Amines, N-tallow alkyltrimethylenedi-, propoxylated

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981-06-02 to 1981-08-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions ( medullar toxicity is not checked through PCE/NCE ratio but through haematological analysis, 5 animals per sex are usually required (instead of only 4 here))

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

4 instead of 5 animals per sex

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

1-({3-[(2-hydroxypropyl)[(9E)-octadec-9-en-1-yl]amino]propyl}amino)propan-2-ol; 1-({3-[(2-hydroxypropyl)amino]propyl}(octadecyl)amino)propan-2-ol; 1-({3-[hexadecyl(2-hydroxypropyl)amino]propyl}amino)propan-2-ol

EC Number:

614-637-2

Cas Number:

68603-75-8

Molecular formula:

R-N(CH2CHOHCH3)xCH2CH2CH2N(CH2CHOHCH3)y with x+y=3 and where R = alkyl

IUPAC Name:

1-({3-[(2-hydroxypropyl)[(9E)-octadec-9-en-1-yl]amino]propyl}amino)propan-2-ol; 1-({3-[(2-hydroxypropyl)amino]propyl}(octadecyl)amino)propan-2-ol; 1-({3-[hexadecyl(2-hydroxypropyl)amino]propyl}amino)propan-2-ol

Details on test material:

- Name of test material (as cited in study report): DINORAM SL
- Physical state: dark brown liquid
- Lot/batch No.: 2884
No other data available

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River France (76410 Saint-Aubin-lès-Elbeuf, France)
- Age: 13-17 weeks
- Body weight at study initiation: no data

Administration / exposure

Route of administration:

other: test substance gavage, positive controls intraperitoneal

Vehicle:

Vehicle: CMC at 1%

Duration of treatment / exposure:

2 administrations separated by 24h

Frequency of treatment:

2 administrations separated by 24h

Doses / concentrations

Remarks:

Doses / Concentrations:
0.1, 0.2 and 0.5 ml/kg
Basis:

No. of animals per sex per dose:

4 males + 4 females

Control animals:

yes, concurrent vehicle

Positive control(s):

Benzo(a)pyrene (500 mg/kg/day) and Cyclophosphamide (100 mg/kg/day) in corn oil

Examinations

Details of tissue and slide preparation:

- Haematology: blood samples were withdrawn from retro-orbital sinus for measuring red blood count, mean cell volume, hematocrit, hemoglobin, mean cell hemoglobin concentration and white cell count
- Tissue examined: blood and bone marrow - Actual dose (mg/kg body weight): not determined
- Slide preparation: At the scheduled sacrifice times (30 hours after the second administration for test substance and negative control groups, 48h hours after the second administration for positive control groups), mice were sacrificed by vertebras dislocation. Immediately following sacrifice, the femurs were removed and the bone marrow was flushed with fetal calf serum. The bone marrow cells were transferred to labelled centrifuge tubes. The bone marrow cells were pelleted by centrifugation at 1200 g for 5 minutes and the supernatant was drawn off, leaving a small amount of serum with the remaining cell pellet. The cells were resuspended with serum and a small volume of bone marrow suspension was spread onto two clean glass slides. The slides were stained with May-Grünwald-Giemsa.
- PCE/NCE ratio was determined until a total of at least 1000 cells (PCE+NCE) were counted Each slide is examined by two persons.
- A total of 1000 PCE was examined for micronuclei.

Statistics:

Comparisons between treated and control groups were performed using a Student Fischer test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

- Mortality: No death occured in test substance group but a male was found dead after the second administration.
- Clinical findings: No pathological effects were reported.
- Haematology: No significant differences in haematological parameters between treated and negative control groups were noted. Notably, no anemia were recorded.
- Micronuclei count: No significant differences were observed between treated and negative control group. In contrast, positive control slides showed an increased micronuclei count.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Under these experimental conditions, the substance did not show a clastogenic potential.

Executive summary:

Four male and four female mice were treated with 0.1, 0.2 or 0.5 mg/kg/d of Amines, N-tallow alkyltrimethylenedi-, propoxylated on two days. Blood of the animals was taken for hematological observations, bone marrow samples were taken for investigation of micronucleus formation. Neither in the blood samples nor in the bone marrow samples, differences between control animals and dosed animals were observed. The animals treated with positive controls (Benzo(a)pyrene and Cyclophosphamide), however did show a markedly increased number in micronuclei.