Reaction product of: stearyl-diethanol-amine with C16-C18 saturated fatty acids

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Remarks:

other: 13 weeks

Type of information:

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

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study design appears to follow OECD guideline without detailed documentation.

Data source

Reference

Reference Type:

publication

Title:

Acute and Subacute Toxicity Studies of Polyoxyethylene Alkylamine Fatty Acid Ester

Author:

Yukio Yanagimoto, Seiji Asayama, Tamihei Kamaguchi, Takashi Daimon and Mayumi Murano

Year:

1976

Bibliographic source:

Oyo Yakuri (1976) 11(6) 901-916 (Special Issue)

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:

No information on purity of the test substance, temperature, humidity, and light condition; Homogeneity, concentration, stability of the test substance in the application media not analyzed; Several observations/parameters were not performed/measured.

GLP compliance:

no

Remarks:

Study pre-dates GLP requirements.

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Polyoxyethylene (1-6) alkylamine (C12-C22) fatty acid (C12-C22) ester

IUPAC Name:

Polyoxyethylene (1-6) alkylamine (C12-C22) fatty acid (C12-C22) ester

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

other: mice and rats

Strain:

other: Mice: ICR; Rats: SD-JCL

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: feed

Details on oral exposure:

Concentration in feed were 0% (vehicle), 0.03% , 0.1% , 0.3% and 1%.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

104.0 mg/kg/day for male and 116.2 mg/kg/day for female rats obtained from average food consumption represent the dose of 0.1% added group.
104.8 mg/kg/day for male and 132.7 mg/kg/day for female mice obtained from average food consumption represent the dose of 0.1% added group.

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

No. of animals per sex per dose:

10 per sex per dose

Examinations

Observations and examinations performed and frequency:

Body weights and food intakes were measured once a week. However, it was difficult to measure the food intake so that measurement was omitted.
The general conditions were observed when bodyweights were measured and optionally for some other items.
Urinalysis was conducted when administration ended after 13 weeks. For fresh urine, glucose, protein, occult blood, pH and urobilinogen were measured.
Hematological tests and hematological biochemical tests were performed at the end of administration after 13 weeks.

Sacrifice and pathology:

Autopsies were performed on animals after withdrawal of blodd samples. Pathohistological examinations were carried out for major organs.

Statistics:

t-test

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

1) Body Weight Gains
Body weight gains for the test mice at 1% level were significantly lower than those for the controls. In rats, body weight gains for the males at 0.3% and 1% levels and for the females at 1% level showed a significant decrease compared to those for the controls.
2) Food Consumption
Food consumption values for the male and female rats at 1% level were significantly lower than those for the other test rats at the beginning of the tests. Food was given freely to the test animals as accurate weighting of the food consumed was very difficult.
3) Haematology
Red cell counts and Hb values for the test mice and rats showed a dose-related decrease. This trend was remarkable for the male rats at 0.3% and 1% levels and for the female rats at 1% level.
4) Blood biochemistry
Total protein values for the male at 0.3% and 1% levels and for the female rats at 1% level showed a significant decrease. Urea-N values showed a dose-related increase. For the male and female rats at 1% level the values were significantly higher than those for the controls. No other abnormalities were found in the test animals.
5) Organ weights
Examination of the relative organ weights for the testing animals revealed the liver weights for the mice at 1% level, the liver weights and the spleen weights for the rats of both sexes at 1% level to be significantly higher than those for the controls.
6) Patho-histological findings
The white pulp of the spleen of the mice of both sexes at 0.3% and 1% levels were found to be in proliferation and growth of the ovarian follicles of the female mice at 1% level insufficient. For the male rats at 1% level, atrophy in the glomerulus, degenerated epithelial cells of the seminiferous tubule of the seminal glands, and abnormal spermatogenesis were found.

Effect levels

1

Dose descriptor:

NOEL

Effect level:

ca. 104 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Based on no abnormalities should occur.

2

Dose descriptor:

NOEL

Effect level:

ca. 116.2 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Based on no abnormalities should occur.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The max. level of the substance at which no abnormalities should occur is in between 0.1% and 0.3%. Consequently, if 0.1% is determined as the max. Safety level of the substance, values of 104.0 mg/kg/day for the male and 116.2 mg/kg/day for the female rats will be obtained from their average food consumption. For the mice, the values will be 104.8 mg/kg/day for the males and 132.7 mg/kg/day for the females as their average food consumption is 4 g/day.

Executive summary:

Polyoxyethlene (1-6) alkylamine (C12-C22) fatty acid (C12-C22) ester was added to the feed at a concentration of 0.03% , 0.1% , 0.3% and 1%. Mice and rats were fed this diet for 3 months. The results showed body weight gains for the test mice at 1% level were significantly lower than those for the controls. In rats, body weight gains for the males at 0.3% and 1% levels and for the females at 1% level showed a significant decrease compared to those for the controls.

Food consumption values for the male and female rats at 1% level were significantly lower than those for the other test rats at the beginning of the tests.

As hematological finding, red cell counts and Hb values for the test mice and rats showed a dose-related decrease. This trend was remarkable for the male rats at 0.3% and 1% levels and for the female rats at 1% level.

As hematological biochemical findings, total protein values for the male at 0.3% and 1% levels and for the female rats at 1% level showed a significant decrease. Urea-N values showed a dose-related increase. For the male and female rats at 1% level the values were significantly higher than those for the controls. No other abnormalities were found in the test animals.

Regarding organ weights, the liver weights for the mice at 1% level, the liver weights and the spleen weights for the rats of both sexes at 1% level were found to be significantly higher than those for the controls.

Regarding pathohistological findings, the white pulp of the spleen of the mice of both sexes at 0.3% and 1% levels were found to be in proliferation and growth of the ovarian follicles of the female mice at 1% level insufficient. For the male rats at 1% level, atrophy in the glomerulus, degenerated epithelial cells of the seminiferous tubule of the seminal glands, and abnormal spermatogenesis were found.

The max. level of the substance at which no abnormalities should occur is in between 0.1% and 0.3%. Consequently, if 0.1% is determined as the max. Safety level of the substance, values of 104.0 mg/kg/day for the male and 116.2 mg/kg/day for the female rats will be obtained from their average food consumption. For the mice, the values will be 104.8 mg/kg/day for the males and 132.7 mg/kg/day for the females as their average food consumption is 4 g/day.