N,N,N',N'-tetramethylhexamethylenediamine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1981-05-12)

Deviations:

yes

Remarks:

limit dose level: 400 mg/kg bw (recommended dose level by guideline 2000 mg/kg bw)

GLP compliance:

no

Remarks:

(GLP was not mandatory when study was done)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethylhexamethylenediamine

EC Number:

203-842-9

EC Name:

N,N,N',N'-tetramethylhexamethylenediamine

Cas Number:

111-18-2

Molecular formula:

C10H24N2

IUPAC Name:

[6-(dimethylamino)hexyl]dimethylamine

Specific details on test material used for the study:

- Name of test material (as cited in study report): N,N,N',N'-Tetramethyl-1,6-hexanediamine
- Analytical purity: 97.5 %
- Expiration date of the lot/batch: 1983-11
- Impurities (identity and concentrations): N,N',N'-Trimethyl-1,6-hexanediamine 2 %

Test animals

Species:

rabbit

Strain:

Vienna White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: mean (females): 2.74 kg, mean(males): 3.16 kg
- Housing: individual animals in steel cages, floor area 40 x 51 cm, no bedding
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm; Muskator-Werke Düsseldorf, Germany (about 130 g per day)
- Water (e.g. ad libitum): 250 ml per animal per day, fully demineralized water at workday, on other days: tap water
- Acclimation period: about 8 days before study begin, same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 30 - 70
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 395 cm²
- Type of wrap if used: inert foil

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing with warm water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Concentration (if solution): 30 %

Duration of exposure:

24 hrs

Doses:

400 mg/kg bw

No. of animals per sex per dose:

5 female and 5 male animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: signs and symptoms were recorded several times on day of application and then once per workday. Check for moribund and dead animals twice each workday and once on other days. Check for skin was done 30-60 minutes after removal of occlusive dressing and then each workday. Weighing was done immediately after beginning of the test and after 4, 7, 11 and 15 days
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights, histopathology

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 400 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 0/5 male animals died; 2/5 female animals died after 8 d

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 400 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no male animals died

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 400 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/5 female animals died

Mortality:

male animals: 0/5 died
female animals 2/5 died after 8 days

Clinical signs:

other: male animals: apathy from day 1 to 11 female animals: dyspnea at day 4 apathy: from day 1 to day 8 abnormal position, diarrhoe: at day 4

Gross pathology:

Animals that died (females):
Skin: deep necrosis; general passive hyperemia
Sacrificed animals (males and females):
Skin: deep necrosis at the application site with callous thickening of the subcutis and edematization of the muscles
Organs: no abnormalities detected

Other findings:

local findings on male and female animals:
erythema: from day 1 to 6
deep necrosis: from day 1 to 15
edema: from day 1 to 15

Any other information on results incl. tables

Table 1: Mortality

Dose [mg/kg bw]	Toxicological results*	mortality
Males
400	0/5	0%
Females
400	5/5	20%
LD50 > 400 mg/kg bw
* first number = number of dead animals, second number = number of animals used

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The substance is classified for acute dermal toxicity in Category 3 (CLP); toxicity is attributable to local corrosivity.

Executive summary:

A test of acute dermal toxicity was conducted on 5 male and 5 female rabbits with the test substance. Substance was applied occlusive at a dose of 400 mg/kg bw. Test deviated from OECD guideline 402 in limitation of dosage to 400 mg/kg bw and the occlusive application. After 8 days 2/5 female animals died whereas all males survived. Therefore a mortality of 40 % for female rabbits and 0 % for male rabbits can be derived resulting in a LD50 > 400 mg/kg bw.