Fatty acids, C9-13-neo-, calcium salts

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Only limited data are available on effects of calcium compounds on the reproductive performance of male and female mice and rats, respectively. A preliminary NOAEL for calcium effects on reproduction and development of offspring may be derived from a CaCO3 feeding study in mice (Richards and Greig, 1952). The study design was similar to that of a one-generation reproductive toxicity study. The highest dose of 2 % CaCO3 (corresponding to 1.1 % Ca) resulted in reduced numbers and total weight of litters, and increased both the number and proportion of litter deaths, hence being considered as LOAEL for effects on reproductive performance. The dose level of 0.73 % Ca may be established as NOAEL although there were some sporadic effects without statistical significance. However, no daily dose levels could be calculated due to lack of data on daily food intake.

However, with respect to potential hazards of calcium for reproduction the following aspects have to be taken into account:

i) Calcium, released as calcium cations in aqueous media is a physiologically essential element and nutrient for all mammals including humans. Comprehensive evaluations of possible adverse health effects of individual nutrients at intakes in excess of dietary requirements have been presented in the scientific opinions of the Scientific Committee on Food (SCF). Where possible, tolerable upper intake levels (UL) for different human populations have been established. The UL is an estimate of the highest level of intake entailing no appreciable risk of adverse health effects. In the opinion on calcium (EFSA 2006), the sources, properties and effects of calcium on animals as well as on different subgroups of the human population have been re-evaluated and a tolerable upper intake level for calcium has been defined. The SCF decided to base the derivation of an UL for calcium on the evidence of different interventional studies of long duration in adults, some of which were placebo-controlled and in which total daily calcium intakes of 2500 mg from both the diet and supplements were tolerated without any adverse effects. Based on the findings, a tolerable upper intake level of 2500 mg of calcium per day for calcium intake from all sources is proposed for adults, corresponding to a dose of about 36 mg calcium/kg bw/d taking into account an average body weight of 70 kg/person. The UL is considered to also cover any potential reproductive effects.

ii) Supportive information is available in section 7.12 of the technical dossier (Mortimer, 1988) showing that calcium is essential for the function of human spermatozoa (acrosome reaction), i.e. calcium has a beneficial effect on reproductive performance.

iii) Supportive information is available in section 7.12 of the technical dossier (Han, 2000) showing that calcium has a protective effect against lead accumulation in dams and their offspring, i.e. acts beneficially.

Short description of key information:
Calcium, as an essential and abundantly available mineral nutrient, is not toxic to reproduction/fertility.

Effects on developmental toxicity

Description of key information

Calcium, as an essential and abundantly available mineral nutrient, is not foetotoxic or teratogenic.

Additional information

Two pre-natal developmental toxicity studies establishing a dose- response relationship of potential adverse effects of calcium after oral administration of calcium carbonate to rats were identified (Shackelford et al., 1993, 1994). The design of these studies was comparable to the OECD guideline 414. In all studies no adverse developmental, foetotoxic or teratogenic effects were noticed up to and including the highest dose levels tested. These studies allow the derivation of a NOAEL value for developmental effects of calcium.

From the study on rats given CaCO3 in feed (Shackelford et al., 1993) the highest dose of 1.25 % Ca is established as the NOAEL for developmental effects, corresponding to a daily dose of 938 mg Ca/kg bw/d.

However, with respect to potential hazards of calcium for developmental toxicity the following aspects have to be taken into account:

i) Calcium, released as calcium cations in aqueous media is a physiologically essential element and nutrient for all mammals including humans. Comprehensive evaluations of possible adverse health effects of individual nutrients at intakes in excess of dietary requirements have been presented in the scientific opinions of the Scientific Committee on Food (SCF). Where possible, tolerable upper intake levels (UL) for different human populations have been established. The UL is an estimate of the highest level of intake entailing no appreciable risk of adverse health effects. In the opinion on calcium (EFSA 2006), the sources, properties and effects of calcium on animals as well as on different subgroups of the human population have been re-evaluated and a tolerable upper intake level for calcium has been defined. The SCF decided to base the derivation of an UL for calcium on the evidence of different interventional studies of long duration in adults, some of which were placebo-controlled and in which total daily calcium intakes of 2500 mg from both the diet and supplements were tolerated without any adverse effects. Based on the findings, a tolerable upper intake level of 2500 mg of calcium per day for calcium intake from all sources is proposed for adults, corresponding to a dose of about 36 mg calcium/kg bw/d taking into account an average body weight of 70 kg/person. The UL is considered to also cover any potential developmental effects and will be used further in the risk assessment.

ii) Lack of developmental/teratogenic effects or even beneficial effects of calcium supplementation on foetal development is further supported by human data (Villar, 1990; Levine, 1997; Koo, 1999; Section 7.10.1 of the technical dossier).

Justification for classification or non-classification

Calcium is an essential mineral nutrient for mammals including humans. Based on evaluation of a wealth of human medical and nutritional data (WHO 2001; EFSA 2006), it is concluded that calcium, does not pose any hazard for reproduction and/or developmental toxicity. Classification for toxicity to reproduction is not warranted.