Fatty acids, tallow, calcium salts

Carcinogenicity

Description of key information

The 2-year oral carcinogenic study in rats with sodium oleate administered in the drinking water (no guideline specified) gave a NOAEL of 5% sodium oleate in the water, the maximum concentration administered. No evidence of increased incidence of tumours was observed following treatment. On the basis of the long history of safe use of fatty acid soaps in greases, the substances in the category are not considered to be carcinogens.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP status not known, guideline study, published in a regulatory document. Only summary of study is available, limitations in design and/or reporting but otherwise adequate for assessment.

Principles of method if other than guideline:

- Method: 2.5 and 5.0 % sodium oleate in drinking water was administered orally to 50 male and 50 female rats for 108 weeks.

GLP compliance:

not specified

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Age: 7 weeks at test initiation

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

- Dose concentration: 2.5 and 5.0 % in drinking water
- Control: Distilled water only

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data reported

Duration of treatment / exposure:

- Duration of exposure: 108 weeks

Frequency of treatment:

No data reported

Post exposure period:

No data reported

Remarks:

Doses / Concentrations:
2.5 %
Basis:
nominal in water

Remarks:

Doses / Concentrations:
5.0 %
Basis:
nominal in water

No. of animals per sex per dose:

- Number of animals: 50 male and 50 female

Control animals:

yes, plain diet

Details on study design:

No data reported

Positive control:

No data reported

Observations and examinations performed and frequency:

No data reported

Sacrifice and pathology:

No data reported

Other examinations:

No data reported

Statistics:

No data reported

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Bodyweight gain was slightly reduced in males but not in females.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

effects observed, treatment-related

Description (incidence and severity):

Water consumption was slightly depressed in females but not in males.

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

A slight depression in the serum bilirubin of males in the 5.0 % treatment group was the only statistically significant finding (p<0.05) in the serum and urine analyses and in the haematological determinations of treated and control groups.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

A slight depression in the serum bilirubin of males in the 5.0 % treatment group was the only statistically significant finding (p<0.05) in the serum and urine analyses and in the haematological determinations of treated and control groups.

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

A slight depression in the serum bilirubin of males in the 5.0 % treatment group was the only statistically significant finding (p<0.05) in the serum and urine analyses and in the haematological determinations of treated and control groups.

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

In the 5 % treatment group, the mean weights of the liver of males and of the heart, pancreas and adrenals of females were significantly lower (p<0.05) than the respective controls, while the weight of the thymus in the females was significantly higher.

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

Tumours developed in various organs but there was no significant difference between their incidence in oleate-treated and control rats.

Details on results:

- Pancreatic tumours: A significant difference between the incidence in oleate-treated and control rats of pancreatic tumors was observed (0 % - 0/41 M, 1/43 F; 2.5 % - 4/40 M, 1/39 F; 5 % - 7/45 M, 1/45 F). However, there was an unusual absence of pancreatictumors in the control rats and the incidence of pancreatic tumors in the treated rats was considered to be within the normal background level for this strain of rat.

Relevance of carcinogenic effects / potential:

The weight of evidence approach, including consideration of the historical range of pancreatic tumors, indicates that sodium oleate orally administered to rats does not induce tumors.

Dose descriptor:

NOEL

Effect level:

5 other: % in drinking water

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: The weight of evidence approach, including consideration of the historical range of pancreatic tumours, indicates that sodium oleate orally administered to rats does not induce tumours.

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Conclusions:

Under the test conditions, the carcinogencity NOEL for sodium oleate in rats is 5 % in drinking water.

Executive summary:

The weight of evidence approach, including consideration of the historical range of pancreatic tumors, indicates that sodium oleate orally administered to rats does not induce tumors. Under the test conditions, the carcinogencity NOEL for sodium oleate in rats is 5 % in drinking water. The carcinogenicity to rats was determined in a two year oral study (Hiasa et al. 1985) in which 50 male and 50 female rats were given 2.5 % and 5.0 % sodium oleate in drinking water for 108 weeks. Only a summary of the study is available but the information is taken from a peer reviewed article and can be considered adequate for use for this endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

Study duration:

chronic

Species:

rat

Quality of whole database:

Limited. The study is taken from a review documents (HERA 2002) citing a published test. No guideline was stated but a standard procedure was used. The data are considered reliable and suitable for use for this endpoint since they are peer-reviewed prior to publication.

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

Not classified for carcinogenicity. No treatment-related increase in tumour incidence

Additional information

The substances in the category are considered to be similar on the basis that they have common structures of a calcium ion varying only by the length of the fatty acid chain and the presence of unsaturated and/or hydroxyl functional groups. As a result it is expected that the substances will have similar, predictable properties. REACH Annex V, Entry 9, groups fatty acids and their potassium, sodium, calcium and magnesium salts, including C6 to C24, predominantly even-numbered, unbranched, saturated or unsaturated aliphatic monocarboxylic acids. Provided that they are obtained from natural sources and are not chemically modified, the substances included in REACH Annex V, Entry 9 are exempt from registration, unless they are classified as dangerous (except for flammability, skin irritation or eye irritation) or they meet the criteria for PBT/vPvB substances. The metal fatty acid substances in the category are therefore not expected to be hazardous. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the carcinogenicity properties are expected to be predictable across the category.

Since REACH Annex V groups together calcium, potassium, sodium and magnesium salts of C6 to C24 fatty acids as being potentially exempt from registration, these metal cations are therefore not considered to contribute to any health hazard. On this basis, relevant published or proprietary data on any potassium, sodium or magnesium salt within the fatty acid category range of C14 to C22 can be used to read across to the calcium salts of C14-C22 fatty acid category.

Fats and oils are commonly used as controls and vehicle diluents/solvents in long term toxicity studies, e.g. corn (mazola) oil. On this basis they are considered not to possess carcinogenic activity.

A two-year carcinogenicity study in rats with sodium oleate (C18 unsaturated) administered in drinking water showed no significant difference between the incidence of tumours between the treated and control groups, and it was concluded that this substance did not exhibit tumourigenic potential in rats under the conditions of the test.

On the basis of long history of safe use of fatty acid soaps in greases, the substances in the category are not considered to be carcinogens.

Justification for selection of carcinogenicity via oral route endpoint:
A valid carcinogenicity study on sodium oleate (C18) that is relevant to the calcium salts of C14-C22 fatty acids and the results can be read across to the category members.