Hexamethylenediamine

Repeated dose toxicity: dermal

Administrative data

Endpoint:

repeated dose toxicity: dermal

Remarks:

other: no data

Type of information:

experimental study

Adequacy of study:

other information

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The document is insufficient for assessment (protocol, test animal, test material, parameters examined......)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1937

Report date:

1937

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

The aim of this study was to test the toxicity of Hexamethylene Diamine in white rats, by application to the skin.
Six white rats were treated daily on 5 days of the week on their shaved backs with a 1% paste of crude hexamethylene diamine in vaseline. No precautions were taken to prevent licking. Animals were killed on the twenty-first day of the experiment, after 16 applications.
In a second series of experiments, 6 rats were similarly treated with a 2% paste of crude HMD. Rats were killed on the ninth day of the experiment, after 7 applications of test substance.

GLP compliance:

no

Remarks:

Study performed before GPL establishment

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hexamethylenediamine

EC Number:

204-679-6

EC Name:

Hexamethylenediamine

Cas Number:

124-09-4

Molecular formula:

C6H16N2

IUPAC Name:

hexane-1,6-diamine

Details on test material:

- Name of test material (as cited in study report): Hexamethylene Diamine (HMD)
- Substance type: no data
- Physical state: no data
- Analytical purity: no data
- Lot/batch No.: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Type of coverage:

open

Vehicle:

other: vaseline

Details on exposure:

TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: open
- Time intervals for shavings or clipplings: no data


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1% paste of crude HMD in vaseline and 2% paste of crude HMD in vaseline
- Concentration (if solution): 1% and 2%
- Constant volume or concentration used: no data
- For solids, paste formed: no


VEHICLE
no data


USE OF RESTRAINERS FOR PREVENTING INGESTION: no

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

First group: 16 applications
Second group: 7 applications

Frequency of treatment:

Daily on 5 days of the week

No. of animals per sex per dose:

No data

Details on study design:

No data

Positive control:

no

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: no data

BODY WEIGHT: No data

FOOD CONSUMPTION: no data

FOOD EFFICIENCY: no data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No data

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

not specified

Dermal irritation:

effects observed, treatment-related

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

No additional data

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

First group: the first few applications produced erythema and scaling of the skin, but these gradually dissapeared. At the end of the experiment, when animals were killed on the twenty-first day, new hair had grown almost completely over the shaved area. With the exception of mild degenerative changes in the liver cells in 3 out of 6 rats and mild to moderate regressive lesions of the renal tubules in 2 out of 6 animals, the pathological examination gave no evidence of any toxic effect in these animals.

Second group: rats showed sclaing of their epidermis and cracking of the skin developed after the third treatment and in five this lasted until they were killed on the ninth day of the experiment.

Upon autopsy, the treated area showed some sero-sanguinous crusts and liver and kidneys were mildly hyperemic.

Microscopically the skin showed small ulcerative defects of the epidermis, in other parts this was atrophic and contained small purulent. There were also inflammatory reactions in the lower layers of the skin. The only other pathological finding in these animals was a moderate degenerative in certain parts of the kidney.

Applicant's summary and conclusion

Executive summary:

The aim of this study was to test the toxicity of Hexamethylene Diamine in white rats, by application to the skin. Six white rats were treated daily on 5 days of the week on their shaved backs with a 1% paste of crude hexamethylene diamine in vaseline. No precautions were taken to prevent licking. Animals were killed on the twenty-first day of the experiment, after 16 applications. In a second series of experiments, 6 rats were similarly treated with a 2% paste of crude HMD. Rats were killed on the ninth day of the experiment, after 7 applications of test substance.

With the first group, the first few applications produced erythema and scaling of the skin, but these gradually dissapeared. At the end of the experiment, when animals were killed on the twenty-first day, new hair had grown almost completely over the shaved area. With the exception of mild degenerative changes in the liver cells in 3 out of 6 rats and mild to moderate regressive lesions of the renal tubules in 2 out of 6 animals, the pathological examination gave no evidence of any toxic effect in these animals.

For the second group, rats showed sclaing of their epidermis and cracking of the skin developed after the third treatment and in five this lasted until they were killed on the ninth day of the experiment.

Upon autopsy, the treated area showed some sero-sanguinous crusts and liver and kidneys were mildly hyperemic.

Microscopically the skin showed small ulcerative defects of the epidermis, in other parts this was atrophic and contained small purulent. There were also inflammatory reactions in the lower layers of the skin. The only other pathological finding in these animals was a moderate degenerative in certain parts of the kidney.

These experiments indicated that Hexamethylene Diamine is strongly alkaline and extremely irritating. Systemic effects resulted in damage to the kidney.