Zinc dilactate

Carcinogenicity

Description of key information

In a two year carcinogenicity study the read-across partner calcium lactate did not induce any carcinogenic effects after oral application via the drinking water.

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 451 (Carcinogenicity Studies)

Principles of method if other than guideline:

2 year exposure to substance in drinking water.

GLP compliance:

not specified

Specific details on test material used for the study:

- Calcium lactate (CAS No. 814-80-2, C6H10CaO6 5H2O, MW 308.30) was a commercial sample obtained from Musashino Chemical Inst Ltd (Tokyo, Japan),
- It was an odour-less white powder,
- purity > 97%,
- clarity and colour of solution: colourless and clear,
- pH 6.0-8.0

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

Dose / conc.:

25 000 ppm

Remarks:

nominal in water

Dose / conc.:

50 000 ppm

Remarks:

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 weeks, 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

Description (incidence and severity):

Compared with the controls, a 13% decrease in body weight gain was observed in male and female rats of the high-dose group.

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

no effects observed

Description (incidence and severity):

Throughout the administration period, daily water consumption was almost constant in all groups of both sexes.

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Females in the 5% group exhibited slightly but significantly higher kidney weights compared with controls. Histologically, however, there was no difference in the severity of chronic nephropathy between different groups. No toxic lesions such as severe cortico-medullary nephrocalcinosis were observed in the kidney of females in the 5% group despite a slight increase in calcium deposition in the papilla compared with controls. A significant dose-dependent increase was observed in the relative brain weights of both male and female rats although no histological change was detected. The observed increase in relative brain weights of males and females in the high-dose group may result from the decrease in body-weight gains and not to the toxic effect of calcium lactate.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

A number of nonneoplastic lesions (e.g. myocardial fibrosis, bile-duct proliferation, hepatic microgranulomas and chronic nephropathy) were observed in all groups, with no difference in their incidences and/or degrees.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

None of the experimental groups showed a significant increase in the incidence of any specific tumours compared with the corresponding control value (chisquare and/or Fisher's test)

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)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Calcium lactate had neither toxic nor carcinogenic activity in F344 rats.

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 years.

Executive summary:

In a carcinogenicity study Calcium lactate (>97%) 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. 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.

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 from a suitable read-across partner, zinc lactate does not warrant classification for carcinogenicity.

Additional information

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.