Registration Dossier

Administrative data

Description of key information

Based on the results of GLP-compliant guideline study, calcium chloride is found to be not irritating to skin. Anhydrous calcium chloride is severely irritating to rabbit eyes; however, irritating properties seem to diminish with a higher degree of hydratation for calcium chloride hydrates. There is limited evidence that calcium chloride may cause respiratory tract irritation; however, this evidence is concluded to be not sufficient for classification and labelling.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study according to GLP
Qualifier:
according to
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
Score:
0
Remarks on result:
other: no effects seen
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
- 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
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study according to GLP
Qualifier:
according to
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:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: 0 score after 21 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: 0 score after 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
2
Reversibility:
other: score 0 after 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
other: score ) after 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
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:
highly irritating
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study
Qualifier:
according to
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:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
other: score 0 after 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not damage
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: in one animal
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: 0 score after 14 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not damage
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: 0 score after 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
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:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: 0 score after 21 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
2
Reversibility:
other: score 0 after 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
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 o paque 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 c onjunctiva 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:
other: irritating
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study
Qualifier:
according to
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:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: 0 score after 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: 0 score after 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: 0 score after 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: 0 score after 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
other: 0 score after 72h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
other: 0 score after 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
other: 0 score after 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
other: 0 score after 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
other: score 0 after 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.78
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
The conjunctiva was slightly irritated in one rabbit (No. 2), till 48 hours; the irritation had disappeared a t 72 hours. The cornea was slightly irritated at 24 hours after treatment. In a second rabbit (No. 1), 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 conj unctiva had disappeared at 7 days after treatment. In the third rabbit (No. 3), 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.

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

Interpretation of results:
other: moderately irritating
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study, with diluted test substance.
Qualifier:
according to
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
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: after 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: o score after 72h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: 0 score after 72h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 48 h
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:
moderately irritating
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

Calcium chloride was found to be not irritating to rabbit skin in the GLP-compliant study, performed according to OECD Guideline 404 (Koopman et al., 1986e). No effects were noted in any of three rabbits at any observation time points (1, 24, 48 and 72 hours) following an application of the anhydrous substance under occlusive dressing for 4 hours.

Eye irritation

Good quality eye irritation studies are available with anhydrous calcium chloride, calcium chloride dihydrate, calcium chloride hexahydrate and 33% aqueous solution (Koopman et al., 1986i, 1986j, 1986k, 1986l), 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.

Respiratory tract irritation

In the acute inhalation toxicity study of low reliability, signs of irritation of the respiratory tract were described at both exposure levels (40 and 160 mg/m3), suggesting that inhalation of calcium chloride can cause an irritation of the respiratory tract. In the study with tuberculosis patients who were treated with aerosol inhalations of 2-5% aqueous solution of calcium chloride, with the number of inhalations varyings from below 10 to over 30 (Vinnikov et al., 1962), irritation of mucos membranes of pharinx and throat and unpleasant sensation in mouth was reported by some patients. However, the frequency of such cases was described as minor by the authors. Overall calcium chloride inhalations were said to have beneficiary effects on disease symptoms (improved quality of spatum, decreased amounts of spatum, improved ease of spatum expellance, decreased frequency of coughing). In summary, the evidence that calcium chloride can cause respiratory tract irritation is considered to be inconclusive.

Justification for classification or non-classification

Based on the results of GLP-compliant guideline studies, calcium chloride does not need to be classified for skin irritation.

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 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 as 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 dissolution 81.3 kJ/mol), while calcium chloride hydrates 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 in 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 in 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.

No classification of calcium chloride as a respiratory tract irritant is proposed based on the available data.