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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:
1989-03-08 to 1989-06-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it closely followed OECD 407 guidelines and was GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Oronite XS101
- Substance type: C10/C12 poly alpha olefin
- Physical state: Liquid
- Analytical purity: Not reported
- Lot/batch No.: KWA 88-01217
- Stability under test conditions: Considered stable
- Storage condition of test material: Ambient temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories (Portage, Michigan)
- Age at study initiation: 41 days old
- Weight at study initiation: Males: 161 to 204 grams; Females: 133 to 169 grams
- Housing: Individually in hanging stainless steel wire-bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23
- Humidity (%): 46 to 76%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light


IN-LIFE DATES: From:1989-04-06 To:1989-06-14

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: Test compound was mixed weekly by weight per volume in peanut oil.

VEHICLE
- Justification for use and choice of vehicle (if other than water): Not reported
- Concentration in vehicle: Not reported
- Amount of vehicle (if gavage): Adjusted weekly to body weight
- Lot/batch no. (if required): Not reported
- Purity: Not reported
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples were found to be stable and homogeneous. Doses were generally within 10% of the nominal concentration.
Duration of treatment / exposure:
29 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 200, 500, or 1000 mg/kg/day
Basis:
other: nominal in oil
No. of animals per sex per dose:
6 animals per sex per dose
Control animals:
yes
Details on study design:
- Dose selection rationale: Based on a pilot 2 week repeat dose toxicity study
- Rationale for selecting satellite groups: Not reported
- Post-exposure recovery period in satellite groups: 2 weeks

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations included viability checks.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily for changes in skin, fur, eyes, mucus membrane, respiratory system, autonomic and central nervous system, somatomotor activity, and behavioural patterns; Pupil response was checked on day 0 and then weekly


BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, twice weekly, and once weekly during recovery period


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


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: Yes


WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: Terminal sacrifice
- Anaesthetic used for blood collection: Yes (sodium pentabarbitol)
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in Table 1 were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Terminal sacrifice
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in Table 2 were examined.


URINALYSIS: Yes
- Time schedule for collection of urine: Overnight prior to study termination
- Metabolism cages used for collection of urine: No data
- Animals fasted: Yes
- Parameters checked in Table 3 were examined.


NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, included external surfaces; all orifices; the cranial, thoracic, and abdominal cavities
HISTOPATHOLOGY: Yes (see table 4)
Other examinations:
The following organs were weighed: Brain, kidneys, adrenals, and testes/ovaries.
Statistics:
A one-way analysis of variance and Dunnett's test on continuous variables in the main study. An analysis of variance followed by a Student's t-test was used on the data from the recovery groups. Differential white blood cell counts were analysed using a non-parametric Kruskal Wallis ANOVA followed by 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:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
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:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Although there were some statistically significant effects, none of the effects were considered toxicologically significant or treatment-related.

Applicant's summary and conclusion

Conclusions:
The test compound did not cause any toxicologically significant or treatment-related results. Therefore, the NOAEL is 1000 mg/kg/day.
Executive summary:

In a repeated dose oral toxicity study, Oronite XS101 was administered to 6 Sprague-Dawley rats/sex/dose at dose levels 0, 200, 500, or 1000 mg/kg bw/day for 29 days. A recovery group (6 rats), dosed with 0 or 1000 mg/kg/day of the test substance, was observed for two weeks post-dosing. Each animal was observed daily for toxicological changes one hour post-dosing. Blood analysis, urinalysis, and necropsies were conducted post-sacrifice. The test conditions complied with the guideline requirements for this study type and the statistical methods used were appropriate.

No mortality, compound-related systemic toxicity or pathological changes were observed in the study or recovery groups at the limit dose of 1000 mg/kg ORONITE XS 101. Statistically significant changes occurred in food consumption, haematology, serum chemistry, and organ weights; however, none of the changes were considered to be of toxicological significance. No LOAEL could be determined due to lack of any affects. The NOAEL is 1000 mg/kg/day.

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

This study will influence the DNEL.