Copyright
National Institute of Environmental Health Science.

Annual report : National Institute of Environmental Health Sciences (Volume 1985) online

. (page 68 of 114)
Online LibraryNational Institute of Environmental Health ScienceAnnual report : National Institute of Environmental Health Sciences (Volume 1985) → online text (page 68 of 114)
Font size
QR-code for this ebook


the data obtained, additional testing in the form of long-term toxicologic/
carcinogenic evaluations are pursued in order to provide sufficient data to
establish the relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) are also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the NTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.

MAJOR FINDINGS AND PROPOSED COURSE :

Barium Chloride - Prechronic reports submitted and accepted following
review by the PWG. Work on this project is complete.

Tetrahydrocannabi no! - Prechronic report submitted for rats; mouse report
near completion; awaiting PWG review.



656



SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : Results
of these studies will provide information about the toxicity of chemicals in
experimental animals, which can be used to predict possible hazard to humans,
and determine dose levels for a chronic study, if needed.



657



BIOASSAY SYSTEMS CORPORATION

Woburn, Massachusetts 01801

(NIH-N01-ES-28022)

TITLE: Chronic Study of Hydroquinone

CONTRACTOR'S PROJECT DIRECTOR: Indu Muni, Ph.D.

PROJECT OFFICER (NIEHS): June K. Dunnick, Ph.D., Toxicologist,

Carcinogenesis and Toxicology Evaluation Branch/TRTP

DATE CONTRACT INITIATED: April, 1982

CURRENT ANNUAL LEVEL: Funded in previous year

PROJECT DESCRIPTION

OBJECTIVES : Within the oast 25 years the number of chemicals introduced into
the environment has increased dramatically. There is relatively little known
about the toxicologic and/or carcinogenic potential of many of them, even though
their use may be widespread and the potential for human exposure is relatively
high. The National Toxicology Program is attempting to fill this gap in
knowledge through the sponsorship of well-defined bioassay evalua-tions on a
number of these materials. As part of this program, the studies conducted under
these contracts were designed to establish basic toxicity data on specific
chemicals, using Fischer 344 rats and B6C3Fi mice. Then, based on the data
obtained, additional testing in the form of long-term toxicologic/carcinogenic
evaluations are pursued in order to provide sufficient data to establish the
relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) dre also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the NTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.

MAJOR FINDINGS AND PROPOSED COURSE : The laboratory is in the process of con-
ducting chronic toxicity studies with hydroquinone. These studies are performed
in accordance with the NTP Master Agreement and involve dosing the animals by
the gavage route of exposure; noting clinical signs, body weight and food con-
sumption during the study; and performing a gross and microscopic evaluation of
animal tissues at the conclusion of the study. This laboratory is also per-
forming clinical chemistry evaluations on plasma enzyme levels. All studies are
in progress and final results are not yet available.



658



SIGNIFICANCE TO BIOMEDICAL RESEARCH AMD THE PROGRAM OF THE INSTITUTE : Results
of these studies will provide information about the toxicity of chemicals in
experimental animals, which can be used to predict possible hazard to humans,
and determine dose levels for a chronic study, if needed.



659



HAZLETON LABORATORIES AMERICA, INC.

Vienna, Virginia 22180

(NIH-N01-ES-28023-04)

TITLE: Chronic Toxicity and Carcinogenicity Studies of C.I. Direct 31ue 15,
C.I. Acid Red 114, 3,3 '-Dimethylbenzidine and 3 ,3 '-Dimethoxybenzidine
in Fischer 344 Rats

CONTRACTOR'S PROJECT DIRECTOR: Borge inland, Ph.D.

PROJECT OFFICER (NIEHS): John H. Mennear, Ph.D., Pharmacologist

Carcinogenesis and Toxicology Evaluation Branch/TRTP

DATE CONTRACT INITIATED: September 30, 1981

CURRENT ANNUAL LEVEL: $188,000

PROJECT DESCRIPTION

OBJECTIVES : Within the past 25 years the number of chemicals introduced into
the environment has increased dramatically. Surprisingly, there is relatively
little known about the toxicologic and/or carcinogenic potential of many of
them, even though their use may be widespread and the potential for human expo-
sure is relatively high. The National Toxicology Program is attempting to fill
this gap in knowledge through the sponsorship of well-defined bioassay evalua-
tions on a number of these materials. As part of this program, the studies
conducted under these contracts were designed to establish basic toxicity data
on specific chemicals, using Fischer 344 rats and B6C3Fi mice. Then, based on
the data obtained, additional testing in the form of long-term toxicologic/
carcinogenic evaluations are pursued in order to provide sufficient data to
establish the relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) are also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the NTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.

MAJOR FINDINGS AND PROPOSED COURSE :

N01-ES-28023-04 - Chronic studies in progress.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : Results
of these studies will provide information about the toxicity of chemicals in
experimental animals, which can be used to predict possible hazard to humans.

660



SOUTHERN RESEARCH INSTITUTE
Birmingham, Alabama 35255
(NIH-N01-ES-28024)

TITLE: Bioassay Testing for Disperse Blue 1, H.C. Blue 2, Nitrofurantoin,

Rhodamine 5G, H.C. Red 3, Chlorowax 500C, Acid Orange 3, Dichlorvos,
Chlorowax 40, Roxarsone, and Pentachloroanisole

CONTRACTOR'S PROJECT DIRECTOR: J. David Prejean, Ph.D.

PROJECT OFFICER (NIEHS): Jeffrey J. Collins, Ph.D., Toxicologist

Carcinogenesis and Toxciology Evaluation Branch/TRTP

DATE CONTRACT INITIATED: May 31, 1982

CURRENT ANNUAL LEVEL: $300,000

PROJECT DESCRIPTION

OBJECTIVES : Within the past 25 years the number of chemicals introduced into
the environment has increased dramatically. Surprisingly, there is relatively
little known about the toxicologic and/or carcinogenic potential of many of
them, even though their use may be widespread and the potential for human expo-
sure is relatively high. The National Toxicology Program is attempting to fill
this gap in knowledge through the sponsorship of well-defined bioassay evalua-
tions on a number of these materials. As part of this program, the studies
conducted under these contracts were designed to establish basic toxicity data
on specific chemicals, using Fischer 344 rats and B6C3F} mice. Then, based on
the data obtained, additional testing in the form of long-term toxicologic/
carcinogenic evaluations are pursued in order to provide sufficient data to
establish the relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) are also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the NTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.



661



MAJOR FINDINGS AMD PROPOSED COURSE :

C.I. Disperse Blue 1 - Technical Report Peer Reviewed (3/85).

H.C. Blue 2 - Technical Report Peer Reviewed (7/84).

Nitrofurantoin - Chronic histopathology completed; PWG pending.

Rhodamine 6G - Chronic histopathology in progress.

H.C. Red 3 - Technical Report Peer Reviewed (3/85).

Chlorowax 500C - Technical Report being drafted.

Acid Orange 3 - Rat chronic histopathology PWG approved (3/85); mouse
chronic histopathology completed (PWG pending).

Dichlorvos - Chronic histopathology completed; PWG pending.

Chlorowax 40 - Technical Report being drafted.

Roxarsone - Chronic histopathology in progress.

Pentachl oroani sol e - Chronic studies in progress.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : Results
of these studies will provide information about the toxicity of chemicals in
experimental animals, which can be used to predict possible hazard to humans,
and determine dose levels for a chronic study, if needed.









662



PAPANICOLAOU CANCER RESEARCH INSTITUTE
Miami, Florida 33136
(NIH-N01-ES-28025)

TITLE: Bioassay Testing of Trichloroethylene, Isophorone, Glycidol, 2,2-Bis-
(bromomethyl )l,3-propanediol , and 2,3-Dibromo-l-propanol .

CONTRACTOR'S PROJECT DIRECTOR: Fred G. Sock, Ph.D.

PROJECT OFFICER (NIEHS): Michael P. Dieter, Ph.D., Physiologist

Carcinogenesis and Toxicology Evaluation Branch/TRTP

DATE CONTRACT INITIATED: July 15, 1982

CURRENT ANNUAL LEVEL: $ 00.00

PROJECT DESCRIPTION

OBJECTIVES : Within the past 25 years the number of chemicals introduced into
the environment has increased dramatically. Surprisingly, there is relatively
little known about the toxicologic and/or carcinogenic potential of many of
them, even though their use may be widespread and the potential for human expo-
sure is relatively high. The National Toxicology Program is attempting to fill
this gap in knowledge through the sponsorship of well-defined bioassay evalua-
tions on a number of these materials. As part of this program, the studies
conducted under these contracts were designed to' establish basic toxicity data
on specific chemicals, using Fischer 344 rats and B6C3Fi mice. Then, based on
the data obtained, additional testing in the form of long-term toxicologic/
carcinogenic evaluations are pursued in order to provide sufficient data to
establish the relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) are also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the NTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.

MAJOR FINDINGS AND PROPOSED COURSE : Chronic testing for trichloroethylene and
isophorone are completed; testing for glycidol is awaiting verification of
pathology findings. Subchronic testing for 2,2-Bis(bromomethyl )l,3-propanediol
and 2,3-dibromo-l-propanol are awaiting pathology completion.



663



SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : Results
of these studies will provide information about the toxicity of chemicals in
experimental animals, which can be used to predict possible hazard to humans,
and determine dose levels for a chronic study, if needed.



664



MICROBIOLOGICAL ASSOCIATES
Bethesda, Maryland 20816
(NIH-N01-ES-28026)

TITLE: Bioassay Testing of D-Limonene, Succinic Anhydride, Alpha-Methyl benzyl
Alcohol, Benzyl Alcohol and Methyl Carbamate.

CONTRACTOR'S PROJECT DIRECTOR: Lois T. Mulligan, Ph.D.

PROJECT OFFICER (NIEHS): Kamal M. Abdo, Ph.D., Chemist

Carcinogenesis and Toxicology Evaluation Branch/TRTP

DATE CONTRACT INITIATED: August 2, 1982

CURRENT ANNUAL LEVEL: $3,200

PROJECT DESCRIPTION

OBJECTIVES : Within the past 25 years the number of chemicals introduced into
the environment has increased dramatically. Surprisingly, there is relatively
little known about the toxicologic and/or carcinogenic potential of many of
them, even though their use may be widespread and the potential for human expo-
sure is relatively high. The National Toxicology Program is attempting to fill
this gap in knowledge through the sponsorship of well-defined bioassay evalua-
tions on a number of these materials. As part of this program, the studies
conducted under these contracts were designed to establish basic toxicity data
on specific chemicals, using Fischer 344 rats and B6C3Fi mice. Then, based on
the data obtained, additional testing in the form of long-term toxicologic/
carcinogenic evaluations are pursued in order to provide sufficient data to
establish the relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) are also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the NTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.

MAJOR FINDINGS AND PROPOSED COURSE : The laboratory materials and methods
reports and draft pathology narrative for the studies with the above chemicals
were received by NTP for quality assurance and pathology working group eval-
uation.



665



SIGNIFICANCE TO BIOME DICAL RESEARCH AND THE PROGRAM OF 'HE INSTITUTE

provide information about the



Results
chemicals in



of these studies will provide information about the toxicity of ,

experimental animals, which can be used to predict possible hazard to humans, \

and determine dose levels for a chronic study, if needed.









666



LITTON BIONETICS, INC.

Rockville Facil ity
Kensington, MD 20795

(NIH-N01-ES-38040)

TITLE: Bioassay Testing of Various Chemicals (Dimethyl methyl phosphonate and
Dimethyl vinyl chloride)

CONTRACTOR'S PROJECT DIRECTOR: Alan G. Manus, Ph.D.

PROJECT OFFICER (NIEHS): Richard D. Irwin, Ph.D., Chemist

Carcinogenesis and Toxicology Evaluation Branch/TRTP

DATE CONTRACT INITIATED: March, 1983

CURRENT ANNUAL LEVEL: $ 00.00

PROJECT DESCRIPTION

OBJECTIVES : Within the past 25 years the number of chemicals introduced into
the environment has increased dramatically. Surprisingly, there is relatively
little known about the toxicologic and/or carcinogenic potential of many of
them, even though their use may be widespread and the potential for human expo-
sure is relatively high. The National Toxicology Program is attempting to fill
this gap in knowledge through the sponsorship of well-defined bioassay evalua-
tions on a number of these materials. As part of this program, the studies
conducted under these contracts were designed to establish basic toxicity data
on specific chemicals, using Fischer 344 rats and B6C3Fi mice. Then, based on
the data obtained, additional testing in the form of long-term toxicologic/
carcinogenic evaluations are pursued in order to provide sufficient data to
establish the relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) are also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the MTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.

MAJOR FINDINGS AND PROPOSED COURSE :

Dimethylmethyl phosphonate - Chronic sacrifice completed; pending PUG.

Dimethyl vinyl chloride - Technical Report in preparation.



667



SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : Results
of these studies will provide information about the toxicity of chemicals in
experimental animals, which can be used to predict possible hazard to humans,
and determine dose levels for a chronic study, if needed.

PUBLICATIONS

Kluwe, W.M., Parker, G.A. and Manus, A.G.: Chronic toxicity of dial lylphthal ate
in mice. Toxicol. Lett., (in press), 1984.



668



PHYSIOLOGICAL RESEARCH LABORATORIES
Division of Medtronic, Inc.
Minneapolis, Minnesota 55433
(NIH-N01-ES-38041)

TITLE: Bioassay Testing of 2-Amino-4-nitrophenol , 2-Amino-5-nitrophenol ,
Ephedrine Sulfate, Erythromycin Stearate, Hexylresorcinol ,
Mercaptobenzothiazole, Methyldopa, Nalidixic Acid, Nitrofurazone,
Oxytetracycl ine Hydrochloride, Phenylephrine Hydrochloride, and
Tetracycline Hydrochloride.

CONTRACTOR'S PROJECT DIRECTOR: Morris J. Cowan, Jr.

PROJECT OFFICER (NIEHS): Ronald L. Melnick, Ph.D., Chemist

Carcinogenesis and Toxicology Evaluation Branch/TRTP

DATE CONTRACT INITIATED: March 1, 1983

CURRENT ANNUAL LEVEL: $225,665

PROJECT DESCRIPTION

OBJECTIVES : Within the past 25 years the number of chemicals introduced into
the environment has increased dramatically. Surprisingly, there is relatively
little known about the toxicologic and/or carcinogenic potential of many of
them, even though their use may be widespread and the potential for human expo-
sure is relatively high. The National Toxicology Program is attempting to fill
this gap in knowledge through the sponsorship of well-defined bioassay evalua-
tions on a number of these materials. As part of this program, the studies
conducted under these contracts were designed to establish basic toxicity data
on specific chemicals, using Fischer 344 rats and B6C3Fi mice. Then, based on
the data obtained, additional testing in the form of long-term toxicologic/
carcinogenic evaluations are pursued in order to provide sufficient data to
establish the relative safety or hazard to humans.

METHODS EMPLOYED : Prechronic (repeated-dose and subchronic) investigations con-
ducted under these contracts include the extensive use of clinical chemistry
evaluations, hematology profiles, sperm morphology and vaginal cytology eval-
uations, and histopathology. Design of the chronic studies varies depending
upon the prechronic data, however, the basic format used consists of the admin-
istration of 2 or 3 dose levels to groups of 50 animals/sex/species for 103
weeks followed by a one-week observation period. Matched control groups are
included in each study. In some cases, additional dose levels, additional ani-
mals for interim evaluation, and certain special studies (hematology and clini-
cal chemistry profiles, etc.) are also employed. Histopathologic evaluation is
performed on all animals in each study. All studies are being conducted in
compliance with the FDA Good Laboratory Practice Regulations. In-life and
histopathologic observations are being collected by computer using the NTP
Toxicology Data Management System. Other data, including gross observations at
necropsy, are collected using manual methods.



669



MAJOR FINDINGS AND PROPOSED COURSE : The two-year treatments with all of the 12
chemcials have been completed. All studies are in various stages of histopatho- ^
logic evaluation. These evaluations are expected to be completed in FY85. All вДҐ
findings from these studies will be reported after audits and internal and peer
reviews of the data have been performed.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : Results
of these studies will provide information about the toxicity of chemicals in
experimental animals, which can be used to predict possible hazard to humans,
and determine dose levels for a chronic study, if needed.



%



%



670



MIDWEST RESEARCH INSTITUTE

Kansas City, Missouri 64110

(NIH-N01-ES-38042)

TITLE: Chronic Toxicity Testing of Vinyl Toluene and Tetranitromethane

CONTRACTOR'S PROJECT OIRECTOR: James M. Cholakis, Ph.D.



Online LibraryNational Institute of Environmental Health ScienceAnnual report : National Institute of Environmental Health Sciences (Volume 1985) → online text (page 68 of 114)