Hydrogen chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified; published in 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Minor reporting deficiencies. (Substance purity, bodyweight data, individual data not reported). Not GLP. However, reporting is in most respects fully adequate for this endpoint, and study design exceeds guideline requirement in many respects.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1974

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

Study conducted according to the "Guide for Laboratory Animal Facilities and Care" (1965), prepared by the Committee on the Guide for Laboratory Animal Resources, Natl. Acad. Sci./Natl. Research Council: and Public Law 89-544, "Laboratory Animal Welfare Act," (1967)

GLP compliance:

no

Remarks:

not compulsory at the time the study was conducted

Test type:

other: Rats were exposed for 5 or 30 minutes in a whole body chamber and observed for 7 days for clinical signs and mortality followed by gross and histopathological examinations

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

HCl gas or HCl aerosol

IUPAC Name:

HCl gas or HCl aerosol

Details on test material:

- Name of test material (as cited in study report): HCl gas or HCl aerosol
- Substance type: gas or aerosol
- Physical state: gas
- Analytical purity: not specified
- Impurities (identity and concentrations): not specified
- Composition of test material, percentage of components: not specified
- Isomers composition: not specified
- Purity test date: not specified
- Lot/batch No.: not specified
- Expiration date of the lot/batch: not specified
- Stability under test conditions: not specified
- Storage condition of test material: not specified
- Other: HCl gas was supplied in a cylinder obtained from Matheson Company.

Test animals

Species:

rat

Strain:

other: CFE (Sprague-Dawley derived)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Carworth Farms Inc.
- Age at study initiation: not specified
- Weight at study initiation: 250 - 300 g
- Fasting period before study: not specified
- Housing: not specified
- Diet (e.g. ad libitum): not specified
- Water (e.g. ad libitum): not specified
- Acclimation period: not specified


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

IN-LIFE DATES: not specified

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Modified Rochester chamber (gas) or Longley chamber (aerosol)
- Exposure chamber volume: not specified
- Method of holding animals in test chamber: not specified
- Source and rate of air: predried air at a constant rate of 10 cfm (283.169 L/min)
- Method of conditioning air: sliding cage "drawers" in the wall of the chamber
- System of generating particulates/aerosols:
HCl Gas was metered through a corrosion resistant gas regulator and a flow-meter and introduced into a modified Rochester chamber. The input air to the chamber was pre-dried and supplied at the constant rate of 10 cfm (ca. 283.169 L/min).
HCl Aerosol was produced introducing HCl gas into a Longley chamber which was filled with a saturated water droplet mist. Water was supplied to the DeVilbiss ultrasonic nebulizer at the flow rate of 6.8 mL/min while predried air was maintained at the constant rate of 10 cfm (ca. 283.169 L/min).
- Method of particle size determination: The nebulizer was evaluated to confirm the production of droplets in the range specified by the manufacturer (i.e. 0.5 to 9 microns). Particle size distribution was determined by measuring 456 droplets which were rended visible in the filter by adding a 5% congo red solution.
- Treatment of exhaust air: not specified
- Temperature, humidity, pressure in air chamber: not specified


TEST ATMOSPHERE
- Brief description of analytical method used: Concentrations were measured continuously during exposures using a chloride ion specific electrode with double distilled water as an absorber.
- Samples taken from breathing zone: not specified


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: reported in "Any other information on materials and methods incl. tables"
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not specified

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Concentrations were measured continuously during exposures using a chloride ion specific electrode with double distilled water as an absorber.

Duration of exposure:

>= 5 - <= 30 min

Remarks on duration:

5 minutes or 30 minutes

Concentrations:

Gas concentrations (5 min exposure): 30000, 32255, 39850, 45200 and 57290 ppm
Gas concentrations (30 min exposure): 2078, 2678, 3071, 5180, 6068 and 6681 ppm
Aerosol concentrations (5 min exposure): 9.7, 28.4, 37.3, 43.6, 57.0, 60.1 and 91.3 mg/litre (equivalent to 6571, 19312, 25324, 29648, 38746, 40810 and 62042 ppm)
Aerosol concentrations (30 min exposure): 4.3, 6.6, 9.0 and 9.8 mg/litre (equivalent to 2910, 4481, 6078 and 6640 ppm)

No. of animals per sex per dose:

10 rats per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Daily observations
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, other: food consumption

Statistics:

Not specified.

Results and discussion

Preliminary study:

Not applicable; not a fixed dose study.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

40 989 ppm

Exp. duration:

5 min

Remarks on result:

other: HCl gas, range: 34803 - 48272 ppm

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

4 701 ppm

Exp. duration:

30 min

Remarks on result:

other: HCl gas, range: 4129-5352 ppm

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Effect level:

45.6 mg/L air

Exp. duration:

5 min

Remarks on result:

other: HCl aerosol, range: 39.5-52.8 mg/L. Equivalent to 31008 ppm, range: 26824-35845 ppm

Effect levels 4

Sex:

male

Dose descriptor:

LC50

Effect level:

8.3 mg/L air

Exp. duration:

30 min

Remarks on result:

other: HCl aerosol, range: 7.2-9.7 mg/L. Equivalent to 5666 ppm, range: 4855-6614 ppm

Mortality:

Mortalities were observed at all the doses, with the exception of the lowest ones. Mortality tables are described in an attached document (PDF).

Clinical signs:

other: Toxic signs during exposure to HCl gas or aerosol were essentially identical. HCl was severely irritating to the eyes, mucous membranes and exposed areas of skin. Animals usually exhibited a rapid and shallow breathing pattern by the end of the exposure p

Body weight:

Weight loss following exposure was noted.

Gross pathology:

Gross examination of the animals which died during or at some time following exposure showed that the respiratory tract was the main target for the HCl damage. Moderate to severe alveolar emphysema, atelectasis and oedema of the lungs were observed, and occasional ‘spotting’ of the lung tissue was also noted. The upper respiratory tract was severely irritated with severe damage of the epithelia tissue of nose and trachea. Animals surviving up to terminal sacrifice (7 days after exposure) showed that recovery was not complete with abnormally coloured grey lungs failing to collapse upon opening the chest cavity. There was also evidence of consolidation of lung tissue.

Other findings:

- Histopathology: Histopathological examination confirmed the damage of respiratory tract while no abnormality was detected in other tissues.
- Other observations: Decrease in food consumption was noted

Any other information on results incl. tables

Mortalities were observed at all the doses, with the exception of the lowest ones. HCl was severely irritating to the eyes, mucous membranes and exposed areas of skin. Animals usually exhibited a rapid and shallow breathing pattern by the end of the exposure period. Corneal erosion and clouding were noted, as well as excessive grooming and ulceration of the scrotum. Animals which survived the exposure, especially at the higher concentrations of either HCl gas or aerosol, had bloody discharges from their nostrils and exhibited audible difficulty in breathing (producing a laboured ‘clicking’. The fur had a ‘singed’ appearance and was discoloured to a greenish hue. Decrease in food consumption and weight loss following exposure was also noted.

Gross examination of the animals which died during or at some time following exposure showed that the respiratory tract was the main target for the HCl damage. Moderate to severe alveolar emphysema, atelectasis and oedema of the lungs were observed, and occasional ‘spotting’ of the lung tissue was also noted. The upper respiratory tract was severely irritated with severe damage of the epithelia tissue of nose and trachea. Animals surviving up to terminal sacrifice (7 days after exposure) showed that recovery was not complete with abnormally coloured grey lungs failing to collapse upon opening the chest cavity. There was also evidence of consolidation of lung tissue.

Histopathological examination confirmed the damage of respiratory tract while no abnormality was detected in other tissies.

Table A6.1.3/01-1: HCl gas (5 min exposure) Acute Inhalation Toxicity in Rats

Concentration (ppm)	Mortality ratio	Time of deaths (No./day)
		0(during exposure)	1	2	3	4	5	6	7
30000	0/10
32255	1/10			1
39850	6/10		2	3			1
45200	7/10		5	2
57290	9/10		5	4

LC50 value: 40989 ppm (34803-48272)

Table A6.1.3/01-2: HCl gas (30 min exposure) Acute Inhalation Toxicity in Rats

Concentration (ppm)	Mortality ratio	Time of deaths (No./day)
		0(during exposure)	1	2	3	4	5	6	7
2078	0/10
2678	1/10	1
3071	0/10
5180	5/10	2	1			1	1
6068	8/10	7	1
6681	10/10	7		1		2

LC50 value: 4701 ppm (4129-5352)

Table A6.1.3/01-3: HCl aerosol (5 min exposure) Acute Inhalation Toxicity in Rats

Concentration		Mortality ratio	Time of deaths (No./day)
mg/L	ppm		0(during exposure)	1	2	3	4	5	6	7
9,7	6571	0/10
28,4	19312	1/10			1
37,3	25324	3/10		2		1
43,6	29648	6/10		1	4	1
57	38746	6/10		2	1			3
60,1	40810	7/10		2	4				1
91,3	62042	10/10		8	1	1

LC50 value: 45.6 mg/L (39.5-52.8) equivalent to 31008 ppm (26824-35845)

Table A6.1.3/01-4: HCl aerosol (30 min exposure) Acute Inhalation Toxicity in Rats

Concentration		Mortality ratio	Time of deaths (No./day)
mg/L	ppm		0(during exposure)	1	2	3	4	5	6	7
4,3	2910	1/10			1
6,6	4481	0/10
9	6078	6/10	1	3	1			1
9,8	6640	8/10	3	1	2		2

LC50 value: 8.3 mg/L (7.2-9.7) equivalent to 5666 ppm (4855-6614)

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

Toxic signs during exposure to HCl gas or aerosol were essentially identical. HCl was severely irritating to the eyes, mucous membranes and exposed areas of skin. The calculated LC50 values were the following:
HCl gas (5 min exposure): 40989 ppm (34803-48272)
HCl gas (30 min exposure): 4701 ppm (4129-5352)
HCl aerosol (5 min exposure): 45.6 mg/L (39.5-52.8) equivalent to 31008 ppm (26824-35845)
HCl aerosol (30 min exposure): 8.3 mg/L (7.2-9.7) equivalent to 5666 ppm (4855-6614)