Hexyl laurate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (test substance purity not specified, limited documentation, no ophthalmoscopic and neurobehavioural examination.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

test substance purity not specified, no ophthalmoscopic and neurobehavioural examination

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hexyl laurate

EC Number:

251-932-1

EC Name:

Hexyl laurate

Cas Number:

34316-64-8

Molecular formula:

C18H36O2

IUPAC Name:

hexyl dodecanoate

Details on test material:

- Name of test material (as cited in study report): Only trade name given
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 180 - 250 g
- Housing: The animals were kept in groups of 2 per cage (Makrolon III)
- Diet: The diet was offered via automatic feeding systems, Altromin R (powder), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24
- Humidity (%): 50 - 60

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
The mixtures were newly prepared each week.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

16 weeks

Frequency of treatment:

also: daily, 7 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10,000 ppm
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
ca. 800 mg/kg bw/day
Basis:
other: mean dose value as calculated using an approximate diet conversion factor for rats of 10 for young animals (1-10 weeks in the present study) and of 20 for old animals (11-16 weeks in the present study). No data on food intake available.

No. of animals per sex per dose:

10

Control animals:

other: liquefied margarine was added to the food

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Before and on completion of administration

BODY WEIGHT: Yes
- Time schedule for examinations: twice per week

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Time schedule: twice per week
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- 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

WATER CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule for examinations: twice per week

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Before and on completion of administration
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All animals
- Parameters examined: hemoglobin, red and white blood corpuscle count and differential blood picture count

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Before and on completion of administration
- Animals fasted: No data
- How many animals: All animals
- Parameters examined: glucose, albumin, calcium, urea, Serum Glutamate Oxalacetate Transaminase (SGOT) Serum Glutamate Pyruvate Transaminase.

URINALYSIS: Yes
- Time schedule for collection of urine: Before and on completion of administration
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined: pH value, specific gravity, glucose, protein, albumin, hemoglobin, bilirubin, ketone bodies, sediment.

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, at the end of the test, all animals were dissected, with a macroscopic assessment of the internal organs, these being weighed and preserved for histological investigations.

ORGAN WEIGHTS: Yes, liver, kidney, adrenal glands, spleen, testicles, heart, lungs, thyroid gland, thymus, brain, ovaries.

HISTOPATHOLOGY: Yes, the organs (paraffin sections) were stained with haematoxylin and eosin, with the exception of the brain which, according to Nissl, together with the liver, was stained not only with haematoxylin and eosin but also with Sudan III (frozen sections). The following organs were analyzed: the brain (the cerebrum, the cerebellum), the salivary gland, the thyroid gland with the parathyroid glands, the heart, the lungs, the liver, the spleen, the abdominal salivary gland, the gastro-intestinal tract, the lymph nodes, the kidneys, the suprarenals and reproductive glands, and in the female animals, the uterus.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

non adverse

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
During the period of application and at the end of the test, all animals were free of symptoms.

BODY WEIGHT AND WEIGHT GAIN
The body weights increased steadily and were comparable to the body weights of the control animals.

HAEMATOLOGY
No deviations in comparison with the control animals.

CLINICAL CHEMISTRY
No deviations in comparison with the control animals.

URINALYSIS
No deviations in comparison with the control animals.

ORGAN WEIGHTS
Organ weights were within the normal range.

GROSS PATHOLOGY
Under macroscopic examination, dissection revealed some small, limited pneumonic foci in some of the experimental animals and also in some of the controls. Apart from this, there were no findings of note in the macroscopic examinations.

HISTOPATHOLOGY: NON-NEOPLASTIC
The Kupffer cells in the liver were more adipose in some of the experimental animals than among the controls. The liver cells also showed an increased eosinophilia of certain cells in some of the experimental animals. The remaining organs showed the customary histological pictures for adult rats, consisting of bronchiolitis, slight alterations in the lung structure, varying activity of the thyroid glands, hemosiderosis of the spleen, milky albumen in the uriniferous tubules, slight inflammation of the bowel and occasionally marked sinus catarrh of the mesenteric lymph nodes.

Effect levels

Dose descriptor:

NOAEL

Effect level:

800 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: clinical observations, body weight gains, appearance of the feces, hematology, clinical chemistry, urinalysis, organ weights, histopathology

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The test substance is not considered to be toxic after repeated oral exposure. Changes in the liver and lung frequently occur in untreated ageing animals of both sexes and therefore, are not considered as adverse effects.