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Annual report : National Institute of Environmental Health Sciences (Volume 1981) online

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Dr. Dieter with Dr. Irwin, Dr. Melnick and Dr. Abdo and the other group is
headed by Dr. Chhabra with Dr. Mennear, Dr. Kluwe and Dr. Dunnick.

Other Activities :

Dr. Kluwe : Prepared a review of available toxicology information on ortho-
phthalate esters and organized and participated in a conference on phthalate
esters. Developed future research and testing plans on phthalates for NTP.

Dr. Melnick : Was an invited speaker for Phthalate Ester Conference.



762



Dr. Dunnick : The results of chronic toxicity studies are being compared and
correlated to a variety of vn vitro tests to determine to what extent the in
vitro tests can be used to predict or substitute for animal tests. Dr. Dunnick
and Dr. Melnick organized a seminar series covering topics on various aspects of
toxicity evaluation.

Dr. Mennear : Organized a course, "Special Problems in Toxicology" for the N.C.
Society of Toxicology Education Committee. Dr. Mennear organized and chaired
the first scientific symposium during the first annual meeting of N.C. Society
of Toxicology.



763



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Oo NOT use this space)



U.S. DEPARTMENT OF

HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE

NOTICE OF

INTRAHURAL RESEARCH PROJECT



PROJECT NUMBER

ZOl ES 21000-01 CTEB



PERIOD COVERED

October 1, 1980 to April 30, 1981



TITLE OF PROJECT (80 characters or less)

Evaluation of Clinical Chemistry Used in NTP Standard Protocol



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT

PI: Michael P. Dieter Physiologist CTEB/TRTr niEHS

Other: Ralph Wilson Technician CPB/TRTP NIEHS

Daryl Coston Technician CTEB/TPTP NIEHS



COOPERATING UNITS (if any)



Systemic Toxicology Branch and Chemical Pathology Branch



LAB/BRANCH



SECTION



Carc in ogenesis and Toxicology Evaluation Br anch



INSTITUTE AND LOCATION

NIEHS, NIH, Research Triangle Park, North Carolina 27709



TOTAL MANYEARS:
1 .5



PROFESSIONAL:



0.5



OTHER:



1.0



CHECK APPROPRIATE BOX(ES)
D (a) HUMAN SUBJECTS

D (al) MINORS □ (a2) INTERVIEWS



□ (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

Effects of immunotoxic chemicals on non-target organs are being assessed by
evaluating a battery of clinical chemistry tests utilizing serum samples from
B6C3F1 mice. Some assays that have been found most useful and reliable includ
serum glutamic pyruvic transaminase, sorbitol dehydrogenase, creatinine, and
chol inesterase. We are currently evaluating the utility of serum creatinine
kinase, al pha-hydroxybutryic dehydrogenase, acid and alkaline phosphatase and
lactate dehydrogenase to detect general or specific organ toxicity.



PHS-6040
(Rev. 2-81)



JM^



ZOl ES 21000-01 CTEB
PROJECT DESCRIPTION

METHODS EMPLOYED : Current biochemical methods utilizing microvolumes suitable
for centrifugal analysis spectrometry are utilized.

MAJOR FINDINGS AND PROPOSED COURSE : More than a half dozen chemicals have been
evaluated this fiscal year in the immunotoxicity program. We have performed a
variety of clinical chemistry assays to evaluate responsiveness to toxic chemicals,
reproducibility, sensitivity, prognostic value for target organ toxicity, and
practicality for contract laboratory use. Some of those assays that have been
found most useful and reliable include serum glutamic pyruvic transaminase,
sorbitol dehydrogenase, creatinine and chol inesterase. Some assays that have
been discontinued include serum gamma-glutamyl transferase, ornithine carbamyl
transferase, cholesterol and triglycerides. We are currently evaluating the
utility of serum creatine kinase to detect muscle and brain toxicity, alpha-
hydroxy butyric dehydrogenase for heart toxicity, acid and alkaline phosphatase
for bone and intestinal toxicity, and lactate dehydrogenase for general toxicity.
The effects of species, sex and age on clinical chemistry parameters are being
evaluated at NTP and in contract labs.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : The
development of a sensitive, specific and reliable battery of clinical chemistry
assays is a non-destructive technique to evaluate target organ toxicity of a
wide range of xenobiotics in rodents and humans.



765



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
1 HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl ES 21001-01 CTEB



PERIOD COVERED , ^

October 1, 1980 to September 30, 1981



TITLE OF PROJECT (80 characters or less)

Mechanisms of chemical nephrotoxicity



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI.: William M. Kluv^e



Pharmacologist, CTEB/TRTP



NIEHS



COOPERATING UNITS (if any)



lab/branch
Carcinogenesis and Toxicology Evaluation Branch



INSTITUTE AND LOCATION

NIEHS, NIH, Research Triangle Park, NC 27709



TOTAL MANYEARS:

3/4



PROFESSiONALt

3/8



OTHER:



3/8



CHECK APPROPRIATE BOX(ES)
n (a) HUMAN SUBJECTS

n(al) MINORS D (a2) INTERVIEWS



□ (b) HUMAN TISSUES



1^1 (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

Time- and dose-dependent effects of selected nephrotoxic agents on the
ultrastructure and biochemical status of target and non-target cells in the
kidney are evaluated to determine basic mechanisms of injury to various renal
cell populations. Comparisons are made between chemical structures and the
types of subcellular lesions induced, or the target cells affected, to
elucidate common pathophysiological sequences of chemically-induced renal cell
injury.



765



PHS-6040
(Rev. 2-81)



ZOl ES 21001-01 CTEB



PROJECT DESCRIPTION



METHODS EMPLOYED : At several times post-dosing and at multiple dose levels
(range of non-toxic to maximally- toxic), evaluations are made of organ morpholo-
gies by light microscopy and of subcellular organization by transmission electron
microscopy. Evaluations are also made at the same times of biochemical and
physiological parameters indicative of the status of cell function in general
and subcellular organelle (e.g., plasma membrane, mitochondria) lability more
specifically.

MAJOR FINDINGS AND PROPOSED COURSE : Many nephrotoxic organohalide compounds that
selectively injure cells of the pars recta (S3) initially cause vesiculation of
the cytoplasm in the apical portion of the cell. Later-appearing morphological
effects include microbody proliferation, mitochondrial swelling, increased smooth
endoplasmic reticulum and aggregation of chromatin at the periphery of the
nucleus.

Assessments are being made of ATP concentration, mitochondrial function,
pinocytotic reabsorption, lysosomal lability, endoplasmic reticulum integrity
and enzymatic activities and incorporation of precursors into RNA, DNA, protein
and lipid to correlate the morphological changes with biochemical effects and
to suggest mechanisms of action.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAMS OF THE INSTITUTE :
Kidney disease is a major cause of debilitation in the U.S. Though the extent
of chemicals as causative agents in toxic nephropathy in humans is unknown,
animal studies suggest considerable susceptibility of mammalian kidneys to
halogenated hydrocarbons and organic amines. Mechanistic studies are necessary
to assess experimental animals as models of human response to nephrotoxicants
and for the extrapolation of animal safety studies to the human situation.

PUBLICATIONS

Kluwe, W. M. and Hook, J. B.: Effects of Environmental Chemicals on Kidney
Metabolism and Function. Kidney Intl. 18: 648-655, 1980.

Kluwe, W. M. and Hook, J. B.: Metabolic Activation of Nephrotoxic Haloalkanes.
Federation Proc. 39: 3129-3133, 1980.

Kluwe, W. M. and Hook, J. B.: Potentiation of acute Chloroform Nephrotoxicity
by the Glutathione Depletor Diethyl Maleate and Protection by the Microsomal
Enzyme Inhibitor Piperonyl Butoxide. Toxicol. Appl . Pharmacol., 1981 (in press).

Kluwe, W. M.: The Nephrotoxicities of Low Molecular Weight Halogenated Aliphatic
Solvents, Pesticides and Chemical Intermediates. In Toxicology of the Kidney ,
(J. B. Hook and R. L. Dixon, eds.), 1981 (in press).



767



ADDITIONAL PROJECTS
Chemical Manager for the following chemicals:
Agent



Chi oro benzene

Bromo benzene

Benzaldehyde

Nitrofurantoin

4,4'-Diamino-2,2'-

stibene-disulfonic acid

Methyl pheni date



Current Testing Phase

Chronic

Prechronic

Prechronic

Prechronic

Prechronic

Pretesting



2, Phthalate Ester Toxicology

An evaluation is currently being made of the adequacy of available toxicology
information on ortho-phthalate esters. A NTP-sponsored conference on phthalate
esters is being planned and guideline proposals for future NTP endeavors in
phthalate ester research are being formulated.



768



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
I HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER

Z01 ES 21002-01 CTEB



PERIOD COVERED

October 1, 1980 to April 30, 1981



TITLE OF PROJECT (80 characters or less)

Effects of Immunotoxic Chemicals on Intermediary Metabolism of Mouse Lymphoid
Tissues



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI: Michael P. Dieter Physiologist
Other: Ralph Wilson Technician

Daryl Coston Technician



CTEB:/TRTP NIEHS
CPB/TRTP NIEHS
CTEB/TRTP NIEHS



COOPERevTING.UNIJS ^if any)

Chemical Pathology Branch



lab/branch

Carcinogenesis and Toxicology Evaluation Branch



INSTITUTE AND LOCATION

NIEHS, NIH, Research Triangle Park, North Carolina 27709



TOTAL MANYEARS:

1 .5



PROFESSIONAL;



0.5



1.0



CHECK APPROPRIATE BOX(ES)
D (a) HUMAN SUBJECTS

D (al) MINORS D (a2) INTERVIEWS



□ (b) HUMAN TISSUES



[^ (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

The correlation between chemically induced immune defects and biochemical
defects in lymphoid tissues (thymus, spleen, bone marrow) and specific-
populations of lymphoid cells (pleuripotent stem cells, granulocyte-macrophage
precursors, T-cells, B-cells, macrophages) are being investigated. Rate
limiting enzymes in monophosphate shunt, glycolysis and tricarboxylic
acid, marker enzymes in macrophages, and enzymes of heme metabolism are being
assayed. Change in substrate flow through these biosynthetic pathways were
caused by immunotoxic chemicals and correlated with specific functional defectjs
in the immune system.



769



PHS-60A0
(Rev. 2-81)



PROJECT DESCRIPTION "^ " 21002-01 CTEB

METHODS EMPLOYED : Current biochemical methods utilizing conventional UV and
centrifugal analysis spectrometry, and radioenzymatic assays are utilized.

MAJOR FINDINGS AND PROPOSED COURSE : Assay of 6 rate limiting enzymes for glucose
metabolism via monophosphate shunt, glycolysis or tricarboxylic acid cycle were
standardized in bone marrow, macrophages, thymus and spleen. Change in substrate
flow through these biosynthetic pathways were caused by immunotoxic chemicals and
correlated with specific functional defects in the immune system. Additional
enzymes in macrophages served as markers to differentiate between toxic chemical
effects in activated and non-activated cells.

I will continue to participate in a screening program for immunotoxic chemicals
by providing correlative evidence of metabolic derangement with immune dysfunction
in specific populations of lymphoid cells and macrophages. Whenever feasible
and promising, mechanistic studies to elucidate the metabolic basis of specific
immunotoxicity will be pursued.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : Information
regarding the immunotoxicity of each chemical may be useful in therapeutic inter-
vention and will provide another sensitive measure of the potential chemical
hazard to man.



770



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Oo NOT use this space)



U.S. DEPARTMENT OF
I HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER

ZOl ES 21 on -01 CTEB



PERIOD COVERED

October 1, 1980 to September 30, 1981



TITLE OF PROJECT (80 characters or less)

The Comparative Toxicities and Carcinogenicities of C.I. Direct Blue 6 and
Benzidine in Rats.



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI: John H. Mennear
Co-PI: Bhola N. Gupta
Other: Martha Harris



Expert CTEB/trtP NIEHS
Pathologist CPB/jRTP NIEHS
Bio. Lab. Tech. STB/ JRTP NIEHS



COOPERATING UNITS (if any)

Biometry



I ab/branch



Carcinogenesis and Toxicology Evaluation Branch



INSTITUTE and LOCATION

NIEHS; NIH Research Triangle Park, North Carolina



27709



TOTAL MANYEARS:

1.25



PROFESSIONAL:

0.5



OTHER:



0.75 (technician)



CHECK APPROPRIATE BOX(ES)
D (a) HUMAN SUBJECTS

D (al) MINORS D (a2) INTERVIEWS



P (b) HUMAN TISSUES



[3 (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

C.I. Direct Blue 6 , a commercially available textile dye, has been shov^n to
produce hepatocellular carcinoma in rats fed diets containing from 1,500 to
3,000 ppm ot test chemical. TTie dye is derived from benzidine , a known hepato-
carcinogen in rats, and vihen administered orally to rats the dye is metabolized
to the carcinogen. Hepatocellular carcinomas induced by the dye appeared after
only five v/eeks of treatment, an onset time which is much shorter than has ever
been reported for benzidine-induced carcinomas in rats. This observation
raises the question of whether the dye-induced carcinomas were mediated through
the dye per se , benzidine produced through the biotransformation of the dye, or
some other metabolite. When considered on a molar basis, the benzidine equiv-
alents of the dye were far in excess of any dosage levels of benzidine reported
in the literature. The objective of this study is to compare the toxicities and
carcinogenicities of benzidine and Direct Blue 6 (in molar equivalent doses with
respect to benzidine).



771



PHS-6040
(Rev. 2-81)



ZOl ES 21011-01 CTEB
PROJECT DESCRIPTION

METHODS EMPLOYED : Benzidine and C.I. Direct Blue 6 will be compared with
respect to effects on: 1) food consumption, 2) survival, 3) organ function,
4) urinary excretion of benzidine metabolites, and 5) the development of
neoplastic and preneoplastic lesions.

MAJOR FINDINGS AND PROPOSED COURSE : The study is scheduled to begin on
4/29/81. There are no results to report at this time.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE :
This study is the intramural portion of the National Toxicology Program's
benzidine congener dye initiative. The results will be used to facilitate the
interpretation of the pharmacokinetics and genetic toxicology portions of the
initiative. The results will also aid in the interpretation of the earlier
Direct Blue 6 study.



772



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
1 HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl-ES-301 00-02 CTEB



PERIOD COVERED

October 1, 1980 to September 30, 1981



TITLE OF PROJECT (80 characters or less)

Toxic Effects of 1 ,2-Dibronio-3-chloropropane on the Urogenital System



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



P.I. : William M. Kluv\/e
Others: James C. Lamb, IV
Bhola N. Gupta



Pharmacologist, TRIP
Biologist, TRIP
Pathologist, TRIP



NIEHS
NIEHS
NIEHS



COOPERATING UNITS (if any)



lab/branch
TRTP/NIEHS



SECTION



Carcinogenic and Toxicologic Evaluation Branch



INSTITUTE AND LOCATION

NIEHS, NIH, Research Triangle Park, NC 27709



TOTAL MANYEARS:

7/8



PROFESSIONAL:

3/8



OTHER:



1/2



CHECK APPROPRIATE BOX(ES)
D (a) HUMAN SUBJECTS

D (al) MINORS D (a2) INTERVIEWS



D (b) HUMAN TISSUES



^ (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

The acute and subchronic toxic effects of the pesticide 1 ,2-dibromo-3-chloro-
propane (DBCP) and structurally-related compounds are studied from functional
and mechanistic viewpoints. A reported chemo-sterilant in humans, DBCP is no
longer manufactured in the U.S., but its presence in ground water and on edible
imports and its illegal bulk transport into certain areas of the U.S. require
its further toxicological characterization. Effects of DBCP on hepatic , renal
and reproductive functions are evaluated at several dose levels, after various
treatment regimens and under differing conditions such as age, chemical or
physical stress and the like. The distribution and disposition of DBCP is
being studied in rats, as well as selected aspects of its metabolism and the
effects of metabolic modulation on DBCP toxicities.

Comparative toxicities of DBCP and its metabolites are being evaluated to
ascertain the toxic chemical moiety.



773



PHS-6040
(Rev. 2-81)



ZOl ES 30100-02 CTEB



PROJECT DESCRIPTION



METHODS EMPLOYED : Toxic effects are being studied in male and female Fischer
344 rats using a variety of functional, biochemical and pathological techniques.
Disposition, distribution and metabolism studies are conducted in, or with
tissues from, male Fischer 344 rats by standard techniques.

MAJOR FINDINGS AND PROPOSED COURSE : Acute intoxication with DBCP causes dose-
dependent injury to the kidney, testis, epididymis and liver. Effects on the
liver, epididymis and kidney appear to be reversible, but testicular damage is
progressive and may be irreversible following significant acute injury.
The acute toxic manifestations of DBCP treatment bear many similarities with the
acute toxic effects of the DBCP metabolites epi- and alpha-chlorohydrin, but not
with oxalic acid, another DBCP metabolite. These results suggest that DBCP,
epichlorohydrin and alpha-chlorohydrin may exert their effects via a common
patholophysiological mechanism. DBCP nephrotoxicity and testicular toxicity is
blunted by pretreatment with the microsomal enzyme inducer phenobarbital , but
enhanced by pretreatment with cobaltous chloride or by partial hepatectomy. DBCP
metabolism, therefore, appears to be involved in the expression of toxicity,
though the mechanism of metabolic modulation remains to be elucidated.
Repeated exposure to acutely less-than-toxic DBCP doses produces a transient
period of infertility in male rats, but no change in epididymal sperm number,
motility or morphology. Future studies will continue to characterize the dose-
response relationship for DBCP and examine cumulative toxic effects. Pharmaco-
kinetic studies will determine tissue repositories, the relationships of
metabolite patterns to tissue injuries and the propensity of DBCP or metabolites
to interact with genetic materials.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAMS OF THE INSTITUTE :
Characterization of the toxic effects of DBCP and elucidation of the mechanisms
of action of this and similar toxic halocarbon compounds will allow better
estimates of human risk to be made. Observance of reduced fertility at doses
below those which reduce sperm number suggest that sperm counts (currently used
as an index of human DBCP toxicity) are inadequate to ensure safe human exposures.
Similarities between the toxic actions of DBCP, epi- and alpha-chlorohydrin
indicate the possibilities of "DBCP-like" effects for many chemicals that have
similar structures.

PUBLICATIONS

Kluwe, W. M.: Acute Toxicities of 1 ,2-Dibromo-3-chloropropane in the Fischer 344
Male Rat. I. Dose-Response Relationships and Differences in Routes of Exposure.
Toxicol. Appl. Pharmacol., 1981 (in press).

Kluwe, W. M.: Acute Toxicities of 1 ,2-Dibromo-3-chloropropane in the Fischer 344
Male Rat. II. Development and Repair of the Renal, Epididymal, Testicular and
Hepatic Lesions. Toxicol. Appl. Pharmacol., 1981 (in press).



774



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Oo NOT use this space)



U.S. DEPARTMENT OF

HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE

NOTICE OF

INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



Z01 ES 30101-02 CTEB



PERIOD COVERED

October 1, 1980 to September 30, 1981



TITLE OF PROJECT (80 characters or less)

Renal function tests as indicators of nephrotoxicity.



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, ANO TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI: William M. Kluwe



Pharmacologist, CTEB/TRTP NIEHS



COOPERATING UNITS (if any)



lab/branch

Carcinogenesis and Toxicology Evaluation Branch

SECT I ON ' '



INSTITUTE AND LOCATION

NIEHS, NIH, Research Triangle Park, NC



2770



TOTAL MANYEARS:

3/8



PROFESSIONAL:

1/8



1/4



CHECK APPROPRIATE BOX(£S)
n (a) HUMAN SUBJECTS

n (al) MINORS D (a2) INTERVIEWS



□ (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

Renal function tests are conducted after single or multiple exposures of rats
to a variety of chemical agents to assess the sensitivities and versatilities
of the various tests for detecting subtle kidney injury. When appropriate,
nev/ or improved methodologies are designed and evaluated. The development of
resistance to injury upon repeated chemical exposure and the effect of such
or other chemical stresses to the body are also studied.



775



PHS-6040
(Rev. 2-81)



ZOl ES 30101-02 CTEB



PROJECT DESCRIPTION



METHODS EMPLOYED : Following chemical exposure, the animals are placed in
metabolic cages and urine is collected under appropriate conditions. Urinalyses
of varying completeness are performed to assess the functional status of the
kidney. Animals are sacrificed as necessary and the morphological appearance of
the kidney compared to the functional effects of chemical treatment.

MAJOR FINDINGS AND PROPOSED COURSE : Tests that measure functional capacities
of the kidney are the most sensitive and versatile indicators of subtle kidney
injury, while standard tests such as blood urea nitrogen and serum sodium
concentrations are relatively poor diagnostic tools.

The resistance to Mercuric chloride (HgCl2) nephrotoxicity induced by repeated
treatment with HgCl2 does not extend to other chemical nephrotoxicants that
damage the same or dissimilar sections of the proximal tubule as does HgClp-

Since many nephrotoxicants appear to interfere with protein handling by the
proximal tubules, comparisons are being made by electrophoretic methods of the
distribution of low molecular weight proteins from the urines of rats treated
with selected nephrotoxicants.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAMS OF THE INSTITUTE :
Sensitive and appropriate endpoints, as are being studied or developed in this
project, are essential to the conduct of meaningful toxicology studies, including
those conducted by the National Toxicology Program. In addition, sensitive
function tests may suggest mechanisms of nephrotoxic action.

PUBLICATIONS

Kluwe, W. M., Renal Function Tests as Indicators of Kidney Injury in Subacute
Toxicity Studies. Toxicol. Appl . Pharmacol. 57: 414-424, 1981.

Kluwe, W. M.: Rapid, Automated Measurements of Urinary Protein and Glucose
Concentrations. Pharmacol. Meth. 5: 395-400, 1981.



776



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF

HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE

NOTICE OF

INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl ES 30102-02 CTEB



PERIOD COVERED

October 1, 1960 to September 30, 1981



TITLE OF PROJECT (80 characters or less)

Interactions between halogenated aliphatic chemicals and renal tubular cells
in vitro.



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



P.I.



William M. Kluwe



Pharmacologist, CTEB/TRTP NIEHS



COOPERATING UNITS (if any)



lab/branch

Carcinogenesis and Toxicology Evaluation Branch



SEO'^ I ON



INSTITUTE AND LOCATION

NIEHS, NIH, Research Triangle Park, NC



Online LibraryNational Institute of Environmental Health ScienceAnnual report : National Institute of Environmental Health Sciences (Volume 1981) → online text (page 68 of 92)