Alcohols, C6-24 and C6-24-unsatd., distn. residues

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Orientating repeated dose toxicity study, conducted prior to the implementation of currently acknowledged testing guidelines such as the OECD TG 408, and according to an in-house protocol. Even if the study conduct does not fulfill current requirements, suitable basic data were given.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Materials and methods

Principles of method if other than guideline:

The study was an orientating repeated dose toxicity study conducted according to an in house protocol, prior to the implementation of currently acknowledged testing guidelines such as the OECD TG 408. A group of 20 male and 20 female Wistar rats received a single daily dose of 250 mg/kg bw/day of the test material by gavage (vehicle: 1% CMC), five days a week, for 84 days. A group of 20 male and 20 female rats were kept as controls and treated with the vehicle only. Additionally, satellite groups consisting of 10 males and 10 females per group were added. The animals were observed/examined for mortality, clinical symptoms, changes in body weight and body weight gain, changes in haematology, clinical chemistry and urine, changes in organ weights, gross pathology and histopathology.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C6-24 and C6-24-unsatd., distn. residues

EC Number:

310-079-6

EC Name:

Alcohols, C6-24 and C6-24-unsatd., distn. residues

Cas Number:

102242-48-8

Molecular formula:

Not available due to the complexity of the substance

IUPAC Name:

Alcohols, C6-24 and C6-24-unsatd. even numbered, distn. residues

Details on test material:

- Name of test material (as cited in study report): Pernil RU
- Chemical designation: 18:1 fatty alkohol, unsaturated, distillation residue
- Physical state: brown liquid
- No more details provided

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mus-Ratus Breeder, Brunntal, Germany
- Age at study initiation: approx. 40 days
- Weight at study initiation: males, 130 g; females, 118 g
- Housing: males were housed in groups of 2 to 3 animals and females in groups of 5 per cage
- Diet: Altromin pelleted diet (Altromin R- Pressling-Haltungsdiät Nr. 1324), ad libitum
- Water: tap water, ad libitum
- Acclimatization: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 50 - 55
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1%

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS
The test solution consisted of an emulsion of the test material using 1% CMC as vehicle and was prepared freshly each day.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

12 - 13 weeks

Frequency of treatment:

5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
250 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

The test group consisted of 20 male and 20 female animals; additionally, 10 animals of each sex were added as satellite group.
The control group consisted similarly of 20 + 10 animals per sex.
An additional control group consisted of 20 animals per sex; these animals were used for blood sampling.

Control animals:

yes, concurrent vehicle

Details on study design:

Each animal of the test group received a single dosage of the test solution by gavage on 5 days per weeks. Similarly, each animal of the vehicle control groups received a single dosage of 1% CMC by gavage. The application volume was 10 mL/kg bw.

Examinations

Observations and examinations performed and frequency:

CLINICAL PARAMETERS
The rats were checked daily for mortality and clinical symptoms. The body weights were recorded once a week. No further parameters were considered.
HAEMATOLOGY AND CLINICAL CHEMISTRY
At test initiation, blood samples were collected from the additional control group, and at test ending, blood samples were collected from all animals. Following haematological parameters were considered:leukocyte count (WBC), erythrocyte count (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and differential blood count. Referring to clinical chemistry, following parameters were considered: sodium, potassium, urea, calcium, alkaline phosphatase, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), glucose, and total protein.
URINALYSIS
At test initiation, urine was collected from the additional control group, and at test ending, urine was collected from all animals. For this purpose, the animals were placed individually in metabolism cages for 24 hours and received feed and water ad libitum. Following parameters were considered: volume, pH, protein, glucose, ketones, urobilinogen, blood, specific gravity, and sediment.
The amount of excreted feces during holding of the animals in the metabolism cages was recorded.

Sacrifice and pathology:

NECROPSY
At test ending, all animals were sacrificed for the purpose of necropsy. The organs were macroscopically examined for gross pathological lesions or changes. The main organs were collected for determination of absolute weight. Following organs were fixed in formalin for the purpose of histopathological examination:
eyes, tongue, salivary glands, oesophagus, trachea, lungs, aorta, heart, lymph nodes, thymus, liver, pancreas, spleen, kidneys, fore stomach, glandular stomach, duodenum, colon, urinary bladder, testes, epididymides, adrenals, seminal vesicle, prostate, uterus, ovaries, thyroid, parathyroid, brain, skeletal muscle, skin, sciatic nerve
These organs/tissues were paraffin embedded, sectioned, and the sections were stained for purpose of light microscopy with hematoxylin and eosin. The organs and tissues of 6 animals per sex and group were finally subjected to histopathological examination.

Statistics:

Calculation of means and standard deviations, statistical assessment of the significance by means of the t-test and the U-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):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

changes in GPT and GOT in treated females only

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:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

MORTALITY AND CLINICAL SYMPTOMS
Neither mortalities nor clinical symptoms indicating toxicity were noticed.
BODY WEIGHT
The body weight and body weight gain of the treated males over the testing period was similar to control, and thus, showed not treatment-related changes. For the treated females, a weak and transient decrease in body weight was noticed on week 11 of treatment, but was not considered to be due to treatment.
HAEMATOLOGY
At test ending the haematocrit value for the treated male animals was significantly increased compared to control and both, treated males and females showed an increase in MCV. Nevertheless, the measured values still were within the range considered as normal for the strain used and the age of the animals. Thus, the findings were not considered to be adverse effects due to treatment.
CLINICAL CHEMISTRY
The treated female animals showed a weak increase in alanine aminotransferase (GPT), which however was not to be considered as an adverse effect. In five treated females, a clear increase in aspartate aminotransferase (GOT) was noticed, which was considered to be treatment-related. The alkaline phosphase (AP) also was significantly increased in the treated female animals, however, this was almost due to one animal showing a high AP level. The alkaline phosphase (AP) also was increased in the treated males, but the finding was considered to be incidental and not due to treatment since the measured values did not indicate that the finding was adverse. The treated female animals further showed a significant decrease in sodium level.
URINALYSIS
In both, the treated and control groups, some animals of both sexes showed slight increased protein content and ketones in the urine, and occasionally blood cells were found. These findings were incidental and related to the strain used and the age of the animals; they were not treatment-related.
FECES
No difference in excretion was noticed between treated and control animals.
NECROPSY
At necropsy, neither organ weighing nor the gross and histological examination of organs and tissues revealed any treatment-related changes.
In fact, it was reported that at necropsy all animals showed signs of respiratory infection such as tracheitis. Furthermore, it was noticed that in the liver of nearly all animals, signs of lysis (almost low grade) of the hepatocytes were observed, and more often in females, intrahepatocytic pigment accumulation also was seen. In addition, some animals further displayed subcapsular lymphohistiocytic granuloma. Nevertheless, all these findings were equally distributed between treated and control animals, and thus, no relationship to treatment could be evidenced.

Effect levels

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no clear treatment-related effects could be evidenced at the dose level of 250 mg/kg bw/day

Target system / organ toxicity

Critical effects observed:

not specified