2,3-dihydroxypropyl laurate

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

ORAL TOXICITIES OF LAURIC ACID AND CERTAIN LAURIC ACID DERIVATIVES.

Author:

Fitzhugh, O.G.

Year:

1960

Bibliographic source:

Toxicol Appl Pharmacol 2:59-67

Materials and methods

Principles of method if other than guideline:

2 year feeding study in rats

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

mixture of mono-, di-, and triglycerides of lauric acid

IUPAC Name:

mixture of mono-, di-, and triglycerides of lauric acid

Details on test material:

- Name of test material (as cited in study report): mixture of mono-, di-, and triglycerides of lauric acid
- Analytical purity: no data
- Composition of test material, percentage of components: 40-45% monoglyceride, 45% diglyceride, 8% triglyceride, 3-5% glycerine

Test animals

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: animals were individually housed in cages
- Diet: commercial rat biscuit, ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): every two weeks
- Mixing appropriate amounts with (Type of food): commercial rat biscuit

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

2 years

Frequency of treatment:

daily, 7 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
25%
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
12500 mg/kg bw/day (females)
Basis:
other: calculated according to ECHA, Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, Version:2, 2010

Doses / concentrations 3

Remarks:

Doses / Concentrations:
10000 mg/kg bw/day (males)
Basis:
other: calculated according to ECHA, Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, Version:2, 2010

No. of animals per sex per dose:

24

Control animals:

yes, plain diet

other: hydrogenated cottonseed oil at 25% in the diet

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the test period
- How many animals: 5 or more per group

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

Records of mortalities and abnormalities of the rats in regard to general physical condition, appearance, and behaviour were kept (no further details).

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

higher weight gain in groups treated with the test susbtance or hydrogenated cottonseed oil in comparison to the control group with plain diet (non adverse)

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

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

25%: slight excess of hepatic cell fatty change

Histopathological findings: neoplastic:

not specified

Details on results:

Records of mortalities and abnormalities of the rats with regard to general physical condition, appearance, and behaviour were kept (no further details).

CLINICAL SIGNS AND MORTALITY
After 2 years there were no significant differences in the total number of deaths that occurred in the dosing group in comparison with the groups fed either hydrogenated vegetable oil or the basal diet.

BODY WEIGHT AND WEIGHT GAIN
The groups of rats fed with the test compound were compared with the corresponding group fed with hydrogenated cottonseed oil. There was no significant difference in weight gains after 26 or 52 weeks. However, weight gains were greater than for the rats fed the basal diet which reflected the higher caloric intake.

GROSS PATHOLOGY
Autopsies revealed no gross pathology attributable (no further details).

HISTOPATHOLOGY: NON-NEOPLASTIC
Detailed histological examination of all three groups of rats revealed as the only effect a slight excess of hepatic cell fatty change as compared to the small amount in the controls fed with basal diet, but this excess was no greater than that observed in the group fed the hydrogenated cottonseed oil at the same dosage level. The same difference occurred to a lesser degree for intrahepatic bile duct proliferation (no further details).

Effect levels

1

Dose descriptor:

dose level:

Effect level:

25 other: %

Based on:

other: in diet

Sex:

male/female

Basis for effect level:

other: no adverse effects observed on clinical signs, mortality, body weight, gross pathology and histopathology.

2

Dose descriptor:

dose level:

Effect level:

12 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: calculated according to ECHA, Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, Version:2, 2010

3

Dose descriptor:

dose level:

Effect level:

10 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: calculated according to ECHA, Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, Version:2, 2010

Target system / organ toxicity

Critical effects observed:

not specified