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Reference Dose for Chronic Oral Exposure( RfD ) 

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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. Supp orting 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 Assessme nt (I.B.) on-line 07/01/1995 Carcinogenicity Assessment (II.) no data 

### _I. Chronic Health Hazard Assess ments 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.htmCritical 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 an alogous to the oral RfD and is likewise based on the assumption that thresholds exist for cert ain 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 respirat ory system (extrarespiratory effect s). It is expre ssed 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 apprecia ble risk of deleterious e ffects during a lifetime. Inhalation RfCs were derived ac cording to the Interim Methods for Development of Inhalation Reference Doses (EPA/600/8-88/066FAugust 1989) and su bsequently, according to Methods for Derivation of Inhalation Reference Concentrat ions 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 carc inogens. Therefor e, 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 Supp orting Studies (Inhalation RfC) Sellakumar, A.R., C.A. Snyder , J.J. Solomon and R.E. Albe rt. 1985. Carcinogenicity for formaldehyde and hydrogen ch loride in rats. Toxicol. Appl. Pharmacol. 81: 401-406. 

### http://www.epa.gov/iris/subst/0396.htmAlbert, 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, di scussed 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, ki dneys, testes, and other organs where gross pathological signs were pres ent. However, Sellakumar et al. (1985) did not discuss histopathological events in organs other than th e 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 gr oup. Incidence of squamous metaplasia was 9 and 5 in the exposed and control rats, respective ly. 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 severityof 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 Modi fying Factors (Inhalation RfC) UF — The uncertainty factor includ es a factor of 3 for interspeciesdifferences, 10 for intraspecies extrapolations, and 10 to extrapolate from a LOAEL to a NOAE L. Because of the expected portalof-entry effect of HCl, an uncertainty factor toaccount 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 es timate of the NOAEL in humanswould be between 300 and 3000 micrograms/cu.m (Kamrin, 1992). Thisestimate resulted from an ex pert review wo rkshop and is based on examination of the HCl literature, a co mparison 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 st ated above and due to the limite d available information, use of uncertainty factors to address these da ta gaps is considered appropriate.

MF — None
__I.B.4. Additional Studie s/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 immediat ely after exposure were compared to baseline levels (Stevens et al., 1992). No exposure-related effects were observed in subjec tive 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, re spiratory resistance, and peak fl ow. This is the only available controlled human exposure study of HCl. In a 90-day inhalation study using B6C3F1 mi ce 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; howeve r, the deaths did not appear to be exposure related. There was a slight but si gnificant decrease in body weightgain in male and female mice 

### http://www.epa.gov/iris/subst/0396.htmand in male Fischer 344 rats in the high-exposur e 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 an d 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 abnormalitie s. The upper airways of the baboon, compared with other mammalian species (rodents), have th e greatest similarity to those of the human child, and the complexity of the respiratory tr act 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 th ose of other mammalian species (rod ents). Based on the results of this study, the authors suggested that the human isprobably much less sensitive to HCl than is the mouse. Burleigh-Flayer et al. (1985) exposed male gu inea 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 ex posure of 6 minutes, whereas less severe effe cts were observed at concentratio ns of 680 ppm or higher during a 1-minute exposure. The concentrat ion of HCl exposure was inverse ly related to the onset interval of pulmonary irritation. Buckley et al. (1984) attempted to determine th e potential for pathologic damage following exposure to sensory irritants at concentrations el iciting 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 abnormalit ies were noted in the trachea or lungs. Darmer et al. (1974), in an attempt to determin e 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 (mic e). Thus, it appeared that mice are 2 to 3 times more sensit ive 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) HC l for 1 hour. One group was exposed 12 days prior to mating, and the other group on day 9 of gestation. In both gr oups, signs of severe dyspnea and cyanosis were note d, and mortality occurred in one-third of the animals. Fetal mortality was significantly higher in rats expo sed 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 we re 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. Exposurekilled 20-30% of the ra ts. In rats surviving 6 days after exposure, a decrease in blood oxygen saturation was no ted, as was kidn ey, 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 fetuse s, 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 limi ted toxicological measurements. The supporting data consist of two subchronic bioassays; the data base does not provide any additional chronic or reproductive studies. Therefore, low confidencewas 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 cons idered in the revision and finalization of this IRIS Summary. A record of these comments is included in the IRIS documentation files.
Other EPA Documentat ion — 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 literat ure pertinent to the RfC for Hydrogen chloride conducted in August 2003 did not identify any critical new stud ies. 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 co ncerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).



### _II. Carcinogenicity Asse ssment for Lifetime Exposure Substance Name — Hydrogen chloride CASRN — 7647-01-0 Primary Synonym — Hydrocloric acid This substance/agent has not undergone a comp lete evaluation and de termination 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. Biblio g raphy 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 th e pulmonary effects of hydrochloric-acid using carbon di oxide challengesin guinea-pigs. Fund . Appl. Toxicol. 5(5): 978- 985. Darmer, K.I., E.R. Kinkead and L. C. Dipasquale. 1974. Acute toxicityin rats and mice exposed to hydrogen chloride gas an d aerosols. Am. Ind. Hyg. Assoc. J. 35(10): 623-631. GEOMET Technologies, Inc. 1981. Hy drogen chloride: Report 4, O ccupational Hazard Assessment. U.S. Department of Health and Human Services, NIOSH, Ci ncinnati, OH. NTIS PB83-105296. Kamrin, M.A. 1992. Workshop on the health effect s of HCl in ambient air. Reg. Pharm. Toxicol. 15: 73-82. Kaplan, H.L., A. Anzueto, W.G. Sw itzer and R.K. Hinderer. 1988. Ef fects 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. Albe rt. 1985. Carcinogenicity of formaldehyde and hydrogen ch loride in rats. Toxicol. A ppl. Pharmacol. 81: 401-406. Stevens, B., J.Q. Koenig, V. Re bolledo, Q.S. Hanley, and D.S. Covert. 1992. Respiratory effects from the inhalation of hydrogen chloride in young adult asthma tics. 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. Stud y conducted for CIIT, Research Triangle Park, NC. CIIT Docket No. 20915. 

### http://www.epa.gov/iris/subst/0396.htmDate Section Description U.S. EPA. 1988. Health Assessme nt 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. CarcinogenicityAssessment 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.htmIRIS Home Chronic HealthHazards 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