Glycerides, C16-18

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Not available

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1981

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

Remarks:

only single dose level used; not all parameters examined

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerides, C16-18

EC Number:

268-084-3

EC Name:

Glycerides, C16-18

Cas Number:

68002-71-1

Molecular formula:

C55H98O6

IUPAC Name:

Glycerides, C16-18

Details on test material:

- Name of test material (as cited in study report): Fully hydrogenated soybean oil (CAS N° 8016-70-4, EC N° 232-410-2); under the SDA nomenclature, the name of this substance is ‘Glycerides, C16-18’
- Other: The test material was made fully hydrogenated using a commercial nickel-based catalyst

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 Breeding Laboratories, Wilmington, MA
- Housing: The animals were housed in individual stainless steel wire-mesh cages
- Diet: Ad libitum
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±1
- Humidity (%): 50±5%
- Photoperiod (h dark / h light): 12/12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Mixing appropriate amounts with (Type of food): Normal diet containing 11.5% soybean oil as fat source

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not applicable

Duration of treatment / exposure:

91 d

Frequency of treatment:

Daily ad libitum in food

Doses / concentrations

Dose / conc.:

7.5 other: %

Remarks:

Basis: nominal in diet

No. of animals per sex per dose:

20 animals/sex/group

Control animals:

other: yes, 19% soybean oil

Details on study design:

- Rationale for animal assignment: Animals were distributed into groups of 20 rats per sex so that the litter mates were distributed evenly among the groups and the mean body weights did not vary more than 0.5 g

Positive control:

Not applicable

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION (if feeding study): Yes
- Time schedule for examinations: Weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At time of sacrifice (end of study)
- Anaesthetic used for blood collection: Yes
- Animals fasted: No data
- How many animals: 10 animals/sex/group
- Parameter examined: Standard hemograms done

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At time of sacrifice (end of study)
- Animals fasted: No data
- How many animals: 10 animals/sex/group
- Parameter examined: Serum cholesterol and phospholipids

URINALYSIS: Yes
- Time schedule for collection of urine: 24 h collection in 11th wk of study
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameter examined: Volume, nitrogen, ketones, glucose, bilirubin, albumin and pH

OTHER: During the 3rd and 11th wks, feces were collected from 10 animals/sex/group for fat absorption analysis.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
(The heart, liver, kidneys and gonads were removed and weighed. Sections of these organs and of lung, pancreas, stomach, jejunum, adrenals, spleen, mesenteric lymph nodes and gastrocnemius muscle were examined)

Other examinations:

None

Statistics:

All of the data were analyzed by the Analysis of Variance and partitioned by the Tukey minimum significant difference method.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

effects observed, treatment-related

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

Details on results:

There were no significant differences in growth and weight gain; however, food intake and caloric efficiency (kcal/g gain) was slightly increased in treatment group after 4 wks. The mean caloric efficiency of treatment group (18.9 and 26.9 kcal/g gain in males and females respectively) was significantly higher than that of control group (16.8 and 23.6 kcal/g gain in males and females respectively). This was attributed to the lower absorbability of the fully hydrogenated soybean oil. No effects on any other parameter as mentioned above.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

7.5 other: % in diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical biochemistry

gross pathology

haematology

histopathology: neoplastic

urinalysis

Target system / organ toxicity

Key result

Critical effects observed:

no

Any other information on results incl. tables

Fat Absorbability: Low absorption was observed for experimental fat i.e. fully hydrogenated soybean oil (17±8% - males; 17±7% - females). The total fat absorption was significantly lower in treatment group (64±4% - males; 68±3% - females) with respect to control group (95±1% - males; 98±1% - females).

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the NOAEL of the substance in rats was determined to be 7.5% in
diet.

Executive summary:

A subchronic toxicity study was conducted in rats to investigate the effect of 'glycerides, C16-18' (as fully hydrogenated soybean oil) in diet.

Diets containing 7.5% of the substance (plus 11.5% soybean oil as normal fat source) were fed to 20 Sprague-Dawley rats/sex for 91 d. A control group was fed with 19% soybean oil for same duration. There was no indication of any systemic toxicity (including body weight gain, organ weights, urinalysis, clinical chemistry, haematology, gross and histopathology). Only observable effect was slightly increased feed consumption (and thus increased caloric efficiency) in treatment group after 4 wks which was attributed to the lower absorbability of the substance.

Hence, under the conditions of this study, the NOAEL of the substance in rats was determined to be 7.5% in diet (Nolen, 1981).