mice; Request for Public Comment and 
Notice of Public Meeting

Summary

    Hexavalent chromium (CAS number 18540-29-9) was nominated to the 
NTP for study of its potential toxicity and carcinogenicity when 
administered to animals in drinking water (see Federal Register: May 7, 
2001, Vol. 66, No. 88, pages 23037-23039). Members of the California 
legislative delegation, the California Environmental Protection Agency, 
and the California Health and Human Services Agency nominated 
hexavalent chromium to the NTP for study. The basis for the nomination 
is a document prepared by the California Environmental Protection 
Agency's (EPA) Office of Environmental Health Hazard Assessment titled 
``Public Health Goal for Chromium in Drinking Water'', a copy of which 
is available on the NTP's Web site http://ntp-server.niehs.nih.gov (see 
NTP Studies of Hexavalent Chromium Compounds under What's New?).
    The purpose of this notice is to announce:
    (1) The availability of data from studies designed to assess the 
absorption of chromium by rats, mice and guinea pigs receiving 
hexavalent chromium, as sodium dichromate dihydrate, in drinking water;
    (2) The design and availability of data from 90-day oral toxicity 
studies in rats and mice receiving hexavalent chromium in drinking 
water;
    (3) A proposed design for 2-year rodent cancer studies of 
hexavalent chromium in drinking water;
    (4) A public meeting to discuss these data and the proposed design 
for 2-year studies; and
    (5) A request for public comments on these data and the proposed 
design for the 2-year studies.

Public Meeting

    A public meeting will be held July 24, 2002 in the Rodbell 
Auditorium, Rall Building, South Campus, National Institute of 
Environmental Health Sciences (NIEHS), 111 T.W. Alexander Drive, 
Research Triangle Park, North Carolina. The meeting will begin at 8:30 
AM and is open to the public. Attendance at this meeting is limited 
only by the space available. Individuals who plan to attend are asked 
to register with the NTP executive secretary (see contact information 
below). The names of those registered to attend will be given to the 
NIEHS Security Office in order to gain access to the campus. Persons 
attending who have not pre-registered may be asked to provide pertinent 
information about the meeting, i.e., title or host of meeting before 
gaining access to the campus. All visitors will need to be prepared to 
show 2 forms of identification (ID), i.e., driver's license and one of 
the following: company ID, government ID, or university ID. Also those 
planning to attend who need special assistance are asked to notify the 
NTP executive secretary in advance of the meeting (see contact 
information below).
    A tentative agenda is provided below and includes opportunity for 
oral public comment. A scientific panel of experts (``the Panel'') will 
discuss the data, to date, obtained from NTP studies of hexavalent 
chromium administered as sodium dichromate dihydrate and the proposed 
study design for 2-year rodent cancer studies (see below, NTP Studies). 
The agenda and roster of the Panel will be available prior to the 
meeting on the NTP Web site (http://ntp-server.niehs.nih.gov) and upon 
request to the executive secretary at the address given below. 
Following the meeting, summary minutes will be available electronically 
on the NTP Web site and in hardcopy upon request to the executive 
secretary.

Tentative Agenda

8:30 AM
    Welcome and introductions

8:40 AM
    Overview of the NTP
    Hexavalent chromium nomination
    NTP studies on hexavalent chromium
    Proposed design for 2-year studies
    Public comments

Noon
    Lunch

1:00 PM
    Presentation of remarks by scientific expert panel
    General discussion

3:30 PM
    Adjourn

Request for Public Comment

    The NTP meeting on hexavalent chromium is open to the public and 
public comment is welcome on the data from the 21-day and 90-day 
studies, the proposed NTP 2-year study plans, and any other issues 
related to the evaluation of the toxicity and carcinogenicity of 
hexavalent chromium in drinking water. Time will be provided at the 
meeting for oral public comments and persons requesting time for an 
oral presentation are asked to contact the NTP Executive Secretary Dr. 
Mary S. Wolfe, (P.O. Box 12233, MD A3-01, Research Triangle Park, NC 
27709, phone: 919-541-0530, fax: 919-541-0295, e-mail: 
[email protected]). Persons registering to make oral 
comments are asked to provide contact information, including name, 
affiliation, mailing address, phone, fax, e-mail, and supporting 
organization (if any). Each speaker is also asked to provide, if 
possible, a written copy of the statement by July 15, 2002, to enable 
review by the Panel and NTP staff prior to the meeting. The written 
statement can supplement and may expand the oral presentation. At least 
seven minutes will be allotted to each speaker, and if time permits, 
may be extended to ten minutes. Each organization is allowed one time 
slot for an oral presentation. Registration for making public comments 
will also be available on-site. If registering on-site to speak and 
reading comments from printed copy, the speaker is asked to provide 15 
copies of the statement. These copies

[[Page 36621]]

will be distributed to the Panel and NTP staff and will be used to 
supplement the record.
    Written comments, in lieu of an oral presentation, are also 
welcome. The comments should include contact information, including 
name, affiliation, mailing address, phone, fax, e-mail, and sponsoring 
organization (if any) and preferably be received by July 15, 2002, to 
enable review by the Panel and NTP staff prior to the meeting as well 
as to supplement the record.

NTP Studies

    Hexavalent chromium (CAS number 18540-29-9) was nominated to the 
NTP for study of its potential toxicity and carcinogenicity when 
administered to animals in the drinking water. Hexavalent chromium is a 
known human carcinogen (http://ntp-server.niehs.nih.gov, see Report on 
Carcinogens). It has been proposed that the reduction of hexavalent 
chromium to the trivalent form in the gut provides a physiological 
barrier such that when exposure to hexavalent chromium occurs from 
drinking water, the absorption of hexavalent chromium would not be 
sufficient to cause cancer. Public comments received in response to the 
earlier Federal Register notice (see above) suggested that this 
reductive mechanism would be expected to be more effective in humans 
and other animals lacking an anatomical forestomach than in rats and 
mice that have a forestomach.
    To address these considerations, the NTP carried out studies in 
which rats, mice and guinea pigs (which lack a forestomach) received 
drinking water containing sodium dichromate dihydrate for 21 days. 
After that time, the animals were sacrificed and blood, kidney and bone 
were collected and analyzed for total chromium. The complete protocol 
and data from these studies are available on the NTP Web site (http://ntp-server.niehs.nih.gov).
    Additionally, the NTP has completed 90-day toxicity studies of 
standard design in which F344/N rats and B6C3F1 mice of both sexes 
received control water or one of 5 concentrations (62.5, 125, 250, 500, 
or 1000 mg/L) of hexavalent chromium in their drinking water. The 
studies included measurements of clinical chemistry indices and the 
animals received a complete histopathological evaluation. The protocol 
outline for these studies is also available on the NTP Web site and 
data from the 90-day studies are anticipated to be available on the NTP 
Web site approximately one month prior to the meeting.
    Also available on the NTP Web site is a draft protocol that 
outlines 2-year toxicity and carcinogenicity studies of hexavalent 
chromium in rats and mice. The NTP will establish the final design for 
these studies following completion and evaluation of the 90-day 
studies, evaluation of the data for total chromium tissue concentration 
from the 21-day studies, and consideration of input from the Panel, all 
written received in response to this notice, and oral public comments 
received at the public meeting.

Background

    Chromium is a naturally occurring element, present in several 
valence states. The most common valence states are trivalent (Chromium 
III), hexavalent (Chromium VI), and elemental chromium (0). Chromium 
III is an essential nutrient forming part of a complex known as the 
glucose tolerance factor. Chromium compounds are stable in the 
trivalent state and occur in nature most commonly at this oxidation 
level. Hexavalent chromium compounds are the next most stable forms, 
although these rarely occur in nature and are typically associated with 
anthropogenic (human activities) sources.
    Hexavalent chromium is more toxic than trivalent chromium, and is 
absorbed from the gut more readily than trivalent chromium. Hexavalent 
chromium is an oxidant and it reduces to trivalent chromium, passing 
through the intermediate reactive V and IV valence states. The toxicity 
of hexavalent chromium is thought to result from either direct binding 
of these intermediates to cellular constituents or through the 
generation of free radicals.
    Prolonged inhalation of hexavalent chromium is an established cause 
of occupational lung cancer in chromate production workers and people 
engaged in the manufacture of chromate pigments. This finding is 
supported by inhalation studies in rats and mice that have shown lung 
tumors following exposure to calcium chromate or sodium dichromate.
    Orally administered chromium compounds are relatively poorly 
absorbed, with most estimates in the range of 0.5 to 2%. The absorption 
of trivalent chromium is approximately one quarter that of the 
hexavalent form. Hexavalent chromium reduces to trivalent chromium in 
the stomach, and this reduction may potentially limit its systemic 
availability. This ``protective'' mechanism is not complete, however, 
because studies have shown that orally administered hexavalent 
chromium, when given at doses far below those where trivalent chromium 
showed no adverse effect, caused liver and kidney toxicity. Other 
concerns with hexavalent chromium given orally involve gastrointestinal 
effects. Acute gastritis is a common finding in humans who accidentally 
or intentionally ingested various hexavalent chromium compounds. Also, 
in a study reported in 1968, a small increase in primarily benign 
forestomach papillomas was seen in mice exposed to potassium chromate 
in the drinking water at 9 mg/kg Chromium VI for three generations over 
880 days.

    Dated: May 16, 2002.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 02-13059 Filed 5-23-02; 8:45 am]
BILLING CODE 4140-01-P