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Toxicological information

Repeated dose toxicity: oral

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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

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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
25%
Basis:
nominal in diet
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
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

open allclose all
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.
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
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

Applicant's summary and conclusion