COOING FORM FOR SRC INOEXING REVISED 10/15186

OTS0000607-2

ACUTE INHALATION TOXICITY OF HYDROGEN FLUORIDE IN RATS

(FINAL REPORT) WITH ATTACHMENTS AND COVER LETTER DATED
082390

HYDROGEN FLUORIDE
. '-. ...
'
 CCONTAINS NO CBI'.

E. I. DU PONT DE NEMOURS AND COMPANY

Haskell laboratorY for TOlCicoIogy
and Industrial Medicine
P.O. Box SO, Ellctoo Road
Newark, Delaware 19714
A&oJst 23, 1990
CE:>;TRAL RESEARCH AND DEVELOPMENT DEflII.RTMENT

40- pqge5
EXPRESS MAIL - RETURN RECEIPT REQUESTED

DoaJment Processing Center (TS-790) ~

o
Attn: F.Y.I. Coordinator ~ -.
OffICe of Toxic SubsIances G'i '--
U.S. Environmental Protection Agency
401 M Street, SW
"''..:;:-" ...,
~
Washington, D.C. 20460 ~
:s! ~

Dear Coortflllator: -..

~ ~

-<
~

Hydrogen Ruorlda (HF)

FYI-OTS-0388-0607

On March 16, 1988, we reported preliminary results of a series of acute inhalation studies
coilduded by Hask6iI Laboratory with anhydrous hydrogen fkJoricIe (HF) whk:h suggested that
the loxicily of HF Ir.ay be related to relative Iunidity. We submIIIed the fn"il report (HLR 281'-)
for these studies to the Agency on June 21, 1988. In addition, since we were unsure whether
the observed LCso under moist conditions was aIbiJutabIe to Iunidity or ella to
procedurallanalytical problems. we indicaled thai supplemental analytical validation studieS wouk.I
be undertaken to clarify the preliminary resuDs.

Enclosed is a copy of the final report fo!" the additional studies we conduded.

These data indicate that the 1-hour LCso for head-onIy exposure to anhydrous HF is
approximately 2300 ppm and is not dependent upon relative t&Jrnidity. The previously desCI ibed
increase in HF toxicity (HLR 281-88) with oomidily could not be repeated and may have been elle
to the corJ1)aralive1y low recovery of HF using glass ~ and 0Ih8r analytical dlliculties
associated wiIh HF measurement.

Please contact me if you have any CJJ8$IiOnS abOut the study.

Sincerely,

('Je ~ F." /i2e- ~, ~_,d-

Charles F. Reinhardt. M.D.
Direclor

CFR:dj
Phone (302)366-5285
Enclosure: Final Report, Du Pont HLR 365-90 -Acute Inhalation
Toxiciy of HyaDgen RJoride t'I RaIs"'.
IR DU FONT USE ONLY Du Pont HLR 365-·90
)"

Study Title
Acute Inhalation Toxicity of Hydrogen Fluoride in Rats

Author
Rudolph Valentine

Study Completed On
August 14. 1990

Performing Laboratory
E. I. du Pont de Nemours and Company. Inc.
Haskell Laboratory for Toxicology and Industrial Medicine
Elkton Road, P. O. Box 50
Newark, Delaware 19714

Medical Research No.

5645-001

Laboratory Project 10
Haskell Laboratory Report No. 365-90
 Du Pont .HlR 365-90

GENERAL INFORMATION

Materi al Tested: Hydrofl uori c Aci d

Medical Research No.: 5645-001

Haslcell No.: 17,742

Synonyms: HF

CAS Registry No.: 7664-39-3

Physical Properties: Molecular Weight--20.01 g/mole

Boiling Point--19.50 C
Vapor Pressure--760 mm Hg at 200 C
Conversion Factor--1 mg/L = 1222 ppm
Physi cal Fonn: Liquefied gas

Purity: 99.~

Other Codes: Mati1eson Gas Co.

Material Submitted By: R. Valentine

Haskell Laborato~ for Toxicology
and Industrial Medicine
Central Research and Development Department
E. I. du Pont de Nemours and Company. Inc.
Newa~. Delaware 19714

Stability: The test material was asslllled to be stable

throughout the exposure phase of the test.

Sponsor: Central Re~reh and Develo~nt Depar1ment

E. I. du Pont de Nemours and Callpany, Inc •
. Wf1mington, Delaware 19898 .

"
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 Du Pont HLR 365-90

GENERAL INFORMATION (Cont'd)

Stcdy Initiated: 11/21/89

In-Life Phase
Initiated - Completed: 10/27/89 - 6/12/90

Notebooks: E-54696. pp. 22-156.

E-58578
E-63781
E-63908

There are 39 pages in this report.

Distribution: K. D. Dastur (1)

C. F. Reinhardt (1)
N. C. Chromey/R. Valentine (1)
D. T. Cline (1)

,: .'

,;fl~~f~
 Du Pont HLR 365-90

Acute Inhalation Toxicity of Hydrogen Fluoride in Rats

SUMMARY

In the preliminary studies with hydrogen fluoride (HF) described in HlR

281-88, the inhalation toxicity of HF increased approximately 3-fold as the
relative humidity {RH) of the dilution air was increased from approximately
10 to approximately 60S. Although the basis for this difference could not be
determined, it was believed to have resui~d from the formation of aerosols
which escaped collection within the sampling train. To determine whether the
apparent increase in HF toxicity was real or related to the presence of
aerosols or due to a sampling artefact, additional analytical trials and
animal experiments were conducted.
Prior to the animal exposures, the sampling efficiency of glass impingers
(as used in the previous toxicologic work with HF) and glass impingers fitted
with TeflonB-lined inlet and outlet tubes were compared. Although ~oth
impinger systems yielded a collection efficiency (i.e., ratio of front:back
impinger HF concentrations) of over 97S, the total amount of HF collected
using the glass impingers underestimated the actual HF concentration. For
example, approximately 26S more HF was collected using the Tef1~-lined
impingers compared to the glass impingers under either dry or humid
conditions. Based on the trivial amounts of HF collected on a pTFE filter
medium placed upstream from the impinger system, no evidence was found for
the formation of HF aerosol at low or high RH, even at concentrations over
3000 ppm.
In the animals studies, groups of 4 male Crl:CD8BR rats (240-307 g) were
inserted into a 23-L polymethylmethacrylate exposure chamber lined with
TeflonS FEP film and exposed head-only to atmospheres of HF for a 1 hour
period. Although anhydrous HF was diluted in either dry (approximately lOS
RH) or humid (approximately 60S RH) air, the actual chamber humidfties with
rats present increased to approximately 43 and 767. RH with dry and humid
dilution air, respectively. HF was collected in tandem, TeflonS-lined.
midget, glass impingers and analyzed with a fluoride ion selective electrode.
Mortality data were obtained over a 14-d~ recovery period and LCSO values
were calculated by probit analysis. To evaluate respiratory tract
histopathology, 2 groups of 4 rats were exposed to a sublethal HF
concentration (approximately 1800 ppm) at low and hig~ hUlridities; 2 rats
from each group were killed 1 and 14 d~s after exposure and tissues fro. the
nose. larynx/pharynx, trachea and lung were examined by light II1croscopy.
In contrast to the previous findings presented 1n HLR 281-88. no
difference in toxicity was associated with exposure to HF at high hliZllidity.
The observed I-hour LCSO values for HF at low or high RH were 2240 and 2340
ppm, respectively and were not significantly different. Most deaths due to
HF exposure occurred 1-7 days post exposure follo.1ng prolonged weight

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 Du Pont HlR 365-90

SUMMARY (Cont'd)

losses; clinical signs indicative of respirato~ tract irritation (lung

noise. labored breathing. gasping. and nasal discharges). ocular irritation
(discharges and opacity) and dermai corrosion (necrotic lesions of the nose.
face and ears) were commonly seen. Pathologic examination of rats killed 1
day after exposure showed that compound-related microscopic lesions occurred
exclusively in the nose. Nasal lesions were characterized by extensive acute
necrosis and infiaoaation of the respiratory epithelium in the anterior nose;
minimal necro~is of olfacto~ epithelium was also found in 1 rat from the low
humidity group. In all rats. evidence of epithelial regeneration/re~air was
noted 14 days after exposure.
These data indicate that the 1 hour LeSO for head-only exposure to
anhydrous HF is approximately 2300 ppm and 1s not dependent upon relative
h'umidity. The previously described increase in HF toxicity with humidity
coul d not be repeated and may have been due to the cDlllparatively 1ow recove~
of HF using glass impingers and other analytical difficulties associated with
HF measurement. No evidence for the role of HF aerosols was found.

Work by:
alne T~ine. Jr.
Technician

Study Di rector:
Rudolph Valent1ne. Ph.D.
Research Toxicclogist

Reviewed and Approved for Issue:

Ru Olp alentine
Study Di rector
Acknowledgments: The technical assistance of James C. Mackay. 11 is gratefully
acknowledged in the development of the llethods used in this
study.
RY:alr:137.7

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 Du Pont BLR 365-90

QUALITY ASSURANCE DOCUHENTAnON

STUDY: HR 5645-001 Acute Inhalation Toxici~ of Hydrogen Fluoride in Rats

HI 17,142

AUDITS:

Items Audited Audit Dates

Conduct 11128/89
Pathology Report 55-90 6/22/90
Recordsl ReportlProtocol 1119,20,23-21,30,31/90
8/1,2190

SHORT-TERM AUDIT REPORT NUMBER: P-666

DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR: 6/22190,
8/2/90

Reported by: ~JI1J'iO

r te
Melissa R. "oolle
Quality Assurance Auditor

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 Du Pont HlR 365-90

INTRODUCTION

In the pre11mina~ studies with anhyctrous hydrogen fluoride (HF)

described in HLR 281-88 (ll. the relationships between exposure duration.
concentration and lethality were investigated. The data indicated that the
product of exposure concentration and duration was a constant for both dry
and humid dilution air but that HF appeared to be approximately 3-fold more
toxic as the humidity of the dilution air was increased from approximately 10
to 60'. This difference was unexpected and problems with the generation
(i.e •• possible aerosol formation) or sampling/analytical methods were
suspected. This study was conducted to investigate several possible sources
of error in HF sampling and to reevaluate the role of humidity on the I-hour
inhalation LC50. Except as documented in the study records. this study was
conducted according to the applicable Good Laboratory Practice Regulations.

MATERIALS AND METHODS

A. Analytical
Prior to the animal exposures. the sampling methods used for HF were
reevaluated. For the work presented in HLR 281-88. atmospheriC HF
sampling was conducted essentially following the NIOSH Analytical Method
for HF (2). All samples were collected from the rats' breathing zone
through a short (approximately 20 em) length of Teflon8 PFA tubing (6.4
mm o.d. x 4.0 mm i.d.) connected to tandem. midget. glass impingers whose
internal surfaces were coated with a thin Teflon8 film by immersion.
Known volumes of chamber atmospheres were drawn into the impingers which
contained approximately 10 mL of 0.1 N NaOH as the collection medium.
Aliquots of impinger solutions were mixed with an equal volume of total
ionic strength adjusting buffer (Orion Research Inc •• Cambridge MA) and
analyzed using an Orion Model 96-09-00 combination fluoride specific ion
electrode with either Corning Model 125 (Corning, Inc •• Ithaca. NY) or
Beckman Model 4500 (Beckman Instruments Co., Irvine. CA) digital pH
meters. Atmospheric HF concentrations were calculated from 0.1 N sodium
fluoride standards. prepared daily by the quantitative dilution of sodium
fluoride (Orion Research Inc.) in 0.1 N NaOH.
Although not reported previously. the Teflon- coating applied to the
impingers was not very durable and would erode. particularly in the inlet
tu~ of the impinger. after several days of sampling. To mnni.nze
contact of HF directly with glass. for these studies the two glass
impingers were modified by inse~ing a Teflon8 pTFE tube (Engineered

. ~7-
 Du Pont HlR 365-90
,
Plastics. 9ranchburg. NJ) 0.059 inch i.d. into the entire length of the
inlet and outlet tubes of each impinger. The collection efficiency of
this modified sampling system was compared to the glass impinger system
at different atmospheric HF concentrations and relative humidities. The
glass impinger system essentially duplicated the original Teflone-coated
impingers used in the previous toxicity studies since once the Teflon-
film had eroded, the glass surfaces were exposed.
The effect of the air sampling rate on collection efficiency was also
investig~ted. HF was collected at either approximately 0.2 or 1.4 L/min
using two. glass impingers or two. Teflon8-lined glass impingers
connected in series. This work showed that sampling at 1.4 Llmin
collected approximately 121. more HF than was collected at the lower flow
rate using either impinger system. For all subsequent analyses. airflow
through the impingers was maintained at approximately 1.2 - 1.6 L/min.
Flowrates were determined immediately before sampling using a Buck Model
M-5 Calibrator (A. P. Buck Inc •• Orlando. FL). Sampling was typically
conducted for 2-3 minutes to obtain an air sample with a total volume of
approximately 3 L.
As a screening method for the presence of HF aerosols. several filter
types were placed in unheated 25 or 37 mm plastic filter cassettes
immediately upstream from the impingers. These filters consisted of 25
mm Gelman (Gelman Sciences. Ann Arbor. MI) Type AlE glass fiber. 37 mm
Gelman Zefluor Teflon8 pTFE membrane (0.45 um pore size). or 37 m
Millipore (Millipore Corp •• Bedford. MA) Type HA Teflon- pTFE/high
density polyethylene membrane (0.5 um pore size) filters. Immediately
after sampling. the filters were placed in 0.1 N NaOH and the fluoride
concentration determined using a selective ion electrode. Filter
extraction efficiency was evaluated by spiking Millipore Type HA filters
(prewetted with ethanol) with small amounts of 0.1 N NaF. mixing with 0.1
N NaOH and measuring the fluoride ion concentration with a selective ion
electrode.
B. Atmosphere Generation
Test atmospheres of hydrogen fl uori de were generated by meteri ng
anhydrous HF (Matheson Gas Co) into a polymethyl-methacrylate (PMA)
exposure chamber (19.5 em x 19.5 em x 61 em) with an intemal vola.e of
approximately 23.2 L. The exposure chamber was fitted with 4 PMA tubes
(6.2 em i .~. ;t 24 em) which contained the animal restrainers. The animal
restrainers were coated with a Teflon8 fnm and the exposure chamber was
lined with Teflon- FEP fnm (Bytac4D overlay. VWR Scientific. Bridgeport.
NJ) to minimize acisorptive/reactf'Ve losses.

Cylinders of anhydrous HF were placed in a tearperature-~ntrolled

water bath heated to approximately 30-4Q°C. HF was metered through 1/4-
stainless steel tubing using a Model CST-M mass flow controller (Teledyne
Hastings Co •• Hampton. VA). Houseline air. previously conditioned by

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 Du Pont HLR 365-90

filtration and drying, was metered uting a Brooks Model 5851 mass flow ~
controller (Brooks Instrument Division, Hatfield, PAl and mixed with HF
prior to entering the chamber. Additional mixing of the test atmospheres
was accomplished with a perforated polyethylene baffle to promote
turbulent flow in the chamber inlet. Total airflow through the exposure
chamber was approximately 13.5 L/min. All stainless steel tubing
cor.taining HF vapor was insulated and heated with electrical heating tape
to prevent condensation of HF. Chamber atmospheres were exhausted
through tandem scrubbing flasks each containing approximately 1 L of 0.2
M NaOH, a MSA charcoal/HEPA filter cartridge and a dry ice cold trap
prior to discharge into a fume hood.
The flowrate of HF through the mass flow controller was determined by
measuring the time required to effect neutralization of a known
concentration of aqueous NaOH to a phenolphthalein endpoint. The
dilution air mass flow controller was calibrated using a dry test mater.
Atmospheres of HF were generated at either of low or high RH. Low RH
trials were conducted using house-supplied dilution air with an RH of
approximately 1~. To increase humidity, houseline air was passed
through a flask containing water at ambient temperature which raised the
RH of the dilution air to approximately 60~. The RH of the dilution air
was monitored with an Airguide Model P-4759 dial hygrometer (Airg~ide
Co., Chicago, IL) prior to adding HF. To monitor the exposure chamber
humidity, a hygrometer was fabricated from two, Type K chromel-alumel
thermocouples (Omega Scientific Co., Stamford, eT) placed at the outlet
of the exposure chamber. The tip of one thermocouple was fitted with a
fabric sleeve dipped in water and the other was left bare; this
thermocouple arrangement provided wet and dry -bulb- temperatures in the
corrosive HF environment. This hygrometer was checked against a Reuter
Stokes {Reuter Stokes canada, Ltd., Cambridge, Ontario} Model RSS-230
hygrometer with air only and found to measure RH with acceptable
accuracy; absolute RH values ~etween the improvised and the Reuter Stokes
hygrometers were within 6~ of each other at humidities ranging from
approximately 10 to 60~. In addition, exposure chamber temperature was
measured with a Type K chromel-alumel thermocouple.

C. Exposure Protocol
The inhalation toxicity of HF at high and low RH was reevaluated
using the improved sample collection system developed in the analytical
trials, i.e., the tandem, Teflon4D-lined, glass, nrfdget illlpinger system.
Groups of 4 male rats, approximately 8 weeks old and weighing between 240
and 307 grams, were restrained in perforated, Teflon4D-coated, stainless
steel cylinders fitted with conical nose pieces. Each group was exposed
head-only (i.e., the nose and potentially part of the head) fOr 1-hour
(exposures described in this report actually ranged from 60-63 minutes)
to atmospheres of anhydrous hydrogen fl uori de IIi xed wi th ei ther dry or
hlJDidified air.

-9-
 Du Pont HLR 365-90

Based on the analytical trials with HF, the following methods were
used during the animal exposures. HF was sampled from the rats'
breathing zone using a short (approx. 20 em) length of Teflone PFA tubing
(6.4 mm o.d.) at approximately 10-20 minute intervals. HF was collected
at a sampling rate of approximately 1.4 L/min using tandem,
Teflone-lined, glass, midget impingers (as described earlier) each
containing approximately 10 mL of 0.1 N NaOH. In some exposures, 37 mm
Millipore Type HA membrane filters were placed in the sample train
immediately upstream from the impingers to monitor for the possible
presence of aerosol. Atmospheric HF concer.trC!tions were determined
following the techniques described earlier.
All rats were weighed prior to exposure and surviving rats were
weighed and observed daily (weekends and holidays were generally
excluded) for 14 days post exposure. In addition, two groups of 4 male
rats were exposed to a sublethal HF concentration (approximately 1800
ppm) at high and low RH. Two rats from each group were killed after 1
day and after 14 days of recovery; representative samples of respirato~
tract tissues (i.e., nose, larynx/pharynx, trachea and lungs) were
obtained and examined by light microscopy.

O. Animal Husbandry
young adult male Crl:C08BR rats were received from Charles River
Breeding Laboratories, Kingston, New York. Each rat was assigned a
unique 6-digit identification number which corresponded to a numbered
card affixed to the cage. Rats were quarantined for one week prior to
testing, and were weighed and observed three times during the quarantine
period. During the test, rats were housed in pairs in SU x 14M X Sn
suspended. stainless steel, ~re-mesh cages. The rat assigned the lower
number in each cage was identified by a slash in the right ear. Prior to
exposure, rats' tails and cage cards were color-coded with water-
insoluble markers so that individual rats could be identified after
exposure. Except during exposure, Purina Certified Rodent Ch~ '5002
and water were available ad libitum.
Animal rooms were maintained on a timer-controlled. 12 hour/12 hour
light/~ark cycle. Environmental conditions of the rooms were targeted
for a temperature of 23° + 2°C and relative humidity of 50S + lOS.
Excursions outside these ranges were judged to have been of Tnsufficient
magnitude and/or duration to have adversely affected the validity of the
study.

.:: _- ,1Q.,~_' '.

 \.,
Du Pont HLR 365-90

E. Statistical Methods -
The median lethal concentration (LCSO) of HF was calculated for the
two relative humidity conditions by probit analysis as described by
Finney (3). Data from the trials of the analytical methods were analyzed
using Student's t test and flowrate data were analyzed by linear
regression (4); significant differences were declared at a probability
level of p < 0.05.
F. Records Retention
All raw data and the final report will be stored in the archives of
Haskell Laboratory for Toxicology and Industrial Medicine. Newark,
Delaware. or in the Du Pont Records Management Center. E. I. du Pont de
Nemours and Company. Inc., Wilmington, Delaware.

RESULTS

A. Analytical Methods
The initial analytical trials ex~ined impinger construction,
sampling rate. chamber humidity, and the use of filter media as
determinants of HF collection efficiency. A glass impinger system,
mimicking the type of impinger used in the time course studies described
in HLR 2S1-88, and a Teflons-lined, glass impinger were compared for
collection efficiency at both high and low RH. These trials showed that
while the impinger collection efficiency (i.e., the ratio of the front
impinge-,. HF concentration to the sum of the front and back impinger HF
concentrations) for both impinger types was greater than 97', the
Teflon*-lined impingers had a slightly higher efficiency than the glass
impingers (i.e •• 99.6' vs. 9S.1' as noted in Table Il. The magnitude of
this difference was much greater than expected however. when these
impingers were used to measure atmospheric HF concentrations. For
example, mean HF concentrations were approximately 28' and ISS higher
when measured with the TeflonB-lined impingers compared-to the glass
impingers ;~ either low or high RH environments, respectively; these •
values were not significantly different and the pooled mean increase was
26S (Table II). The higher HF concentrations obtained us~ng the -
TeflonB-lined impingers more closely approximated the calculated nominal
HF concentrations, especially for dry air (Table Ill). Indeed, the mean
measured HF concentration was 106S of nominal for dr,y ai~, indicating the
accuracy of the analytical methods. Upon introducing humid air, ,however, " ,..,

the recovery of HF was significantly lower (approximately 84S of,

nom; na1 l, i ndi cat; n9 thatabsorpti ve losses wi thin the test. system -bad
occurred. It should be noted that the ratios ofthe'llieasured HF -' -
.' ..
 Du Pont HLR 365-90

concentrations to the nominai HF concentrations obtained .rtth the

Teflone-l1ned impinge,..s ~:; this study were approximately 2- and 4-fold
-
rr)

higher than those noted but not reported for the time-course studies .rtth
HF (HLR 281-88) at low and high RH. respectively. Due to the higher
recovery attained with the Teflone-lined impinger system. this apparatus
was subsequently used as the basis for determining the chamber HF
concentrations in the animal studies.

Table 1
Impinger Collection Efficiencya
Dry Air - Dilution air RH = 6'
G1ass ImpinJers Tefloft8-lined Impingers
97.3 + 0.1 99.6 !. 0.2'£

Humid Air - Dilution air RH = 52'

Glass Impingers Teflon®-lined Impingers
98.9 ! 0.1' 99.5 + 0.5'

a Values are expressed as the percentage of the amount of HF found in the

front impinger to the total amount of HF detected in the front and back
impingers.

Table II
Summary of HF Recovery in Teflone-Lined vs. Glass Impingers a

Dry Air - Mean Chamber RH = 43' Humid Air - Mean Chamber RH = 76'
1.28 + 0.22 n = 33 1.18 !. 0.20 n = 10

a Values represent the mean, standard deviation and number of samples(n) for
the ratios of the Teflon®-lined impinger HF concentrations to the.glass
impinger HF concentrations. These values were not significantly different
by Student's t test (0.1 < p < 0.2), and yielded a pooled mean and standard
deviation of 1.26 + 0.22. .
 Du Pont HLR 365-90

Table III --
~

Ratios of Measured to Nominal HF Concentratfonsa

D!2 Air Humid Air
Measured Nomlnai Measured Nomlnai
HF Conc. HF Conc. HF Conc. HF Conc.
(EEm) ( EE!!!) Ratio (EEm) ( EE!!!) Ratio
950 1070 0.89 1290 2300 0.56
1550 1520 1.0Z 1940 2120 0.92
1690 2000 0.85 2060 2700 0.76
1730 1500 1.15 2200 2850 0.77
1800 1340 1.34 2210 2450 0.90
2030 1540 1.32 2490 2760 0.90
2040 2230 0.92 2620 2540 1.03
2260 2200 1.03
2420 2420 1.00
2730 2620 1.04

a Nominal concentrations were based on the calculated flows of HF and

dilution air into the exposure chamber. Measured HF concentrations were
based on the use of TeflonB-lined glass impingers. Mean ratios for d~ and
humid air were 1.06 + 0.17 and 0.84 + 0.15, respectively, and are
significantly different by Student1s-t test ( 0.01 < P < 0.02).

To monitor for the possible presence of HF aerosol in the chamber,

either glass fiber, or two types of TeflonB pTFE membrane filters were
placed in filter cassettes upstream from the ilDpingers. Preli.ina~
trials were conducted without rats, using dry air and at an atmospheric
HF concentration of approximately 700 ppm; the HF concentration from
glas~ fiber filters was approximately 250 ppm compared to about 70 ppm
for the pTFE membrane filters. It is believed that the HF found on the
filter media. especially by the glass filters, represents nonspecific
absorptive or reactive processes and not due to aerosols since Schotte
(5) has indicated that HF aerosols may be formed at concentrations
exceeding approximately 1300 ppm at 23°C and 65~ RH. Due to the
relatively high absorption of HF by the glass fiber filters, further
trials were conducted at high and low RH with tile Mi11ipore type HA pm
filters at approximately 1000 or 3000 ppm. The measured atmospheri(; HF
concentrations based on the filter samples were relatively constantin
these trial s. ranging from approximately 1-70 ppm. In general. IDOre HF
was detected on the filters at 1000 ppm than at 3000 ppm HF and roughly
the same amount of HF was found on the filters sampled from either high

.:·::i~~" 'to
:":~:~:~.~-~.~~ ';.•:: - -!: .:"
 Du Pont HLR 365-90

or low RH environments. Filter spiking studies. conducted by applying

0.1 N NaF to the Type HA filter membranes and extracted with 0.1 N NaOH.
-
showed that recovery averaged 102'1.. In several animal experiments where
the chamber humidity was approximately 70'1. and chamber HF concentrations
ranged from approximately 1300-2500 ppm. the amount of HF collected on
filters was less than 10 ppm.

8. Exposure Conditions and Associated Mortality

The relative humidity of both the dilution air and the exposure
chamber was measured during this study. While the dilution air RH was
typically about 10 or 60'1. RH for dry or humid air. respectively. the
exposure chamber RH with rats present increased to approximately 43 and
76'1. RH for dry and humid dilution air. respectively. Upon introducing
humid air, the initial amount of HF recoverable with the Teflone-lined
impingers decreased by at least 20'1. (Figure 1). The decreased recovery
of HF noted upon adding water vapor was transient as within approximately
1 hour, HF concentrations generally tended to increase towards
prehumidification levels. suggesting that non-specific absorptive losses
occurred at the higher humidity but that HF concentrations slowly
increased as a new equilibrium was established.
The analytical data obtained with the different impingers suggested
that the measured HF concentrations obtained with the glass impingers
were underestimating the actual HF concentrations by approximately 26'1..
To confirm that the actual LC50 would be higher than that reported in HLR
281-88. additional animals exposures were performe6 to determine the
I-hour Le50 values for HF at high and low RH. The results of these
studies are summarized in Table IV. These data show that the dry and
humid air LC50's for HF are 2240 and 2340 ppm. respectively and are not
significantly different. Exposure data and LeSO calculations under dry
and humid air conditions are presented in Appendix A. The chamber
temperature and relative humidity conditions are summarized in Table v•

. '.

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 Du ?ont HLR 365-90

Table IV
I-Hour LCSO Results
Calculated 95~ Confidence Limits
lCSO (ppm) Lower Upper Slope n

D~ Air--Mean Chamber Humidity = 43~ RH

2240 2060 2580 14.8 10
Humid Air--Mean Chamber Humidity = 76~ RH
2340 2180 2630 21.8 7

Table V
Chamber Conditions During Exposurea
Relative Humidity (~)
lemperature (OC) Dl1ution Alr EXposure chamber
Mean Range Rean Range Rean Range
Dry Air
23.6 21.3 - 26.9 7 S - 9 43 20 - 61

Humid Air
22.8 21.6 - 23.5 65 61 - 68 76 65 - 82

a Represents the means and ranges of temperature and relative humidi~ values
observed for each exposure.

c. Clinical Observations
During the 14-day recove~ period, similar clinical signs as those
described in HLR 281-88 were observed. Briefly, these signs ~re
indicative of the corrosive nature of HF to the cutaneous, respiratory
and ocular systems. Generally observed signs of toxicity included
respirato~ distress {labored breathing, lung noise and/or gasping>,
oral, nasal and ocular discharges, corneal opaci~, shut or partially

." .~. ··~····15-~.

. . --'?-
.:"
 Du Pont HLR 365-90

closed eyes, facial hair loss, nasal, facial, and ear erosion/necrosis.
lethargy, hunched posture, yellow- or brown-stained perineum, and
-
I"-

piloerection were observed. Typically. deaths occurred 1-7 days post

exposure; deaths during exposure occurred rarely. In surviving rats.
resolution of clinical signs did not always occur within the 14-day
recovery period as lung noise, corneal opacity, ocular discharge,"facial
nair loss, and facial scabs persisted in some rats until study
termination. Animals exposed to HF generally incurred severe weight
losses within 1 day of exposure which persisted for several days; in
surviving rats, wei9~t recove~ usually began within 3-5 days.

D. Pathology
Representative sections of the nose, la~nx/pha~nx, trachea and
lungs were examined from rats exposed to HF at either l630 ppm in dr,y air
or 1910 ppm in humid air. One day after expcsure, pathologic injur,y was
limited exclusively to the anterior section of the nose although mnnimal
olfactor,y epithelial necrosis was noted in 1 rat from the d~ air group.
The nasal injury was characterized by axtensive acute, necrosis of
respiratory epithelium with inflammation and vascular thrombosis in
adjacent submucosal tissues. No compound-related injur,y was observed in
either the more posterior portions of the nose, nor in the trachea or
lung. By 14 days after treatment, some squamous metaplasia of
respiratory epithelium and slight infiamation in the 1630 ppm group was
observed suggesting that epithelial regeneration/repair was underway.
pathology Report No. 55-90 is attached as Appendix B.

DISCUSSION AND CONCLUSIONS

The pre-exposure analytical studies indicated that the glass-impinger

system used in the previously reported time-course studies were probably
underestimating the actual HF concentration by approximately 26~. This
factor, if applied to the I-hour low RH LC50 value reported in HLR 281-88
gives a corrected LC50 of 2040 ppm. The observed LCSO for HF in this study
was was comparable (2240 ppm).
This value is approximately 2-fold higher than the 1-hour LCSO values for
HF reported in the literature, i.e •• approximately 970-1400 ppm (5-9).
Several explanations may be offered to account for this difference. First._
the choice and operation of the sampling apparatus is ve~ important. The
use of glass impingers underestimated the HF concentration by approximately
26~. presumably by reaction with Si~ groups in glass. While it is well
known that HF may react with glass fOrming SiF , a gas. the reactivi~ of HF
with glass was not investigated in this study.4 It is pllssible that the loss

- -16,;:<
 Du Pont HLR 365-90

of SiF from the sample train could result in a lower apparent HF

-
concentration. However, ~th TeflonS-lined impingers, annimal losses of
fluoride occurred since the measured atmospheric concentration of HF was 106'
of the nominal concentration. The nominal concentrations reported here are
at least 2- and 4-fold higher than those noted but not reported for HF at low
and high RH. respectively. in HLR 281-88.
In comparison to the dry air LCSO value, no significant increase in HF
toxicity was associated with higher relative humidity. The previously
described increase in HF toxicity with humidity could not be repeated and may
have been due to the comparatively low recovery of HF using glass impingers
and other analytical difficulties associated with HF measurement. In HLR
281-88, it was hypothesized that aerosols may have been formed at the higher
humidity and may have facilitated penetration of HF to the lung to increase
the apparent toxicity. Aerosols, while expected to be present at
concentrations greater than 1200 ppm at 65' RH and 23°C. were not detected on
filter samples from chambers operated at high RH in amounts much greater than
that found at low RH. While it is possible that HF may have volatilized from
the filters during sampling, the very low amounts detected suggested that
aerosols were not a major contributor to the total amount of HF present.
Moreover. histopathologic examination of rats exposed to HF at concentrations
approaching the LC50 revealed that respiratory tract injury was limited
exclusively to the nose. No difference in the distribution of injury was
noted at either humidity condition, indicating that the deposition of HF at
high and low RH is similar. Nearly 100' nasal deposition of HF and extensive
nasal tissue destruction has been reported by Morris and smith (10) although
the HF concentration was much lower, typically 220 ppm. Although respirato~
tract pathology was not evaluated at lethal HF concentrations in this study.
the available information suggests that the deaths foll~ng HF exposure were
due to systemic fluoride toxicity arising from absorption of HF deposited in
the nose rather than acute pulmonary involvement.

- 17 -
 Du Pont HLR 365-90

REFERENCES
-
.,j-

1. Prelimina~ Report on the Concentration-Time-Response Relationships for

~drogen Fluoride. Haskell Laboratory Report No. 281-88.
2. National Institute for Occupational Safety and Health: Criteria for a
Recommended Standard ••• Occupational Exposure to ~drogen Fluoride.
DHEW/NIOSH Publication No. 76-143. Cincinnati.OH. 1976.
3. Finney. OJ. Probit Analysis. 3rd Ed. Cambridge University Press, 1971.
4. Zar. JH Biostatistical Analysis. Second Edition. Prentice Hall. Inc ••
Englewood CliffS, N.J. 1984.
5. Schotte. W. Personal Communication.
6. Darmer. KI. Haun. CC and MacEwen JO. The Acute Toxicity of Chlorine
Pentafluoride. Am Ind ~g Assoc J. 33:661-'--'. 1972.
7. Rosenholtz. MJ. Carson. TR. Weeks. MH. Wilinski. F. Ford. DF. and Oberst.
FW. A Toxicopathologic Study in Animals after Brief Single Exposures to
~drogen Fluoride. Am Ind ~9 Assoc J. 24:253-261, 1963.

8. Vernot. EH. MacEwen. JD. Haun. CC and Kinkead. ER. Acute Toxicity and
Skin Corrosion Data for Some Organic and InorganiC Compounds and Aqueous
S01utions. Toxicol Appl Phanmacol. 42:417-423. 1977.
9. Wohlslagel, J. DiPasquale. LC. and Vernot. EH. Toxicity of Solid Rocket
Motor Exhaust: Effects of Hel. HF and Alumina on Rodents. J Combust
Toxicol, 3:61-70, 1976.
10. Morris JB and Smith, FA. Regional Deposition and Absorption of Inhaled
~drogen Fluoride in the Rat. Taxicol Appl Pharmacol. 62:81-89, 1982.

:' ,,'( ~." ~

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 Du Pont HlR 365-90

Figure 1

Effect of Humidity on Exposure Chamber HF Concentration

......
 HIGH AND LOU RELATIVE HUHIOITY EFFECTS
ON HF CONCENTRATION AT 3000 ppM HF
3300 100

3200 Q
.0 ············· . 90
3100
0 ............ 0 .../ \ BO
H3000 ....... ..0·,,······0
"0
F 2900 ~
2800 GO
o
P 2"00 --50 r
.... P 26QO H
0
>,' N m2800
O.
"
.. ..
2400 o
2300
2200 J-I I:
S"O 100 150 200

HINUTES ~
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"""0"'" ppH HF ~
10)

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 Du Pont HLR 365-90 ~
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Appendix A
LCSO Calculations for HF

l~, ~"
 Du Pont HlR 365-90 r'1
N
LCSO Calculation for Ex~sure to MF
DRY AIR
Concentration (Conc) is expressed as ppm

STANDARD
CONC. DEVIATION LOG CONC. I EXPOSED I RESPONDING RATE PROBIT
953 26 2.9791 4. o. 0.0001 1.2809
1547 164 3.1895 4. O. 0.0001 1.2809
1691 102 3.2281 4. O. 0.0001 1.2809
1732 155 3.2385 4. 1. 0.2500 4.3258
1798 36 3.2548 4. O. 0.0001 1.2809
2033 29 3.3081 4. O. O.OOO~ 1.2809
2036 138 3.3088 4. 2. 0.5000 5.0000
2262 91 3.3545 4. 1. 0.2500 4.3258
2417 54 3.3833 4. 3. 0.7500 5.6742
2734 114 3.4368 4. 4. 0.9999 8.7191

HETEROGENEITY FACTOR = 1.0000

NUMBER OF POINTS = 10
DEGREES OF FREEDOM = 8
DEVIATE = 1.9600
G = 0.3359
NUMBER OF CYCLES = 6
AVG X = 3.3274
AVG Y = 4.6532
AVG V = 0.0000
SLO~E = 14.8369 LL = 6.2383 UL = 23.4354
INTERCEPT = --44.7146
CHI SQUARED = 8.3393
95' CONFIDENCE LIMITS
POINT CONC LOWER UPPER
P=O.OI 1563.0011 1004.7972 1781.9530
P=0.05 1737.3427 1281.1301 1921.6967
P=0.10 1838.1114 1452.7173 2008.3335
P=0.20 1968.0126 1676.9927 2136.9425
P=0.50 2242.5978 2061.6160 2575.9355
P=0.80 2555.4943 2319.8997 3392.2849
P=0.90 2736.0937 2439.4956 3962.4933
P=0.95 2894.7916 2537.6124 4514.2141
P=O.99 3217.6849 2725.4546 5779.2560

.. - 22. ~ ..... .
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 Du Pont HLR 365-90

LC50 calculation for EX20sure to HF

HUMID AIR
Concentration (Cone) is expressed as ppm

STANDARD
CONC. DEVIATION lOG CONC. I EXPOSED # RESPONDING RATE PROBIT
1290 171 3.1106 4. o. 0.0001 1.2809
1935 68 3.2867 4. 1. 0.2500 4.3258
2063 108 3.3145 4. O. 0.0001 1.2809
2202 131 3.3428 4. 1. 0.2500 4.3258
2213 150 3.3450 4. O. 0.0001 1.2809
2490 17 3.3962 4. 3. 0.7500 5.6742
2617 75 3.4178 4. 4. 0.9999 8.7191

HETEROGENEITY FACTOR = 1.0000

NUMBER OF POINTS = 7
DEGREES OF FREEDOM = 5
DEVIAT'; = 1.9600
Ci = 0.4848
NUMBER OF CYCLES = 6
AVG X = 3.3582
AVG Y = 4.7714
AVG V = 0.0000
SLOPE = 21.7879 LL = 6.6181 UL = 36.9577
INTERCEPT = -68.3967
CHI SQUARED = 8.0711

95~ CONFIDENCE LIMITS

POINT CONC LOWER UPPER
P=O.OI 1827.7571 1085.7085 2027.4782
P=0.05 1964.2325 1368.3845 2127.4496
P=0.10 2041.1133 1544.1433 2188.2866
P=O.20 2138.2669 1776.7583 2277.9998
P=0.50 2337.1618 2176.3307 2626.6074
P=O.80 2554.5572 2381.7670 3389.6806
P=0.90 2676.1499 2463.3927 3925.6775
P=0.95 2780.8955 2527.7900 4440.4873
P=0.99 2988.5400 2647.0703 5607.9636

-23-
 Du Pont HLR 365-90 \
'{J

Appendix B

Pathology Report No. 55-90

 <@PO[i)
-. ---.-.-
Du Pont HLR 365-90

E. I. DU PONT DE NEMOURS & COMPANY

HASKELL LABORATORY FOR TOXICOLOGY

ANI) INI)USTRIAL MEI)ICINE

P.O. Box 50. ELKTON ROAI)

NEWARK. DELAWARE 19714

CENTRAL RESEARCH ANI) CEVELOPMENT CEPARTMENT

PATHOLOGY REPORT NO. 55-90

MEDICAL RESEARCH PROJECT NO. 5645 HASKELL LABORAIORY NO. 17742

ACUTE INHALATION TOXICITY OF HYDROGEN FLUORIDE IN RATS

CR&D DEPARTMENT

DATE ISSUED: AUGUST 13. 1990

;",. ..... .
 Du Pont BLR 365~90

ACUTE INHALATION TOXICITY OF HYDROGEN FLUORIDE

SUMMARY

Groups of 4 male Crl:coesR rats were exposed by inhalation to hydrogen

fluoride at concentrations of 1630 ppm in low relative humidity and 1910 ppm
in hi.gh relative humidity for 60 minutes. All animals were ex.em1ned grossly
and selected tissues were examined microscopically.

Exposure to hydrogen fluoride, at both doses studied. produced

microscopic lesiono in the anterior nasal passages. These were characterized
by necrosis of respiratory epithelium with inflammation and vascular
thrombosis in adjaceut submucosal tissues. Lesions appeared reversible in
both groups, however, some squamous metaplasia of respiratory epithelium and a
slight degree of inflammation (1630 ppm group only) were present following the
14-day recovery period.

Report by,.P~~ t--Lr

: Tracy Hakovec, D.V.M.
Diplomate, A.C.V.P.
J ___
Staff Pathologist

Approved bY:._=,,~11tJ.=~~'trvl.~~t-J~J~L~~~~
Theodore w. Slone, 3r., Dtv.K.
__
Diplomate, A.C.V.P.
Manager, Pathology Division

(;!M!TWS/wfd
GTMl 1.24

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INTRODUCTION AND METHODS

Gross and mdcroscopic findings from male Crl:co&BR rats exposed via
inhalation to hydrogen fluoride are summarized in this report. Expo~~e
groups were as follows:

CONCENTRATION OF
GROUP RATS/GROUP HYDROGEN FLUORIDE (ppm)

HF-20 4 1630 (low relative humidity)

HF-22 4 1910 (high relative humidity)

Animals were exposed to their respective concentrations of hydrogen

fluoride for 60 mdnutes. A control group was not present. One day after the
end of the exposure period. 2 rats/group were sacrificed for pathologic
evaluation. The remaining 2 rats/group were sacrificed follo~ng a 14-day
recovery period.
Following euthanasia by sodium pentobarbital anesthesia and exsanguina-
tion. all animals were examined for gross alterations. Representative
sections from the following organs and tissues were collected from all animals
for microscopic evaluation: nose, larynx/pharynx, trachea (to include carina),
lungs, and any gross lesions. All tissues were fixed in 10% neutral buffered
formalin. Following decalcification, the nose wBf sectioned to produce 4
levels according to the method described by Young. Fixed tissues were
embedded in paraffin, sectioned at a nominal thickness of 5 micrometers, and
stained ~th hematoxylin and eosin.

RESULTS AND DISCUSSION

Incidences of microscopic observations, ~th lesion grades, for I-day and
14·-day recovery animals are tabulated in Tables 1 aDd 2, respectively.
Appendix A contains individual animal gross and microscopic pathol~gy data.
Compound-related effects were present in noses of animals from both
groups. There vas extensive acute necrosis of respiratory epithelium present
in all animals from both groups sacrificed the day after exposure. An acute
inflammatory response and fibrin thrombi within blood vessels were present in
submucosal tissue adjacent to the necrotic epithelium. In one rat frgm the
BF-20 group (#476146) there was also minimal necrosis of olfactory epithelium.
The previously described lesions (not including olfactory epithelial necrosis)
were located in the anterior region of the nose, pr~ly level I •

. ':'-,

~.:--"27 _- .
 Du Pont BLR 365-90 t,)-
~

In the 14-day recovery animals, compound-related lesions were present in

both groups. Squamous metaplasia of respiratory epithelium was present in the
anterior section (level I) of nose in all animals from both groups. There was
also mi~a1 inflammation present in the noses, at level I, of the HF-20 group
animals. These lesions represent an attempt to repair damaged respirat~ry
epithelium. With a longer recovery period, the squamous metaplasia may be
replaced by respiratory epithelium.

The other lesions noted in these animals, minimal inflammation of the

trachea in animal 1476776 ac1 minimal inflammation of the lung in animal
1476775 (both from group RF-22), were considered to be incidental findings.
In summary, bydrogen fluoride in concentrations of 1630 ppm in low
humidity and 1910 ppm in high humidity produced acute necrosis of respiratory
epithelium, inflammation, and vascular thrombosis of the anterior nasal
cavity. Residual lesions characterized by squamous metaplasia of respiratory
epithelium and/or inflammation were present in the noses of 14-day recovery
animals.

Reference

1. Young, J.T. Histopathology examination of the rat nasal cavity. Fundam.

Appl. Toxicol., 1:309-312, 1981.

~ 28:--
 INHALATION TOXICITY OF HYDROGEN FLUORIDE
HN-I7742 TABLE 1
HC-720 INCIDENCES OF HICROSCOPIC OBSERVATIONS IN HALE RATS
HR-5645
(ANIHAlS NECROPSIED FROH DAY 0 TO DAY 2)
GROUP DESIGNATION: HF-20 HF-22
LESION GRADES DOSE (PPH): 1630 1910
TISSUE/LESION (l,2,',4,P) NUHBEA IN GROUP: 2 2
. ...•......................•..•.•....•.....•.....................................................•......................•

NOSE 2 2
INFLAHHATION L ACUTE, RESPIRATORY EPITHELIUH --2-11,1'-'-'-1
NECROSIS, OL~ACTORY EPI1"HELIUH 1 1,-,-,-,- -2-(-.2,-.-.-)
-
NECROSIS, RESPIRATORY EPITHELIUH 2 -.-.2.-.- 2 (-.-,2.-,->
THROHBI, SUBHUCOSAL VESSELS 2 -,2,-,-.- 2 (1.-.1.-.-)
LARYNX/PHARYNX _.1_ ~-
TRACHEA ~- 2
INFLAHHATION, ACUTE -r(l.-.-.-.-)
; ,
'.iif LUNGS _2_ _L
I' '

'.~ .
." ~.. ;,' .NOT~S:THE NUHBER OF ORGANS EXAHINED FOR EACH GROUP IS UNDERLINED,
o LESION GRADES: HINIHAL' HILD' HODERATE' SEVERE; PRESENT,
o LESION GRADES CORRESPON6 BY P6SITION WItH THE NUHBERS IN PARENTHESES L WHICH INDICATE HOW OFTEN EACH GRADE
WAS OBSERVED. FOR EXAHPLE: (- 1.2 - .) HEANS NO LESIONS WERE GRAD~D HINIMAL 1 LESION WAS GRADED MILD.
2 LESIONS WERE GRADED MODERATE. NO LtsloMS WERE GRADED SEVERE AND NO LESIONS wtRE GRADED "PRESENT"
,(NON-GRADED LESIONS),

f?
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 INHALATION TOXICITY OF HYDROGEN FLUORIDE
HN-I7742 TABLE 2
HC-720 INCIDENCES OF HICROSCOPIC OBSERVATIONS IN HALE RATS
HR-5645
(ANIHALS NECROPSIED FROH DAY 3 TO DAY 15)
GROUP DESIGNATIONI HF-20 HF-22
LESION GRADES DOSE (PPH): 1630 1910
TISSUE/LESION (1,2,3,4,P) NUHBEA IN GROUP: 2 2
.....•.................................................................................•.•.....•••..................•...
NOSE 2
INFLAHHATION, ACUTE, RESPIRATORY EPITHELIUH ~-(2,-,-,:,:)
-+2 (2,-,-,-,-)
SQUAHOUS HETAPLASIA, RESPIRATORY EPITHELIUH 2 (-,2,-, , )
LARYNX/PHARYNX _...L __
2
TRACHEA ---.l_ _2
. LUNGS _2 2
INFLAHHATION, SUBACUTE -r(1,-,-,-.-)
,-.~ .. --.-- ...------.---.-----.---------------.------- ------------_._._-----_.- -------- ... -- ........................... .
. NOTES: "
.. 1 :~.' . 0 THE NUHBER OF ORGANS EXAHINED FOR EACH GROUP IS UNDERLINED,
.. W· o LESION.LAADES: HINIHAL' HILD' HODERATE' SEVERE; PRESENT,
",0
.:j '.
o LESION GRADES CORRESPONb BY pbSITION Wlt~ THE NUHBERS IN PARENTHESES, WHICH INDICATE HOW OFTEN EACH GRADE
WAS OBSERVED, FOR EXAHPLE: (- 1,2 - - HEANS NO LESIONS WERE GRADtD HINIHAL 1 LESION WAS GRADED HILD,
2 'LESIONS WERE 6RAD~D HODERATE. ~O Ltsio S WERE GRADED SEVERE AND NO LESIONS WtRE GRADED "PRESENT"
. (NON-GRADED LESIONS) •
.\>
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31
 INHALATION TOXICITY STUDY OF HYDROGEN FLUORIDE
HN-17742
HC-720 Key to Appendix A
HR-5645

Hode of Oeath
SD • Sacrificed by Design (study termination)
SE • Sacrificed In extre~is

Leston Codes
Gross and 11croscopic changes are described according to thetr morphological character, distribution, and
severity. The distribution (extent of tissue involvement) is Indicated, where appropriate by .odlflers sucn
as focal, lultlfocal. diffuse, unilateral, bilateral, etc.: a severity score, If approprlaie, Is also assigned
as follows:
"Inllal • the alount of change present barely exceeds that which Is considered to be within
norlal Hilts
I "lId - the alount of change present is eastly detected
~, "oderate • a large alount of change is present
"I
Severe • the degree of change within the affected area(s) is essentially as severe and cDlplete
as Is thought possible

, In ter.s of Quantification, the terms Mild and ~oderate represent progressive Involvelent/severlty along a
,continuuM. Thus, "Ind" represents a change felt to be approxlMatel)' one-third of the way along the contlnuulI
between IIInllal and severe. and "Moderate" is approximately two-thlrils of the 'rIay along this salle continuul.

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32-
 INHALATION TOXICITY OF HYDROGEN FLUORIDE
HN-I7742 APPENDIX A (continued)
HC-720 INDIVIDUAL ANIHAL PATHOLOG~ DATA
HR-5645
HALE RAT GROUP: HF-20 DOSE: 1630 PPH

ANIHAL 'I 476145 DAYS ON TEST: 15 HODE OF DEATH: SO

GROSS OBSERVATIONS:
NO ABNORMALITIES DETECTED

MICROSCOPIC OBSERVATIONS:
NOSE - INFLAHMATION 1 ACUTE, RESPIRATORY EPITHELIUM, HINIMAL
- SQUAHOUS HETAPLASIA, RESPIRATORY EPITHELIUH, HILD
THE FOLLOWING TISSUES WERE UNREHARKABLE HICROSCOPICALLY: LARYNX/PHARYNX, LUNGS, TRACHEA
THE FOLLOWING TISSUES WERE AUTOLYZED; DEGREE OF AUTOLYSIS DID NOT PRECLUDE HICROSCOPIC EXAHINATION: NONE
THE FOLLOWING TISSUES WERE SEVERELY AUTOLYZED: HICROSCOPIC DIAGNOSES NOT HADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
NONE
W
SECTIONS OF THE FOLLOWING TISSUES WERE NOT PRESENT FOR HICROSCOPIC EXAMINATION: NONE
.N SECTIONS OF THE FOLLOWING TISSUES WERE INSUFFICIENT FOR HICROSCOPIC EXAHINATlON: ORGAN NOT COUNTED IN INCIDENCE TABLES:
... I NONE
\

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~
~

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33
 INHALATION TOXICITY OF HYDROGEN FLUORIDE
HN-I7742 APPENDIX A
HC-720 INDIVIDUAL ANIHAL PATHOLOGY DATA
HR-5645
HALE RAT GROUP: HF-20 DOSE: 1630 PPH

ANIHAL ,: 476146 DAYS ON TEST: 2 HODE OF DEATH: SD

GROSS OBSERVATIONS:
NOSE - STAIN, RED

HICROSCOPIC OBSERVATIONS:
NOSE - INFLAHHATION L ACUTE, RESPIRATORY EPITHELIUH, HINIHAL
- NECROSIS, OLtACTORY EPITHELIUH, HINIHAL
- NECROSIS, RESPIRATORY EPITHELIUH HODERATE
• THROHBI, SUBHUCOSAL VESSELS, HIL b
THE FOLLOWING TISSUES WERE UNREHARKABLE HICROSCOPICALLY: LARYNX/PHARYNX, LUNGS, TRACHEA
THE FOLLOWING TISSUES WERE AUTOLYZED: DEGREE OF AUTOLYSIS DID NOT PRECLUDE HICROSCOPIC EXAHINATION: NONE
,. THE FOLLOWING TISSUES WERE SEVERELV AUTOLYZED; HICROSCOPIC DIAGNOSES NOT HADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
.~NE .
w
,c;~· SECTIONS OF THE FDtLOWING TISSUES WERE NOT PRESENT FOR HICROSCOPIC EXAHINATION: NONE
SECTIONS OF THE FOLLOWING TISSUES WERE INSUFFICIENT FOR HICROSCOPIC EXAHINATION; ORGAN NOT COUNTED IN INCIDENCE TABLES:
NONE

~
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 •

INHALATION TOXICITY OF HYDROGEN FLUORIDE

HH-I7742 APPENDIX A (continued)
HC- 720 INDIVIDUAL ANIHAL PATHOLOG~ DATA
HR-5645
HALE RAT GROUP: HF-20 DOSE: 1630 PPH

ANIHAL', 476147 DAYS ON TEST: 2 MODE OF DEATH: SD

GROSS OBSERVATIONS:
NOSE - STAIN, RED

HICROSCOPIC OBSERVATIONS:
NOSE - INFLAHHATION 1 ACUTE L RESPIRATORY EPITHELIUH, HILD
- NECROSIS, RE~PIRATOHY EPITHELIUHL MODERATE
- THROHBI, SUBMUCOSAL VESSELS, MILv
THE FOLLOWING TISSUES WERE UNREHARKABLE MICROSCOPICALLY: LARYNX/PHARYNX, LUNGS, TRACHEA
"."',
. ~', - THE FOLLOWING TISSUES WERE AUTOLYZED: DEGREE OF AUTOLYSIS DID NOT PRECLUDE MICROSCOPIC EXAHINATION: NONE
':>
, '~': THE FOLLOWING TISSUES WERE SEVERELY AUTOLYZED: HICROSCOPIC DIAGNOSES NOT HADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
""",, ·1 NONE
:."" W SECTIONS or THE rOLLOWING TISSUES WERE NOT PRESENT FOR HICROSCOPIC EXAHINATION: NONE
-. .ll-

I SECTIONS or THE rOLLOWING TISSUES WERE INSUFFICIENT FOR HICROSCOPIC EXAHINATION; ORGAN NOT COUNTED IN INCIDENCE TABLES:
NONE

5'
61
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~
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35
 •

INHALATION TOXICITY OF HYDROGEN FLUORIDE

HN-17742 APPENDIX A (continued)
He-720 INDIVIDUAL ANiMAL PATHOLOGY DATA
HR-5645
MALE RAT GROUP: HF-20 DOSE: 1630 PPM

ANIMAL ,: 476148 DAYS ON TEST: 15 MODE OF DEATH: SO

GROSS OBSERVATIONS:
NO ABNORHALITIES DETECTED

MICROSCOPIC OBSERVATIONS:
NOSE • INFLAMMATION, ACUTE, RESPIRATORY EPITHELIUM, HINIMAL
• SQUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM, MILD
THE FOLLOWING TISSUES WERE UNREMARKABLE MICROSCOPICALLY: LARYNX/PHARYNX, LUNGS, TRACHEA
THE FOLLOWING TISSUES WERE AUTOLYZEDj DEGREE OF AUTOLYSIS DID NOT PRECLUDE HICROSCOPIC EXAHINATION: NOHE
THE FOLLOWING TISSUES WERE SEVERELY AUTOLYZEDj MICROSCOPIC DIAGNOSES HOT HADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
I.
NONE
t.) SECTIONS OF THE FOLLOWING TISSUES WERE NOT PRESENT rOR MICROSCOPIC EXAMINATION: NONE
,VI
I SECTIONS OF THE FOLLOWING TISSUES WERE INSUFFICIENT FOR HICROSCOPIC EXA"INATION; ORGAN NOT COUNTED IN INCIDENCE TABLES:
HONE

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INHALATION TOXICITY OF HYDROGEN FLUORIDE

HN-I7742 APPENDIX A (contInued)
HC-720 INDIVIDUAL ANIHAL PATHOLOG~ DATA
HR-5645
HALE RAT GROUP: HF-22 DOSE: 1910 PPH

ANIHAL I: 476774 DAYS ON TEST: 15 HOD~ OF DEATH: SO

GROSS OBSERVATIONS:
NO ABNORHALITIES DETECTED

HICROSCOPIC OBSERVATIONS:
NOSE - SQUAHOUS HETAPLASIA, RESPIRATORY EPITHELIUH, HINIHAL
THE FOLLOWING TISSUES WERE UNREHARKABLE HICROSCOPICALLY: LARYNX/PHARYNX, LUNGS, NOSE, TRACHEA
V:,
t" THE FOLLOWING TISSUES WERE AUTOLYZ[D; DEGREE OF AUTOLYSIS DID NOT PRECLUDE HICROSCOPIC EXAHINATION: NONE
<•• ' "
THE FOLLOWING TISSUES WERE SEVERELY AUTOLYZED: HICROSCOPIC DIAGNOSES NOT HADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
~~.' .. ~ , NONE
~.
:~'....
.' ~\ ' SECTIONS OF THE FOLLOWING TISSUES WERE NOT PRESENT FOR HICROSCOPIC EXAHINATION: NONE
'J(A~!.'"" '-
:';;;'\'t, ,< W
SECTIONS OF THE FOLLOWING TISSUES WERE INSUFFICIENT FOR HICROSCOPIC EXAHINATION; ORGAN NOT COUNTED IN INCIDENCE TABLES:
NONE
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 "
INHALATION TOXICITV OF HVDROGEN FLUORIDE
HN-I7742 APPENDIX A (conttnuedl
HC-720 INDIVIDUAL ANIHAL PATHOLOG~ DATA
HR-S645
HALE RAT GROUP: HF-22 DOSE: 1910 PPH

ANIHAL I: 476775 DAYS ON TEST: 15 HODE OF DEATH: SO

GROSS OBSERVATIONS:
NO ABNORHALITIES DETECTED

HICROSCOPIC OBSERVATIONS:
NOSE - SOUAHOUS HETAPLASIA, RESPIRATORV EPITHELIUH, HINIHAL
LUNGS - INFLAHHATION, SUBACUTE, HINIHAL
THE FOLLOWING TISSUES WERE UNREHARKABLE HICROSCOPICALLY: LARYNX/PHARYNX, NOSE, TRACHEA
THE FOLLOWING TISSUES WERE AUTOLYZED; DEGREE OF AUTOLYSIS DID NOT PRECLUDE HICROSCOPIC EXAHINATION: NONE
THE FOLLOWING TISSUES WERE SEVERELY AUTOLYZED; HICROSCOPIC DIAGNOSES NOT HADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
NONE
f_ ~_ SECTIONS OF THE FOLLOWING TISSUES WERE NOT PRESENT FOR HICROSCOPIC EXAHINATION: NONE
.~
¥,: .... SECTIONS OF THE FOLLOWING TISSUES WERE INSUFFICIENT FOR HICROSCOPIC EXAHINATION; ORGAN NOT COUNTED IN INCIDENCE TABLES:
NONE
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 INHALATION TOXICITY OF HYDROGEN FLUORIDE
HN-17742 APPENDIX A (continued)
HC-720 INDIVIDUAL ANIHAL PATHOLOG~ DATA
HR-5645
HALE RAT GROUP: HF-22 DOSE: 1910 PPH

ANIHAL I: 476776 DAYS ON TEST: 2 HODE OF DEATH: SE

GROSS OBSERVATIONS:
NASAL CAVITY - DISCHARGE RED
PERIOCULAR • CHROHODACkYORRHEA, BILATERAL

HICROSCOPIC OBSERVATIONS:
NOSE - INFLAHHATION L ACUTE L RESPIRATORY EPITHELIUH, HILD
• NECROSIS, RE)PIRATOKV EPITHELIUH L HODERATE
- THROHBI 1 SUBHUCOSAL VESSELS HDDtRATE
TRACHEA - INFLAHHRTION, ACUTE, HINIHA L
'., " THE FOLLOWING TISSUES WERE UNREHARKABLE HICROSCOPICALL Y: LARYNX/PHARYNX, LUNGS
- _THE. FOLLOWING TISSUES WERE AUTOLYZED: DEGREE OF AUTOLYSIS DID NOT PRECLUDE HICROSCOPIC EXAHINATION: NONE
:. :"i':·\ THE FOLLOWING TISSUES WERE SEVERELY AUTOLYZED: HICROSCOPIC DIAGNOSES NOT HADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
!,w -NONE
",00
'l::;" ,SECT.JONS OF THE FOLLOWING TISSUES WERE HOT PRESENT FOR HICROSCOPIC EXAHINATlON: NONE
f{~pi):·\/, . SECTIONS OF THE FOLLOWING TISSUES WERE INSUFFICIENT FOR HICROSCOPIC EXAHINATlON: ORGAN NOT COUNTEO IN INCIDENCE TABLES:
'{.~~~F):i.: ::,NQNE
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 INHALATION TOXICITY OF HYDROGEN FLUORIDE
HN·I7742 APPENDIX A (continued)
HC·720 INDIVIDUAL ANIMAL PATHOLOG~ DATA
MR·5645
HALE RAT GROUP: HF·22 DOSE: 1910 PPM

ANIMAL ,: 476777 DAYS ON TEST: 2 MODE OF DEATH: SE

GROSS OBSERVATIONS:
NASAL CAVITY • DISCHARGE, RED, MODERATE

MICROSCOPIC OBSERVATIONS:
HOSE • IHFLAHHATION~ ACUTE~ RESPIRATORY EPITHELIUM, HILD
• NECROSIS, RE~PIRATOHY EPITHELIUM MODERATE
• THROMBI, SUBHUCOSAL VESSELS, HIN IMAL
THE FOLLOWING TISSUES WERE UNREHARKABLE HICROSCOPICALLY: LARYNX/PHARYNX, LUNGS, TRACHEA
THE FOLLOWING TISSUES WERE AUTOLYZEDj DEGREE OF AUTOLYSIS DID NOT PRECLUDE MICROSCOPIC EXAMINATION: NONE
I
THE FOLLOWING TISSUES WERE SEVERELY AUTOLYZEDj HICROSCOPIC DIAGNOSES NOT MADE, ORGAN NOT COUNTED IN INCIDENCE TABLES:
~'i::' ri-, " HONE
;tJ::~: : SECTIONS OF TH[FOLLOWING TISSUES WERE NOT PRESENT FOR MICROSCOPIC EXAMINATION: NONE
,:,;'L SECTIONS O~ THE FOLLOWING TISSUES WERE INSUFFICIENT FOR MICROSCOPIC EXAHINATIONj ORGAN NOT COUNTED IN INCIDENCE TABLES:
, , NONE
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