11-aminoundecanoic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

may 1976 to august 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 2e: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1982

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:

hematological, clinical biochemistry, urine analysis and FOB were not performed and daily intake, clinical signs, food consumption, and organ organ weights were not reported.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

11-aminoundecanoic acid

EC Number:

219-417-6

EC Name:

11-aminoundecanoic acid

Cas Number:

2432-99-7

Molecular formula:

C11H23NO2

IUPAC Name:

11-aminoundecanoic acid

Details on test material:

- Name of test material (as cited in study report): 11-aminoundecanoic acid
- Physical state: white cristalline
- Analytical purity: 99.13 ± 0.03 wt%
- Lot/batch No.: 503
no other data

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: NCI Frederick Cancer Research Center
- Age at study initiation: five-week old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: four per cage
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: Two weeks


ENVIRONMENTAL CONDITIONS
no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Test diets were prepared by first mixing a small amount of Purina Lab Chow and the required amount of 11-aminoundecanoic acid with a mortar and pestle and then adding this premix to the required amount of animal meal and mixing for 20 minutes in a Patterson-Kelly twin shell blender equipped with an intensifier bar. Prepared diets containing 100,000 ppm 11-aminoundecanoic acid were analyzed at Midwest Research Institute and were found to be stable for 2 weeks at temperatures up to 45°C. Test diet were stored in the dark at 4°C for no longer than 2 weeks.


DIET PREPARATION
- Rate of preparation of diet (frequency): at least every two weeks.
- Mixing appropriate amounts with (Type of food): Purina Lab Chow
- Storage temperature of food: in the dark at 4°C

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

continuous

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 9,000; 12,000; 15,000; 18,000; 20,000
Basis:
nominal in diet

No. of animals per sex per dose:

10 per sex per dose

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): Mice were randomized by weight and assigned to test groups so that average cage weights were approximately equal for all animals of the same sex and species.

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

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: No data

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: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No


CLINICAL CHEMISTRY: No


URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

No

Statistics:

no statistics were performed.

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):

not specified

Food efficiency:

not examined

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

not examined

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:

not examined

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY: Deaths occured in 2/10 male and 2/10 female mice administered 15,000 ppm, 4/10 males and 2/10 females receiving 18,000 ppm, and 3/10 males receiving 20,000 ppm. The cause of death of animals dying during the study was not determined.

BODY WEIGHT AND WEIGHT GAIN: Mean body weight gain was depressed 20 % in male mice receiving 15,000 ppm, but only 10 % in male mice receiving 18,000 or 20,000 ppm. Mean body weight gain was depressed by more than 10 % in female mice fed diets containing 18,000-20,000 ppm 11-aminoundecanoic acid.

HISTOPATHOLOGY: NON-NEOPLASTIC: Focal mineralization of the kidney was noted in males that received 15,000-20,000 ppm and in females that received 15,000-18,000 ppm, particulary in males that received 15,000-20,000 ppm and in females that received 15,000-18,000 ppm, particulary in those mice that died.

Effect levels

Dose descriptor:

NOAEL

Effect level:

9 000 ppm

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Under the conditions of this test, deaths occured in mice administered with doses above 15,000 ppm in male and female mice.The administration of up to 20,000 ppm 11-aminoundecanoic acid in the diet of mice for 13 weeks leads to focal mineralisation of the kidneys and body weight depression.

Executive summary:

In a 91-day oral range finding studies in mice (NTP, 1982), five-week-old male and female B6C3F1 mice were fed with diets containing 0, 9,000, 12,000, 15,000, 18,000 or 20,000 ppm 11-aminoundecanoic acid. Groups of 10 male and 10 female mice were used. Animals were checked for mortality and signs of mortality. Each animal was given a clinical examination weekly, including palpation for tissue masses or swelling body weight and feed consumption data were collected weekly. Deaths occured in 2/10 males and 2/10 females administered 15,000 ppm, 4/10 males and 2/10 females receiving 18,000, and 3/10 males receiving 20,000 ppm. The cause of death of animals dying during the study was not determined. Mean body weight gain was depressed 20 % in male mice receiving 15,000 ppm, but only 10 % in male receiving 18,000 or 20,000 ppm. Mean body weight gain was depressed by more than 10 % in female mice fed diets containing 18,000 -20,000 ppm 11 -aminoundecanoic acid. Focal mineralization of the kidney was noted in males that received 15,000 -20,000 ppm and in females that received 15,000-18,000 ppm, particularly in those mice that died. The NOAEL was estimated to be 9000 ppm.