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

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

Eye irritation

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

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 limited 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.


Effects on eye irritation: irritating

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 Xi, R41 (risk of serious damage to eyes) according to EU Directive 67/548 EEC and 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 with Xi, R36 (irritating to eyes) and 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 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 Xi, R41 (risk of serious damage to eyes) according to EU Directive 67/548 EEC and 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 with Xi, R36 (irritating to eyes) and Category 2, H319 (causes serious eye irritation) is proposed. However, calcium chloride is already classified with Xi, R36 (irritating to eyes) on Annex I of EU Directive 67/548/EEC and 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.