Branched hexatriacontane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-09-29 to 1993-10-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restriction because although the study closely adhered to OECD 407 guidelines, haematology, clinical biochemistry, and neurobehavioral assessments were not conducted.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

Haematology, clinical chemistry, and neurobehavioural tests were not performed

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dec-1-ene, homopolymer, hydrogenated Dec-1-ene, oligomers, hydrogenated

EC Number:

500-183-1

EC Name:

Dec-1-ene, homopolymer, hydrogenated Dec-1-ene, oligomers, hydrogenated

Cas Number:

68037-01-4

IUPAC Name:

Dec-1-ene, homopolymer, hydrogenated

Details on test material:

- Substance type: 1-Decene, homopolymer, hydrogenated
- Physical state: Liquid
- Analytical purity: Not reported
- Composition of test material, percentage of components: Not reported
- Lot/batch No.: 2309
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported
- Storage condition of test material: Cool temperature (not to exceed 15 decrees Celsius) in the dark
- Other: Identity, strength, composition, and stability were stated to be the responsibility of the sponsor.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Limited, England
- Age at study initiation: 35 to 42 days old
- Weight at study initiation: Not reported, but stated to weight between 59 and 76 grams the day after arrival
- Housing: Five per stainless steel cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


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


IN-LIFE DATES: From:1993-09-29 To: 1993-10-28

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with ground diet
- Storage temperature of food: 21 degrees Celsius

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Homogeneity was tested on the lowest and highest concentration by taking 6 samples from different positions in the mixer. The dose formulation was determined to be homogeneous. Stability was determined on the highest and lowest concentrations after 1 and 2 weeks. The dose formulation was determined to be stable for at least 2 weeks. Dietary concentrations were analysed during week 1 and 4. Dose formulations were within 10% of nominal dose.

Duration of treatment / exposure:

29 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 8000; 20,000; or 50,000 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

Five per sex per dose

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: Based on studies performed using similar materials
- Rationale for animal assignment (if not random): Random

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations included overt signs of toxicity and faecal examination.


DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: Yes
- Time schedule for examinations: Study initiation, twice weekly during treatment, and at study termination


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: 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: Yes
- Time schedule for examinations:No quantitative measurement was made, but water bottles were observed daily to check for any changes that might indicate a treatment-related change in fluid balance


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: No


CLINICAL CHEMISTRY: No


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, detailed necropsy was performed.
HISTOPATHOLOGY: Yes, although numerous tissues and organs were preserved, only the liver and mesenteric lymph nodes were examined histologically.

Other examinations:

Organs provided in table 1 were weighed.

Statistics:

A Bartlett's test was used to test for homogeneity of the data. Depending on the results a Behrens-Fisher or Dunnett's test were performed. Fischer's exact test was used on microscopic and macroscopic findings.

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 specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

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:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY: There were no treatment-related effects.


BODY WEIGHT AND WEIGHT GAIN: High-dose females had a marginal increase in body weight gain. However, this was related to increased food consumption so was considered due to individual variability and not treatment-related.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): High-dose females had a slight increase in food consumption. Compound intake in males was 1030, 2538, and 6248 mg/kg/day for the 8000 ppm; 20,000 ppm; and 50,000 ppm dose groups, respectively. Compound intake in females was 995, 2481, and 6771 mg/kg/day, respectively.


FOOD EFFICIENCY: There were no treatment-related effects.


ORGAN WEIGHTS: There was a slight, but dose-related, decrease in absolute and relative mandibular weight in males and females that reached statistical significance in high-dose females only.


GROSS PATHOLOGY: There were no treatment-related effects.


HISTOPATHOLOGY: There were no treatment-related effects.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

6 245 mg/kg bw/day (actual dose received)

Sex:

male

Basis for effect level:

other: Overall effects

2

Dose descriptor:

NOAEL

Effect level:

6 771 mg/kg bw/day (actual dose received)

Sex:

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 was an apparent dose-related decrease in mandibular lymph node weight, the results only reached significance in high-dose females; therefore, this is not considered biologically significant and not likely adverse since there were no other findings.

Applicant's summary and conclusion

Conclusions:

The systemic NOAEL for dec-1-ene, homopolymer, hydrogenated in the diet is 50,000 ppm, which is equivalent to a daily intake of 6245 mg/kg/day in males and 6771 mg/kg/day in females.

Executive summary:

In a repeated dose oral toxicity study, dec-1 -ene, homopolymer,hydorgenated was administered to F-344 rats (5 sex/dose) in the diet for four weeks at nominal concentrations of 0, 8000; 20,000; or 50,000 ppm (equivalent overall mean daily intakes were 1039, 2538, or 6245 mg/kg/day for males and 995, 2481, or 6771 mg/kg/day for females).

 

There was no overt toxicity or mortality observed in male or female rats during the study. Overall body weight gain and food consumption of females in the 50,000 ppm dose group was higher than the corresponding controls. A dose-dependent decrease in mandibular lymph node weights (absolute and relative to body weight) was observed in males and females; however, these results were statistically significant only for 50,000 pm females. Gross necroscopy, histopathology, and microscopic findings did not reveal any significant treatment-related findings in either male or female rats. Dietary administration of dec-1 -ene, homopolyer, hydrogenated to male and female F-344 rats at levels up to 50,000 ppm for 4 weeks did not produce toxicologically significant effects. Therefore, the subacute oral NOAEL for dec-1 -ene, homoopolymer, hydrogenated is 6245 mg/kg/day in males and 6771 mg/kg/day in females.

 

 This study received a Klimisch score of 2 and is classified as reliable with restrictions because although the study closely adhered to OECD 407 guidelines, haematology, clinical biochemistry, and neurobehavioral assessments were not conducted. This study will influence the DNEL.