Calcium (S)-2-hydroxypropionate

Carcinogenicity

Description of key information

Not carcinogenic.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Publication that provides sufficient details for evaluation.

Principles of method if other than guideline:

2 year exposure to substance in drinking water.

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female 5-wk-old specific-pathogen-free (SPF) Fischer (F344) rats were purchased from Charles River Japan Inc. (Kanagawa, Japan) They were mamtained on the basal diet (CRF-1, Onental Yeast Inc., Tokyo, Japan) and tap-water until they were 6wk old (i.e. when the study starled).

Route of administration:

oral: drinking water

Vehicle:

unchanged (no vehicle)

Details on exposure:

Ad libitum exposure to drinking water containing 2.5 or 5% calcium lactate. Daily water intake was recorded, and daily calcium lactate intake was calculated from this. High dose males were exposed to a grand total of 625.4 g calcium lactate, and low dose males to a grand total of 329.4 g calcium lactate. For females, these numbers were 412.1 g and 237.7 g, respectively.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 years

Frequency of treatment:

daily, ad lib.

Post exposure period:

9 weeks

Remarks:

Doses / Concentrations:
2.5% calcium lactate in drinking water
Basis:
nominal in water

Remarks:

Doses / Concentrations:
5% calcium lactate in drinking water
Basis:
nominal in water

No. of animals per sex per dose:

50

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: Autopsy on rats that died during study and those killed at the end. Examinations macro- and microscopically for presence of non-neoplastic and neoplastic lesions.

Observations and examinations performed and frequency:

Rats were randomly allocated to three groups, each consistmg of 50 males and 50 females. They were housed three (or four) males or five females to a plastic cage and kept m an air-conditioned ammal room ( 2 4 ± P C , 55 ± 5% relative humidity) Calcium lactate was dissolved in distilled water_at Ievels_of_0_£control)r"2 5 or 5%.. These doses were selected after a 13-wk subchronic toxicity study done pnor to the present study v«i
CC: -fcr^r
589
/"-i (Matsushima et al, 1989) Rats were given these •^
solutions ad lib as their dnnking-water The calcium lactate solutions were replaced with freshly prepared solutions three times a week, on which occasions the amount of solutions consumed was measured m order to calculate the intake of calcium lactate Administration of the compound ended after 104 wk, and the rats were then given distilled water for a recovery penod of 9wk. At wkl!3, all surviving animals were killed and autopsied Haematological and biochemical exammations were also camed out m these rats
Throughout the expenment, rats in all groups were given the basal diet ad lib. They were observed daily and chnical signs and deaths were recorded. Body weights were measured once a week for the first 13 wk of the study, and every 4 wk thereafter

Sacrifice and pathology:

An autopsy was immediatelyperformed on rats that died (or were killed when moribund) during the study and those killed at the end of the study The animals were then examined macro- and microscopically for the presence of non-neoplastic and neoplastic lesions All organs and/or tissues were routinely fixed m 10% buffered formahn, sectioned and stained with haematoxylm and eosin.

Statistics:

Statistical analyse swere performed using Fisher's exact probabihty test and/or the chi-square test, and also the age-adjusted statistical test recommended by Peto et al. (1980).

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

Result (carcinogenicity): negative

Relevance of carcinogenic effects / potential:

It was concluded that calcium lactate had neither toxic nor carcinogenic activiity in F344 rats when it was given continuously in the drinking-water for 2 yr.

Conclusions:

It was concluded that calcium lactate had neither toxic nor carcinogenic activiity in F344 rats when it was given continuously in the drinking-water for 2 yr.

Executive summary:

The long-term toxicity carcinogenicity of calcium lactate, a food additive, was examined in F344 rats. Calcium lactate was given ad lib in the drinking-water at levels of 0, 2.5 or 5% to groups of 50 male and 50 female rats for two years. No clear toxic lesion was specifically caused by long-term administration of calcium lactate. No significant dose-related increase was found in the incidences of tumours in any organ or tissue. The results indicated that calcium lactate had neither toxic nor carcinogenic activity in F344 rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the above provided information, classification of calcium lactate is not warranted in accordance with Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Additional information

The long-term toxicity/carcinogenicity of calcium lactate, a food additive, was examined in F344 rats. Calcium lactate was given ad lib in the drinking-water at levels of 0, 2.5 or 5% to groups of 50 male and 50 female rats for two years No clear toxic lesion was specifically caused by long-term administration of calcium lactate. No significant dose-related increase was found in the incidences of tumours in any organ or tissue. The results indicated that calcium lactate had neither toxic nor carcinogenic activity in F344 rats.

Calcium lactate fully dissociates into Ca2+ ions and lactate. Therefore, its toxicological properties, if any, can be assessed based on data for calcium chloride and lactic acid (see read-across statement).

Lactic acid is a major and essential species in mammalian primary metabolism and a ubiquitous ingredient in all kinds of food. Carcinogenicity is not a relevant end point for such a substance, since there is no way of lowering exposure below minimum required levels or normal (or even abnormal) internal levels.

Calcium chloride is not genotoxic in vivo.Calcium and chloride are both essential nutrients for humans and a daily intake of more than 1000 mg for each of the ions is recommended. As for healthy humans, the tolerable upper intake level for calcium is set at 2500 mg per day (equivalent to 6.9 g CaCl₂per day) [1]. For chloride, the reference nutrient intake is set at 2500 mg/day (equivalent to 3.9 g CaCl₂per day) [2]. The estimated intake of calcium chloride in a form of food additives (160-345 mg/day) is considerably smaller than these values. Consistent with this, the establishment of an ADI for calcium chloride has not been deemed necessary by JECFA [3]. Based on this information, it is concluded that the substance is not carcinogenic and the performance of a carcinogenicity study for calcium chloride is not indicated.

Based on the above information calcium lactate shall not be considered to be carcinogenic to humans.

[1] Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, 1999

[2] Department of Health, UK, 1991

[3] Joint FAO/WHO Expert Committee on Food Additives; 1974, 2001