Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M) EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Calcium lactate is a food ingredient, and it is used as a food additive both in Europe and in the US. It is classified as a GRAS (Generally Recognised As Safe) substance by FAO, with an unlimited ADI (Acceptable Daily Intake). In the EU, calcium lactate as a food additive is given thequantum satisstatus, which means that no maximum numerical level is specified (EU Regulation No 1129/2011) based on the evaluation by JECFA [1].

 

Only one limited study is available, adressing repeated exposure to calcium lactate (Matsushimaet al., 1989; only publication available). In this study, exposure of rats to 5% calcium lactate in drinking water resulted in minor toxicological findings, which could not be supported by histopathological data. The NOAEL was set at 1840 mg/kg bw, which was the highest dose tested.

Since calcium lactate fully dissociates into Ca2+ions and lactatein aqueous solutions and/or physiological conditions, its toxicological profile (systemic endpoints) was described to a great extent based on information on the toxicity of lactic acid, calcium and calcium chloride (see read across statement attached in section 13).

Lactic acid is a common biological molecule, with low acute and no chronic toxicity, to which humans are continuously exposed, from diet (as a natural food ingredient), from bacterial generation in the gut, and from intra-mitochondrial (innate) processes. Natural concentrations in vivo can and will vary widely. Lactic acid is also applied in foodstuffs as food additive, with a no established ADI (EURegulation No 1129/2011). A more elaborate explanation on the biology and human exposure to lactic acid can be found in the document attached in the Section 7.1.1 (Sterenborg, 2007) of this IUCLID5 file.The information presented in this document unambiguously shows that exposure to lactic acid is a normal aspect of human life. Therefore, it is considered unnecessary to derive a DNEL for lactic acid.

 

Similarly, calcium is an essential nutrient for humans, with a strict self regulatory system. As a natural constituent of man, animals and plants it occurs in several foodstuffs. The European Committe categorizes calcium cation in a group of substances were no ADI is specified, despite the fact that exhaustive systematic toxicological data with the individual cation are not available [2]. According to EFSA, the tolerable upper intake level for calcium is set at 2500 mg per day for healthy humans [3], based on various interventional studies of long duration in adults, in which total daily calcium intakes of 2500 mg from both diet and oral supplements were tolerated without adverse effects.This level is also supported by the IOM in the US [4]: “Currently, the available data on the adverse effects of excess calcium intake in humans primarily concerns calcium intake from nutrient supplements. Of the many possible adverse effects of excessive calcium intake, the three most widely studied and biologically important are: kidney stone formation (nephrolithiasis), the syndrome of hypercalcemia and renal insufficiency with and without alkalosis (referred to historically as milk-alkali syndrome when associated with a constellation of peptic ulcer treatments), and the interaction of calcium with the absorption of other essential minerals. These are not the only adverse effects associated with excess calcium intake. However, the vast majority of reported effects are related to or result from one of these three conditions”[4]. The reviews of EFSA[3] and IOM[4&5] are summarized under section 7.12.

 

Considering the above information, derivation of a DNEL on systemic effects for calcium lactate is considered irrelevant.

 

Endpoints related to local effects were adressed with the substance itself. Calcium lactate is not a skin or eye irritant and therefore, no DNEL needs to be derived for local effects.

[1]Joint FAO/WHO Expert Committee on Food Additives, 1973; Tox MonographFAS 5/NMRS 53A-JECFA 17/461

[2] Report of the Scientific Committee for Food, 1990; 13416 EN

[3] EFSA. Scientific Opinon on the Tolerable Upper Intake Level of Calcium, 2012; EFSA Journal 2012;10(7):2814

[4]Institute of Medicine. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, 1997

[5]Institute of Medicine. DRI Dietary Reference Intakes Calcium Vitamin D, 2011.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M) EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Calcium lactate is a food ingredient, and it is used as a food additive both in Europe and in the US. It is classified as a GRAS (Generally Recognised As Safe) substance by FAO, with an unlimited ADI (Acceptable Daily Intake). In the EU, calcium lactate as a food additive is given thequantum satisstatus, which means that no maximum numerical level is specified (EURegulation No 1129/2011) based on the evaluation by JECFA [1].

 

Only one limited study is available, adressing repeated exposure to calcium lactate (Matsushimaet al., 1989; only publication available). In this study, exposure of rats to 5% calcium lactate in drinking water resulted in minor toxicological findings, which could not be supported by histopathological data. The NOAEL was set at 1840 mg/kg bw, which was the highest dose tested.

Since calcium lactate fully dissociates into Ca2+ions and lactatein aqueous solutions and/or physiological conditions, its toxicological profile (systemic endpoints) was described to a great extent based on information on the toxicity of lactic acid, calcium and calcium chloride (see read across statement attached in section 13).

Lactic acid is a common biological molecule, with low acute and no chronic toxicity, to which humans are continuously exposed, from diet (as a natural food ingredient), from bacterial generation in the gut, and from intra-mitochondrial (innate) processes. Natural concentrations in vivo can and will vary widely. Lactic acid is also applied in foodstuffs as food additive, with a no established ADI (EURegulation No 1129/2011). A more elaborate explanation on the biology and human exposure to lactic acid can be found in the document attached in the Section 7.1.1 (Sterenborg, 2007) of this IUCLID5 file.The information presented in this document unambiguously shows that exposure to lactic acid is a normal aspect of human life. Therefore, it is considered unnecessary to derive a DNEL for lactic acid.

 

Similarly, calcium is an essential nutrient for humans, with a strict self regulatory system. As a natural constituent of man, animals and plants it occurs in several foodstuffs. The European Committe categorizes calcium cation in a group of substances were no ADI is specified, despite the fact that exhaustive systematic toxicological data with the individual cation are not available [2]. According to EFSA, the tolerable upper intake level for calcium is set at 2500 mg per day for healthy humans [3], based on various interventional studies of long duration in adults, in which total daily calcium intakes of 2500 mg from both diet and oral supplements were tolerated without adverse effects.This level is also supported by the IOM in the US [4]: “Currently, the available data on the adverse effects of excess calcium intake in humans primarily concerns calcium intake from nutrient supplements. Of the many possible adverse effects of excessive calcium intake, the three most widely studied and biologically important are: kidney stone formation (nephrolithiasis), the syndrome of hypercalcemia and renal insufficiency with and without alkalosis (referred to historically as milk-alkali syndrome when associated with a constellation of peptic ulcer treatments), and the interaction of calcium with the absorption of other essential minerals. These are not the only adverse effects associated with excess calcium intake. However, the vast majority of reported effects are related to or result from one of these three conditions”[4]. The reviews of EFSA[3] and IOM[4&5] are summarized under section 7.12.

 

Considering the above information, derivation of a DNEL on systemic effects for calcium lactate is considered irrelevant.

 

Endpoints related to local effects were adressed with the substance itself. Calcium lactate is not a skin or eye irritant and therefore, no DNEL needs to be derived for local effects.

[1]Joint FAO/WHO Expert Committee on Food Additives, 1973; Tox MonographFAS 5/NMRS 53A-JECFA 17/461

[2] Report of the Scientific Committee for Food, 1990; 13416 EN

[3] EFSA.Scientific Opinon on the Tolerable Upper Intake Level of Calcium, 2012; EFSA Journal 2012;10(7):2814

[4]Institute of Medicine. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, 1997

[5]Institute of Medicine. DRI Dietary Reference Intakes Calcium Vitamin D, 2011.