Registration Dossier

Administrative data

Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data are available for interpretation of results.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
A Study on the Chronic Toxicity of Diethylene triamine on the Rat
Author:
Fujino, M.
Year:
1970
Bibliographic source:
Igaku Kenkyu, Vol. 40 , No. 2, p. 23-48

Materials and methods

Principles of method if other than guideline:
Not indicated
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-iminodi(ethylamine)
EC Number:
203-865-4
EC Name:
2,2'-iminodi(ethylamine)
Cas Number:
111-40-0
Molecular formula:
C4H13N3
IUPAC Name:
N-(2-aminoethyl)ethane-1,2-diamine
Details on test material:
No additional information available.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Pure Bred Animal Breeding Lab of the Faculty of Medicine of Kyushu University.
- Diet: Oriental solid feed NMF was fed to rats during the experiment period
- Water: ad libitum

Administration / exposure

Vehicle:
other: a special reagent obtaind from Katayama Kagaku Kogyo K.K
Details on exposure:
TEST SITE
-A 100 mg/cc solution was painted twice at the size of 2 x 3 cm on the hair of the back scapula portion once a day for six times a week using a marten hair brush. The total amount of DETA applied was 0.4 cc of solution.


TEST MATERIAL
A solution for dermal application was prepared by diluting a special reagent obtained from Katayama Kagaku Kogyo K.K to 100 mg/cc.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
Chronic
Frequency of treatment:
once a day for six times a week
Doses / concentrations
Remarks:
Doses / Concentrations:
0.4 ml of 10 times diluted solution
Basis:
nominal per unit area
No. of animals per sex per dose:
Five
Control animals:
yes
Details on study design:
No additional information available.
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily (to record the number of births and observe the effect of continuous administration of DETA on the fertility.



BODY WEIGHT: Yes
- Time schedule for examinations: weekly



HAEMATOLOGY: Yes
- Time schedule for collection of blood: Every four weeks
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals:all
- Parameters examined: erythrocyted and leucocytes


Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
Fertility
Statistics:
No indicated

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
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:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
1.The average number of survival days for the skin painted animals was 407.1. The control group had the span of 1010 days at the longest and the average of ten cases was 580.5 days. There were no particular symptoms.
2. no marked abnormalities were noted in the numbers of leucocytes and erythroyctes, the body weight and the number of births.
3. The skin painted animals were observed with chronic changes in the kidney and liver toxication and also the pneumonis images, whihc were suspected to result from a decrease in the resistance of lung.
4. Slight changes were also noted in spleen and adrenal glands.

Effect levels

Remarks on result:
other: No notable effects when 4/10mL of DETA was diluted 1:10 solution.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

There were no notable pathologic findings in the rats of each experimental group.

Applicant's summary and conclusion

Conclusions:
Average survival was 407 days in rats dermally exposed to DETA and 581 days in the control group. Histopathologic changes were noted in the liver and kidney of DETA treated animals.
Executive summary:

The chronic toxicity of diethylenetriamine (DETA) was studied by subcutaneous injeciton and by painting on the skin of rats. Inasmuch as diethylenetriamine has an irritative and corrosive action on the skin, it was diluted with distilled water for the experiments, 1:10 dilution was also made for the painting. The animals were kept in pens to observe the toxic effects of DETA on them during their life spans. After the animal's death, the histopathological changes produced thereby in the visceral organs were studied.

The results were obtained as follows:

1.) Four-tenths ml of the DETA diluted solution (1:10) was applied every day on the back of rats in group C.

2.) The average days of survival was 407 days in group C, and 581 days for the rats in control group D. The maximum survival day of the rats among group D was 1010 days.

3.) There were no notable gross pathologic findings in the rats of each experimental group. The numbers of erythrocytes and leucocytes, the change of body weight and the numbers of litter were not markedly different between the rats given DETA and the control.

4.) The histopathological changes produced by the administration of DETA were obseved mainly in kidney and liver. The damages were noticed in the rats in group C. Pneumonia, which seemed to be resulted from the decrease of physical resistance was also observed in both group C and D. Some slight histopathological changes were observed in both spleen and adrenal.