N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine

Endpoint summary

Description of key information

N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine causes skin and cornea necrosis in rabbits (Smyth et al., 1962). 

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Qualifier:

no guideline followed

Principles of method if other than guideline:

Primary skin irritation on rabbits is recorded in a 10-grade ordinal series for the severest reaction that develops on the clipped skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 ml of test substance (undiluted or as solution in water, propylene glycol, or acetone). The scoring system was slightly similar to the method reported by Draize and associates.

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
not reported


ENVIRONMENTAL CONDITIONS
not reported

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.01 ml undiluted test substance or as solution in water, propylene glycol, or acetone (not specified)

Duration of treatment / exposure:

24 hours

Observation period:

not reported

Number of animals:

5

Details on study design:

TEST SITE
- Area of exposure: unspecified; rabbit belly
- % coverage: not specified; uncovered application

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: 24 hours

SCORING SYSTEM:
The following scoring table was used:
- Grade 1: no reaction whatever from undiluted sample,
- Grade 2: an average reaction equivalent to a trace of capillary injection from undiluted sample,
- Grade 3: strong capillary injection from undiluted sample,
- Grade 4: slight erythema from undiluted sample,
- Grade 5: strong erythema, edema or slight necrosis from undiluted sample,
- Grade 6 and higher: necrosis from undiluted sample,
- Grade 6: a 10% solution gives no reaction more severe than edema
- Grade 7: indicates necrosis from a 1%s olution
- Grade 8: indicates necrosis from a 0.1% solution
- Grade 9: indicates necrosis from a 0.01% solution
- Grade 10: indicates necrosis from a 0.01% or any weaker solution.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: no data

Score:

6

Max. score:

10

Remarks on result:

other: the score grade of 6 indicates that the undiluted test substance caused necrosis

Interpretation of results:

other: corrosive

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Qualifier:

no guideline followed

Principles of method if other than guideline:

To evaluate the eye irritation potency of the test substance, a flooding volume (0.5 ml) was instilled directly into the eye of 5 rabbits (not rinsed). Eye injury in rabbits was then recorded in a 10-grade ordinal series and is based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
not reported


ENVIRONMENTAL CONDITIONS
not reported

Vehicle:

unchanged (no vehicle)

Remarks:

Where dilution of a chemical is necessary, the preferred solvent was propylene glycol from a batch shown to cause no injury, followed by water, and in some cases a deodorized kerosene known as "Deobase" has been used.

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.005, 0.02, 0.1 or 0.5 mL. Guided by the result and the table of injury grades below, additional applications are made until the chemical can be assigned to one of the defined grades. If large volumes are applied, the lids are held closed for one minute before the animal is released.

Duration of treatment / exposure:

unrinsed

Observation period (in vivo):

18-24 h

Number of animals or in vitro replicates:

5

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM:
The individual numerical scores of eye treated with a given volume or concentration of a chemical are added together and then divided by the number of eyes (usually 5) to obtain the score injury caused by the treatment. The level of 5.0 was selected as representative of severe injury. This figure corresponds to necrosis visible only after staining and covering about three fourths of the surface of the cornea; or a more severe necrosis covering a smaller area.

1) Generally the symptoms were scored as followed:
- Symptom visible before Fluorescein staining:
cornea dull: 2 points
cornea opaque, less than half of area: 4 points
cornea opaque, more than half of area: 6 points (Maximum points)
Keratoconus: 6 points (Maximum points)
Iritis, slight internal congestion: 1 point
Iritis, marked internal congestion: 2 points (Maximum points)

- Symptom visible after Fluorescein staining:
Necrosis on less than 5% of cornea: 1 point
Necrosis on 5 to 12%: 2 points
Necrosis on 13 to 37%: 3 points
Necrosis on 38 to 62%: 4 points
Necrosis on 63 to 87%: 5 points
Necrosis on 88 to 100%: 3 points (Maximum points)

- Total maximum points: 20 points

2) The injury was then graded according to the following table:
- Grade 1: 0.5 ml undiluted gives injury of 0 to 1.0 points
- Grade 2: 0.5 ml undiluted gives injury of over 1.0 up to 5.0 points
- Grade 3: 0.1 ml undiluted gives injury of up to 5.0 points (0.5 ml gives over 5.0)
- Grade 4: 0.02 ml undiluted gives injury of up to 5.0 points (0.1 ml gives over 5.0)
- Grade 5: 0.005 ml undiluted gives injury of up to 5.0 points (0.02 ml gives over 5.0)
- Grade 6: excess of 40% solution gives injury of up to 5.0 points (0.005 ml gives over 5.0)
- Grade 7: excess of 15% solution gives injury of up to 5.0 points (40% gives over 5.0)
- Grade 8: excess of 5% solution gives injury of up to 5.0 points (15% gives over 5.0)
- Grade 9: excess of 1% solution gives injury of up to 5.0 points (5% gives over 5.0)
- Grade 10: excess of 1% solution gives injury of over 5.0 points

TOOL USED TO ASSESS SCORE: the eye is examined in strong diffuse daylight, then stained with fluorescein and the injury scored.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 18-24 h after treatment

Score:

9

Max. score:

10

Reversibility:

other: necrosis

Remarks on result:

other: The test substance was attributed to Grade 9 on a scale of 10, indicating that excess of 1% solution gives injury of up to 5.0 points (5% gives over 5.0), corresponding to necrosis on 63 to 87% of the cornea.

Interpretation of results:

corrosive

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

In study of Smyth et al. (1962, Rel 2) primary skin irritation on rabbits was recorded in a 10-grade ordinal series and is based upon the severest reaction that develops on the clipped skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 mL of undiluted sample. The observed grade 6 indicates necrosis of the skin when applied undiluted (no further details).

 

Eye Irritation

 

The eye irritation potency of Bis-DMAPA was also evaluated in the Smyth publication (Smyth et al., 1962; Rel 2). When a flooding volume (0.005, 0.02, 0.1 or 0.5 mL) of test substance at concentration levels of 1, 5, 15, 40 or 100% in propylene glycol, water or deodorized kerosene (not further specified) was instilled into the rabbit eye (5 animals, no washing) and observed 18-24 hours thereafter, the test substance was attributed to Grade 9 on a scale of 10, indicating that excess of 1% solution caused injury of up to 5.0 points (5% caused over 5.0), corresponding to necrosis on 63 to 87% of the cornea.

 

 

 

Justification for classification or non-classification

N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine causes skin and cornea necrosis in rabbits (Smyth et al., 1962).Since the test method does not allow to subcategories the skin irritating potential, the classification is based on the experimental results and the structural hints on a corrosive potential of the substance (secondary amine) by expert judgement.

 

Classification,Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for skin and eye irritation (cat. 1B, H314) under Regulation (EC) No. 1272/2008, as amended for the third time in Directive (EC 618/2012).