Hexamethylenediamine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 conducted before GLP 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.3

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 conducted before GLP establishment.

Test type:

standard acute method

Limit test:

no

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

Constituent 2

Reference substance name:

Hexane-1, 6-diamine

IUPAC Name:

Hexane-1, 6-diamine

Details on test material:

- Name of test material (as cited in study report): Hexamethylene diamine, 7273 RP
- 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: 120 to 150g
- 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

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 X 6 cm2
- % coverage: No data
- Type of wrap if used: aluminium + adhesive plaster


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with soapy water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): volume of the substance itself
- Constant volume or concentration used: no

Duration of exposure:

24 hours

Doses:

950, 1400, 2000, 3000 or 4800 mg/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:

LD 50 was calculated according to Dragstedt & Lang

Results and discussion

Preliminary study:

no data

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 900 mg/kg bw

Mortality:

See table 7.2.3/1

Clinical signs:

other: Lower motricity in the three higher dose groups, closed eyes and low body temperature in some animals of the three higher dose groups.

Gross pathology:

At dose levels of 4300, 3000 and 2000 mg/kg bw, 24 hours after treatment, necrosis appeared on all the treated surface, without cicatrisation at death time.
At dose levels of 1400 and 950 mg/kg bw, necrosis formation was observed in day 1 after exposure. Necrosis was recovered every day by a scab, up to the end of the observation period.

Other findings:

No data

Any other information on results incl. tables

Table 7.2.3/1: Number of animals dead

Dose (mg/kg bw)	Mortality (x/number of rats)	DL50 after 15 observation days (mg/kg bw)
4800	10/10	Approximately 1900
3000	10/10
2000	6/10
1400	0/10
950	0/10

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, dermal LD50 combined = 1900 mg/kg bw . HMD is classified as Harmful in contact with skin (Xn R21) and in category 4 according to the CLP regulation (1272/2008).

Executive summary:

In an acute dermal toxicity study (Marzin, 1978), groups of Sprague-Dawley rats (5/sex) were given a single dose of undiluted liquid HMD at doses of 0, 950, 1400, 2000, 3000 or 4800 mg/kg bw using an occlusive patch held in place for 24 hours. Following the HMD 24 -hour exposure, the patch were removed and the skin was rinsed with soapy water. Then, the animals were observed for 15 days.

A body weight loss was observed in the higher dose group on day 10.

Clinical signs included lower motricity in the three higher dose groups, closed eyes and low body temperature in some animals of the three higher dose groups.

At both lowest dose levels (2000 to 4300 mg/kg bw), necrosis appeared on all the treated surface 24 hours after treatment, without cicatrisation at death time.

At both lower dose levels, necrosis formation was observed the first day following treatment and was recovered every day by a scab, up to the end of the observation period.

Dermal LD50 combined = 1900 mg/kg bw.

This acute dermal study is considered as acceptable. It does satisfy the guideline requirement for an acute dermal study (method B3 in the Directive 92/69/EEC) in the rat. Based on the results of this study, HMD is classified as Harmful in contact with skin (Xn R21) and in category 4 according to the CLP regulation (1272/2008).