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

Endpoint summary

Description of key information

An in vitro Membrane Barrier Test for Skin Corrosion (Corrositex^®) according to OECD guideline 435 was performed with the test substance itself (K1; Groot A, 2021). The test substance is classified as UN packing group III (= GHS 1C) in the Corrositex^® assay, meaning that it is corrosive to the skin.

An in vivo skin irritation test was performed with the read-across substance DMAPA according to OECD Guideline 404 (Mallory et al., 1993). The substance was observed to be corrosive to the skin. In addition, in an acute dermal toxicity study with the test substance itself, the substance was observed to be corrosive (American Cyanamid Company, 1964). In a K4 in vivo skin irritation study of Smyth et al. (1962) the substance might have been necrotic to the skin in rabbits. Based on the available information, the test substance is classified as skin corrosive substance category 1B following the precautionary principle.

A supporting in vivo eye irritation study performed according to OECD 405 with acceptable restrictions (K2; American Cyanamid Company, 1964) is available. Instillation of the substance caused immediate signs of discomfort and shortly thereafter corneas appeared to be completely opaque and lids were burned and hemorrhagic. No improvement occurred during the 7 days eyes were examined, and by that time the lids were closed, dry and necrotic. This indicates that the substance is corrosive to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Remarks:

In vitro Membrane Barrier Test for Skin Corrosion

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-10-22 to 2021-11-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)

Version / remarks:

28 July 2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch (Lot) Number: PFW210614
- Expiry date: 20 September 2023 (retest date)
- Physical Description: Clear amber liquid
- Purity/Composition: 99.0 A% by GC
- Purity/Composition correction factor: No correction factor required

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature protected from light container flushed with nitrogen

FORM AS APPLIED IN THE TEST: liquid

OTHER SPECIFICS
- Test item handling: Use amber glassware or wrap container in aluminum foil. Handle in glove box or AtmosBag (nitrogen environment). An inert gas such nitrogen blanketing is recommended.
- For each batch (lot) of test item, a reserve sample (about 0.5 gram) was collected and maintained under the appropriate storage conditions by the Test Facility.
- pH: 11.4 at a concentration of 1%
12.0 at a concentration of 10%

Test system:

artificial membrane barrier model

Remarks:

Corrositex® is a test system that is composed of two components, a hydrated collagen matrix (bio-barrier) on a supporting filter membrane and CDS, an underlying aqueous solution of two pH indicator dyes.

Source species:

other: artificial bio-barrier (hydrated collagen matrix)

Justification for test system used:

Recommended test system in international guideline (OECD 435).

Vehicle:

unchanged (no vehicle)

Details on test system:

SOURCE AND COMPOSITION OF MEMBRANE BARRIER USED:
- Batch number: CT051021
- Source: InVitro International Inc., Irvin CA, USA.
- Components: Bio-barrier matrix, Bio-barrier diluent, Vials with Chemical Detection System (= CDS), Membrane discs, Compatibility test tubes, Timescale categorize test tubes with buffer A and B, Confirm reagent.

PREPARATION PROCEDURES:
- Preparation of the Bio-Barrier:
The bio-barrier diluent (10 mL) was added to the bio-barrier matrix powder (1 gram) which contained a micro stir bar. This was stirred and heated slowly to 68°C in a water bath container. The membrane discs (at room temperature) were filled with 200 µL solubilized bio-barrier matrix. The entire membrane was covered with matrix and care was taken to avoid air bubbles. Membrane disks were stored in the refrigerator set to maintain 4°C until use. The membrane discs with biobarrier were used the day after preparation.

- Test Item Compatibility Test:
Prior to performing the membrane barrier penetration study, the test item was evaluated for the compatibility with the CDS. The test item (150 µL) was added to the compatibility test tubes filled with CDS fluid. The tube was shaken to dissolve solids. In case the test item was immiscible, the vial was shaken and the color change was read at the interface after 1 minute. If the CDS solution detected a color or consistency change within 5 minutes, the test item was tested for corrosivity using the Corrositex® kit. In case the CDS solution detected no color or consistency change the membrane barrier penetration study was not performed with Corrositex®.

- Test Item Timescale Category Test:
The test item was classified into one of the two timescale categories. This category determined how the penetration response time (if one occurs) was interpreted. The two different penetration response timescales were based on the acid or alkali reserve of the chemical. The test item (150 µL) was added to both buffers A and B, shaken vigorously for 10 seconds and after 1 minute the color change was read on the chart. In case the test item was immiscible, the color change was read at the interface after another minute. Buffer A detected weak or strong acids and buffer B detected strong or weak bases. The tube was shaken vigorously for 5 seconds and the color of the solution was read on the chart confirming that the item is a timescale category 2 item.

TEMPERATURE USED DURING TREATMENT: All tests were performed at room temperature. The samples were at room temperature when applied.

METHOD OF DETECTION
- Indicator solution: CDS fluid
- Dye(s) used: not specified
- Chemical or electrochemical detection system: Changes in the CDS may be color changes (red, orange or lightening) and flaking or precipitation.

METHOD OF APPLICATION:
A disc was placed on a vial with CDS fluid. The test item (500 µL) was applied on top of the matrix within two minutes after the disc was placed on the CDS fluid. One disc was exposed to 500 µL citric acid (10%, negative control) and one disc was exposed to 110 ± 15 mg of the positive control sodium hydroxide. The test item and controls were evenly distributed. Each vial was at least monitored for the first 5 minutes and 5 minutes before and after each packing cut-off time. The time of a change in the CDS fluid was recorded. Changes in the CDS may be color changes (red, orange or lightening) and flaking or precipitation. The elapsed time between application and penetration of the membrane was determined.

NUMBER OF REPLICATES: The test was performed on a total of 4 membrane discs with bio-barrier matrix together with a negative and positive control.

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if 3 and 30 minutes elapsed between application of the test substance to the membrane barrier and barrier penetration.
- The test substance is considered to be non-corrosive to skin if the penetration response time > 60 minutes.
- Justification for the selection of the cut-off point(s): not indicated

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Classified as a timescale 1 compound
- Amount(s) applied (volume or weight with unit): 500 µL (undiluted), directly on top of the bio-barrier matrix

NEGATIVE CONTROL
- 10% citric acid (Merck, Nottingham, United kingdom; CAS number 5949-29-1; batch number 1.00244.100; purity ≥ 99%).
- Amount(s) applied (volume or weight): Approximately 500 µL was applied, directly on top of the biobarrier.

POSITIVE CONTROL
- Sodium hydroxide (GHS corrosive subcategory 1B; category obtained from OECD 435) as it is (Merck, Nottingham, United kingdom; CAS number 1310-73-2; batch number B1835898 027: purity ≥ 99%).
- Amount(s) applied (volume or weight): 110 ± 15 mg was applied, directly on top of the biobarrier.

Duration of treatment / exposure:

not indicated

Number of replicates:

four

Irritation / corrosion parameter:

penetration time (in minutes)

Remarks:

Mean

Value:

84

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

ACCEPTABILITY CRITERIA

The in vitro membrane barrier test is considered acceptable if it meets the following criteria:

The negative control citric acid (10%) should be non-corrosive (category obtained from OECD 435) and have a penetration response time > 60 minutes.
The positive control time falls within ± two standard deviations of the positive control historical mean breakthrough time.
The breakthrough time of the positive control sodium hydroxide (as it is) should be between the 3 and 30 minutes (GHS corrosive subcategory 1B; category obtained from OECD 435).

All results presented in the tables of the report are calculated using values as per the raw data rounding procedure and may not be exactly reproduced from the individual data presented.

Test Item Compatibility Test
The test item was evaluated for the compatibility with the CDS. Because a color change (to red) was observed after 1 minute, the test item was compatible with the Corrositex® test system.

Test Item Timescale Category Test
The test item was classified into one of the two timescale categories. The timescale category test showed that the test item is a timescale 1 item (after one minute tube B showed a color change into purple). Since there appeared a color change after 1 minute, the addition of the confirm reagent to tube B was not performed.

 

Membrane barrier penetration test

Since the test item is a timescale 1 test item and showed a mean penetration time of 84 minutes, the test item is classified in UN packing group III (= GHS 1C).

The test passed all acceptance criteria:

1. The negative control citric acid (10%) showed a mean penetration time of >60 minutes (110 minutes) and was therefore non-corrosive.


2. The positive control sodium hydroxide (as it is) breakthrough time (20 minutes) falls within within ± two standard deviations of the positive control historical mean breakthrough time (Appendix 5).


3. The positive control sodium hydroxide (as it is) showed a mean penetration time of
   20 minutes and was therefore classified as UN packing group II (=GSH 1B).

 

Overall it was concluded that the test system functioned properly.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

In conclusion, the test substance is classified as UN packing group III (= GHS 1C) in the Corrositex® assay under the experimental conditions described in this report.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

read-across from related substance

Justification for type of information:

Data from the related substance DMAPA is used to cover this endpoint. The justification for read across is attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 and 24h exposure

Score:

>= 8

Max. score:

8

Remarks on result:

other: severe dermal irritation at 4 and 24h exposure

Irritation parameter:

erythema score

Basis:

animal: 4/6

Time point:

other: immediately after unwrapping

Score:

>= 3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: moderate to severe erythema immediately after unwrapping, 3 min exposure

Irritation parameter:

erythema score

Basis:

animal: 2/6

Time point:

other: immediately after unwrapping

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: severe erythema immediately after unwrapping, 3 min exposure

Irritation parameter:

erythema score

Basis:

animal: 6/6

Time point:

other: immediately after unwrapping, at 24, 48, 72h and 4d through 14d

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: severe erythema, necrosis; 60min, 4h or 24h exposure

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

other: immediately after unwrapping

Score:

>= 1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: very slight edema immediately after unwrapping; 3 min exposure

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

other: immediately after unwrapping

Score:

>= 2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: slight edema immediately after unwrapping; 3 min exposure

Irritation parameter:

edema score

Basis:

animal: 6/6

Time point:

other: immediately after unwrapping, at 24, 48, 72h and 4d through 14d

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: severe edema, necrosis; 60min, 4h or 24h of exposure

Irritant / corrosive response data:

Sloughing of the skin at the application site was observed on Days 7 through 14 at the 60 min exposure site, on Days 6 through 14 at the 24 h intact exposure site and on Days 12 through 14 at the abraded site. No sloughing of the skin was observed in any animal at the 4 h exposure site.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

No reliable skin irritation/corrosion study with the test substance is available. Data generated with the related substance DMAPA is used for endpoint coverage.
An in vivo skin irritation test was performed according to the OECD guideline 404 with read across substance DMAPA. 0.5 mL unchanged test substance was applied to the shaved or abraded skin site for 3 min (upper dorsal site for shaved skin) or 60 min, 4 and 24 hours (upper trunk site for shaved skin) of 6 NZW rabbits, secured with semi-occlusive patch and washed out with water and gauze. The skin reaction was evaluated according to the Draize scoring system. The test substance was severely irritating to corrosive at both the 4 and 24h exposures.
The same is assumed to be correct for the test substance.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-05-18 - 1992-06-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

control test was not performed

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material (as cited in study report): 6398-35-1
- Physical state: clear, colorless liquid
- Purity test date: responsibility of the Sponsor
- Stability under test conditions: no apparent change in the physical stage during storage
- pH 8 (litmus paper)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Denver, PA
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 2.348-2.618 kg
- Housing: Rabbits were housed individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council.
- Diet (e.g. ad libitum): Purina Lab Rabbit Chow (H.F.) ad libitum
- Water (e.g. ad libitum): Fresh tap water, ad libitum.
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C±3°C (63-73°)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light):12h light, 12h dark

IN-LIFE DATES: From: 1993-01-14 To: 1993-01-29

Type of coverage:

semiocclusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml/site, 5 sites per animal

Duration of treatment / exposure:

-3 min (upper dorsal site 1, intact), 60 min (upper dorsal site 2, intact), 4h (mid-dorsal site, intact)
-24h (lower dorsal trunk site 1 = intact, lower dorsal site 2 = abraded)

Observation period:

14 days

Number of animals:

6 animals (3 males and 3 females)

Details on study design:

TEST SITE
- Area of exposure: 5 sites (6 cm² per site) per animal : 3 intact sites on the dorsal area of the trunk, 1 intact site on the lower area of the trunc, 1 abraded site on the lower area of the trunk. intact and abraded:lower dorsal trunk)-clipped free of fur.
- Type of wrap if used: covered with gauze patch, suitable semi-occlusive dressing, covered with impervious material held in place with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water and gauze
- Time after start of exposure: respectively at 3 min, 60min, 4h and 24h

SCORING SYSTEM:
Draize Evaluation of Dermal Irritation, Primary Irritation Index

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 and 24h exposure

Score:

>= 8

Max. score:

8

Remarks on result:

other: severe dermal irritation at 4 and 24h exposure

Irritation parameter:

erythema score

Basis:

animal: 4/6

Time point:

other: immediately after unwrapping

Score:

>= 3

Max. score:

4

Reversibility:

not reversible

Remarks:

moderate to severe erythema immediately after unwrapping

Remarks on result:

other: 3 min exposure

Irritation parameter:

erythema score

Basis:

animal: 2/6

Time point:

other: immediately after unwrapping

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks:

severe erythema immediately after unwrapping

Remarks on result:

other: 3 min exposure

Irritation parameter:

erythema score

Basis:

animal: 6/6

Time point:

other: immediately after unwrapping, at 24, 48, 72h and 4d through 14d

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks:

severe erythema, necrosis

Remarks on result:

other: 60 min, 4h, or 24h exposure

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

other: immediately after unwrapping

Score:

>= 1

Max. score:

4

Reversibility:

not reversible

Remarks:

very slight edema immediately after unwraping

Remarks on result:

other: 3 min exposure

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

other: immediately after unwrapping

Score:

>= 2

Max. score:

4

Reversibility:

not reversible

Remarks:

slight edema immediately after unwrapping

Remarks on result:

other: 3 min exposure

Irritation parameter:

edema score

Basis:

animal: 6/6

Time point:

other: immediately after unwrapping, at 24, 48, 72h and 4d through 14d

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks:

severe edema, necrosis

Remarks on result:

other: 60 min, 4h or 24h of exposure

Irritant / corrosive response data:

Sloughing of the skin at the application site was observed on Days 7 through 14 at the 60 min exposure site, on Days 6 through 14 at the 24h intact exposure site and on Days 12 through 14 at the abraded site. No sloughing of the skin was observed in any animal at the 4h exposure site.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

An in vivo skin irritation test was performed according to the OECD Guideline 404 with read-across substance DMAPA. 0.5 mL unchanged test substance was applied to the shaved or abraded skin site for 3 min (upper dorsal site for shaved skin) or 60 min, 4 and 24 hours (upper trunk site for shaved skin) of 6 NZW rabbits, secured with semi-occlusive patch and washed out with water and gauze. The skin reaction was evaluated according to the Draize scoring system. The test substance was severely irritating to corrosive at both the 4 and 24 h exposures.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

Original reference is not available.

Principles of method if other than guideline:

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 or of solutions in water, propylene glycol or acetone.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Bis-[3-aminopropyl]amine

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.01 mL

Duration of treatment / exposure:

24 hours

Observation period:

No data

Number of animals:

No data

Details on study design:

Scoring: Grade 1 indicates no irritation and grade 2 the least visible injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted.

Remarks on result:

other: The observed grade 7 indicates necrosis of the skin for an undiluted sample of the test substance.

Remarks:

The test substance is hence corrosive

Irritant / corrosive response data:

Grade 7 was observed which indicates necrosis.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

The observed grade 7 indicates necrosis of the skin for an undiluted sample of the test substance.

Reference 5

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Reference 2

Endpoint:

eye irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study was performed, comparable with OECD 405. However, documentation of information was very limited.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): bis-dimethyl aminopropylamine; 3,3'-bis (dimethylamino) dipropylamine; bis (N,N'-dimethylaminopropoyl) amine
- Other: density: 0.84 g/L

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

No data

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

No data

Details on study design:

No data

Irritation parameter:

overall irritation score

Remarks on result:

other: After instillation to 0.1 mL of the substance, rabbits showed immediate signs of discomfort when eyes were dosed

Remarks:

Shortly thereafter corneas appeared to be completely opaque and lids were burned and hemorrhagic. No improvement occurred during the 7 days that eyes were examined, and by that time the lids were closed, dry and necrotic.

Irritant / corrosive response data:

Rabbits showed immediate signs of discomfort when eyes were dosed, and shortly thereafter corneas appeared to be completely opaque and lids were burned and hemorrhagic. No improvement occurred during the 7 days that eyes were examined, and by that time the lids were closed, dry and necrotic.

Interpretation of results:

study cannot be used for classification

Conclusions:

After instillation to 0.1 mL of the substance, rabbits showed immediate signs of discomfort when eyes were dosed, and shortly thereafter corneas appeared to be completely opaque and lids were burned and hemorrhagic. No improvement occurred during the 7 days that eyes were examined, and by that time the lids were closed, dry and necrotic.

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin corrosion

An in In vitro Membrane Barrier Test for Skin Corrosion (Corrositex^®) with the test item was performed according to the OECD guideline 435 (Groot A, 2021). The test item was applied undiluted (500 µL) on top of the bio-barrier matrix. The elapsed time between application and penetration was determined by monitoring changes in the chemical detection system. Overall it was concluded that the test system functioned properly. Since the test item was a timescale 1 test item and showed a mean penetration time of 84 minutes, it is classified in group III (= GHS 1C). The test item is therefore corrosive to the skin.

Skin irritation

Mallory et al. (1993) performed an in vivo skin irritation test according to the OECD Guideline 404 with read-across substance DMAPA. 0.5 mL unchanged test substance was applied to the shaved or abraded skin site for 3 min (upper dorsal site for shaved skin) or 60 min, 4 and 24 hours (upper trunk site for shaved skin) of 6 New Zealand White rabbits, secured with semi-occlusive patch and washed out with water and gauze. The skin reaction was evaluated according to the Draize scoring system. The test substance was severely irritating to corrosive at both the 4 and 24 h exposures. 

In a K4 study of Smyth et al. (1962) 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 7 indicates necrosis of the skin.

No in vitro skin irritation study was performed as adequate data from an in vivo study are available.

 

Eye irritation

A supporting K2 eye irritation study in New Zealand White rabbits (American Cyanamid Company, 1964) observed that after instillation of 0.1 mL of the substance, rabbits showed immediate signs of discomfort when eyes were dosed, and shortly thereafter corneas appeared to be completely opaque and lids were burned and hemorrhagic. No improvement occurred during the 7 days that eyes were examined, and by that time the lids were closed, dry and necrotic.

No in vitro eye irritation study is performed as the substance is considered to be corrosive to the skin.

Justification for classification or non-classification

An acute dermal toxicity study in rabbits indicated necrosis, fissuring and sloughing of the skin at the application site after 24 hours of exposure (American Cyanamid Company, 1964). In addition, the structural analogue DMAPA was demonstrated to be a skin corrosive substance category 1B (Mallory VT, 1993). More information on DMAPA can be found in the read-across justification attached in section 13 of this IUCLID dossier. In addition, signs of necrosis were observed in a K4 in vivo skin irritation study (Smyth et al., 1962). The test substance was classified as UN packing group III (= GHS 1C) in the Corrositex® assay. Based on all information available and the criteria of the CLP Regulation, the test substance should be classified as category 1C skin corrosive substance (H314).

In addition, based on the available data and the corrosive nature of the test substance to the skin, the test substance is classified as category 1 serious eye damage (H318).