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National Institute of Environmental Health Science.

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

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260



PHS-6040
(Rev. 2-81)



ZOl ES 50041-03 LEB
PROJECT DESCRIPTION

METHODS EMPLOYED : Guinea pigs anesthetized with sodium pentobarbital were used.
The endocochlear potential (EP) and K concentrations of the endolymph and peri-
lymph were simultaneously measured in the basal turn of the cochlea with a pair
of double barreled K selective liqijiid membrane electrodes. When the active
transport is abolished by anoxia, K ions diffuse passively from the endolymph to
perilymph. If the volume of the cocjjilear endolymph is assumed to remain unchanged
during anoxia, the passive flow of K ions from the endolymph can be expressed by

,diffusion ^ ., ^^^ end^
"^K "end dt

The K conductance of the endolymph-peri lymph barrier, G|, can be computed by

^^'"end^

V F

r - end dt ,,

RT , ^^ end^
_ In — _

^^ peri^
The relationship between the permeability coefficient, Pj. and G|, is given by

P - RT . ^K

where D?J ^ '^^ end-peri^

in ^' -d^
In —^

^^ peri^

Three groups of guinea pigs were used: one group of guinea pigs was treated
with kanamycin 400 mg/kg for 3 weeks and tested 2 weeks after treatment. A
second group was exposed to broad band noise at 115 dBA for 11 to 15 days. A
third group was used as control animals.

MAJOR FINDINGS AND PROPOSED COURSE : 1. Cochlear potentials. The CM sensitivity
(expressed by sound intensity required to elicit 100 yv CM) was reduced to 88.8
+ 5.3 dB SPL and the maximum CM output was suppressed to 270 + 90 yV in noise
exposed guinea pigs. The CM max in all kanamycin-treated guinea pigs was less

than 80 yV.

+ +

2. K conductance and K ^permeability constant of the endolymph-peri lymph barrier.

The preanoxic values of K electrochemical potential difference between endolymph

and perilymph were 189.6 + 4.9 mV, 190.4 + 5.9 mV and 90'' '^ ■_^.^ ;tiV v'. :,

noise exposed and kanamycin-treated guinea pigs respectively. The rate of decline

of the electrochemical potential difference during anoxia was slower in noise

exposed guinea pigs and kanamycin treated tuinea pigs than control animals In

control guinea pigs, the mean rate of fall of [K ^^j] decreased with time and

261



ZOl ES 50041-03 LEB

reached the minimum value (250 yM/min) 30 min after anoxia. In noise exposed
guinea pigs the time course was similar to that observed in control animals, but
in kanamycin treated guinea pigs the rate of fall of [K .] was markedly reduced.
The mean G^ value averaged from 10 to 30 min after onset^of anoxia was (34.85 +
5.60) x 10 ^ mho in normal guinea pigs, whereas the mean G|, averaged during the
same period was (20.43 + 2.53) x 10"^ mho in noise exposed guinea pigs and (8.13
+ 1.82) X 10"^ mho in kanamycin treated guinea pigs.

The P|, values of the endolymph-peri lymph barrier averaged from 10 to 30 min after
anoxia were (112.33 + 16.98) x 10"^ cm^sec"^ in kanamycin treated guinea pigs.
These values were considerably lower than that of (193.62 +34.81) x 10"^ cm^sec"^
of observed in control guinea pigs.

The mean value^ of G|, and Pj, were compared with those computed from the rate
constant for K , x,,. p

^ -^Vend^^end^



I



^K=



Ap



where AU|^ is electrochemical potential difference between endolymph and perilymph.

The values of G|- derived from the rate constant in normal and noise exposed

guinea pigs were calculated to be 34.46 x 10"^ mho and 16.77 x 10"^ mho respectively.



A manuscript has been published and this project has been completed.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : It is
impossible at present to measure the permeability of the various cochlear membranes
and one useful approach is to determine the diffusional alterations in the
endolymphatic ion concentration during anoxia. The present study demonstrates
that the magnitude of decrease of K permeability of the endolymph-peri lymph barrier
by noise or kanamycin is corrleated with suppresion of hair cell function. The
results obtained will shed light on the physiological mechanisms of noise or drug
induced ear damage.

PUBLICATIONS

Konishi, T. and Salt, A.N.: Permeability to potassium of the endolymph-peri lymph
barrier and its possible relation to hair cell function. Exp. Brain Res. 40:
457-463, 1980. —



1



4







262



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 50042-03 LEB



PERIOD COVERED



1981



, nzi

TITLE OF PRO'JECT (80 characters or less)

Comparison of Impact Noise and Continuous Noise Effects on Cochlear Function



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



PI: Teruzo Konishi

Reginald 0. Cook
Alec N. Salt
Hirohiko Mori



Medical Officer
Acoustical Engineer
Visiting Fellow
Visiting Associate



LEB


NIEHS


LEB


NIEHS


LEB


NIEHS


LEB


NIEHS



COOPERATING UNITS (if any)

^one



lab/branch

Laboratory of Environmental Biophysics



SECTION

Moise Effects Research Workgroup



INSTITUTE AND LOCATION

NIEHS, NIH. Research Triangle Park. North Carolina 27709



TOTAL MANYEARS:

0.8



PROFESSIONAL:

0.7



OTHER:



0.1



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

n (al) MINORS n (a2) INTERVIEWS



□ (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less -underline keywords) . .-, r- ^ ■

Although the physiological effects of ^continuous noise on cochlear function are
well documented, the effects arising from impact noise exposure have not yet
been characterized. The purpose of this project is to compare the early electro-
physiological changes occuring during exposure to energy equivalent impact or
continuous noise exposure in guinea pigs .



263



PHS-6040
(Rev. 2-81)



ZOl ES 50042-03 LEB

PROJECT DESCRIPTION

METHODS EMPLOYED : Impact noise with peak sound pressure of 132 dB SPL and a B M\
duration of 29 msec was generated by a mechanical impact noise generator. ■
Continuous broad band noise of equal energy to a given intensity of impact noise
was generated by a loud speaker system. Conscious guinea pigs with implanted
round window electrodes, or anesthetized guinea pigs with differential electrodes
placed in the perilymphatic space, were exposed to a 20 min period of impact
noise or broad band noise of equal energy. The suppression of tone induced
responses (cochlear microphonics and action potentials) during and 1 hour follow-
ing noise exposure was monitored by presenting 6 kHz test tones at 72 dB SPL.

MAJOR FINDINGS AND PROPOSED COURSE : When anesthetized guinea pigs were exposed
to 132 dB peak SPL impact noise at 1.2 impacts/sec (Leq-lin level of 105 dB) for
20 mins the cochlear microphonics (CM) and action potentials (AP) were suppressed
to 24.0% and 49.5% of their pre-exposure values respectively. During 1 hour
recovery the CM and AP increased to 88.9% and 101.4% of their pre-exposure
magnitudes respectively. In anesthetized guinea pigs exposed to 105 dB SPL
continuous noise for 20 mins the CM was reduced to 80.5% of the pre-exposure
level and in all cases the AP was totally abolished. During 1 hour recovery the
CM and AP increased to 106.0% and 61.4% of their pre-exposure values respectively.
Similar results were found when guinea pigs with chronically implanted round
window electrodes were exposed to continuous or impact noise.

Our results indicate that during noise exposure and for 1 hour following the
exposure the degree of response suppression produced by impact and continuous i
noise of equal energy is not equivalent. It is not possible to infer from these
data whether the differences would persist during chronic, long term exposure. A
pneumatically driven impact noise generator has been developed to improve durability.
The measurements of acoustic characteristics was recently completed.

Using a pneumatically driven impact noise generator, effects of exposure to
impact or continuous noise of long duration will be compared with those found in
short term experiments.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE PROGRAM OF THE INSTITUTE : The equal
energy hypothesis has been widely employed in the development of European noise
regulations. Our results indicate that the measurement of energy may not be
adequate to predict hearing loss in situations where impact noise is present.
Further study of the relationship between hearing loss and the parameters of
impact noise exposure are essential for the development of adequate noise regu-
lations.

PUBLICATIONS

Salt, A.N., Konishi, T. , Cook, R.O. and Akay, A.: Comparison between the effects
of continuous and impact noise on cochlear potentials in guinea pigs. J. Acoust.
Soc. Amer. (In press)



264



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



U.S. DEPARTMENT OF

HEALTH M'.D HUMAN SERVICES

PUBLIC HEALTH SERVICE

NOTICE OF

INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl ES 50043-03 LEB



PERIOD COVERED

nrtnhPr 1, 1 qfiO tn Sppt.pmber 30. 1981



, -, lUl

TITLE OF PROJECT (80 characters or less)

Effect of Noise on Embryo/ Fetal Development in the Guinea Pig



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



PI



Peter Nawrot
Reginald Cook



Visiting Associate LEB NIEHS
Acoustical Engineer LEB NIEHS



COOPERATING UNITS (if any)



None



lab/branch

Laboratory of Environmental Biophysics



SECTION

Noise Effects Research Workgroup



INSTITUTE and LOCATION

^lEHS, NIH, Research Triangle Park, North Carolina 27709



TOTAL MANYEARS:



,75



PROFESSIONAL:



,50



OTHERS



,25



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

n(al) MINORS D (a2) INTERVIEWS



n (b) HUMAN TISSUES



H (c) NEITHER



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

All laboratory studies on teratogenic potential of noise reported to date, have
used the rat or mouse as the experimental animal. Yet the guinea pig is probably
a more suitable experimental animal for such studies. In addition to endocrine
similarity to man, the audibility curve for the guinea pig is probably closer to
that of the human than any other mammal except primates and chinchillas. The
auditory sensitivity of rats or mice is such that the most sensitive frequency is
nearly a decade above that of humans. While the guinea pig has been extensively
used to investigate the effects of noise on the inner ear and on basic mechanisms
of hearing the teratogenic potential of noise in the guinea pig has not been
assessed.



265



PHS-6040
(Rev. 2-81)



ZOl ES 50043-03 LEB



PROJECT DESCRIPTION

METHODS EMPLOYED : Weaving room noise was selected as the exposure agent since it
was utilized in the only study on the effects of noise on the guinea pig fetus and
since it is experienced at high levels (105 dBA) by a significant number of women
worldwide (in the hundred of thousands), and is a relatively broad band steady
state noise which does not vary greatly worldwide. Mated females will be assigned
randomly to one of four experimental groups; i.e. to a "Noise" group or to a
"Control". Each group will contain at least 20 pregnant females. The guinea pigs
in the "Noise" groups will be housed in an lAC animal exposure chamber from days
1 through 11 or from days 11 through 34 of gestation (postimplantation exposure).
The days of exposure (1 through 11 and 11 through 34 of gestation) were chosen
because implantation in the guinea pig takes place on day 6, but the connection
with the uterine lumen is not lost until day 11 of gestation. Continuous weaving
room noise will be presented at an intensity of 115 dBA for 8 hours daily. During
the quiet period, the animals will be housed in a different chamber without the
noise stimulus.

Body weights of all mated animals will be taken on days 1, 11, 34 and 35 of
gestation. On day 35 of gestation, the guinea pigs will be coded before being
transported to RTI where they will be sacrificed by CO^ inhalation. Their
reproductive status will be determined, the fetuses will be counted and then each
will be examined for external, visceral and skeletal alterations.

The guinea pigs will be exposed to noise in an lAC animal exposure chamber modified
for optimum sound field uniformity. The chamber provides ample protection from
sound penetration through the walls. The data will be analyzed by the Mann-Whitney
U-test with the litter considered as the experimental unit. A 5% probability level
will be accepted.

MAJOR FINDINGS AND PROPOSED COURSE : The special acoustic chamber needed to
efficiently carry out this experiment has been designed and ordered. The experi-
ment will begin after the chamber is equipped with a process which has been subject
to unanticipated procurement delays. This project has been discontinued due to
the departure from the Institute of one of the Principle Investigators.

SIGNIFICANCE TO BIOMEDICAL RESEARCH AND THE INSTITUTE : Because of the rapid
movement of females of childbearing age into occupations traditionally dominated
by men, some of them very noisy, increasing concern has been expressed regarding
possible general teratogenic and specific auditory risks to fetuses of mothers
so exposed. The ability to predict risk factors for human exposure is to some
degree related to the occurance of similar effects in different species and to
the occurance of effects in species whose auditory systems more closely resemble
those of humans. Use of guinea pigs rather than rats or mice satisfies both
criteria.



266



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



PERIOD COVERED , „„ ,„„,

October 1, 1980 to September 30, 1981



TITLE OF PROJECT (80 characters or less)

Relationship of Catecholamine Levels and Fetolethality in Noise Exposed Mice



U.S. DEPARTMENT OF

HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE

NOTICE OF

INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl ES 50045-03 LEB



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



PI: Reginald 0. Cook
Peter Nawrot



Acoustical Engineer LEB NIEHS
Visiting Associate LEB NIEHS



COOPERATING UNITS (if any)

Research Triangle Institute



lab/branch

Laboratory of Environmental Biophysics



Noise Effects Research Workgroup



INSTITUTE AND LOCATION

NIEHS. NIH. P. 0. Box 12233. Research Triangle Park. NC 27709



CHECK APPROPRIATE B0X{ES)
n (a) HUMAN SUBJECTS

n (a1 ) MINORS n (a2) INTERVIEWS



TOTAL MANYEARS:

4



PROFESSIONAL:

.3



n (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords) j: nr i

Since a previous experiment revealed that late stage pregnancy exposure of CF-1
mice to high frequency noise resulted in a significant increase in fetolethality.
the hormonal /biochemical correlates of this effect were sought. Since corti-
costerone levels were measured in a previous experiment (see ZOl ES 50044-02
LEB) and found to be unaffected by noise exposure, this experiment focused on
catecholamines. Exogenous introduction of these substances has been found to
increase fetolethality. Exposure period was 12 hours (noon to midnight) and
noise was a swept band at 18-20 KHz. Reproductive-teratogenic effects determined
by standard techniques included lower maternal and fetal weights increased
entire litter resorption, and a significant increase in the total number of
malformed fetuses. A suggestive increase in plasma epinepherine levels was noted
(p < 0.06) and a significant increase in plasma norepinepherine levels was
associated with late stage exposure. Uterine norepinepherine levels were not
affected when measured on days 1 and 6 of gestation but were significantly
elevated when measured on days 15.



l£J-



PHS-6040
(Rev. 2-81)



ZOl ES 50045-03 LEB

PROJECT DESCRIPTION

METHODS EMPLOYED : Noise exposure: Mated mice assigned to the noise exposed
groups were exposed from noon to midnight to a cycled high frequency tone which
swept from 18 KHz to 20 KHz in 3 seconds then repeated the process after a 100
msec delay. The noise source was a device commerically marketed for repelling
feral rodents. A completed description of the sound production and monitoring
system and of the spectral characteristics of the sound is contained in an ear-
lier report. There were two noise exposed groups. One group was exposed from
day 1-6 of gestation and a second group was exposed from day 6-15. Both groups
were housed in one chamber from day 1-18 of gestation or until sacrificed.

Teratology study: On day 18 of gestation the dams from each group (control,
noise exposed days on 1-6, or days 6-15) involved in the teratogenicity study
were killed by cervical dislocation and their reproductive status was noted. The
conceptus at each site was examined and classified as being resorbed, dead or
alive. The uteri of females designated as non-pregnant on the basis of visual
examination were immersed in a 10% solution of ammonium sulfide for at least 10
minutes to identify early entire litter resorptions. The full-termed fetuses
(live and dead) were sexed, weighed, and examined for external malformations.
Any fetus weighing less than 0.5g or less than two-thirds the average of the
larger litter mates were termed stunted. At least one-third of the fetuses of
each litter were examined for visceral alterations. In addition, all stunted
fetuses, and those with external malformations were examined for visceral alter-
ations. The heads of the fetuses examined for visceral alterations were severed,
fixed in Bouin's solution, and subsequently were examined by the free-hand razor
section technique. All live and dead fetuses were cleared with KOH, stained
with Alizarin Red and examined for skeletal alterations.

Catecholamine study: Blood and uterine samples were obtained on days 1 and 6 of
gestation from the group exposed to noise on days 1-6; and on days 6, 10 and 15
of gestation from the group exposed to noise on days 6-15; and on days 1, 6, 10
and 15 of gestation from the control group. One each collection day blood and
uterine samples were obtained at 3 invariant times (12:15 PM, 2:15 PM, and 4:15
PM). For the noise exposed groups, these collection times occurred 15 minutes,
135 minutes, and 255 minutes after initiation of noise exposure on day of
collection. In the collection procedure, mice were anesthesized by intraperitoneal
injection of 3 ml/kg pentobarbital sodium and the blood samples were taken after
incision from the subclavian arteries directly into cold heparimized collecting
tubes. To prevent oxidation of catecholamines, blood was immediately mixed with
reduced gluthathione (approximately 2 mg of gluthathione per 1 ml of blood) and
the tubes placed in an ice bath. The blood samples were centrifuged at 4°C to
separate plasma from cells. The plasma was removed, placed in a screw-top vials,
frozen on dry ice, then stored at -80°C until assayed for catecholamines.
Immediately after blood sample collection the uterus was dissected, opened, and
implantation sites removed. The uterine tissues were place in screw-top vials
and frozen on dry ice for subsequent determination of catecholamine level. Blood
and uterine samples were retained only from females determined to be pregnant.

Uterine catecholamine levels were measured by an HPLC method based on modifica-
tions of a technique described by Keller et^ al_. (1976). Modification consisted

268



ZOl ES 50045-03 LEB

Of the use of pre-extracted (with alumina) plasma as standard curve vehicle. The
zero corrected standard curve using this modification was accurate at + 20 pico-
grams wherease when acid or water alone was used, accuracy was on the order of
200 picograms.

Plasma catecholamine levels were measured twice for each sample; once by the
HPLC method described above and once by a radioenzymatic method modified.

MAJOR FINDINGS AND PROPOSED COURSE : Although the late stage of fetolethality
response of the CF-1 mouse to this noise paradigm was not duplicated by the
response of the CD-I mouse, the latter demonstrated a significant increase in
the total number of malformations in addition to the early stage resorption,
slightly reduced pregnancy maintainence, and reduced fetal and maternal weight
responses noted in most other experiments in this series. Of nine groups of
pregnant mice exposed in experiments spanning five years, pregnancy maintainence
was lower in all noise exposed groups relative to controls, while teratogenic
responses and late stage fetolethality occurred only once, suggesting that
interference with pregnancy maintainence is a highly probable result of noise
stress while overt teratogenicity or late stage fetolethality require synergism
with with some unknown, possibly genetic, factor.

Although this experiment is apparently the first in which catecholamine levels
have been measured in the plasma and uteri of pregnant mice, the course of
uterine norepinepherine (NE) levels in controls was similar to that observed in
other species (rats and guinea pigs). Noise exposure corresponded to failure of
the normally rapid reduction in uterine NE levels during the last half of
gestation. The significance of this development cannot be assessed from this
experiment, but it is interesting to note that the normal rise in plasma cortices-
terone between days 10-15 corresponds to the same period in which uterine NE
levels are normally in rapid decline. Experiments where catecholamines have
been exogenously applied have shown that these substances interfere with implan-
tation possibly through tubal motility changes, and with the conceptus after
implantation with effects ranging from reduced fetal weights at near physiological
levels to fetal death at high levels. As a result, future experiments should
investigate the effect of more precisely timed noise applications immediately
preceding implantation, and during very late stage pregnancy (days 15-18). The
latter has not been investigated during noise experiments.

SIGNIFICANCE TO BIOLOGICAL RESEARCH AND PROGRAMS OF THE INSTITUTE : Identification
of the hormonial/biochemical correlates of the non auditory effects of noise is
a necessary step toward understanding these effects sufficiently for predictive
purposes.



269



SMITHSONIAW 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 50046-03 LEB



PERIOD COVERED . ^- .„„-

October 1, 1980 to September 30, 1981



TITLE OF PROJECT (80 characters or less)

Mechanisms of Chemically Induced Photosensitivity



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



PI: Colin F. Chignell
OTHERS: Ann Motten



Chief

NRS Postdoctoral
Fellow



LEB NIEHS
LEB NIEHS



COOPERATING UNITS (if any)



None



lab/branch

Laboratory of Environmental Biophysics



SECTION

Molecular Biophysics



INSTITUTE AND LOCATION

NIEHS. NIH, Research Triangle Park, North Carolina 27709



TOTAL MANYEARS:

1.1



PROFESSIONAL:
1.1



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

D (al) MINORS D (a2) INTERVIEWS



1.1



D (b) HUMAN TISSUES



(c) NEITHER



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

The objective of this study is to determine the role played by light induced
free radicals in chemically induced skin photosensitivity . Light irradiation of
4-aminobenzenesulfonamide (sulfanilamide) resulted in the production of the
following radicals: 'NH^, 4-I^HCgH^S02NH2, H*, 4-H2N02SC6H^, SO2NH2, 4-NH2C6H^S02,
SO3. Which radicals were produced depended on the pH of the solution and the
wavelength of irradiating light. Under the same conditions, sulfacetamide,
sulfadiazine, sulfathiazole, carbutamide, and tolbutamide each gave rise to
several of the same radicals, notably S0*3". The generation of these free radical
species may explain the phototoxic and photoallerqic properties of these com-
pounds.



270



PHS-6040
(Rev. 2-81)



ZOl ES 50046-03 LEB



PROJECT DESCRIPTION



METHODS EMPLOYED : Many chemicals are known to cause photosensitivity in certain
individuals. The photosensitive response may be one of two types, either photo-
toxic or photoallergic. The phototoxic reaction generally occurs during a



Online LibraryNational Institute of Environmental Health ScienceAnnual report : National Institute of Environmental Health Sciences (Volume 1981) → online text (page 22 of 92)