12-hydroxystearic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is well documented, meets generally accepted scientific principles and is acceptable for assessment.

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Hydroxystearic acid deposition and metabolism in rats fed hydrogenated castor oil

Author:

Binder RG, Booth AN, Robbins DJ and Fuller G

Year:

1970

Bibliographic source:

Lipids 5(10):832-837

Materials and methods

Principles of method if other than guideline:

90 young male rats were fed diets containing either 20% corn oil (controls), 1% hydrogenated castor oil and 19% corn oil or 10% hydrogenated castor oil and 10% corn oil. After eight weeks of feeding, half of the groups of rats on hydrogenated castor oil diets were given the corn oil diet until the end of the experiment.

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Castor oil, hydrogenated

EC Number:

232-292-2

EC Name:

Castor oil, hydrogenated

Cas Number:

8001-78-3

IUPAC Name:

8001-78-3

Details on test material:

- Name of test material (as cited in study report): Hydrogenated castor oil
- Physical state: solid (granulated powder)
- Composition of test material, percentage of components: 12-hydroxystearic acid: 86.5%; non-oxygenated acids: 10.3%; 12-ketostearic acid: 3.2%

Test animals

Species:

rat

Strain:

other: Slonaker (substrain of Wistar strain)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:43-83 g (main study) no data in the feeding trial
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: Unchanged in the first feeding trial. Mixed with corn oil in the second feeding trial and the 16 wk study

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: In the first feeding trials hydrogenated castor oil was mixed directly into the diets. In the second feeding trial and in the main 16 wk study, hydrogenated castor oil was melted and mixed with corn oil, then blended with the diet.
- Mixing appropriate amounts with (Type of food): Purina Laboratory Chow
VEHICLE
- Concentration in vehicle: In the second preliminary study: 1, 5 and 10% hydrogenated castor oil. In the main study: 1% and 10% hydrogenated castor oil.
- Amount of vehicle (if gavage): In the second preliminary study: 19, 15 and 10% corn oil, respectively. In the main study: 19% and 10% corn oil, respectively.
- Other: After 8 wk of feeding in the main study half of the groups of rats on the hydrogenated castor oil diets was given the corn oil diet until the end of the experiment.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The fatty acids of the test sample (hydrogenated castor oil) contained: 12-hydroxystearic acid: 86.5%; non-oxygenated acids: 10.3%; 12-ketostearic acid: 3.2% .

Duration of treatment / exposure:

The two feeding trials: 90 d
The main study: 16 wk

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0%
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1%
Basis:
nominal in diet

Doses / concentrations 3

Remarks:

Doses / Concentrations:
5%
Basis:
other: nominal in diet in the first and second feeding trial

Doses / concentrations 4

Remarks:

Doses / Concentrations:
10%
Basis:
nominal in diet

Doses / concentrations 5

Remarks:

Doses / Concentrations:
20%
Basis:
other: nominal in diet in the first feeding trial

No. of animals per sex per dose:

No data

Control animals:

other: yes, concurrent no treatment in the 2 feeding trials and concurrent vehicle (castor oil) in the 16 wk study

Details on study design:

- Dose selection rationale: two preliminary studies were conducted for selecting the test doses. The only abnormality noted was a reduced growth rate in the first preliminary study at the concentrations 10% and 20% hydrogenated castor oil. The same observation was made in the second preliminary study at a concentration of 10% hydrogenated castor oil.

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: Yes
- Time schedule for examinations: Weekly records


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data


FOOD EFFICIENCY: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

CLINICAL CHEMISTRY: Yes


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: yes
HISTOPATHOLOGY: yes

Other examinations:

Microscopic pathological examination

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

BODY WEIGHT AND WEIGHT GAIN: In the first feeding trial a reduced growth rate was observed in rats fed diets containing 10% of hydrogenated castor oil. The test substance is probably poorly digested because of its high melting point, so poor body weight gains may due to the lower caloric density of the diets containing 10% test substance or more.
After mixing the diets with corn oil in the second feeding trial the growth of rats fed 10% diet seemed equivalent to that of rats on other diets.

ORGAN WEIGHTS: No adverse effects observed.

HAEMATOLOGY: No adverse effects observed.

HISTOPATHOLOGY: NON-NEOPLASTIC: No adverse effects observed.

Effect levels

Dose descriptor:

NOAEL

Effect level:

5 000 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: Treatment-related adverse effects were not observed, apart from reduced growth rate in rats given 10% test substance in their diet

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Under the test conditions of the two feeding trials (90 d) and the 16 wk main study, hydrogenated castor oil caused no adverse effects except reduced growth in rats given 10% test substance. Therefore 10% (i.e., ca 5,000 mg/kg bw/day)per day was selected as the NOAEL for this study.

Executive summary:

A 16 wk study, including two feeding trials (90 d, respectively), were conducted to investigate the subchronic oral toxicity of the test substance in Wistar rats (Slonaker substrain of Wistar strain).

In the 90 d subacute toxicity feeding trial, weanling female rats (three per group) were fed diets containing 0-20% test substance. Prior to autopsy, blood samples were taken for hematological study. At autopsy,organ weights were recorded and numerous tissues were preserved for microscopic pathological examination.

The trial was repeated but the test substance was dissolved in corn oil before being added to the diet.

In the main study, of 16 wk, a total of 90 young albino male rats were segregated into groups of six. Weekly records of individual body weights and food intake by group were maintained. The diet fed contained either 20% corn oil (control diet), 1% test substance and 19% corn oil or 10% test substance and 10% corn oil. After eight wk of feeding, half of the groups of rats on diets containing the test substance were given the corn oil diet until the end of the experiment at 16 wk. On the fifth wk, three rats fed 1% and 10% test substance were autopsied. At eight weeks and twelve weeks, sets of three rats on the corn oil diet were also autopsied.

Treatment-related effects were not observed, except for reduced growth rate in rats given 10% test substance in their diet. A No Observed Effect Level (NOAEL) was therefore established to 10% (ca. 5,000 mg/kg bw/day).