Registration Dossier

Administrative data

Description of key information

Skin: Primary skin irritation studies in rabbits with the undiluted test substance resulted in (very) strong necrosis after exposures of 1, 5, and 15 minutes (reading at 24h and 8 days). In an in vitro membrane barrier test method for skin corrosion according to OECD 435, the break through time indicates that the test substance has an intermediate corrosive potential and should be assigned to UN GHS skin corrosivity subcategories 1B.
Eye: A single instillation 50 µL undiluted material into the conjunctival sac of rabbits caused corrosion of conjunctivae and whole eyeball after 10 minutes and scabs at eyelids at the day after exposure. All effects remained for days until eyelids were closed by scabs and eyeballs were most likely destroyed.

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
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data are given
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
Method: BASF-test
- Exposure period was 1, 5, and 15 minutes.
- Occlusive instead of semi-occlusive dressing
- No scoring at 60 minutes, and at 48 and 72 hours is reported
- No observation up to 14 days after dosing is indicated (with respect to reversibility, etc).
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
Not indicated.
Duration of treatment / exposure:
1, 5, 15 min
Observation period:
24h, 8 days
Number of animals:
2 per duration of exposure
Details on study design:
TEST SITE
- Area of exposure: 2.5 * 2.5 cm
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes (water, sometimes with mild detergent)
SCORING SYSTEM:
Recorded scores:
N++ or N+++: Full thickness necrosis
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 24h
Remarks on result:
other: Strong necrosis in all test groups
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 8 days
Remarks on result:
other: Strong necrosis in 1 and 5 min exposure groups and very strong necrosis in 15 min exposure group
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
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
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data are given
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
Method: BASF-test
0.05 mL instead of 0.1 mL was used as dose level.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Vehicle:
unchanged (no vehicle)
Controls:
other: adjacent eye
Amount / concentration applied:
50 µL
Observation period (in vivo):
1h, 24h, 8 days
Number of animals or in vitro replicates:
2
Details on study design:
The saline-treated (NaCl) adjacent eye served as control.
Irritation parameter:
other: corrosion
Basis:
mean
Time point:
other: 10 min, 1h, 24h
Remarks on result:
other: Corrosion of conjunctivae and whole eyeball; bloody secretion; eyelids: scabs
Irritation parameter:
other: corrosion
Basis:
mean
Time point:
other: 8 days
Remarks on result:
other: Eyelids closed by scabs; eyeball most likely destroyed
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin:

The test substance was applied undiluted to the intact rabbit skin for 1, 5, and 15 min, respectively. The results were read after 24 h and 8 days. In all exposure groups the test substance caused strong necrosis after 24 hours. After 8 days test substance caused strong necrosis in the 1 and 5 min exposure groups and very strong necrosis in the 15 min exposure group (BASF, 1966).

This finding is supported by several reports / publications:

- In a study provided by Union Carbide Corp, the chemical was applied in 0.01 mL amounts to clipped, uncovered skin of rabbit bellies as undiluted sample or diluted sample (10, 1, 0.1 and 0.01 % in distilled water). Ten grades are recognized based on the appearance of moderate or marked capillary injection, erythema, edema or necrosis within 24 hours (No injury from undiluted = Grade 1). Necrosis on 2 of 2 animals from the undiluted material; marked capillary injection on 3 animals, marked erythema in 1 animal, moderate edema in 1 from a 10% dilution; injury grade 6 out of 10. Since application of the undiluted material caused necrosis it was considered a U.S. Dept. of Transportation "corrosive" material. Application of a 10% dilution in distilled water resulted in a minor skin irritation. A relevant excerpt of this data is also reported by Myers and Ballantyne (1997).

Thus, solutions containing less than 10% of the test substance are not irritating to skin.

- 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 the sample. The test substance yielded an injury grade of 7, where 6 indicates necrosis when undiluted and 10 indicates necrosis from a 0.01% solution (Smyth, 1962; Benya, 1994).

The potential of 1,3-Diaminopropane to cause dermal corrosion was assessed by a single topical application of 500 μL of the test substance to the Corrositex® Biobarrier Membrane (Corrositex® assay; BASF SE 2013). The Corrositex® Biobarrier Membrane is the test system consisting of a reconstituted collagen matrix. The assay is based on the time that is required for the test substance to penetrate through the Corrositex® Biobarrier Membrane and produce a change in the Chemical Detection System (CDS). In addition to the test substance a positive and a negative control were assessed. The Corrositex® assay showed the following results: The qualification screen demonstrated that the test substance is able to react with the CDS and produce a visible color change. Therefore the membrane barrier test method was determined to be suitable for the evaluation of the corrosive potential of the test substance. A timescale category test was carried out to distinguish between weak and strong acids or bases. The test substance was assigned to timescale category 1 (having a high acid/alkaline reserve). In the main test four Corrositex® Biobarrier Membranes were treated with the test substance. Based on the observed results and applying the evaluation criteria it was concluded, that 1,3-Diaminopropane shows a corrosive potential in the Corrositex - Skin Corrosion Test under the test conditions chosen. The mean break through time determined in the in vitro membrane barrier test was 14 minutes and 22 seconds. The break through time indicates that the test substance has an intermediate corrosive potential and should be assigned to UN GHS skin corrosivity subcategories 1B.

Eye:

Two Vienna white rabbits received a single instillation 50 µL undiluted material into the conjunctival sac. The adjacent eye served as control. Examinations were made 10 min, 24h, and 8 days after application (BASF, 1966). The reported results are corrosion of conjunctivae and whole eyeball after 10 minutes and scabs at eyelids at the day after exposure. All effects remained for days until eyelids were closed by scabs and eyeballs were most likely destroyed.

This finding is supported by several reports / publications:

- According to a study report provided by Union Carbide Corp. 5 animals received a single instillation of 0.005, 0.02, 0.10 or 0.5 mL undiluted material or of 0.5 mL of 40, 15, 5 and 1% dilutions in distilled water into the conjunctival sac. Examinations were made immediately and 24 hours after instillation; severe corneal injury, iritis and eyelid injury (edema, hemorrhage, pus, necrosis) from 0.005 mL undiluted; severe corneal injury, with iritis, from 0.5 mL per eye of a 5% dilution in distilled water; no corneal injury on 5 eyes from 1% in distilled water. The substance was classified injury grade 9 out of 10, causing severe eye damage. A relevant excerpt of this data is also reported by Myers and Ballantyne (1997).

- The same or identical data is also reported by Smyth (1962) and Benya (1994).

Thus, solutions containing 1% of the test substance are not irritating to eyes.


Justification for selection of skin irritation / corrosion endpoint:
Most reliable study

Justification for selection of eye irritation endpoint:
Most reliable study

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin

Based on the available results obtained in skin irritation studies, the test substance has to be classified with respect to skin corrosion with C; R35 "Causes severe burns" according to Directive 67/548/EEC (DSD) and cat. 1B; H314 "Causes severe skin burns and eye damage" according to Regulation (EC) No 1272/2008 (CLP, GHS).

Eye

Based on the results obtained in a eye irritation study with rabbits (corrosion of conjunctivae and whole eyeball after 10 minutes, scabs at eyelids recorded the day after exposure, all effects remained for days until eyelids were closed by scabs and eyeballs most likely destroyed) the test substance has to be classified with respect to eye irritation / corrosion with C; R41 "Risk of serious damage to eyes" according to Directive 67/548/EEC (DSD) and with eye irrit. cat 1, H318 "Causes serious eye damage" according to Regulation (EC) No 1272/2008 (CLP, GHS).