N,N,N',N'-tetramethylethylenediamine

Endpoint summary

Description of key information

An in vitro assay and four in vivo assays of skin corrosion are available for TMEDA.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

28 June to 30 June 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

In vitro study of skin corrosion, conducted to accepted methodology but prior to development of current guideline.

GLP compliance:

no

Specific details on test material used for the study:

Bulab 600
Lot: 3H-9275
Appearance: clear pale yellow liquid
Storage conditions: Room temperature protected from light

Test system:

artificial membrane barrier model

Source species:

other: Synthetic

Cell type:

other: Hydrated collagen matrix and supporting filter membrane

Cell source:

other: Synthetic

Source strain:

other: Synthetic

Justification for test system used:

The Corrositex assay is a standardised and quantitative in vitro corrosivity test. It is based on the time that is required for the test sample to pass through a biobarrier membrane and produce a change in the Chemical Detection System. The Corrositex Biobarrier Membrane consists of a reconstituted collagen matrix.

Vehicle:

unchanged (no vehicle)

Details on test system:

The experimental design consists of a pH determination, if possible, and a definitive Corrositex assay in the Chemical Detection System. The Corrositex assay is evaluated on the basis of the colour change of the Chemical Detection System. The time that a colour change is observed is recorded manually and the average of the six replicates is used to determine the Packing Group.
The biobarrier is prepared by adding the biobarrier diluent to the biobarrier matrix powder. This is warmed to 67-69 degrees C to aid solubility. Following this, 200 mcL of the matrix is pipetted onto the membrane discs which are refrigerated at 2-8 degrees C for at least 2 hours, up to 7 days.
Seven vials were used (six for the test material and one for the positive control); 22 mL of the Chemical Detection System was dispensed into each of these vials and 12 mL was dispensed into an eighth vial to serve as the blank control. A membrane disc was placed into one vial which contained 500 mcL of the test material. The vial was observed for three minutes. At one minute intervals, the remaining five membrane discs each containing 500 mcL of test material were added to five further vials. A membrane disc containing a pellet of sodium hydroxide was added to the seventh vial.
The vials were observed continuously for the first 10 minutes, and then at approximately 5 minutes intervals for 4 hours. The first indication of a colour change in the Chemical Detection System (as compared to the blank control) was recorded.
The mean time for the colour to change determined the packing group:
<3 minutes – Packing group I
3 mins to 1 hour – Packing group II
1 to 4 hours – Packing Group III
>4 hours – Non-corrosive

Control samples:

yes, concurrent positive control

Amount/concentration applied:

500 mcL for the test material.

Duration of treatment / exposure:

Up to 4 hours or until a colour change was noted.

Number of replicates:

Six

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

1

Value:

>= 40 - <= 43

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

valid

Remarks:

Breakthrough time of 13 min 20 sec

Remarks on result:

positive indication of irritation

Other effects / acceptance of results:

Positive control response met the acceptance criteria (breakthrough time between 9 min 33 sec and 14 min 01 sec).

Test article	Breakthrough time (min)							Packing group	pH
	Vial 1	Vial 2	Vial 3	Vial 4	Vial 5	Vial 6	Mean
Bulab 600	43	40	40	41	41	40	40	II	11.0

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The test material was assigned to Packing Group II based on mean breakthrough time of 40 minutes. The results of this study indicate that TMEDA is corrosive to skin

Executive summary:

Bulab 600 was tested for potential corrosivity using the Corrositex continuous time monitor assay which is a calibrated biobarrier into a chemical detection system. The substance was tested in a single experiment with six replicates. The mean breakthrough time was determined to be 40 minutes and was therefore assigned to Packing Group II. The results of this study indicate that TMEDA is corrosive to skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

25-26 July 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

Guideline:

other: DOT skin corrosion test

Deviations:

no

Principles of method if other than guideline:

Assessment of skin corrosion in vivo following exposure for 3 minutes, 1 hour and 4 hours.

GLP compliance:

no

Specific details on test material used for the study:

Anhydrous TMEDA
Lot #M26000011200446
Clear colourless liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: Davidson’s Mill Farm, South Brunswick, New Jersey
Housing: Single in suspended steel caging with mesh floors.
Photoperiod: 12 hour light-dark cycle.
Food: Purina rabbit chow #5326
Water: Filtered tap water, ad libitum

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

3 minute, 1 hour and 4 hours (exposure terminated after 1 hour)

Observation period:

24 hours

Number of animals:

Three (1 male and 2 females)

Details on study design:

Following acclimatisation, the dorsal area of each animal’s trunk was clipped free of hair. The test areas were 6cm2. The test substance was applied and each test area covered with a 1x1 inch 4-ply gauze pad. The torso of each animal was wrapped with 3 inch Micropore tape to avoid dislocation of the pads. Elizabethan collars were placed on each rabbit and they were returned to their cages. The collars were removed after 1 hour. The patches were removed at the appropriate dose sites at the 3 minute and 1 hour intervals. The 4-hour patches were removed after 1 hour due to the severity of the irritation at the 1-hour dose sites. Following patch removal, the sites were wiped with water and a clean towel to removed residual test substance. All test sites were evaluated for corrosion 1-hour after patch removal. Subsequent evaluations were performed approximately 24 hours after removal of the 1-hour patches. Corrosion was considered to have resulted if the test substance caused full thickness necrosis (or ulceration) at the dose sites in at least one animal. Full-thickness necrosis is defined as moderate to severe tissue destruction with well-defined dark brown or black discoloration and /or stiffened texture, covering a substantial area. Epidermal sloughing, erythema, edema or fissuring was not considered tissue destruction. The dose sites were also evaluations for skin irritation according to Draize’s scoring system at the same intervals.

Irritation parameter:

other: indication of corrosivity

Remarks:

3-minute exposure

Basis:

animal: 1-3

Time point:

other: 1 hour

Remarks on result:

other: no indication of corrosivity

Irritation parameter:

other: indication of corrosivity

Remarks:

3-minute exposure

Basis:

animal: 1-3

Time point:

24 h

Remarks on result:

other: positive indication of corrosivity

Irritation parameter:

other: indication of corrosivity

Remarks:

1-hour exposure

Basis:

animal: 1-3

Time point:

other: 1 hour

Remarks on result:

other: no indication of corrosivity

Irritation parameter:

other: indication of corrosivity

Remarks:

1-hour exposure

Basis:

animal: 1-3

Time point:

24 h

Remarks on result:

other: positive indication of corrosivity

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

4 hour exposure (patches removed after 1 hour due to corrosivity)

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

4 hour exposure (patches removed after 1 hour due to corrosivity)

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

4 hour exposure (patches removed after 1 hour due to corrosivity)

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

4 hour exposure (patches removed after 1 hour due to corrosivity)

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

4 hour exposure (patches removed after 1 hour due to corrosivity)

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 24 hours

Irritant / corrosive response data:

At the 3-minute exposure site, moderate erythema and very slight edema with dark discoloration was observed at all three treated sites one hour after patch removal. At the 24-hour examination interval, corrosive eschar was observed at all dose sites.

At the 1-hour exposure site (which also included the 4-hour exposure site which was terminated after only 1 hour), severe erythema and slight edema with dark discoloration was observed at all treated sites. At the 24-hour evaluation, corrosive eschar was observed at all dose sites.
Due to the severity of irritation noted at the 24-hour scoring interval of all treated sites, the study was terminated early and the animals euthanised for humane reasons.

The test material was considered to be positive for corrosivity 24 hours after patch removal for both 3-minute and 1-hour exposures.
The test material was considered to be negative for corrosivity 1 hour after patch removal for both 3-minute and 1-hour exposures.

Other effects:

Eschar and dark discoloration were observed at the application sites.

Skin corrosion scores

Animal number	Sex	3-minute exposure		1-hour exposure		4-hour exposure (terminated after 1-hour)
		1 hour after patch removal	24 hours after patch removal	1 hour after patch removal	24 hours after patch removal	1 hour after patch removal	24 hours after patch removal
2075	F	Negative	Positive	Negative	Positive	Negative	Positive
2076	M	Negative	Positive	Negative	Positive	Negative	Positive
2077	F	Negative	Positive	Negative	Positive	Negative	Positive

 

Skin irritation scores for erythema and eschar formation/edema formation

Animal number	Sex	3-minute exposure		1-hour exposure		4-hour exposure (terminated after 1-hour)
		1 hour after patch removal	24 hours after patch removal	1 hour after patch removal	24 hours after patch removal	1 hour after patch removal	24 hours after patch removal
2075	F	3/1^1	4/2^2	4/2^1	4/2^2	4/2^1	4/2^2
2076	M	3/1^1	4/2^2	4/2^1	4/2^2	4/2^1	4/2^2
2077	F	3/1^1	4/2^2	4/2^1	4/2^2	4/2^1	4/2^2
Total		9/3	12/6	12/6	12/6	12/6	12/6
Mean		3/1	4/2	4/2	4/2	4/2	4/2

Footnote:
1 Dark discoloration noted at dose site
2 Eschar (corrosive) observed at dose site

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

Visible necrosis of the skin tissue was not observed at any of the 3-minute dose sites within 60 minutes of exposure, but was observed at all dose sites after 1-hour exposure. These results were considered to place the test material into Class 8, Packing Group II. The study indicates that the substance is classified for skin corrosivity

Executive summary:

A DOT skin corrosion test was conducted in New Zealand albino rabbits. Three animals were treated with 0.5 mL of TMEDA for periods of 3 minutes and 1 hour. A 4 -hour exposure was also planned, but was terminated early. Observations were made 1 and 24 hours after removal of the patches. At the 3-minute exposure site, moderate erythema and very slight oedema with dark discoloration was observed at all three treated sites one hour after patch removal. At the 24 -hour examination interval, corrosive eschar was observed at all dose sites. At the 1 -hour exposure site, severe erythema and slight edema with dark discoloration was observed at all treated sites. At the 24-hour evaluation, corrosive eschar was observed at all dose sites. The results of this study indicate that TMEDA is corrosive to skin.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

5 to 7 December 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

Guideline:

other: DOT skin corrosion test

Principles of method if other than guideline:

Assessment of in vivo skin corrosion following application for 1 hour.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: Bayne’s Bunny Barns, Gainesville, Florida
Housing: Individually. Temperature and humidity controlled.
Food: Wayne Rabbit Ration F8600-00 (Continental Grain Co., Chicago, Illinois)
Water: Tap water, ad libitum
Acclimatisation: At least three days
Weight range when tested: 3.4 to 3.5 kg

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

60 minutes

Observation period:

30 minutes, 24 and 48 hours after patch removal.

Number of animals:

Three

Details on study design:

Approximately 24 hours prior to treatment, the skin was prepared by clipping the mid-dorsal region of the back free of hair. Four 1 x 1 inch test sites on the back of each animal were delineated. Body weight was recorded.
The test substance was applied to the anterior right quadrant of each animal. Three other compounds were applied to the remaining three quadrants. A 2 x 2 inch gauze pad was taped over each test site and the trunk of the animal was occluded with latex lined with 2-ply plastic wrap. The rabbits were placed into stocks during the exposure period and first observation to prevent access of the animals to the patch and treated area. After 60 minutes, the patch was removed and any residual test article was gently washed off with tap water. The skin was examined and reaction was graded for erythema and edema according to the Draize scale. Skin examinations were performed at 30 minutes, and at 24 and 48 hours after patch removal.
The Primary Irritation Index was used to determine the irritation potential of the test material. The corrosivity of the test material was determined based on the destruction or irreversible alteration of the tissue. Destruction was defined as ulceration or necrosis was noted at any of the observation timepoints.

Irritation parameter:

erythema score

Basis:

animal: 1-3

Time point:

other: 30 minutes, 24 hours, 48 hours

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

Scores of 4 are reported for all three rabbits at 30 minutes, 24 hours and 48 hours

Irritation parameter:

edema score

Basis:

animal: 1-3

Time point:

other: 30 minutes, 24 hours, 48 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other:

Remarks:

Oedema (Grade 1) was reported in one rabbit at 48 hours only

Irritant / corrosive response data:

Necrosis of the test sites (eschar) was observed for all animals at all timepoints.
Mummification of the test sites was observed for all aniamls after 24 or 48 hours.
The primary irritation index for TMEDA is 4.1.

Other effects:

Necrosis and mummification of the test site was reported

Skin irritation scores for erythema and eschar formation and edema formation

Animal number	Erythema/Eschar			Edema			Mean score
	30 minute	24 hour	48 hour	30 minute	24 hour	48 hour
L-524-88F	4^a	4^a,b	4^a,b	0	0	0	4.0
L-525-88F	4^a	4^a	4^a,b	0	1	0	4.3
L-526-88F	4^a	4^a,b	4^a,b	0	0	0	4.0

 

Footnote:
a Necrosis of test site (eschar)
b Mummification of test site

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

TMEDA is corrosive to the skin of the rabbit.

Executive summary:

A skin corrosion test was conducted in New Zealand albino rabbits. Three animals were treated with 0.5 mL TMEDA for a periods of 1 hour. Animals were observed 30 minutes, 24 and 48 hours after the removal of the patch. Necrosis of the test site was noted in all animals at 30 minutes, and at 24 and 48 hours after patch removal. Mummification of the test site was noted in two of the animals at 24 hours and in all animals 48 hours after patch removal. The results of this study indicate that TMEDA is a skin corrosive.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

21 Feb 1989 to 26 April 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

Guideline:

other: Skin corrosion screening method

Deviations:

no

Principles of method if other than guideline:

In vivo skin corrosion screening assay using a 3-minute exposure.

GLP compliance:

yes

Specific details on test material used for the study:

Anhydrous TMEDA

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: K&W Rabbit Farm, Tice, Florida
Housing: Individually. Temperature and humidity controlled.
Food: Wayne Rabbit Ration F8600-00 (Continental Grain Co., Chicago, Illinois)
Water: Tap water, ad libitum
Acclimatisation: At least three days
Weight range when tested: 3.3 to 3.5 kg

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

3 minutes

Observation period:

30 minutes, 24 and 48 hours after patch removal.

Number of animals:

Three

Details on study design:

Approximately 24 hours prior to treatment, the skin was prepared by clipping the mid-dorsal region of the back free of hair. Four 1 x 1 inch test sites on the back of each animal were delineated. Body weight was recorded. The test substance was applied to the left quadrant of each animal. One other compound was applied to the right quadrant. A 2 x 2 inch gauze pad was taped over each test site and the trunk of the animal was occluded with latex lined with 2-ply plastic wrap. The rabbits were placed into stocks during the exposure period and first observation to prevent access of the animals to the patch and treated area. After 3 minutes, the patch was removed and any residual test article was gently washed off with tap water. The skin was examined and reaction was graded for erythema and edema according to the Draize scale. Skin examinations were performed at 30 minutes, and at 24 and 48 hours after patch removal. The Primary Irritation Index was used to determine the irritation potential of the test material. The corrosivity of the test material was determined based on the destruction or irreversible alteration of the tissue. Destruction was defined as ulceration or necrosis noted at any of the observation timepoints.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Eschar was noted in one animal and transudation was noted in the epidermis in two animals at 30 minutes after patch removal. Scab formation and/or mummification was noted in all animals 24 and 48 hours after patch removal. Moderate edema was noted in two animals and slight edema was noted in one rabbit 30 minutes after patch removal. Slight edema was noted in all animals 24 and 48 hours after patch removal.

Other effects:

Eschar and mummification were also reported.

Skin irritation scores for erythema and eschar formation and edema formation

Animal number	Erythema/Eschar			Edema			Mean score
	30 minute	24 hour	48 hour	30 minute	24 hour	48 hour
L-524-88F	4^*	4^**	4^**	3	2	2	6.3
L-525-88F	4^f	4^**	4^ff	3	2	2	6.3
L-526-88F	4^f	4^ff	4^ff	2	2	2	6.0

Footnote:
* Eschar
** Eschar, scab formation
f Transudation through the epidermis
ff Eschar , mummification

Interpretation of results:

Category 1A (corrosive) based on GHS criteria

Conclusions:

TMEDA is severely irritating and corrosive to the skin of the rabbit. A dose of 0.5 mL/site occluded for 3 minutes caused eschar (transudation through the epidermis, scab formation and mummification) of the test site in all three animals, slight edema in one animal and slight to moderate edema in two animals.

Executive summary:

An in vivo corrosion test was conducted in New Zealand albino rabbits. Three animals were treated with 0.5 mL of test material for 3 minutes. Animals were observed 30 minutes, 24 and 48 hours after the removal of the patch. Eschar was noted in one animal and transudation was noted in the epidermis in two animals at 30 minutes after patch removal. Scab formation and/or mummification was noted in all animals 24 and 48 hours after patch removal. Moderate edema was noted in two animals and slight edema was noted in one rabbit 30 minutes after patch removal. Slight edema was noted in all animals 24 and 48 hours after patch removal. The results of this study indicate that TMEDA is a skin corrosive.

Reference 5

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

17-19 February 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

DOT skin corrosion screen

Deviations:

no

Principles of method if other than guideline:

Assessment of skin corrosion in vivo (4-hour application)

GLP compliance:

no

Specific details on test material used for the study:

TMEDA 100

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: Dutchland Laboratories, Inc. Denver
Housing: Individually in screen bottom cages.
Food: Commercial laboratory feed, ad libitum
Water: Tap water, ad libitum
Acclimatisation: At least seven days
Age: Approximately 14 weeks
Body weight at study initiation: 2125-2420 g (males) and 2383-2600 g (females)

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

4, 24 and 48 hours

Number of animals:

Six (three males and three females)

Details on study design:

Approximately 24 hours prior to treatment, the hair was clipped from the back of each animal. The test material (0.5 mL) was applied to the intact skin. The treated area was covered with a 1 x 1 inch gauze patch which was secured with tape, overwrapped with saran wrap and secured with Elastoplast tape. The rabbits were collared during the 4-hour exposure period. At the end of the exposure period the bandages were removed and the treated are was examined for skin irritation and corrosion. After the initial examination, the application site was washed with water to prevent further exposure. Examinations were repeated at 24 and 48 hours. Bodyweights were recorded immediately before study initiation.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 4 hours

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 4 hours

Score:

1.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

2.1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Other effects:

Blanching of the application site skin was also reported.

Skin irritation scores for erythema and edema formation

Animal number	Sex	Erythema			Edema
		4 hour	24 hour	48 hour	4 hour	24 hour	48 hour
0585	M	4.0^b	4.0	4.0	1.0	1.0	1.0
0580	M	4.0^b	4.0	4.0	1.5	2.0	2.0
0581	M	4.0^b	4.0	4.0	1.5	2.5	2.0
0564	F	4.0^b	4.0	4.0	2.0	3.0	3.0
0583	F	4.0^b	4.0	4.0	1.0	1.5	2.0
0566	F	4.0	4.0	4.0	2.0	2.0	2.5

Footnote:
b Blanching

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The results of this study indicate that TMEDA is a skin corrosive.

Executive summary:

An in vivo corrosion test was conducted in New Zealand albino rabbits. Six animals were treated with 0.5 mL of test material for 4 hours. Animals were observed when the patch was removed after 4 hours and again 24 and 48 hours after the removal of the patch. Erythema (score of 4) was observed at all time points for all six animals. Oedema formation was noted for all time points for all six animals which ranged from very slight to moderate oedema. Blanching of the test area was observed in five animals at 4 hours. The test sites appeared necrotic in all animals at 4, 24 and 48 hours. Based on the results of this study, TMEDA is considered to be corrosive to the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Studies of eye irritation are not required due to the classification of the substance for skin corrosivity.

Justification for classification or non-classification

TMEDA has a harmonised classification for skin corrosivity in Category 1B (Causes severe skin burns and eye damage). No change to this classification is proposed.