Amides, C18 (unsaturated)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well-conducted study, especially considering the time at which the study was run (1960). Protocol could be considered an ancestral version of OECD407; however, the study was done before GLP regulations, only one dose was used, the dose was not confirmed analytically and histopathology was not performed. Test material was well characterized.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1960

Report date:

1960

Materials and methods

Principles of method if other than guideline:

Test material was administered by addition to feed.

GLP compliance:

no

Remarks:

Study performed prior to GLP regulations

Test material

Test material information

Constituent 1

Reference substance name:

(Z)-docos-13-enamide

EC Number:

204-009-2

EC Name:

(Z)-docos-13-enamide

Cas Number:

112-84-5

Molecular formula:

C22H43NO

IUPAC Name:

docos-13-enamide

Details on test material:

Amide content 98.5%; free fatty acid content, 0.8% (as oleic acid); moisture 0.5%; nitrile (as oleyl), 0.2%.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Weanling male rats of the Sprague-Dawley strain weighing 45-50 grams were employed. The animals were divided into 2 groups of 5 rats each and housed in individual screen bottom metabolism cages.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The basal ration consisted of a 20% casein semi-synthetic diet without added fat. The test group was fed the fatty acid amide at a level of 10% in the diet at the expense of sucrose.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

None.

Duration of treatment / exposure:

4 weeks.

Frequency of treatment:

Continuously; test material administered in diet which was available ad libitum.

Doses / concentrations

Remarks:

Doses / Concentrations:
10% w/w
Basis:
nominal in diet

No. of animals per sex per dose:

5 males

Details on study design:

The sample was subjected to a 4-week digestibility study. Water and test ration were provided ad libitum.

Positive control:

None.

Examinations

Observations and examinations performed and frequency:

Individual body weight and food consumption data were collected weekly.

Sacrifice and pathology:

At the end of the four week feeding period the animals were subjected to a routine hematological study and urinalysis, sacrificed, examined grossly for pathology and tissue sections removed for possible future histological examination.

Other examinations:

The total output of feces was collected daily and stored under refrigeration. Pooled weekly fecal samples were weighed and analyzed for their fat content.

Statistics:

None.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

No mortality occurred. No clinical signs reported.

Mortality:

no mortality observed

Description (incidence):

No mortality occurred. No clinical signs reported.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Treated animals grew at a somewhat lower rate than fat-free controls.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption in treated animals was reduced.

Food efficiency:

no effects observed

Description (incidence and severity):

Food efficiency of the two groups was not significantly different.

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Description (incidence and severity):

Clinical testing was negative in that no abnormalities of any sort were noted.

Clinical biochemistry findings:

not specified

Urinalysis findings:

no effects observed

Description (incidence and severity):

Clinical testing was negative in that no abnormalities of any sort were noted.

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Description (incidence and severity):

Gross autopsy was negative in that no abnormalities of any sort were noted.

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

No mortality occurred during the course of the study.

The clinical testing and gross autopsy were all negative in that no abnormalities of any sort were noted.

Under the test conditions outlined above, the sample of erucylamide tested was absorbed from the rat intestinal tract to the extent of 62.2%. Weekly figures of 72.9, 57.3, 68.6 and 52.8% absorption, for the first, second, third and fourth weeks respectively, were obtained.

Animals fed 10% erucylamide in a semi-synthetic diet grew at a somewhat lower rate than fat-free controls but their food consumption was similarly lowered and the feed efficiency of the two groups is not significantly different. Since the caloric content of the two diets differs by approximately 12% on a calculated basis but by only about 4% on the basis of absorbed nutrients this lack of a real difference is not surprising. On the basis of this study one could, with at least some basis in experimental evidence, assume that erucylamide is a moderately absorbed but normally metabolized nutrient for the rat.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

100 000 ppm

Based on:

act. ingr.

Sex:

male

2

Dose descriptor:

NOAEL

Effect level:

ca. 10 000 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: Converted to dose (mg/kg) according to Toxicologist's Pocket Handbook, CRC Press, 2000

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

On the basis of this study one could, with at least some basis in experimental evidence, assume that erucylamide is a moderately absorbed but normally metabolized nutrient for the rat.

Executive summary:

A sample of erucylamide was sumitted for biological study. The sample was subjected to a four-week digestibility study. Water and test ration were provided ad libitum. At the end of the four week feeding period the animals were subjected to a routine hematological study and urinalysis, sacrificed, examined grossly for pathology and tissue sections removed for possible future histological examination. The clinical testing and gross autopsy were all negative in that no abnormalities of any sort were noted. Under the test conditions outlined above, the sample of erucylamide tested was absorbed from the rat intestinal tract to the extent of 62.2%. Weekly figures of 72.9, 57.3, 68.6 and 52.8% absorption, for the first, second, third and fourth weeks respectively, were obtained. Animals fed 10% erucylamide in a semi-synthetic diet grew at a somewhat lower rate than fat-free controls but their food consumption was similarly lowered and the feed efficiency of the two groups is not significantly different. Since the caloric content of the two diets differs by approximately 12% on a calculated basis but by only about 4% on the basis of absorbed nutrients this lack of a real difference is not surprising. On the basis of this study one could, with at least some basis in experimental evidence, assume that erucylamide is a moderately absorbed but normally metabolized nutrient for the rat.