Methyl 12-hydroxyoctadecanoate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity, other

Remarks:

subcutaneous injections

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

The data is from a peer-reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Investigation of Fatty Acids and Derivatives for Carcinogenic Activity

Author:

D. Swern, R. Wieder, M. McDonough, D. R. Meranze, and M. B. Shimkin

Year:

1970

Bibliographic source:

CANCER RESEARCH 1970, 30:1037-1046

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: see Principles below

Principles of method if other than guideline:

A study of Methyl 12-hydroxystearate was conducted in mice to investigate the carcinogenic activity.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 12-hydroxyoctadecanoate

EC Number:

205-471-8

EC Name:

Methyl 12-hydroxyoctadecanoate

Cas Number:

141-23-1

Molecular formula:

C19H38O3

IUPAC Name:

methyl 12-hydroxyoctadecanoate

Test material form:

solid

Details on test material:

- Name of the test material: Methyl 12-hydroxyoctadecanoate- IUPAC name: Methyl 12-hydroxyoctadecanoate- Molecular formula: C19H38O3- Molecular weight: 314.5062 g/mol- Substance type: Organic- Smiles: C(CCCCCCCCCCC(=O)OC)(CCCCCC)O- Inchl: 1S/C19H38O3/c1-3-4-5-12-15-18(20)16-13-10-8-6-7-9-11-14-17-19(21)22-2/h18,20H,3-17H2,1-2H3

Test animals

Species:

mouse

Strain:

other: Swiss-Webster

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Carworth Inc., (New York, NY)- Age at study initiation: 2 months - Weight at study initiation: No data available- Fasting period before study: No data available- Housing: Mice were housed in groups of 8 in plastic shoe-box type cages in air-conditioned quarters with heat-treated absorbent cedar cubed wood as bedding in a controlled environment. - Diet (e.g. ad libitum): Teklad mouse diet pellets, ad libitum.- Water (e.g. ad libitum): Water, ad libitum- Acclimation period: One weekENVIRONMENTAL CONDITIONS- Temperature (°C): No data available- Humidity (%): No data available.- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): No data available

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

other: Tricaprylin

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was dissolved in tricaprylin prior to dosing. DIET PREPARATION- Rate of preparation of diet (frequency): No data available- Mixing appropriate amounts with (Type of food): No data available - Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): Tricaprylin- Concentration in vehicle: 0, 0.5 or 5 mg- Amount of vehicle (if gavage): No data available- Lot/batch no. (if required): No data available- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

40 weeks

Frequency of treatment:

Twice per week

Post exposure period:

14 months (from week 41 and onwards until sacrifice in month 24)

Doses / concentrations

Remarks:

Doses/Concentrations: 0, 0.5 or 5 mg

No. of animals per sex per dose:

Total: 45 miceControl: 15 females0.5 mg: 15 females5 mg: 15 females

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes- Time schedule: No data available- Cage side observations included: Mortality was observed. DETAILED CLINICAL OBSERVATIONS: Yes- - Time schedule: Twice weeklyBODY WEIGHT: Yes - Time schedule for examinations: All mice were weighed at the start of the experiments and at regular intervals throughout the ensuing period of observation of 18 to 24 months.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data availableFOOD EFFICIENCY: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data availableOPHTHALMOSCOPIC EXAMINATION: No data availableHAEMATOLOGY: No data availableCLINICAL CHEMISTRY: No data availableURINALYSIS: No data availableNEUROBEHAVIOURAL EXAMINATION: No data availableOTHER: No data available

Sacrifice and pathology:

GROSS PATHOLOGY: Yes Animals with tumors or those in poor condition were killed and autopsied. Suspected neoplasms and other grossly abnormal tissues were removed and fixed.HISTOPATHOLOGY YesAll diagnoses were based on histological examination of sections stained with hematoxylin and eosin.

Other examinations:

No data available

Statistics:

No data available

Results and discussion

Results of examinations

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, non-treatment-related

Description (incidence):

At 18 months, 6 out of 15 female mice treated with 0.5 mg of the target compound was alive, while 12 females were alive in the 5.0 mg-exposed group. At 6 months, 27 female mice out of 30 treated mice were alive.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No excessive weight losses or gains were found as compared with untreated control groups.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Methyl 12-hydroxystearate produced sarcomas in 8 of 27 mice.

Other effects:

not specified

Relevance of carcinogenic effects / potential:

Since Methyl 12-hydroxystearate produced sarcomas in 8 of 27 mice, the target chemical is classified as tentatively carcinogenic.

Effect levels

Dose descriptor:

LOAEL

Effect level:

0.5 other: mg

Based on:

test mat.

Sex:

female

Basis for effect level:

body weight and weight gain

histopathology: neoplastic

mortality

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

LOAEL was found to be 0.5 mg when female Swiss-Webster mice were exposed with Methyl 12-hydroxystearate by subcutaneous injection.

Executive summary:

A carcinogenic toxicity study of Methyl 12-hydroxystearate was performed in female Swiss-Webster mice. The mice were exposed to the target chemical at a dosage of 0, 0.5 or 5 mg by subcutaneous injection 2 times per week for 40 weeks. All mice were weighed at the start of the experiments and at regular intervals throughout the period of observation of 18 to 24 months (i.e. during the post exposure period). Mice were observed for the appearance of subcutaneous tumors where animals with tumors or those in poor condition were killed and autopsied. Suspected neoplasms and other grossly abnormal tissues were removed and fixed prior to histological examination. No excessive weight losses or gains were found as compared with untreated control groups. At 18 months, 6 out of 15 female mice treated with 0.5 mg of the target compound was alive, while 12 females were alive in the 5.0 mg-exposed group. In addition, Methyl 12-hydroxystearate produced sarcomas in 8 of 27 mice and is thus classified as tentatively carcinogenic. Hence, LOAEL was found to be 0.5 mg when female Swiss-Webster mice were exposed with Methyl 12-hydroxystearate by subcutaneous injection.