N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine

Repeated dose toxicity: dermal

Administrative data

Endpoint:

chronic toxicity: dermal

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: 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:

Dermal Oncogenicity Studies on Various Ethyleneamines in Male C3H Mice

Author:

De Pass LR, Fowler EH, and Weil CS

Year:

1987

Bibliographic source:

FUNDAMENTAL AND APPLIED TOXICOLOGY, 9, 807-811

Materials and methods

Principles of method if other than guideline:

Mice were dosed dermally three times/week for a lifetime. Gross and histopathological examinations were performed on all animals.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-iminodi(ethylamine)

EC Number:

203-865-4

EC Name:

2,2'-iminodi(ethylamine)

Cas Number:

111-40-0

IUPAC Name:

N-(2-aminoethyl)ethane-1,2-diamine

Test animals

Species:

mouse

Strain:

other: C3H/HeJ

Sex:

male

Administration / exposure

Type of coverage:

open

Vehicle:

water

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

complete life span (ca. 20 months)

Frequency of treatment:

3 times weekly

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1.25 mg/animal
Basis:
other: nominal in water 25 µl in 5% solution v/v

Doses / concentrations 2

Remarks:

Doses / Concentrations:
56.3 mg/kg bw
Basis:
other: Estimate as calculated from data from average of initial body weights and milligrams administered

Control animals:

yes, concurrent vehicle

Results and discussion

Results of examinations

Details on results:

See section 7.7

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 56.3 mg/kg bw/day

Sex:

male

Basis for effect level:

other: 3 times weekly

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

Diethylenetriamine (DETA) was tested in a total of 100 male C3H/HeJ mice in a study involving dermal application of two products of different degrees of purity, DETA High Purity (DETA-HP, 96.77% diethylenetriamine, 1.78% N-(2-aminoethyl)piperazine, remaining components other amines) and DETA Commercial Grade (DETA-C 90.8% diethylenetriamine, 8.9% N-(2-aminoethyl)piperazine, 0.34% ethylenediamine). The test substances were applied as a 5% aqueous solution. A 10% diethylenetriamine solution had caused open skin wounds, and so the non-irritating 5% solution was considered to be the highest possible concentration that could be used in a lifetime study. The treatment involved the application of 25 µl of the test solution (1.25 mg) to the dorsal skin of the mice (which was shaved once a week) three times a week for their entire lives. The mice were observed daily. After 18 months, the skin, liver, kidneys and lungs from 10 mice/group were fixed for histological examination. The average survival time for the mice was 587 days in the DETA-HP group and 662 days in the DETA-C group. The animals in the control group, which were treated with 25 µl water, lived for 626 days on average. 2 tumours were found in total. One mouse in the control group had a sebaceous gland adenoma of the thorax, and one in the DETA-C group had a cavernous haemangioma of the neck region. This type of haemangioma was also observed in historical controls in the institute carrying out the study. Also the effects on other organs corresponded to the spontaneous occurrence in the control groups of the strain studied. Diethylenetriamine thus had no carcinogenic activity in this study.