Hexamethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is sufficiently described and the method is similar to EU and OECD test guidelines. Study performed before GPL establishment.

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:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Directive 92/69/EEC, B.1

Deviations:

yes

Remarks:

: Details on test animals and environmental conditions are limited

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

Study performed before GLP establishment.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexamethylene Diamine

IUPAC Name:

Hexamethylene Diamine

Constituent 2

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): 7273 R.P. , Hexamethylene Diamine
- Substance type: technical product
- Physical state: liquid
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ONCINS, IFFA CREDO
- Age at study initiation: no data
- Weight at study initiation: 130 to 160g
- Fasting period before study: no data
- Housing:no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: no data

Doses:

900, 1170, 1530 and 2000mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: animals in the higher non-lethal dose group were weighed once every 5 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

method of Litchfield and Wilcoxon.

Results and discussion

Preliminary study:

No data

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 160 mg/kg bw

Remarks on result:

other: 95% C.L: no data

Mortality:

See Table 7.2.1/1

Clinical signs:

other: For all doses: cries after treatment and excessive salivation. A decrease of the motor activity was observed at dose level of 1170 and 900 mg/kg bw.

Gross pathology:

At dose levels of 2000 and 1530 mg/kg bw, for all died animals, an ulceration of all the surface of the gastric mucous membrane was noted and also the presence of blood in the intestine was observed.
At dose level of 2000 mg/kg bw, for the surviving animal, an ulceration of the 3/4 mucous membrane was observed, with a thickening and an adherence to spleen, stomach and abdominal wall.
At dose level of 1530 mg/kg bw, one surviving animal presented the same lesions of the surviving animal at dose level of 2000 mg/kg bw, and the other surviving animal not presented any lesion.
At dose level of 1170 mg/kg bw, for the 7 died animals, an ulceration of the pylore was noted. No lesions were observed for the surviving animals.
At dose level of 900 mg/kg bw, no lesions were observed.

Other findings:

No data

Any other information on results incl. tables

Table 7.2.1/1 Number of animals dead and time range within which mortality occured

Dose (mg/kg/bw)	Mortality (# dead/total)			Time range o f deaths (hours)
	Male	Female	Combined
Control	-	-	-	-
900	-	-	01/10	D6
1170	-	-	07/10	D2-D4
1530	-	-	08/10	D0-D12
2000	-	-	09/10	D0-D4

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, oral LD50 Combined Males/Females = 1160 mg/kg. HMD is classified as Harmful if swallowed (Xn R22) and in category 4 according to the CLP regulation (1272/2008).

Executive summary:

In an acute oral toxicity study (method B1 in the Directive 92/69/EEC), (Marzin, 1978), groups of Sprague-dawley rats (5/sex) were given a single oral dose of HMD at doses of 0, 900, 1170, 1530 and 2000 mg/kg bw and observed for 15 days. Signs of intoxication were a decrease of the motor activity and exessive salivation. At necropsy, an ulceration of the pylore and all the surface of the gastric mucous membrane was noted. Oral LD50 combined Males/Females of 1160 mg/kg bw was established.

This acute oral study is considered as acceptable. It does satisfy the guideline requirement for an acute oral study (method B1 in the Directive 92/69/EEC) in the rat.

Based on the results of this study, HMD is classified as Harmful if swallowed (Xn R22) and in category 4 according to the CLP regulation (1272/2008).