Plant Sterols

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

90 day study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study closely followed the OECD 408 “Repeat dose 90 day oral toxicity study in rodents” test guidelines & has GLP compliance. However, it does not include any details regarding urine analysis.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Principles of method if other than guideline:

The study closely followed the OECD 408 “Repeat dose 90 day oral toxicity study in rodents” test guidelines & has GLP compliance. However, it does not include any details regarding urine analysis.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phytosterol esters

IUPAC Name:

Phytosterol esters

Details on test material:

Gross composition of the test material as shown below:
Constituent Composition (%w/w)
Total sterol 62.0
Total fatty acid 38.2
Free sterol (as % of the total mixture) 8.4
Free fatty acid <0.3

Sterol profile
Cholesterol (0.4%)
Brassicasterol (1.1%)
Campesterol (25.8%)
Stigmasterol (21.6%)
Beta-sitosterol (48.7%)
Beta-sitostanol (1.8%)
Unknowns (0.8%)

Fatty acid profile
C16:0 (9.6%)
C18:0 (4.1%)
C18:1 (21.6%)
C18:2 (64.6%)

Note, the phytosterols were sourced from a variety of common edible vegetable oil distillates and then re-esterified with fatty acids from sunflower oil.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

7 days/week in diet for 90 days.

Frequency of treatment:

7 days/week in diet for 90 days.

Doses / concentrations

Remarks:

Doses / Concentrations:
Doses of 0.16, 1.6, 3.2, and 8.1% (w/w) equivalent to phytosterol concentrations of 0.1, 1.0, 2.0, and 5.0 % (w/w) respectively
Basis:
nominal in diet

No. of animals per sex per dose:

Male and female (20 of each per group) and one control group and four treatment groups.

Control animals:

yes, concurrent no treatment

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

> 6.6 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Food consumption

No adverse effects noted.

 

Water consumption

No adverse effects noted.

 

Clinical signs

None noted that could be attributed to the test compound.

 

Body weight

No statistically significant differences in mean body weights observed for any treated group compared to the control group.

 

Organ weights

No statistically significant changes in organ weights in comparison to the control group.

 

 

Haematology

Some minor statistically significant changes in some haematology in males and/or females, but none were considered to be of toxicological significance.

 

Clinical Chemistry

Some minor statistically significant changes in some clinical chemistry in males and/or females, but none were considered to be of toxicological significance.

 

Urinalysis

No information provided.

 

Macroscopic examination

No findings noted at necropsy.

 

Histopathology

None attributed to the test substance.

Applicant's summary and conclusion

Conclusions:

The results of this study showed there to be no clinical signs or effects on survival attributed to the administration of the test material. A NOEL of 8.1% (PE) was identified in the study, which is equivalent to a dose of 6.6 g/kg/bw/day PE or 4.1 g phytosterol/kg bw/day.

Executive summary:

In a published study (Hepburnet al., 1999), phytosterol esters (PE) were added to the diet of male and female Wistar derived rats over a period of 90 days, to give concentrations of 0.16, 1.6, 3.2, and 8.1% (w/w) equivalent to phytosterol concentrations of 0.1, 1.0, 2.0, and 5.0 % (w/w) respectively. (Similar to OECD 408 test guideline, Rel. 2)

 

The results of this study showed there to be no clinical signs or effects on survival attributed to the administration of the test material. A NOEL of > 8.1% (PE) was identified in the study, which is equivalent to a dose of 6.6 g/kg/bw/day PE or 4.1 g phytosterol/kg bw/day.