|
Hydrogen chloride
CASRN 7647-01-0
Contents
0396
Hydrogen chloride; CASRN 7647-01-0
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Hydrogen chloride
File On-Line 06/01/1989
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) on-line 07/01/1995
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Hydrogen chloride
CASRN -- 7647-01-0
Primary Synonym -- Hydrocloric acid
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Hydrogen chloride
CASRN -- 7647-01-0
Primary Synonym -- Hydrocloric acid
Last Revised -- 07/01/1995
The inhalation Reference Concentration (RfC) is analogous to the oral RfD and
is likewise based on the assumption that thresholds exist for certain toxic
effects such as cellular necrosis. The inhalation RfC considers toxic effects
for both the respiratory system (portal-of-entry) and for effects peripheral
to the respiratory system (extrarespiratory effects). It is expressed in
units of mg/cu.m. In general, the RfC is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily inhalation exposure of the
human population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Inhalation RfCs
were derived according to the Interim Methods for Development of Inhalation
Reference Doses (EPA/600/8-88/066F August 1989) and subsequently, according to
Methods for Derivation of Inhalation Reference Concentrations and Application
of Inhalation Dosimetry (EPA/600/8-90/066F October 1994). RfCs can also be
derived for the noncarcinogenic health effects of substances that are
carcinogens. Therefore, it is essential to refer to other sources of
information concerning the carcinogenicity of this substance. If the U.S. EPA
has evaluated this substance for potential human carcinogenicity, a summary of
that evaluation will be contained in Section II of this file.
___I.B.1. INHALATION RfC SUMMARY
Critical Effect Exposures* UF MF RfC
-------------------- ----------------------- ----- --- ---------
Hyperplasia of nasal NOAEL: None 300 1 2E-2
mucosa larynx and NOAEL(ADJ): None mg/cu.m
trachea NOAEL(HEC): None
Rat Chronic LOAEL: 15.0 mg/cu.m (10 ppm)
Inhalation Study LOAEL(ADJ): 2.5 mg/cu.m
LOAEL(HEC): 6.1 mg/cu.m
Sellakumar et al.,
1994; Albert et al.,
1982
*Conversion Factors and Assumptions: MW = 36.46. Assuming 25 C and 760 mmHg,
LOAEL(mg/cu.m) = 10 ppm x 36.67/24.45 = 15 mg/cu.m. LOAEL(ADJ) = 15 x 6
hours/24 hours x 5 days/7 days = 2.7 mg/cu.m. The LOAEL(HEC) was calculated
for a gas:respiratory effect in the extrathoracic and tracheobronchial
regions. MVa = 0.5 cu.m/day, MVh = 20 cu.m/day, Sa = (15.0 ET + 22.5 TB) =
37.5 sq.cm., Sh = (200 ET + 3200 TB) = 3400 sq.cm. RGDR(ET+TB) =
(MVa/Sa)/(MVh/Sh) = 2.27. LOAEL(HEC) = LOAEL(ADJ) x RGDR = 2.7 mg/cu.m x 2.27
= 6.1 mg/cu.m.
___I.B.2. PRINCIPAL AND SUPPORTING STUDIES (INHALATION RfC)
Sellakumar, A.R., C.A. Snyder, J.J. Solomon and R.E. Albert. 1985.
Carcinogenicity for formaldehyde and hydrogen chloride in rats. Toxicol.
Appl. Pharmacol. 81: 401-406.
Albert, R.E., A.R. Sellakumar, S. Laskin, M. Kuschner, N. Nelson and C.A.
Snyder. 1982. Gaseous formaldehyde and hydrogen chloride induction of nasal
cancer in rats. J. Natl. Cancer Inst. 68(4): 597-603.
The Albert et al. (1982) study, discussed in detail by Sellakumar et al.
(1985), reported data from a chronic inhalation exposure study in rats. One
hundred male Sprague-Dawley rats were exposed to 10 ppm hydrogen chloride
(HCl) for 6 hours/day, 5 days/week (duration-adjusted concentration = 2.5
mg/cu.m) for their lifetimes. All animals were observed daily, weighed
monthly, and allowed to die naturally or killed when moribund. Complete
necropsy was performed on all animals, with particular attention given to the
respiratory tract. Histologic sections were prepared from the nasal cavity
(one lateral section from each side of the head), lung (one section from each
lobe), trachea, larynx, liver, kidneys, testes, and other organs where gross
pathological signs were present. However, Sellakumar et al. (1985) did not
discuss histopathological events in organs other than the respiratory tract.
HCl-exposed animals showed no differences in body weights or survival when
compared with air controls. The data indicated 62/99 exposed animals with
epithelial or squamous hyperplasia in the nasal mucosa (location not
specified) vs. 51/99 in the concurrent control group. Incidence of squamous
metaplasia was 9 and 5 in the exposed and control rats, respectively. There
was a 24% incidence of hyperplasia of laryngeal-tracheal segments in HCl-
exposed rats (larynx 2/22, trachea 6/26) vs. 6% in the controls. The authors
did not make any comments concerning the severity of these changes. Based on
these results, the 10-ppm (15-mg/cu.m) concentration can be considered a LOAEL
[LOAEL(HEC) = 6.1 mg/cu.m].
___I.B.3. UNCERTAINTY AND MODIFYING FACTORS (INHALATION RfC)
UF -- The uncertainty factor includes a factor of 3 for interspecies
differences, 10 for intraspecies extrapolations, and 10 to extrapolate from a
LOAEL to a NOAEL. Because of the expected portal-of-entry effect of HCl, an
uncertainty factor to account for the lack of both a second-species chronic
bioassay and a reproductive bioassay was not considered necessary. It has
been suggested that a reasonable estimate of the NOAEL in humans would be
between 300 and 3000 micrograms/cu.m (Kamrin, 1992). This estimate resulted
from an expert review workshop and is based on examination of the HCl
literature, a comparison with sulfuric acid toxicity, and the judgment of
those in attendance at the review workshop. However, because the workshop did
not address the areas of uncertainty stated above and due to the limited
available information, use of uncertainty factors to address these data gaps
is considered appropriate.
MF -- None
___I.B.4. ADDITIONAL STUDIES / COMMENTS (INHALATION RfC)
Human asthmatics (5/sex) were exposed to 0.8 or 1.8 ppm HCl for 45
minutes, and pulmonary function tests performed immediately after exposure
were compared to baseline levels (Stevens et al., 1992). No exposure-related
effects were observed in subjective symptoms or in pulmonary function tests,
including forced expiratory volume in 1 second, forced vital capacity, maximal
flow at 50 and 75% of vital capacity, respiratory resistance, and peak flow.
This is the only available controlled human exposure study of HCl.
In a 90-day inhalation study using B6C3F1 mice and Sprague-Dawley and
Fisher 344 rats (Toxigenics, Inc., 1984), groups of 31 males and 31 females of
each species strain were exposed to HCl at 10, 20, or 50 ppm (15, 30, or
mg/cu.m, respectively), 6 hours/day, 5 days/week for 90 days. Several animals
died during the study; however, the deaths did not appear to be exposure
related. There was a slight but significant decrease in body weight gain in
male and female mice and in male Fischer 344 rats in the high-exposure groups.
There was no effect on hematology, clinical chemistry, or urinalysis.
Histologic examination showed minimum to mild rhinitis in both strains of
rats. Lesions occurred in the anterior portion of the nasal cavity and were
concentration and time related. In mice exposed to 50 ppm, there was
cheilitis and accumulation of macrophages in the peripheral tissues after 90
days. Mice in all exposure groups developed eosinophilic globules in the
epithelial lining of the nasal tissues.
In a short-term study, Kaplan et al. (1988) exposed baboons (3
males/group) to 0, 500, 5000, or 10,000 ppm HCl for 15 minutes and observed
them for 3 months. The results indicated dose-related increased frequency of
respiratory rate and minute volume following exposure. The higher doses
caused decreased arterial PO2, but follow-up measurements at 3 days or 3
months following exposure did not show any abnormalities. The upper airways
of the baboon, compared with other mammalian species (rodents), have the
greatest similarity to those of the human child, and the complexity of the
respiratory tract increases with age. It reasonably can be expected that the
more complex structure of the upper airways of the human would remove more of
an airborne chemical than those of other mammalian species (rodents). Based
on the results of this study, the authors suggested that the human is
probably much less sensitive to HCl than is the mouse.
Burleigh-Flayer et al. (1985) exposed male guinea pigs to 0, 320, 680,
1040, and 1380 ppm HCl for 1-6 minutes and measured respiratory rate and
induction of sensory or pulmonary irritation. This study indicated sensory
irritation at 320 ppm (477 mg/cu.m) with an exposure of 6 minutes, whereas
less severe effects were observed at concentrations of 680 ppm or higher
during a 1-minute exposure. The concentration of HCl exposure was inversely
related to the onset interval of pulmonary irritation.
Buckley et al. (1984) attempted to determine the potential for pathologic
damage following exposure to sensory irritants at concentrations eliciting a
50% decrease in respiratory rate in the mouse. The mouse RD50 for HCl was
reported to be 309 ppm. The TWA exposure consisted of three exposures (295-
310 ppm) for 5 days (6 hours/day). The lesions noted were confined to the
upper respiratory epithelium. No abnormalities were noted in the trachea or
lungs.
Darmer et al. (1974), in an attempt to determine the HCl hazard at a
missile test-firing site, reported 30-minute LC50 values for rats and mice of
4701 and 2644 ppm, respectively; the LC50 values for 5-minute exposures were
40,989 (rat) and 13,745 ppm (mice). Thus, it appeared that mice are 2 to 3
times more sensitive than rats to HCl exposure.
Reproductive and development studies of HCl are limited. Pavlova (1976)
exposed two groups of 8-15 female rats to 302 ppm (450 mg/cu.m) HCl for 1
hour. One group was exposed 12 days prior to mating, and the other group on
day 9 of gestation. In both groups, signs of severe dyspnea and cyanosis were
noted, and mortality occurred in one-third of the animals. Fetal mortality
was significantly higher in rats exposed during pregnancy. When the progeny
were subjected to an additional exposure of 35 ppm (52 mg/cu.m) at the age of
2-3 months, functional abnormalities in the organs of the progeny were similar
to those found in the mothers.
In another study from the same laboratory, female rats were exposed to 302
ppm (450 mg/cu.m) HCl for 1 hour prior to mating. Exposure killed 20-30% of
the rats. In rats surviving 6 days after exposure, a decrease in blood oxygen
saturation was noted, as was kidney, liver, and spleen damage. In addition,
treatment altered the estrus cycles. In rats mated 12-16 days postexposure
and killed on day 21 of pregnancy, fewer live fetuses, a decrease in fetal
weight, and an increase in relative lung weights of the fetuses were observed
(GEOMET Technologies, Inc., 1981).
___I.B.5. CONFIDENCE IN THE INHALATION RfC
Study -- Low
Data Base -- Low
RfC -- Low
The chronic study used only one dose and limited toxicological
measurements. The supporting data consist of two subchronic bioassays; the
data base does not provide any additional chronic or reproductive studies.
Therefore, low confidence was recommended for the study, data base, and the
RfC.
___I.B.6. EPA DOCUMENTATION AND REVIEW OF THE INHALATION RfC
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
This assessment was peer reviewed by external scientists. This review was
completed on 05/22/1995. Their comments have been carefully evaluated and
considered in the revision and finalization of this IRIS summary. A record of
these comments is included in the IRIS documentation files.
Other EPA Documentation -- U.S. EPA, 1988
Agency Work Group Review -- 01/19/1989, 02/16/1989, 05/11/1995
Verification Date -- 05/11/1995
___I.B.7. EPA CONTACTS (INHALATION RfC)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Hydrogen chloride
CASRN -- 7647-01-0
Primary Synonym -- Hydrocloric acid
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- Hydrogen chloride
CASRN -- 7647-01-0
Primary Synonym -- Hydrocloric acid
Last Revised -- 07/01/1995
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
Albert, R.E., A.R. Sellakumar, S. Laskin, M. Kuschner, N. Nelson and C.A.
Snyder. 1982. Gaseous formaldehyde and hydrogen chloride induction of nasal
cancer in rats. J. Natl. Cancer Inst. 68(4): 597-603.
Buckley, L.A., X.Z. Jiang, R.A. James, K.T. Morgan and C.S. Barrow. 1984.
Respiratory tract lesions induced by sensory irritants at the RD50
concentration. Toxicol. Appl. Pharmacol. 74: 417-429.
Burleigh-Flayer, H., K.L. Wong and Y. Alarie. 1985. Evaluation of the
pulmonary effects of hydrochloric-acid using carbon dioxide challenges in
guinea-pigs. Fund. Appl. Toxicol. 5(5): 978-985.
Darmer, K.I., E.R. Kinkead and L.C. Dipasquale. 1974. Acute toxicity in rats
and mice exposed to hydrogen chloride gas and aerosols. Am. Ind. Hyg. Assoc.
J. 35(10): 623-631.
GEOMET Technologies, Inc. 1981. Hydrogen chloride: Report 4, Occupational
Hazard Assessment. U.S. Department of Health and Human Services, NIOSH,
Cincinnati, OH. NTIS PB83-105296.
Kamrin, M.A. 1992. Workshop on the health effects of HCl in ambient air.
Reg. Pharm. Toxicol. 15: 73-82.
Kaplan, H.L., A. Anzueto, W.G. Switzer and R.K. Hinderer. 1988. Effects of
hydrogen chloride on respiratory response and pulmonary function of the
baboon. J. Toxicol. Environ. Health. 23(4): 473-493.
Pavlova, T.E. 1976. Disturbance of development of the progeny of rats
exposed to hydrogen chloride. Bull. Exp. Biol. Med. 82: 1078-1081.
Sellakumar, A.R., C.A. Snyder, J.J. Solomon and R.E. Albert. 1985.
Carcinogenicity of formaldehyde and hydrogen chloride in rats. Toxicol. Appl.
Pharmacol. 81: 401-406.
Stevens, B., J.Q. Koenig, V. Rebolledo, Q.S. Hanley, and D.S. Covert. 1992.
Respiratory effects from the inhalation of hydrogen chloride in young adult
asthmatics. J. Occup. Med. 34: 923-929.
Toxigenics, Inc. 1984. 90-Day inhalation study of hydrogen chloride gas in
B6C3F1 mice, Sprague-Dawley rats, and Fischer-344 rats. Study conducted for
CIIT, Research Triangle Park, NC. CIIT Docket No. 20915.
U.S. EPA. 1988. Health Assessment Document for Chlorine and Hydrogen
Chloride. Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Research Triangle Park, NC. EPA-600/8-87-
041A. (External Review Draft)
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Hydrogen chloride
CASRN -- 7647-01-0
Primary Synonym -- Hydrocloric acid
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
01/01/1991 I.B. Inhalation RfC summary on-line
01/01/1991 VI. Bibliography on-line
01/01/1992 IV. Regulatory Action section on-line
06/01/1995 I.B. Inhalation RfC noted as pending change
06/01/1995 I.B.6. Work group review date added
07/01/1995 I.B. Inhalation RfC replaced; new RfC
07/01/1995 VI.B. Inhalation RfC references replaced
VIII. SYNONYMS
Substance Name -- Hydrogen chloride
CASRN -- 7647-01-0
Primary Synonym -- Hydrocloric acid
Last Revised -- 01/01/1991
7647-01-0
ACIDE CHLORHYDRIQUE (French)
ACIDO CLORIDRICO (Italian) 362
CHLOORWATERSTOF (Dutch)
CHLOROHYDRIC ACID
CHLOROWODOR (Polish)
CHLORWASSERSTOFF (German)
HYDROCHLORIC ACID
HYDROCHLORIDE
HYDROGEN CHLORIDE
MURIATIC ACID
SPIRITS of SALT
UN 1050
UN 1789
UN 2186
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0396.HTM
|
