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Toxicological information

Repeated dose toxicity: oral

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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:
key study
Study period:
1994-12-05 to 1995-01-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it was GLP compliant and was conducted according to OECD 407 guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
Animals not fasted prior to blood collection
GLP compliance:
yes
Limit test:
yes

Test material

Constituent 1
Reference substance name:
151006-62-1
Cas Number:
151006-62-1
IUPAC Name:
151006-62-1
Details on test material:
This substance is very similar with regard to health endpoints to the substance being registered.
- Name of test material (as cited in study report): Alkane 4
- Substance type: Poly alpha olefin (1-dodecene trimer, hydrogenated)
- Physical state: Liquid
- Analytical purity: Not reported
- Lot/batch No.: C1527-04-4
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature
- Other: Clear colourless 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 (U.K.) Ltd
- Age at study initiation: 6 weeks
- Weight at study initiation: Male - 149-179 grams; Female - 125-170 grams
- Fasting period before study: Not fasted
- Housing: Groups of 5 by sex in polypropylene grid floor cages
- Diet (e.g. ad libitum): Rat and Mouse SQC Expanded Diet No. 1 (Special Diets Services Limited, Essex, U.K.) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): 15 per hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light


IN-LIFE DATES: From: 1994-12-05 To: 1995-01-31

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: The test material was administered daily by gavage using a stainless steel cannula attached to a disposable plastic syringe.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg bw
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1000 mg/kg bw
Basis:
actual ingested
Remarks:
Doses / Concentrations:
0 mg/kg bw (Satellite)
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1000 mg/kg bw (Satellite)
Basis:
actual ingested
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes
Details on study design:
- Dose selection rationale: Not reported
- Rationale for animal assignment (if not random): Random assignment
- Rationale for selecting satellite groups: Not reported
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random): Not reported

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Work week - Prior to dosing and one to five hours post-dosing; Weekend - Prior to dosing and 1 hour post-dosing; Satellite groups - Twice daily on weekdays and once daily on weekends

BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, 7, 14, 21, and 28 and for satellite groups on days 35 and 42 as well.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption was recorded for each cage group at weekly intervals throughout the study.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No

FOOD EFFICIENCY: No

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Water intake was observed daily, for each cage group, by visual inspection of the water bottles for any overt changes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination (Day 28) for animals in dose groups 1 and 2 and on day 42 for satellite groups
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: All animals
- Parameters checked in table [No.1] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At termination (Day 28) for animals in dose groups 1 and 2 and on day 42 for satellite groups
- Animals fasted: No
- How many animals: All animals
- Parameters checked in table [No.2] were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: Organ weights for adrenals, brain, gonads, heart, kidneys, liver, pituitary, and spleen were determined post termination
Sacrifice and pathology:
GROSS PATHOLOGY: Yes. All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded.
HISTOPATHOLOGY: Yes. Although the required tissues were preserved only the adrenals, heart, kidneys, liver, spleen, testes, and macroscopic lesions were examined histologically.
Statistics:
Data were processed t o give group mean values and standard deviations where appropriate. Absolute and relative organ weights, haematological and blood chemical data were analyzed by one way analysis o f variance incorporating 'F-max' test for homogeneity of variance. Data showing heterogeneous variances were analyzed using Kruskal-Wallis non-parametric analysis of variance and Mann Whitney 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):
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:
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
No mortality or clinically observable signs of toxicity was observed in male or female rats in the control or treatment groups through the study period.

BODY WEIGHT AND WEIGHT GAIN
All animals showed normal gain in body weight throughout the study period. Body weight gain in test animals was comparable with that seen
in controls.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
There was no adverse effect on food consumption during the study. Food efficiency in test animals was comparable with that seen in controls.

FOOD EFFICIENCY
Not determined

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Daily visual inspection of water bottles revealed no overt intergroup differences.

OPHTHALMOSCOPIC EXAMINATION
Not determined

HAEMATOLOGY
There were no treatment-related changes in the haematological parameters measured. A statistically significant increase in group mean neutrophil and eosinophil count was detected for treated females in comparison with controls. Individual values were within the normal range for rats of this strain and age, with the exception of one female. This animal showed a general increase in leukocyte fractions but, as an isolated finding, this was considered to be unrelated to test material toxicity.

CLINICAL CHEMISTRY
There were no treatment-related changes in the blood chemical parameters measured. No statistically significant differences were detected between test or control groups.

URINALYSIS
Not determined

NEUROBEHAVIOUR
Not determined

ORGAN WEIGHTS
There were no changes in the organ weights measured which could be considered attributable to treatment with the test material. Treated females showed a statistically significant reduction in group mean relative liver weight in comparison with controls. All values were within the normal range for rats of this strain and age and with no morphological changes to support an effect in this organ the reduction was considered to be of no toxicological significance.

GROSS PATHOLOGY
No treatment-related macroscopic abnormalities were detected.

HISTOPATHOLOGY: NON-NEOPLASTIC
No treatment-related changes were observed.


Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: Based on the lack of systemic toxicity or adverse clinical effects observed at this dose level.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
There were no indications of toxicity based on clinical findings, mortality rates, change in food and water consumption, body weight changes, clinical chemistry examination, haematology, necropsy, change in organ weights, or histopathology. Therefore, the NOAEL for this study is 1000 mg/kg/day.
Executive summary:
In a repeated dose oral toxicity study, Alkane 4 was administered to 5 Sprague-Dawley CD rats/sex/dose at dose levels 0 or 1000 mg/kg bw/day for 28 consecutive days. An additional 2 satellite groups (0 and 1000 mg/kg/bw/day) were also maintained without treatment for a further fourteen days following the end of the dosing period.

 

There were no compound related effects in mortality, clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, or gross and histologic pathology. Thus the NOAEL is 1000 mg/kg/day.

 

This study received a Klimisch score of 1 and is classified as reliable without restrictions because it was GLP compliant and was conducted according to OECD 407 guidelines.