reaction mass of Calcium chloride and Sodium chloride

Endpoint summary

Description of key information

Regarding skin and eye irritation/corrsion no data are available on the reaction mass itself. Data are available on the two components of this reaction mass (calcium chloride and sodium chloride).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1954

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results

Qualifier:

no guideline available

Principles of method if other than guideline:

None

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

not specified

Preparation of test site:

other: intact and abraded

Vehicle:

water

Remarks:

for 5%, 10%, 20% and 50 % NaCl solution

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 5%, 10%, 20% and 50 % and 100% NaCl

Duration of treatment / exposure:

No data

Observation period:

No data

Number of animals:

No data

Details on study design:

Please see the table below.

Irritation parameter:

other: The following responses were observed: reddening skin, presence or absence of edema, of necrosis and of scarbs.

Basis:

other: Not specified

Time point:

other: Not specified

Reversibility:

not specified

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

When in contact with the intact skin, sodium chloride causes no response, either in undiluted form or in solution. However, abraded skin may be appreciably irritated depending upon the concentration of the salt solution. Strong solutions (20% or better) result in scab and scar formation after a few applications. Weaker solutions (10% or 5%) produce slight irritation which delays healing without scarring.

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

When in contact with the intact skin, sodium chloride causes no response, either in undiluted form or in solution. However, abraded skin may be appreciably irritated depending upon the concentration of the salt solution. Strong solutions (20% or better) result in scab and scar formation after a few applications. Weaker solutions (10% or 5%) produce slight irritation which delays healing without scarring.

Executive summary:

When in contact with the intact skin, sodium chloride causes no response, either in undiluted form or in solution. However, abraded skin may be appreciably irritated depending upon the concentration of the salt solution. Strong solutions (20% or better) result in scab and scar formation after a few applications. Weaker solutions (10% or 5%) produce slight irritation which delays healing without scarring.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The report contains sufficient information to permit a meaningful evaluation of study results

Qualifier:

no guideline available

Principles of method if other than guideline:

The study methodology followed was equivalent or similar to OECD 404.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

not specified in the report

Type of coverage:

not specified

Preparation of test site:

other: intact and abraded skin

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

50 mg dry powder moistened with 0.1 ml water

Duration of treatment / exposure:

single exposure

Observation period:

72 hours

Number of animals:

6 rabbits

Details on study design:

not specified in the report

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0.88

Max. score:

8

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The overall irritation score was 0.88 out of a maximum score of 8

Other effects:

not specified in the report

not applicable

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, sodium chloride is slightly irritating to rabbit skin but it is not classified as irritating to skin according to UN and EU GHS criteria.

Executive summary:

A primary skin irritation study was conducted in rabbits on intact and abraded skin and based on the results, sodium chloride induce slight irritation to rabbit skin which is fully reversible within 72h. Therefore sodium chloride is not classified for skin irritation according to UN and EU GHS criteria.

 

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD Guideline study according to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Type of coverage:

occlusive

Amount / concentration applied:

undiluted

Duration of treatment / exposure:

4 hour(s)

Number of animals:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

- Table 1: Scores of the skin reaction of the rabbit after
application of anhydrous calcium chloride at different times after patch  removal.
-----------------------------------------------------
Animal  Symptom      score after
  No.  ----------------------------------------------
                     30-60        24     48      72
                    minutes     hours   hours  hours
-----------------------------------------------------
  1     erythema       0        0        0        0
        oedema         0        0        0        0
-----------------------------------------------------
  2     erythema       0        0        0        0
        oedema         0        0        0        0
-----------------------------------------------------
  3     erythema       0        0        0        0
        oedema         0        0        0        0
-----------------------------------------------------

Interpretation of results:

GHS criteria not met

Conclusions:

Classification: not irritating for skin according to UN and EU GHS criteria.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1960

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was conducted prior to GLP and test guidelines.

Qualifier:

no guideline available

Principles of method if other than guideline:

None

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

not specified

Preparation of test site:

other: intact and abraded

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

Undiluted as well as 10% aqueous solution was applied to the rabbit's skin.

Duration of treatment / exposure:

Duration varied from 3 to 10 applications.

Observation period:

21 days

Number of animals:

No data

Details on study design:

TEST SITE
- Area of exposure: Belly and ear

Irritation parameter:

other: The following responses were observed: absence or presence of hyperemia, edema and necrosis.

Basis:

other: Not specifed

Time point:

other: Not specified

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

Please see the table above

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

To intact skin, undiluted sodium chloride (wet patch) induces slight edema. Dry undiluted sodium chloride induces very slight edema and 10% aqueous solution induces no irritation to skin.

Executive summary:

Undiluted Cubidow is slightly to moderately irritating to intact and abraded skin. Contact for a short period of time would probably result in no appreciable irritation. Skin contact on a prolonged basis, particularly in the case of moist or wet skin and if confined to the surface as exemplified by contaminated gloves or clothing in general, might produce some reddening. If the material were allowed to remain in contact on a continuous basis for a day or two, it is likely that a slight skin burn might result, particularly if the skin were abraded or was otherwise abnormal as exemplified by skin rashes, etc.

However to intact skin, very slight or slight irritation were seen with pur substance. No irritation was induced with a10% aqueous solution.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD Guideline study according to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Controls:

not required

Amount / concentration applied:

undiluted
Amount applied: 100 other: mg

Duration of treatment / exposure:

single

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

Comment: not rinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1.9

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

2.2

Max. score:

4

Irritant / corrosive response data:

The cornea and conjunctiva were moderately to severely irritated in all rabbits from one hour till 14 days after treatment. Thereafter the eye of one rabbit recovered, but there was still a slight haze on the cornea, 21 days after treatment. In the two other rabbits the cornea and conjunctiva were still moderately irritated 21 days after treatment.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the scores (24h, 48h and 72h mean scores on three rabbits) (see table above), undiluted calcium chloride (anhydrous calcium chloride) is considered to be corrosive for eyes and should be classified Eye. Dam. Cat. 1, H318 according to EU GHS criteria.

Executive summary:

Based on the unpublished report performed according to the OECD guideline 405, rabbit eyes were exposed to undiluted calcium chloride. The scores were the following: Cornea score = 2 , iris score = 1 ; conjunctivae score = 1. 9 and chemosis score = 2.2. Based on these scores and since the effect are not fully reversible within 21 days undiluted calcium chloride (anhydrous calcium chloride) is considered to be corrosive for eyes and is classified Eye. Dam. Cat. 1, H318 according to UN and EU GHS criteria.

 

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Amount / concentration applied:

undiluted
Amount applied: 100 other: mg

Number of animals or in vitro replicates:

3

Details on study design:

Comment: not rinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: in one animal

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1.54

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: in one animal

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1.65

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

The conjunctiva of the eye of one rabbit (No. 1) was moderately to severely irritated from one till 24 hours after treatment. Thereafter the irritation diminished and had disappeared at 14 days after treatment, although a slight lacrimation was still noted. The cornea of this rabbit was slightly opaque up to and including 72 hours. The conjunctiva of the eye of the second rabbit (No. 2), was moderately irritated at the one hour reading. Thereafter the irritation diminished, although the conjunctiva was still slightly damaged at the end of the observation period. In the third rabbit (No. 3), the cornea was moderately irritated from 24 till 72 hours. Thereafter the irritation diminished, but was still slight at the end of the experiment. The conjunctiva was moderately irritated from one till 72 hours. Thereafter the eye recovered, but the irritation was still present 21 days after application. The iris was slightly irritated from one hour up to 14 days after treatment.

- Table 1: Numerical grades awarded to the ocular reactions
elicited by calcium chloride dihydrate.
---------------------------------------------------------
Rabbit Region of eye   hours(h)/days(d) after application
 No.                  
---------------------------------------------------------
                       0h  1h  24h  48h  72h  7d  14d  21d
---------------------------------------------------------
1   Cornea  Opacity    0   0    1    1    1   0    0
    Area               0   0    1    1    1   0    0
    involved
---------------------------------------------------------
    Iris               0   0    0    0    0   0    0
---------------------------------------------------------
    Conju-  Redness    0   1    3*   2    2   1    0
    nctiva  Chemosis   0   2    3    2    2   1    0
            Discharge  0   0$  0$   1$   1$   0$   0$
---------------------------------------------------------
2   Cornea  Opacity    0   0    0    0    0    0   0   0
            Area       0   0    0    0    0    0   0   0 
            involved
---------------------------------------------------------
    Iris               0   0    0    0    0    0   0   0
---------------------------------------------------------
    Conju-  Redness    0   2    1*   0*   0*   0*  0*  0*
    nctiva  Chemosis   0   2    1    1    1    1   0   0
            Discharge  0   0$   0$   0$   0    0   0   0
---------------------------------------------------------
3   Cornea  Opacity   0   0    2    2    2    1    1   1
            Area      0   0    4    4    1    1    2   2
            involved     
---------------------------------------------------------
    Iris              0   2    1    1    1    1    0   0 
---------------------------------------------------------
    Conju-  Redness   0   2    2*   2*   2*   1*   2*  2
    nctiva  Chemosis  0   2    2    2    1    0    0   0 
            Discharge 0   0$   0$   1$   1$   0$   0$  0$
---------------------------------------------------------
* - conjunctiva was damaged.
$ - lacrimation

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The scores obtained during this study (mean 24h, 48h and 72h on the three rabbits) are the following: Cornea opacity score = 1 (not fully reversible within 21 days) ; Iris score = 0.33 (fully reversible within 21 days); Conjunctivae score = 1.54 (not fully reversible within 21 days) and Chemosis score = 1.65 (fully reversible within 21 day). Based on the scores and since the effects are not fully reversible within 21 days, undiluted calcium chloride (anhydrous calcium chloride) should be classified as Eye.Dam. Cat. 1, H318 according to EU GHS criteria.

Executive summary:

In a report performed in 1986 according to the guideline OECD 405, three rabbits received in eye 100 mg of undiluted test item. Effects on eyes were observed up to 21 days. The 24h, 48h and 73h mean scores on the 3 rabbits are the following: Cornea opacity score = 1 (not fully reversible within 21 days) ; Iris score = 0.33 (fully reversible within 21 days) Conjunctivae score = 1.54 (not fully reversible within 21 days) and Chemosis score = 1.65 fully reversible within 21 day). Furthermore 2 rabbits on 3 have the following mean scores (24h, 48h and 72h). Rabbit n°1: Conjunctival redness score = 2.3 ; Chemosis score = 2.3. Rabbit n° 3: Cornea opacity score = 2; Conjunctival redness = 2. Based on the results of this study and since the effects are not reversible within 21 days, undiluted calcium chloride is considered corrosive to eyes and should be classified Eye. Dam. Cat. 1, H318 according to UN and EU GHS criteria.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD Guideline study, with diluted test substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Amount / concentration applied:

Concentration: 33 %
Amount applied: 0.1 ml

Number of animals or in vitro replicates:

3

Details on study design:

Comment: not rinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1.22

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: in 1 animal

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 72 hr

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1.11

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 + 48 + 72 hr

Score:

1.22

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

The conjunctiva was slightly irritated in one rabbit (No. 3), from 1 till 48 hours after treatment. The irritation had disappeared at 48 hours, although some lacrimation was still noted. In a second rabbit (No. 2), the cornea and conjunctiva were moderately irritated till 48 hours. Thereafter the eye recovered and the irritation had disappeared 14 days after treatment. In the third rabbit (No. 1), the cornea and conjunctiva were moderately irritated till 72 hours. Thereafter, the cornea and conjunctiva recovered, but 21 days after treatment, the cornea was still slightly irritated.

- Table 1: Numerical grades awarded to the ocular reactions
elicited by calcium chloride 33 %.
---------------------------------------------------------
Rabbit  Region of eye        hours(h)/days(d) after
No.     application
---------------------------------------------------------
                      0h  1h  24h  48h  72h  7d  14d  21d
---------------------------------------------------------
1    Cornea Opacity   0   2    2    2    2    1    1   1
            Area      0   4    4    2    2    1    1   1
            involved
---------------------------------------------------------
     Iris             0   1    0    0    0    0    0   0
---------------------------------------------------------
    Conju-  Redness   0   1    2*   1*   1*   1    1   0
    nctiva  Chemosis  0   2    2    2    2    1    1   0
            Discharge 0   0$   0$   0$   0$   0$   1$  0$
---------------------------------------------------------
2   Cornea  Opacity   0   2    2    2    2    1    0
            Area      0   4    4    4    1    0    0	                 involved
---------------------------------------------------------
    Iris              0   1    0    1    0    0    0
---------------------------------------------------------
    Conju-  Redness   0   2    1*   2*   1*   1    0
    nctiva  Chemosis  0   2    2    1    1    0    0
            Discharge 0   0$   0$   0$   0    0    0
---------------------------------------------------------
3   Cornea  Opacity   0   0    0    0    0
             Area     0   0    0    0    0
            involved
---------------------------------------------------------
    Iris              0   0    0    0    0
---------------------------------------------------------
    Conju-  Redness   0   1    1*   0    0
    nctiva  Chemosis  0   2    1    0    0
            Discharge 0   0$   0$   0$   0
---------------------------------------------------------
* - conjunctiva was damaged.
$ - lacrimation

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In this study the mean scores (24h, 48h and 72 h) on 3 rabbits are the following: Cornea opacity score = 1.22 ; Iris score = 0.11 ; Conjunctivae score = 1.11 and chemosis score = 1.22. Based on the scores, the substance (applied as 33% in aqueous solution) (hydrated form of calcium chloride) is considered as irritant for eye and should be classified Eye. Irrit. Cat. 2, H319 according to EU GHS criteria.

Executive summary:

In a unpublished report performed in 1986 according to the OECD guideline 405, 0.1 ml of calcium chloride (33% in aqueous solution) was applied to rabbit eyes. The mean scores (24h, 48, 72h) on 3 rabbits are the following: Cornea opacity score = 1.22 ; Iris score = 0.11 ; Conjunctivae score = 1.11 and chemosis score = 1.22. Based on the scores, the substance (applied as 33% in aqueous solution) is considered to be irritant for eyes and is classified Eye. Irrit. Cat. 2, H319 according to EU GHS criteria. The classification according to UN GHS criteria is Eye. Irrit. Cat. 2A, H219.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1954

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results

Qualifier:

no guideline available

Principles of method if other than guideline:

None

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

No data

Vehicle:

water

Remarks:

for 5%, 10%, 20% and 50 % NaCl solution

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 5%, 10%, 20% and 50 % and 100% NaCl

Duration of treatment / exposure:

No data

Observation period (in vivo):

No data

Number of animals or in vitro replicates:

No data

Details on study design:

Please see the table below.

Remarks on result:

not measured/tested

Remarks on result:

other: Based on observations, the substance can be considered as irritating for eyes. No scores are available on this study.

Remarks:

The following responses were observed: pain, conjunctival irritation and corneal injury.

Irritant / corrosive response data:

Sodium chloride and its strong solution (50%) present a slight hazard from contact with the eye. Pain and conjunctival inflammation may persist for several days. Transient corneal injury may occur, but is expected to heal completely within a few days. Solution (20% or less) are not likely to cause injury to the eye. Contact is but very slightly painful and irritating.

Other effects:

None

None

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Sodium chloride presents a hazard from eye contact, both in the solid form and at the 50% concentration in water. Lower concentration (20% and 10%) cause slight pain and irritation which heals readily. Solutions of 5% cause only a trace of pain and no irritation.

Executive summary:

Sodium chloride or its concentrated solutions (50% or greater) caused pain and conjunctival inflammation which persisted for several days. Transient corneal injury occurred which resolved completely within a few days. Solutions of 20% or less caused slight pain and irritation which healed readily. Solutions of 5% or less caused only a trace of pain and no irritation.

Pure substance and 50% in solution is considered to induce eye irritation. Solution of 20% or less induces only slight eye irritation.

As a comparative reference, normal seawater is ~3.3% salt solution.

Only pure substance and solution of 50% are considered to be irritating to eyes and are classified Eye. irrit. cat. 2, H319 according to EU GHS criteria.

Reference 5

Endpoint:

eye irritation: in vivo

Type of information:

other: Publication

Adequacy of study:

weight of evidence

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Sufficient information is available for interpretation of results.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

None

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

0.01, 0.05 and 0.1 ml Nacl (20% or granular)

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

1, 2, 3, 4, 7 and 14 days after dosing

Number of animals or in vitro replicates:

3

Details on study design:

Young adult New Zealand albino rabbits of both sexes were selected at random and accepted for testing if free of visible ocular lesions when examined under good illumination with the aid of a magnifying lens. The lids of the test eyes were gently held open and the test material placed directly on the cornea. Only one eye of each animal was used in a test; the other eye being untreated served as a control. Liquid doses were dispensed from a micropipette, solids from a weighing paper. The eyelids were released immediately and not forcibly closed or further manipulated. The eye was not irrigated.

Eyes were examined and scored according to the scale of Draize et al. (1944) 1, 3, 7, and 14 days.
Three eyes were dosed with granular and 20% aqueous sodium chloride using volumes of 0.1, 0.01 and 0.05 ml.

Irritation parameter:

overall irritation score

Remarks:

Maximum draize score

Basis:

mean

Time point:

other: not specified

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 1 day

Remarks on result:

other: 0 ± 0, for Sodium chloride (20%) - 0.01 ml

Irritation parameter:

overall irritation score

Remarks:

Maximum Draize score

Basis:

mean

Time point:

other: not specified

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 1 day

Remarks on result:

other: 0 ± 0, for Sodim chloride (20%) - 0.05 ml

Irritation parameter:

overall irritation score

Remarks:

Maximum Draize score

Basis:

mean

Time point:

other: not specified

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 1 day

Remarks on result:

other: 0 ± 0, for Sodium chloride (20%) - 0.10 ml

Irritation parameter:

overall irritation score

Remarks:

Maximum Draize score

Basis:

mean

Time point:

other: not specified

Score:

9

Max. score:

9

Reversibility:

fully reversible within: 3-4 days

Remarks on result:

other: 9 ± 1, for Sodium chloride (granular) - 0.01 mg

Irritation parameter:

overall irritation score

Remarks:

Maximum Draize score

Basis:

mean

Time point:

other: not specified

Score:

11

Max. score:

11

Reversibility:

fully reversible within: 4-7 days

Remarks on result:

other: 11 ± 1, for Sodium chloride (granular) - 0.05 mg

Irritation parameter:

overall irritation score

Remarks:

Maximum Draize score

Basis:

mean

Time point:

other: not specified

Score:

13

Max. score:

13

Reversibility:

fully reversible within: 4-7 days

Remarks on result:

other: 13 ± 1, for Sodium chloride (granular) - 0.10 mg

Irritant / corrosive response data:

20% Sodium chloride showed negligible irritation (clearing within 24 hour after dosing). Granular sodium chloride showed moderate irritation (clearing within 7 days after dosing).

Other effects:

None

Please see the attachment - Eye irritation for details on results.

Tha attachment contains:

Table 1: Preliminary study Rabbit eye irritation scores and days to clear with different dose volumes of materials.

Table 5: Criteria for a positive reaction: FHSA Rabbit eye irritation test

Table 7: Presumptive assessment of hazardousness from FHSA and Proposed evaluative criteria

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Granular Sodium Chloride is classified as moderate irritant as specified by FHSA criteia (0.01ml).

Executive summary:

Young adult New Zealand albino rabbits of both sexes were selected at random and accepted for testing if free of visible ocular lesions when examined under good illumination with the aid of a magnifying lens. The lids of the test eyes were gently held open and the test material placed directly on the cornea. Only one eye of each animal was used in a test; the other eye being untreated served as a control. Liquid doses were dispensed from a micropipette, solids from a weighing paper. The eyelids were released immediately and not forcibly closed or further manipulated. The eye was not irrigated. Eyes were examined and scored according to the scale of Draize et al. (1944) 1, 3, 7, and 14 days. Three eyes were dosed with granular and 20% aqueous sodium chloride using volumes of 0.1, 0.01 and 0.05 ml.

20% Sodium chloride showed negligible irritation (clearing within 24 hour after dosing). Granular sodium chloride showed moderate irritation (clearing within 7 days after dosing).

Based on the results of the study, granular Sodium Chloride is classified as moderate irritant as specified by FHSA criteia (0.01ml). Therefore granular sodium chloride is considered to be irritating to eyes and should be classified Eye. Irrit. Cat. 2, H319.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation: Calcium chloride (one component of the reaction mass) (administrated as 10% in aqueous solution) is not irritating to rabbit skin in a study performed in 1981 (unpublished report according to OECD guideline 404 with reliability 1). Three unpublished reports with reliability 2 are available on sodium chloride (the second component of the reaction mass). In the first one, sodium chloride moistened with water induced slight irritation to rabbit skin. In the second report (Dow, 1960), no irritation was observed in rabbit skin (sodium chloride in solution and pure sodium chloride). Based on the third study, undiluted sodium chloride induces very slight to slight irritations. 10% aqueous solution induced no skin irritation in rabbit.

In a worst case approach considering the data on the two components, the reaction mass can induce only slight irritation to skin. Based on the data and on the scores for the two components of the reaction mass, no classification for skin irritation is required according to UN and EU GHS criteria.

Eye irritation: For the first component (calcium chloride): Eye irritation studies are available with anhydrous calcium chloride, calcium chloride dihydrate, calcium chloride hexahydrate and 33% aqueous solution (Koopman et al., 1986a, 1986b, 1986c), performed in accordance with OECD Guideline 405. In each study 100 mg of the material was instilled in an eye of three rabbits. No rinsing was performed. The results indicate that anhydrous calcium chloride is severely irritating to rabbit eyes. The cornea and conjunctiva were moderately to severely irritated in all rabbits from one hour till 14 days after treatment. Thereafter the eye of one rabbit recovered, but there was still a slight haze on the cornea, 21 days after treatment. In the two other rabbits the cornea and conjunctiva were still moderately irritated 21 days after treatment.The irritating properties of calcium chloride seem to diminish with a higher degree of hydratation, as can be seen from the results with di- and hexahydrate forms and 33% aqueous solution of calcium chloride. For calcium chloride dihydrate, the conjunctiva of one rabbit was moderately to severely irritated from one till 24 hours after treatment. Thereafter the irritation diminished and had disappeared at 14 days after treatment, although a slight lacrimation was still noted. The cornea of this rabbit was slightly opaque up to and including 72 hours. The conjunctiva of the second rabbit was moderately irritated at the one hour reading. Thereafter the irritation diminished, although the conjunctiva was still slightly damaged at the end of the observation period. In the third rabbit the cornea was moderately irritated from 24 till 72 hours. Thereafter the irritation diminished, but was still slight at the end of the experiment. The conjunctiva was moderately irritated from one till 72 hours. Thereafter the eye recovered, but the irritation was still present 21 days after application. The iris was slightly irritated from one hour up to 14 days after treatment.

In the study with calcium chloride hexahydrate, the conjunctiva of one rabbit was slightly irritated till 48 hours; the irritation had disappeared at 72 hours. The cornea was slightly irritated at 24 hours after treatment. In a second rabbit the conjunctiva was moderately irritated from one till 48 hours after treatment, thereafter the conjunctiva recovered. The cornea was slightly irritated from one till 72 hours. The irritation of cornea and conjunctiva had disappeared at 7 days after treatment. In the third rabbit the cornea was slightly irritated from 24 hours till 72 hours after treatment. The conjunctiva was slightly irritated from 1 hour till 14 days. At day 21 only some lacrimation was noted in this rabbit. 

Finally, in the study with 33% aqueous solution of calcium chloride, the conjunctiva of one rabbit was slightly irritated from 1 till 48 hours after treatment. The irritation had disappeared at 48 hours, although some lacrimation was still noted. In a second rabbit the cornea and conjunctiva were moderately irritated till 48 hours. Thereafter the eye recovered and the irritation had disappeared 14 days after treatment. In the third rabbit the cornea and conjunctiva were moderately irritated till 72 hours. Thereafter, the cornea and conjunctiva recovered, but 21 days after treatment, the cornea was still slightly irritated. In the available eye irritation study with anhydrous calcium chloride, the observed signs of irritation were not fully reversible within 21 days of observation period. This suggests that anhydrous substance should be classified as Eye. Dam. Category 1, H318 (causes serious eye damage) according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

For hydrated forms of calcium chloride classification Eye. Irrit. Category 2, H319 (causes serious eye irritation) is proposed based on the available studies. It should be noted that although (minor) signs of irritation were still present in some animals at the end of 21 days observation period in some cases, classification into a more severe category is considered to be not warranted based on following considerations:

·        No examples of calcium chloride causing irreversible damage to eyes in humans have been reported, despite its long history of widespread use.

·        It is feasible that eye irritating properties of calcium chloride are directly related to its hygroscopic properties. Anhydrous calcium chloride is a highly hygroscopic substance, and its dissolution in water is a highly exothermic process (heat of dissolution81.3 kJ/mol), while calcium chloride hydrtates are significantly less hygroscopic and their dissolution in water is only slightly exothermic.

·        Available studies have been performed in accordance with OECD Guideline 401 adopted in 1981, which stated that eyes can be rinsed 24 hours post-instillation. According to the modern version of the guideline, rinsing of eyes 1 hour post-instillation is allowed. It is thus feasible that more severe effects have been observed due the longer presence of the test substance in a conjunctival sac.

 

In summary, classification with Eye. Dam. Category 1, H318 (causes serious eye damage) according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 is proposed for anhydrous calcium chloride. For calcium chloride hydrates, classification Eye. Irrit. Category 2, H319 (causes serious eye irritation) is proposed. However, calcium chloride is already classified as Category 2, H319 (causes serious eye irritation) on Annex VI of EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. In accordance with Article 4, point 3 of EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, if a substance is subject to harmonised classification and labelling in accordance with Title V through an entry in Part 3 of Annex VI, that substance shall be classified in accordance with that entry, and a classification of that substance in accordance with Title II shall not be performed for the hazard classes or differentiations covered by that entry. Based on this, classification of calcium chloride as Eye Irritant Category 2, H319 shall be followed by the registrant in this dossier.

Three studies are available on sodium chloride showing that sodium chloride induced pain to eyes rabbits. In a conservative approach sodium chloride is considered to be irritating to eyes.

 

In a worst case approach considering the data on the two components, the reaction mass (calcium chloride and sodium chloride in aqueous solution) can induce irritation to eyes and is classified eye; Irrit. Cat. 2, H319.