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Carcinogenicity

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Description of key information

There are no reliable studies for assessing the carcinogenic potential of the target substance, D-(-)-lactic acid itself. Therefore, available data from an oral carcinogenicity study conducted with a suitable read-across partner, calcium lactate was used to assess the carcinogenicity of the target substance. Based on the results, no classification for carcinogenicity is warranted for the target substance D-(-)-lactic acid.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
mortality observed, non-treatment-related
Description (incidence):
In females, the mortality rate in the 5% group was slightly higher than those in the other two groups.
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. The toxicological relevance was not further discussed.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
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.
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
No specific dose-related changes were observed in any of the haematological parameters.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No specific dose-related changes were observed in any of the biochemical parameters.
Endocrine findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
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.
A significant dose-dependent increase was observed in the relative brain weights of both male and female rats although no histological change was detected which may result from the decrease in body weight gains.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
A number of non-neoplastic 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.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
A slight increase in calcium deposition in the papilla compared to controls was observed in females of the 5% dose group. This type of lesion was histologically different from nephrocalcinosis and might depend on the increase in urinary calcium levels.
It is known that these lesions occur spontaneously in old F344 rats (Goodman et al., (1979): "Neoplastic and nonneoplastic lesions in aging F344 rats.", Toxicology and Applied Pharmacology 48, 237-248.). The data show that no clear toxic lesions specifically caused by long-term administration of calcium lactate, except for the slight calcium deposition in the renal papilla, were detected in any organ. The type of lesion observed in the kidney of female rats in the 5% group was histologically different from the so-called nephrocalcinosis, which is characterized by an intraluminal deposition of calcium observed mainly in the cortico-medullary region. The pathogenesis of this lesion is unclear and might depend on the increase in the urinary calcium level; this parameter was not determined in this study.
Histopathological findings: neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Tumours were found in many organs and/or tissues in all groups including the controls. In males from all groups, tumours of the testis were the most frequent, followed by those of the adrenal gland, thyroid gland, pituitary gland, haematopoietic organs, mammary gland, lung and pancreas. In females, the commonest tumours were those of the uterus, pituitary gland, haematopoietic organs, mammary gland, thyroid gland, adrenal gland and pancreas. Tumours were also detected in other organs/tissues from rats of all groups, but at lower incidences. Histologically, all the tumours observed in this experiment were similar to those known to occur spontaneously in F344 rats, as reported in previous studies (Goodman et al.,1979; Maekawa et al.,1983; Maita et al.,1987; Solleveld et al.,1984). None of the experimental groups showed a significant increase in the incidence of any specific tumours compared with the corresponding control value (chi-square and/or Fisher's test), and also no positive trend was noted in the occurrence of any tumour (trend analysis test; Pete et al., 1980). It was therefore concluded that calcium lactate had no carcinogenic activity in F344 rats when it was given continuously in the drinking-water for 2 years.
Other effects:
not specified
Key result
Dose descriptor:
NOAEC
Effect level:
50 000 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no calcium lactate-related carcinogenic activity observed
Key result
Critical effects observed:
no
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% purity) 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.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

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 the read-across partners, the target substance D-(-)-lactic acid does not warrant classification for carcinogenicity in accordance with CLP Regulation 1272/2008.

Additional information

There are no reliable studies for assessing the carcinogenic potential of the target substance, D-(-)-lactic acid itself. Therefore, available data from an oral carcinogenicity study conducted with a suitable read-across partner, calcium lactate, was used to assess the carcinogenicity of the target substance.

The long-term toxicity and carcinogenicity of calcium lactate, a food additive, was examined in F344 rats. Calcium lactate was given ad libitum 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.

Furthermore, 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.