List of IRIS Substances 

Search IRIS by Keyword

IRIS Summaries/Toxicological 

Reviews

Entire IRIS Website

Category (section) Status Last Revised

You are here: EPA Home Research Environmental Assessment IRIS IRIS Summaries

view QuickView 

Reference Dose for Chronic Oral Exposure (RfD) 

0396

Hydrogen chloride; CASRN 7647-01-0

Human health assessment information on a chemical substance is included in the IRIS database 

only after a comprehensive review of toxicity data, as outlined in the IRIS assessment 

development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II 

(Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached 

during the assessment development process. Supporting information and explanations of the 

methods used to derive the values given in IRIS are provided in the guidance documents located 

on the IRIS website. 

STATUS OF DATA FOR Hydrogen chloride

File First On-Line 06/01/1989

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.

Integrated Risk Information System

http://www.epa.gov/iris/subst/0396.htm

Last updated on Thursday, August 09, 2012

http://www.epa.gov/iris/subst/0396.htm
Critical Effect Exposures*

_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

UF MF RfC

Hyperplasia of nasal 

mucosa larynx and 

trachea

Rat Chronic

Inhalation Study

Sellakumar et al., 

1994; Albert et al.,

1982

NOAEL: None 

NOAEL(ADJ): None 

NOAEL(HEC): None

LOAEL: 15.0 mg/cu.m (10 ppm)

LOAEL(ADJ): 2.7 mg/cu.m

LOAEL(HEC): 6.1 mg/cu.m 

300 1 2E-2

mg/cu.m

*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.

http://www.epa.gov/iris/subst/0396.htm
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 portalof-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 

http://www.epa.gov/iris/subst/0396.htm
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 doserelated 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). 

http://www.epa.gov/iris/subst/0396.htm
__I.B.5. Confidence in the Inhalation RfC

Study — Low

Database — Low

RfC — Low

The chronic study used only one dose and limited toxicological measurements. The supporting 

data consist of two subchronic bioassays; the database does not provide any additional chronic or 

reproductive studies. Therefore, low confidence was recommended for the study, database, 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

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the RfC for Hydrogen chloride 

conducted in August 2003 did not identify any critical new studies. IRIS users who know of 

important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or 

202-566-1676.

__I.B.7. EPA Contacts (Inhalation RfC)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, 

at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@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.

_III. [reserved]

_IV. [reserved] 

_V. [reserved]

http://www.epa.gov/iris/subst/0396.htm
_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.

http://www.epa.gov/iris/subst/0396.htm
Date Section Description

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 

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

04/01/1997 III., IV., 

V.

Drinking Water Health Advisories, EPA Regulatory Actions, and 

Supplementary Data were removed from IRIS on or before April 1997. 

IRIS users were directed to the appropriate EPA Program Offices for this 

information.

10/28/2003 I.B.6. Screening-Level Literature Review Findings message has been added.

_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

http://www.epa.gov/iris/subst/0396.htm
IRIS Home

Chronic Health 

Hazards for NonCarcinogenic Effects

Reference Dose for 

Chronic Oral 

Exposure (RfD)

• Oral RfD 

Summary 

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

• Confidence in the 

Oral RfD

• EPA 

Documentation 

and Review

Reference 

Concentration for 

Chronic Inhalation 

Exposure (RfC)

• Inhalation RfC 

Summary

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

• Confidence in the 

Inhalation RfC

• EPA 

Documentation 

and Review

Carcinogenicity 

Assessment for 

Lifetime Exposure

Evidence for Human 

Carcinogenicity

• Weight-ofEvidence 

Characterization

• Human 

Carcinogenicity 

Data

• Animal 

Carcinogenicity 

Data

• MURIATIC ACID

• SPIRITS of SALT

• UN 1050

• UN 1789

• UN 2186

http://www.epa.gov/iris/subst/0396.htm
• Supporting Data 

for 

Carcinogenicity

Quantitative 

Estimate of 

Carcinogenic Risk 

from Oral Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

• Additional 

Comments

• Discussion of 

Confidence

Quantitative 

Estimate of 

Carcinogenic Risk 

from Inhalation 

Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

• Additional 

Comments

• Discussion of 

Confidence

• EPA 

Documentation, 

Review and, 

Contacts

Bibliography

Revision History

Synonyms

http://www.epa.gov/iris/subst/0396.htm