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EC number: 202-468-3 | CAS number: 95-96-5
Carcinogenicity
Administrative data
Description of key information
A 2 year drinking water study in rats with calcium lactate is available (Maekawa, 1991). The calcium salt of lactic acid (calcium lactate) did not induce any dose-related increase in the incidences of tumours in any organ or tissue. The finding is supported by a 5 and 13 m study with lactic acid in rabbits (Shubik 1957 as cited in Anderson, 1998). Lactic acid (and also calcium lactate) is an acceptable read-across partner for dilactide as dilactide is rapidly converted by hydrolysis into lactic acid under aqueous conditions.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Published study with the read-across partner calcium lactate, meets generally accepted scientific standards and is described in sufficient detail
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- not specified
- Principles of method if other than guideline:
- 2 year exposure to substance in drinking water.
- GLP compliance:
- not specified
- 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 maintained on the basal diet (CRF-1, Onental Yeast Inc., Tokyo, Japan) and tap-water until they were 6 weeks old (i.e. when the study started).
- 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 consisting of 50 males and 50 females. They were housed three (or four) males or five females to a plastic cage and kept in an air-conditioned animal room. Calcium lactate was dissolved in distilled water at Ievels of 2.5 or 5%.. These doses were selected after a 13-week subchronic toxicity study done prior to the present study.
Rats were given these solutions ad lib as their drinking-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 in 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 period of 9 weeks. At week 113, all surviving animals were killed and autopsied. Haematological and biochemical examinations were also carried out on these rats.
Throughout the experiment, rats in all groups were given the basal diet ad lib. They were observed daily and clinical signs and deaths were recorded. Body weights were measured once a week for the first 13 weeks of the study, and every 4 weeks thereafter. - Sacrifice and pathology:
- An autopsy was immediately performed 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 in 10% buffered formalin, sectioned and stained with haematoxylin and eosin.
- Statistics:
- Statistical analysis were performed using Fisher's exact probabilty 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
- Description (incidence and severity):
- high levels of serum calcium
- Details on results:
- Result (carcinogenicity): negative
- Relevance of carcinogenic effects / potential:
- Lactic acid is a major metabolic species, and a ubiquitous food ingredient.
- Dose descriptor:
- NOAEC
- Effect level:
- 50 000 ppm (nominal)
- Sex:
- male/female
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
- Conclusions:
- It was concluded that calcium lactate had neither toxic nor carcinogenic activity in F344 rats when it was given continuously in the drinking-water for 2 years
- Executive summary:
In a carcinogenicity study calcium lactate (>97% a.i.) was administered ad libitum to 50 F344 rats per sex per dose in drinking-water at levels of 0, 2.5 or 5 % for two years. Calcium lactate is the calcium salt of lactic acid, which is a major and essential species in mammalian primary metabolism and a ubiquitous ingredient in all kinds of food. Calcium lactate is an acceptable read-across partner for dilactide as dilactide is rapidly converted by hydrolysis into lactic acid under aqueous conditions.
No clear toxic lesion was specifically caused by long-term administration of calcium lactate. No significant dose-related increase in the incidences of tumours in any organ or tissue was found. The results indicate that calcium lactate had neither toxic nor carcinogenic activity in F344 rats.
Reference
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 available data on degradation products, dilactide does not warrant classification for carcinogenicity.
Additional information
Calcium lactate did not induce any tumours in a 2 years carcinogenicity study (Maekawa, 1991). Moreover, in a 16 months study in rabbits, lactic acid did not induce any tumours. These results can be seen as available supporting information for the carcinogenicity evaluation of dilactide.
Justification for selection of carcinogenicity via oral route endpoint:
2 year drinking water study with the read-across partner calcium lactate; meets generally accepted scientific standards and is described in sufficient detail
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