Hydrogen chloride

Endpoint summary

Description of key information

hydrochloric acid solutions are corrosive to the skin from 10%, and is considered to cause severe eye damage from concentrations of 1% and higher.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 05 March 2013 and 18 April 2013.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Justification for type of information:

Study is an acceptable method to evaluate skincorosion potential and does not require the use of animals.

Qualifier:

according to guideline

Guideline:

other: OECD guideline for the testing of chemicals 431

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU B40bis to Com Reg 440/2008

Deviations:

no

GLP compliance:

yes

Remarks:

Date of inspection: 10 July 2012. Date of Signature: 07 November 2013

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: Reconstructed human epidermis

Details on animal used as source of test system:

EPISKIN™ model

Justification for test system used:

Validated and internationally accepted testsystem

Vehicle:

water

Remarks:

deionised water

Details on test system:

EPISKIN™ Model Kit 0.38 cm2

Control samples:

yes, concurrent negative control

yes, concurrent vehicle

yes, concurrent positive control

yes, concurrent MTT non-specific colour control

Amount/concentration applied:

50 µL

Duration of treatment / exposure:

3, 60 and 240 minutes

Duration of post-treatment incubation (if applicable):

No

Number of replicates:

Duplicate

Amount / concentration applied:

TEST ITEM

Concentrations prepared:
Phase 1: 10%, 25% and 30% w/w in deionised water.
Phase 2: 15% w/w in deionised water*.

*The 15% w/w concentration of the test item was applied for an exposure period of 3 minutes only. It was considered that the results of the 10% w/w concentration tested at 60 and 240 minutes were adequate for classification purposes and therefore application of the 15% w/w for 60 and 240 minutes was unnecessary.

Amount(s) applied (volume or weight with unit):
50 µl of each test item concentration was applied topically to the epidermis surface.

VEHICLE
Deionised Water.

Duration of treatment / exposure:

3, 60 & 240 minutes post exposure incubation.

Observation period:

Not applicable

Number of animals:

Not applicable

Details on study design:

TEST SITE:
Area of exposure: 50 µl of each test item concentration was applied to the 0.38cm2 epidermis surface.

PERCENTAGE COVERAGE:
The test item was applied topically to the corresponding tissues ensuring uniform covering.

EXPOSURE TIME:
3, 60 AND 240 minutes.

REMOVAL OF TEST ITEM:
Washing: At the end of each exposure period, each tissue was removed from the well using forceps and rinsed using a wash bottle containing Phosphate Buffered Saline Dulbeccos (PBS) with Ca++ and Mg++. Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of PBS to gently remove any residual test item.

Time after start of exposure:
3, 60 or 240 minutes post exposure.

SCORING SYSTEM:
The relative mean viabilities were calculated in the following way:

Relative mean viability (%) = mean OD540 of test item concentration / mean OD540 of negative control x 100

Classification of corrosivity potential was based on relative viabilities for each test item concentration and exposure time according to the following prediction model (concise):
3 minutes exposure : <35% viability : Prediction = Corrosive
3/60 minutes exposure : ≥35 / <35 viability : Prediction = Corrosive
60/240 minutes exposure : ≥35 / <35 viability : Prediction = Corrosive
240 minutes exposure : ≥35 : Prediction = Non-Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

10% / 3 minutes

Value:

93.3

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: non-corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

10% / 60 minutes

Value:

27.6

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

10% / 240 minutes

Value:

5.4

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

25% / 3 minutes

Value:

30.4

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

25% / 60 minutes

Value:

6.5

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

25% / 240 minutes

Value:

6

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

30% / 3 minutes

Value:

9.5

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

30% / 60 minutes

Value:

4.1

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

30% / 240 minutes

Value:

6.6

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Other effects / acceptance of results:

viability ≤ 35% are indication for corrosive effects.
Phase 1 Exposure period
Concentration 3 minutes 60 minutes 240 minutes
10% Test Item 93.3 27.6 5.4
25% Test Item 30.4 6.5 6.0
30% Test Item 9.5 4.1 6.6

Phase 2 Exposure period
Concentration 3 minutes
15% Test Item 92.3

Other effects:

None

RESULTS

Direct MTT Reduction

The MTT solution containing the undiluted Hydrochloric acid did not turn blue which indicated that the test item did not directly reduce MTT.

Test Item, Positive Control Item and Negative Control Item

For phase 1 of testing, the mean OD₅₄₀ values of individual tissues, mean OD₅₄₀ values of duplicate tissues and relative mean tissue viabilities for the negative, positive and vehicle controls are given in Table 1 and the values for the test item concentrations are given in Table 2. For phase 2 of testing, the mean OD₅₄₀ values of individual tissues, mean OD₅₄₀ values of duplicate tissues and relative mean tissue viabilities for the negative, positive, vehicle controls and the test item are given in Table 3.

Data are presented in the form of relative mean viability (percentage MTT reduction in the test item treated tissues relative to negative control tissues):

Phase 1:

	Exposure period
Concentration	3 minutes	60 minutes	240 minutes
10% Test Item	93.3	27.6	5.4
25% Test Item	30.4	6.5	6.0
30% Test Item	9.5	4.1	6.6

Phase 2:

	Exposure period
Concentration	3 minutes
15% Test Item	92.3

Quality Criteria

The relative mean tissue viability for the positive control treated tissuesin phases 1 and 2 were 0 to 20% relative to the negative control treated tissuesfollowing the 240-Minute exposure period. The positive control acceptance criterion was therefore satisfied in each phase of testing.

The mean OD₅₄₀ for the negative control treated tissues in phases 1 and 2 were ≥0.600 and ≤1.500. The negative control acceptance criterion was therefore satisfied in each phase of testing.

Table 1 : Mean OD₅₄₀ Values and Percentage Viabilities for the Negative, Positive and Vehicle Control Items for Phase 1 of Testing

Item	Exposure Period	Mean OD540 of individual tissues	Mean OD540 of duplicate tissues	Relative mean viability (%)
Negative Control Item	240 Minutes	0.969	0.928	100*
		0.887
Positive Control Item	240 Minutes	0.064	0.065	7.0
		0.065
Vehicle Control Item	240 Minutes	0.941	0.918	98.9
		0.895

*=     The mean viability of the negative control tissues is set at 100%

Table 2 : Mean OD₅₄₀ Values and Viabilities for the Test Item Concentrations for Phase 1 of Testing

Item	Exposure Period	Mean OD540 of individual tissues	Mean OD540 of duplicate tissues	Relative mean viability (%)
10% Test Item	240 Minutes	0.048	0.050	5.4
		0.051
	60 Minutes	0.307	0.256	27.6
		0.204
	3 Minutes	0.850	0.866	93.3
		0.881
25% Test Item	240 Minutes	0.064	0.056	6.0
		0.048
	60 Minutes	0.047	0.060	6.5
		0.072
	3 Minutes	0.279	0.282	30.4
		0.284
30% Test Item	240 Minutes	0.059	0.061	6.6
		0.063
	60 Minutes	0.031	0.038	4.1
		0.044
	3 Minutes	0.090	0.088	9.5
		0.085

Table 3 : Mean OD₅₄₀ Values and Percentage Viabilities for the Negative, Positive and Vehicle Control Items and the Test Item for Phase 2 of Testing

Item	Exposure Period	Mean OD540 of individual tissues	Mean OD540 of duplicate tissues	Relative mean viability (%)
Negative Control Item	240 Minutes	0.979	1.020	100*
		1.061
Positive Control Item	240 Minutes	0.039	0.039	3.8
		0.038
Vehicle Control Item	240 Minutes	1.136	1.153	113.0
		1.169
15% Test Item	3 Minutes	1.053	0.941	92.3
		0.829

*=     The mean viability of the negative control tissues is set at 100%

Interpretation of results:

other: Various concentrations, See below:

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

Based on the resulsults obtained, concentrations of Hydrochloric Acid in deionised water, were classified as follows:
10%: Category 1B, H314 “Causes severe skin burns and eye damage”.
15%: After a 3 minute exposure, a 15% w/w concentration did not induce a reduction of cell viability indicative of skin corrosion.
25% and 30%: Category 1A, H314 “Causes severe skin burns and eye damage”.

Executive summary:

Introduction: The purpose of this test was to evaluate the skin corrosivity potential of various concentrations of the test item, Hydrochloric acid, using the EPISKIN^TM in vitro Reconstructed Human Epidermis (RHE) Model after treatment periods of 3, 60 and 240 minutes. This method was designed to be compatible with the following:

• OECD Guideline for the Testing of Chemicals No. 431 “In Vitro Skin Corrosion: Human Skin Model Test” (adopted 13 April 2004)
• Method B.40bis of CommissionRegulation (EC) No. 440/2008

The EPISKIN^TM model is able to distinguish between corrosive and non-corrosive chemicals for all of the chemical types studied.

Preparation of Test Item: The study was conducted in two phases. The result from the preceding phase was used to determine the concentration to be used in the subsequent phase. The sponsor was consulted prior to determination of the concentrations to be tested.

Concentrations prepared:

Phase 1: 10%, 25% and 30% w/w in deionised water.
Phase 2: 15% w/w in deionised water*.

* The 15% w/w concentration of the test item was applied for an exposure period of 3 minutes only. It was considered that the results of the 10% w/w concentration tested at 60 and 240 minutes were adequate for classification purposes and therefore application of the 15% w/w for 60 and 240 minutes was unnecessary.

Methods: Duplicate tissues were treated with the concentrations of the test item diluted w/w in deionised water for exposure periods of 3, 60 and 240 minutes. At the end of the exposure period the test item was rinsed from each tissue before each tissue was taken for MTT-loading. After MTT-loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues.

At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 µl samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density (OD) was measured at 540 nm (OD₅₄₀).

Results: Data are presented in the form of relative mean viability (percentage MTT reduction in the test item treated tissues relative to negative control tissues):

Phase 1:

	Exposure period
Concentration	3 minutes	60 minutes	240 minutes
10% Test Item	93.3	27.6	5.4
25% Test Item	30.4	6.5	6.0
30% Test Item	9.5	4.1	6.6

Phase 2:

	Exposure period
Concentration	3 minutes
15% Test Item	92.3

Quality criteria: The quality criteria required for acceptance of results in each test phase were satisfied.

Conclusion: According to the Study Plan followed, concentrations of the test item, Hydrochloric Acid, were classified as follows:

10% w/w concentration in deionised water: EU DSD (67/548/EEC) Corrosive requires symbol “C” risk phrase R34 “CAUSES BURNS”. EU CLP (1272/2008/EC) H314 “Causes severe skin burns and eye damage” Category 1B.

15% w/w concentration in deionised water: After a 3 minute exposure, a 15% w/w concentration did not induce a reduction of cell viability indicative of skin corrosion. Given that the preceding 10% w/w concentration had induced a corrosive response after 60 and 240 minute exposures the following classification was considered implicit: EU DSD (67/548/EEC) Corrosive requires symbol “C” risk phrase R34 “CAUSES BURNS”. EU CLP (1272/2008/EC) H314 “Causes severe skin burns and eye damage” Category 1B.

25% and 30% w/w concentrations in deionised water: EU DSD (67/548/EEC) Corrosive requires symbol “C” risk phrase R35 “CAUSES SEVERE BURNS”. EU CLP (1272/2008/EC) and UN GHS Hazard statement H314 “Causes severe skin burns and eye damage” Category 1A.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation

Remarks:

other: ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed on 14 March 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Qualifier:

according to guideline

Guideline:

other: OECD 437

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of Inspection : 10 July 2012 Date of Signature : 19 July 2013

Species:

other: Excised Bovine Cornea

Strain:

other: Strain: not applicable

Details on test animals or tissues and environmental conditions:

Not applicable

Vehicle:

other: Deionised Water

Controls:

no

Amount / concentration applied:

TEST ITEM

Concentrations prepared:
1%, 5% and 10% w/w in deionised water.

Amounts(s) applied (volume or weight with unit):
0.75 mL of the test item was applied to triplicate corneas.

VEHICLE
Deionised Water.

Duration of treatment / exposure:

The test item dilutions were applied for 10 minutes followed by an incubation period of 120 minutes.

Observation period (in vivo):

Not applicable

Number of animals or in vitro replicates:

Not applicable

Details on study design:

TEST SITE
Area of exposure:
0.75 mL of each test item concentration was applied to each cornea.

PERCENTAGE COVERAGE:
The test item was topically applied to the cornea. The holders were gently tilted back and forth to ensure a uniform application of the item over the entire cornea.

EXPOSURE:
The test item dilutions were applied for 10 minutes followed by an incubation period of 120 minutes.

REMOVAL OF TEST ITEM
-Washing (if done):
At the end of the exposure period the test item concentrations were removed from the anterior chamber and the cornea was rinsed three times with fresh complete MEM containing phenol red before a final rinse with complete MEM.

EVALUATION OF RESULTS:
Results from the two test method endpoints, opacity and permeability, were combined in an empirically derived formula to generate an In Vitro Irritancy Score.

Opacity Measurement:
The change in opacity for each cornea (including the negative control) was calculated by subtracting the initial opacity reading from the final opacity reading. These values were then corrected by subtracting from each the average change in opacity observed for the negative control corneas. The mean opacity value of each treatment group was then calculated by averaging the corrected opacity values of each cornea for that treatment group.

Permeability Measurement:
The corrected OD492 was calculated by subtracting the mean OD492 of the negative control corneas from the OD492 value of each treated cornea. The OD492 value of each treatment group was calculated by averaging the corrected OD492 values of the treated corneas for the treatment group.

In Vitro Irritancy Score:
The following formula was used to determine the in vitro score:
In Vitro Irritancy Score = mean opacity value + (15 x mean OD492 value)
Additionally, the opacity and permeability values were evaluated independently to determine whether the test item induced a response through only one of the two endpoints.

Visual Observation:
The condition of the cornea was visually assessed immediately after rinsing and at the final opacity measurement.

DATA INTERPRETATION:
An in vitro irritancy score greater than or equal to 55.1 is defined as an ocular corrosive or severe irritant.

Irritation parameter:

cornea opacity score

Basis:

other: Mean Score of Opacity & Permeability

Time point:

other: 120 Minutes Post Rinsing

Max. score:

1

Reversibility:

other: Not applicable

Remarks on result:

other: See In Vitro Irritancy Scores below:

Irritant / corrosive response data:

Treatment In Vitro Irritancy Score
1% w/w Test Item 2.4
5% w/w Test Item 100.0
10% w/w Test Item 158.1
Negative Control 3.5
Positive Control 35.9
Vehicle Control 0.0

Other effects:

The corneas treated with 1% w/w test item were clear post treatment and post incubation. The corneas treated with 5% w/w and 10% w/w test item were cloudy post treatment and post incubation. The corneas treated with the negative control item were clear post treatment and post incubation. The corneas treated with the positive control item were cloudy post treatment and post incubation. The corneas treated with the vehicle control item were clear post treatment and post incubation.

RESULTS

Corneal Opacity and Permeability Measurement

Individual and mean corneal opacity measurements and individual and mean corneal permeability measurements are given in Tables 1 and 2.

Corneal Epithelium Condition

The condition of each cornea post treatment and post incubation is given in Tables 3 and 4. The corneas treated with 1% w/w test item were clear post treatment and post incubation. The corneas treated with 5% w/w and 10% w/w test item were cloudy post treatment and post incubation. The corneas treated with the negative control item were clear post treatment and post incubation. The corneas treated with the positive control item were cloudy post treatment and post incubation. The corneas treated with the vehicle control item were clear post treatment and post incubation.

In Vitro Irritancy Score

The results are summarised as follows:

Treatment	In VitroIrritancy Score
1% w/w Test Item	2.4
5% w/w Test Item	100.0
10% w/w Test Item	158.1
Negative Control	3.5
Positive Control	35.9
Vehicle Control	0.0

Criterion for an Acceptable Test

The positive control In Vitro Irritancy Score was within the range of 30.9 to 67.7. The positive control acceptance criterion was therefore satisfied.

Table 1 Individual and Mean Corneal Opacity and Permeability Measurements, Control Items

Treatment	Cornea Number	Opacity					Permeability (OD)		In vitroIrritancy Score
		Pre-Treatment	Post-Treatment	Post-Incubation	Post-Incubation-Pre‑Treatment	Corrected Value		Corrected Value
Negative Control	1	2	4	6	4		0.032
	2	2	2	5	3		0.030
	3	2	2	4	2		0.030
					3.0*		0.031 +		3.5
Positive Control	4	2	21	26	24	21.0	1.145	1.114
	5	2	20	25	23	20.0	0.892	0.861
	6	3	23	28	25	22.0	1.034	1.003
						21.0·		0.993·	35.9
Vehicle Control	7	2	3	5	3	0.0	0.039	0.008
	8	3	4	5	2	0.0	0.018	0.000
	9	1	2	2	1	0.0	0.018	0.000
						0.0·		0.003·	0.0

OD= Optical density * = Mean of the post incubation - pre‑treatment values   + = Mean permeability  · = Mean corrected value

Table 2 Individual and Mean Corneal Opacity and Permeability Measurements, Test Item Dilutions

Treatment	Cornea Number	Opacity					Permeability (OD)		In vitroIrritancy Score
		Pre-Treatment	Post-Treatment	Post-Incubation	Post-Incubation-Pre‑Treatment	Corrected Value		Corrected Value
1%w/wTest Item	10	3	9	9	6	3.0	0.028	0.000
	11	3	6	7	4	1.0	0.030	0.000
	12	2	6	8	6	3.0	0.049	0.018
						2.3·		0.006·	2.4
5%w/wTest Item	13	1	40	96	95	92.0	0.025	0.000
	14	2	43	98	96	93.0	0.083	0.052
	15	3	55	120	117	114.0	0.043	0.012
						99.7·		0.022·	100.0
10%w/wTest Item	16	2	117	162	160	157.0	0.045	0.014
	17	4	109	160	156	153.0	0.111	0.080
	18	2	94	165	163	160.0	0.232	0.201
						156.7·		0.099·	158.1

OD= Optical density ·= Mean corrected value

Table 3 Corneal Epithelium Condition Post Treatment and Post Incubation, Control Items

Treatment	Cornea Number	Observation
		Post Treatment	Post Incubation
Negative Control	1	clear	clear
	2	clear	clear
	3	clear	clear
Positive Control	4	cloudy	cloudy
	5	cloudy	cloudy
	6	cloudy	cloudy
Vehicle Control	7	clear	clear
	8	clear	clear
	9	clear	clear

Table 4 Corneal Epithelium Condition Post Treatment and Post Incubation, Test Item Dilutions

Treatment	Cornea Number	Observation
		Post Treatment	Post Incubation
1% w/w Test Item	10	clear	clear
	11	clear	clear
	12	clear	clear
5% w/w Test Item	13	cloudy	cloudy
	14	cloudy	cloudy
	15	cloudy	cloudy
10% w/w Test Item	16	cloudy	cloudy
	17	cloudy	cloudy
	18	cloudy	cloudy

Interpretation of results:

other: Various Concentrations, see below:

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

The test item was considered not to be an ocular corrosive or severe irritant at 1% w/w in deionised water and therefore did not require labelling as severe ocular irritant.
The test item was considered to be an ocular corrosive or severe irritant at 5% and 10% w/w in deionised water and therefore required to be classified as EU DSD Symbol “Xi” Risk Phrase R41, EU CLP and UN GHS H318 Category 1.

Executive summary:

Introduction. A study was performed to assess the ocular irritancy potential of various concentrations of the test item, Hydrochloric acid, to the isolated bovine cornea. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 437 (2009) “Bovine Corneal Opacity and Permeability Assay”

Preparation of Test Item: The sponsor was consulted prior to determination of the concentrations to be tested.

Concentrations prepared:
1%, 5% and 10% w/w in deionised water.

Method. The test item dilutions were applied for 10 minutes followed by an incubation period of 120 minutes. Negative, positive and vehicle control items were tested concurrently. The two endpoints, decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS).

Results. The in vitro Irritancy scores are summarised as follows:

Treatment	In Vitro Irritancy Score
1% w/w Test Item	2.4
5% w/w Test Item	100.0
10% w/w Test Item	158.1
Negative Control	3.5
Positive Control	35.9
Vehicle Control	0.0

Conclusion. The test item was considered not to be an ocular corrosive or severe irritant at 1% w/w in deionised water and therefore did not require labelling as severe ocular irritant.

The test item was considered to be an ocular corrosive or severe irritant at 5% and 10% w/w in deionised water and therefore required to be classified as EU DSD Symbol “Xi” Risk Phrase R41, EU CLP and UN GHS H318 Category 1

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Hydrogen chloride is available commercially as an anhydrous gas or as aqueous solutions (hydrochloric acid), at the concentrations of 33 to 36%. The available information on skin corrosion/irritation is listed below:

 

Study	results	Conclusion
in vitro OECD 431, Warren, 2013a	Viability: ≤ 35% means corrosive. Phase 1: resp. 3 min, 1 hour and 4 hours:   HCl 10% w/w = 93.3%; 27.6%; 5.4%   HCl 25% w/w = 30.4%; 6.5%; 6.0%   HCl 30% w/w = 9.5%; 4.1%; 6.6% Phase 2: only 3 minutes   HCl 15% w/w = 92.3%	≥ 25%: Cat.1A ≥ 10%: Cat.1B
in vitro OECD 439, Warren, 2013b	Viability: ≤ 50% means irritant. Phase 1:   HCl 1%    = 106.8%   HCl 3%    = 99.7%   HCl 10%  = 89.4%   HCl 25%  = 18.1%  Phase 2:            HCl 10%  = 74.6%   HCl 17.5%= 41.1%   HCl 25%  = 28.3%  Phase 3:   HCl 15%  = 101.0%	HCl ≤ 15% non-irritant.
Rabbit, Potokar etal, 1985	0.5 ml, 37%, 1 hr: corrosive	HCl 37% Cat.1B or more severe
Rabbit, Vernot etal, 1977	0.5 ml, 17%, 4 hrs: corrosive 0.5 ml, 15%, 4 hrs: non-corrosive	HCl 17% Cat.1C or more severe HCl ≤ 15% non-corrosive
Human in vivo, York etal, 1996	In vitroTER 9% and 18%: non-corrosive Human: 10%: not classification needed: 6 out of 30 volunteers gave positive reactions following 4 hrs exposure. As reactions were lower than for 20% SDS considered the minimum classification for irritation (23 out of 32 positive, i.e. 72%).	HCl 10% no classification needed.

 

From the above is concluded that concentrations below 10% are not irritating.

Concentrations from 10% and higher should be considered corrosive Cat.1B, and from25% Cat.1A.

 

For the evaluation of possible eye irritation, the following data is available:

Study	results	Conclusion
BCOP, Warren, 2013c	1% - 2.4 5% - 100.0 10% - 158.1	1% ≥ 5%: Cat.1
SkinEthic, Warren, 2013d	30 µL,10 minutes. <60% irritant Phase 1:         1% w/w = 58.1%         3% w/w = 5.5%         10% w/w = 6.1%         25% w/w = 5.0% Phase 2:         1% w/w = 51.7%         3% w/w= 6.5%         10% w/w = 6.5% Phase 3:         0.5% w/w = 84.2%         0.8% w/w = 60.4	≥ 1%: Cat.2
Rabbit, Jacobs, 1988	10% mean over 24/48/72 hrs of iritis >1.5	≥10 Cat.1
Rabbit, P&G, YE7-176, 1976	5% HCl: irreversible effects to rabbit eyes (Cat.1)	≥ 5%: Cat.1

 

From the above can be concluded that concentration from 5% are eye damage Cat.1, and concentrations below 1% do not need to be classified. The SkinEthic data indicates thatr concentrations of 1% and higher are at least irritating to the eyes.

The BCOP data however, leaves uncertainty for concentrations between 1-5%. It was decided to go for the most conservative approach, and to classify corrosive to the eyes from concentrations ≥1%.

Justification for selection of skin irritation / corrosion endpoint:
Most valid, recent guideline study.

Justification for selection of eye irritation endpoint:
Most appropriate, valid and recent guideline study.

Effects on skin irritation/corrosion: highly corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: highly irritating

Justification for classification or non-classification

Skin irritation/corrosion:

Based on available data the following classification is proposed for Hydrogen chloride concentrations:

≥ 25%: Cat.1A, H314: Causes severe skin burns and eye damage

≥ 10%: Cat.1B, H314: Causes severe skin burns and eye damage

< 10% no classification for skin irritation/corrosion

 

Serious eye damage/eye irritation:

Based on BCOP: 5% are eye damage Cat.1:

BCOP and SkinEThic: < 1% no classification for eye irritation.

The BCOP data however, leaves uncertainty for concentrations between 1-5%. It was decided to go for the most conservative approach, and to classify Cat 1 severe eye damage, H318 (Causes serious eye damage) from concentrations of 1% and higher.

Respiratory irritation:

Being a corrosive substance classification the current harmonised classification to STOT SE 3, H335 (May cause respiratory irritation), is appropriate.