Fatty acids, tall-oil, Bu esters

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study with acceptable restrictions (analytical purity of test substance not specified; no urine and neurobihavioural examinations).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: 87/302/EWG, Annex, Part B

Deviations:

yes

Remarks:

analytical purity of test substance not specified; no urine and neurobihavioural examinations

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

analytical purity of test substance not specified; no urine and neurobihavioural examinations

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany.
- Age at study initiation: ca. 40 days
- Weight at study initiation: 143 - 168 g (153.4 g mean body weight)
- Housing: 2-3 animals per Makrolon Type III cage on softwood bedding (ARWI-Center, Essen, Germany).
- Diet: pelleted Altromin 1324, Altromin, Lage, Germany, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 48-60
- Air changes (per hr): nodata, 80-490 Lux (the cages were rotated weekly in the rack)
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: March 28th, 1989 - April 28th, 1989

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
The application volume was 5 mL/kg bw.
The dosing solutions were prepared daily immediately before application.
The following concentrations were prepared: 100 mg/ kg bw /day: 2%; 500 mg/kg bw/day: 10%, 1000 mg/kg bw/day: 20%
The total number of applications was 23 or 24 (depending on the day of necropsy).

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

28 days

Frequency of treatment:

once daily, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 500 and 1000 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Rationale for selecting satellite groups: Additionally 5 male and 5 female animals per dose were dosed with 0 and 1000 mg/kg/day to determine the reversibility of possible compound-related findings (recovery group).
- Post-exposure recovery period in satellite groups: 27 days

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice a day, 5 days a week for mortality and clinical signs

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: Yes
- Time schedule for examinations: weekly

WATER CONSUMPTION: Yes
- Time schedule for examinations: weekly

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: at study termination
- Dose groups that were examined: control group and highest dose group

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at study termination
- Anaesthetic used for blood collection: not reported
- Animals fasted: No data
- How many animals: all animals
- Parameters checked: RBC, HCT, MCV, HGB, WBC, PLT, differential blood count (banded neutrophils, segmented neutrophils, lymphocytes, eosinophils, monocytes, basophils, myelocytes).

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at study termination
- Animals fasted: No data
- How many animals: all animals
- Parameters checked: Urea, Creatinine, Sodium, Potassium, Glucose, Calcium, ASAT, ALAT, AP, gamma-GT, Bilirubin, Chloride, total protein, total Cholesterol.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

ORGAN WEIGHTS:
Absolute and relative organ weights were determined for the following:
Brain, testes, heart, liver, spleen, adrenals, kidneys, thymus.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all animals
HISTOPATHOLOGY: Yes, animals of the control and highest dose group.
Following organs were examined microscopically:
Aorta thoracica, eyes, large and small intestinum, glandular stomach, cerebrum, urinary bladder, skin, heart, testes, pituitary, cerebellum, liver, trachea, lung, maxillary lymph nodes, mesenterial lymph nodes, spleen, epididymides, adrenal, peripheral nerv, kidney, ovaries, pancreas, prostate, vesicular gland, thymus, salivary gland, oesophagus, sceletal muscle, thymus, uterus, stomach, tongue.

Statistics:

T-tests according to Sachs and Dunnett; steel-test

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:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

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:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
All doses applied were tolerated without lethality. No symptoms were noted as compound-related effects.

BODY WEIGHT AND WEIGHT GAIN
The total body weight gain was comparable to control in all male and female test groups.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
The mean food consumption of all groups was comparable to the control.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
The mean water intake of the male groups 2 and 4 showed a slight increase which was not considered to be compound-related.

OPHTHALMOSCOPIC EXAMINATION
The examination of the eyes by slit lamp microscope showed no compound-related effects.

HAEMATOLOGY
The haematological examinations showed no compound-related effects.

CLINICAL CHEMISTRY
The clinical chemistry showed no compound-related effects.

ORGAN WEIGHTS
The absolute and relative organ weights showed no compound-related effects.

GROSS PATHOLOGY
The macroscopical examination of the organs showed no compound-related effects. Some observations like hydrometra, hydronephrosis,
discolouration of the thymus and one suspicion of hydrocephalus internus were considered to be spontaneous.

HISTOPATHOLOGY: NON-NEOPLASTIC
The histological examination of the organs of all groups displayed no compound-related effects.
The histological examination of the organs of the recovery group was not performed, because in the main groups no target organ was evaluated.

Effect levels

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

According to the described study, a daily administration of 2-Ethylhexylstearate up to 1000 mg/kg bodyweight/day for 28 days caused no cumulative-systemic toxicity to rats. The NOAEL was found to be 1000 mg/kg bw/day.

Executive summary:

2-Ethylhexylstearate was tested for systemic toxicity at repeated doses of 0 (group 1), 100 (group 2), 500 (group 3) and 1000 (group 4) mg/kg body weight/day. The compound was administered daily by gavage over a period of 28 days. 10 male and 10 female rats were used for each dose. In addition to the groups 1 and 4, 5 male and 5 female animals were used to determine the reversibility of possible compound-related findings (recovery group).

 

All doses applied were tolerated without lethality. No symptoms were noted as compound-related effects. The mean food consumption of all groups was comparable to the control. The mean water intake of the male groups 2 and 4 showed a slight increase which was not considered to be compound-related. The total body weight gain was comparable to control in all male and female test groups. The haematological examinations showed no compound-related effects. The clinical chemistry showed no compound-related effects. The examination of the eyes by slit lamp microscope showed no compound-related effects. The absolute and relative organ weights showed no compound-related effects. The macroscopical examination of the organs displayed no compound-related effects. Some observations like hydrometra, hydronephrosis, discolouration of the thymus and one suspicion of hydrocephalus internus (animal No. 67) were considered to be spontaneous. The histological examination of the organs of all groups displayed no compound-related effects.The histological examination of the organs of the recovery group was not performed, because in the main groups no target organ was evaluated.