Registration Dossier

Administrative data

Description of key information

Skin: not irritating
Eye: corrosive

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Specific details on test material used for the study:
- Lot No. NPP-41344
- Purity: 85.34%
- By-products
- Methanol: 1.48%
- Monomethyl amino butanol: 10.92%
- Water: 1.89%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals purchased at least 1 week prior to study and allowed to acclimatise. Healthy animlas free of disease were selected for the study. 24 hours prior to test, animals examined for skin injury. Those with no injury were used in test. Animals were fed Purina Certified Rabbit Chow, ad libitum, certified free of contaminants by supplier. Animals were given tap water ad libitum. Water was tested to ensure levels of contaminants are equivalent to or less than recommended levels as per the primary drinking water regulations.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
up to 48 hours following treatment initiation
Number of animals:
6
Details on study design:
The skin corrosion test was carried out in six albino rabbits weighing 2.4 +/- c0.2 kg. The backs were shaved free of hair. A 0.5 m l of liquid t e s t material was applied on the back of each rabbit and the treated skin site was covered with a gauze and a "Dermicel" tape. The animal trunk was then loosely wrapped with an impervious rubberized cloth and a flexible stainless steel protective screen held in place by tape. Following a 4-hour exposure period, the patches were removed and the treated skin sites were gently cleaned. The sites were visually evaluated for erythema, edema, and tissue destruction at 4, 24, and 48 hours after exposure.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: n skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 4 hours
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no skin effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
There was no erythema or edema in any of the rabbits at 4, 24, and 48 hours. The treated skin sites were normal and there was no tissue destruction. Nofurther recordings were made.

The liquid material applied easily on the skin. There was no erythema or edema in any of the rabbits at 4, 24, and 48 hours. The treated skin sites were normal and there was no tissue destruction.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
AEPD was tested for its skin corrosion and irritation potential in rabbits. It resulted in no skin damage; thus AEPD was found to be non-corrosive. There were also no signs of irritation and therefore it is not considered to be irritating.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
exposure period for 24 hours.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals purchased at least 1 week prior to study and allowed to acclimatise. Healthy animlas free of disease were selected for the study. 24 hours prior to test, animals examined for skin injury. Those with no injury were used in test. Animals were fed Purina Certified Rabbit Chow, ad libitum, certified free of contaminants by supplier. Animals were given tap water ad libitum. Water tested to ensure levels of contaminants are equivalent to or less than recommended levels as per the primary drinking water regulations.
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abbraded or unabbraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml of unchanged test substance applied
Duration of treatment / exposure:
Exposure: 24 hours
Observation period:
21 days
Number of animals:
6
Details on study design:
The primary skin irritation test was conducted on a group of six albino rabbits weighing 2.7 +/-0.1 kg. The skin from the back area of each rabbit was clipped free of hair. The skin on the left side of the middorsal line was left intact while the skin on the right side was abraded by making minor epidermal incisions in a tic-tac-toe pattern with a blunt hypodermic needle. The abrasions were minor incisions through the stratum corneum, but not deep enough to disturb the derma or produce bleeding. A 0.5 m l of P-1050, as supplied, was applied to each site and covered w i t h a gauze pad. The entire trunk was then wrapped with a rubberized impervious cloth and a flexible wire screen held in place by tape. After 24 h exposure, the bindings and patches were removed and the treated sites were gently cleaned. The skin reactions were scored immediately (24 h) and at the end of 72 h (48 h after the first scoring).
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Remarks:
intact skin
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #4
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of mild irritation
Irritant / corrosive response data:
AEPD was irritating to both the intact and abraded skin. There was slight erythema and moderate to severe edema on all the intact skin sites. The abraded skin site showed severe edema and necrosis. However, the irritation of intact rabbit skin was normal in all but one animal by day 3 and in all animals by day 7, but the abraded skin site showed eschar formation by day 21.
Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, AEPD was irritating to the skin, however for intact skin the irritation had largely subsided by the 3rd day follwing tratment initiation and the skin had recovered completely by the 7th day following treatment initiation. For the abbraded skin, the reaction was more severe with more significant irritation leading to escher fomation by the 21st day following treatment initiation. Considering the treatment period of 24 hours compared to the 4 hours of the standard assay, and the fact that the intact skin was recovered within 3 days (in all but one animal), this substance appears to eb only mildly irritating and does not meet the criteria for classification as an irritant in the EU
Executive summary:

The primary skin irritation test with AEPD was conducted on a group of six albino rabbits. The skin from the back area of each rabbit was clipped free of hair. The skin on the left side of the middorsal line was left intact while the skin on the right side was abraded by making minor epidermal incisions in a tic-tac-toe pattern with a blunt hypodermic needle. The abrasions were minor incisions through the stratum corneum, but not deep enough to disturb the derma or produce bleeding. A 0.5 ml of P-1050, as supplied, was applied to each site and covered with a gauze pad. The entire trunk was then wrapped with a rubberized impervious cloth and a flexible wire screen held in place by tape. After 24 h exposure, the bindings and patches were removed and the treated sites were gently cleaned. The skin reactions were scored immediately (24 h) and at the end of 72 h (48 h after the first scoring).

AEPD produced slight erythema and moderate to severe edema on all the intact skin sites. The abraded skin sites showed severe edema and necrosis. The average skin irritation score for the six rabbits was 4.6. Since the material produced skin irritation, the animals were held for further observation. All the treated intact skin sites were normal by day 7, but the abraded skin sites showed eschar formation by day 21. The average body weight gains of the treated animals were normal.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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:
3 - 24 November, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Specific details on test material used for the study:
- Lot No. NPP-41344
- Purity: 85.34%
- By-products
- Methanol: 1.48%
- Monomethyl amino butanol: 10.92%
- Water: 1.89%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals purchased at least 1 week prior to study and allowed to acclimatise. Healthy animlas free of disease were selected for the study. 24 hours prior to test, animals examined for eye injury. Those with no injury were used in test. Animals were fed Purina Certified Rabbit Chow, ad libitum, certified free of contaminants by supplier.Animals were given tap water ad libitum. Water was tested to ensure levels of contaminants are equivalent to or less than recommended levels as per the primary drinking water regulations.
Vehicle:
unchanged (no vehicle)
Controls:
other: right eye of each animal served as control
Amount / concentration applied:
0.1 ml of AEPD
Duration of treatment / exposure:
In 6 animals, the test compound was administered into the left eye. No washing of test compound out of eye took place. In three animals, the test compound was washed fromt he eye using water, 20 to 30 seconds after administration.
Observation period (in vivo):
Observation period 21 days. At 24 hours, 7, 14 and 21 days after treatment, the eyes were examined using fluorescein stain to assess corneal damage under UV light.
Number of animals or in vitro replicates:
9
Details on study design:
0.1 ml of AEPD was instilled into the lower conjunctival sac of the left eye. Six rabbits had their treated eyes unwashed while three had there treated eyes irrigated with water at 20 to 30 seconds following treatment. Eyes were examined at 24, 48 and 72 hours for damage and irritation. Additionally, at 24 hours, and then 7, 14 and 21 days, the eyes were examined using Fluorescein and UV light to assess corneal damage.
Irritation parameter:
cornea opacity score
Remarks:
unwashed
Basis:
mean
Time point:
24 h
Score:
2.17
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
cornea opacity score
Remarks:
washed
Basis:
mean
Time point:
24 h
Score:
1.33
Max. score:
2
Irritation parameter:
iris score
Remarks:
unwashed
Basis:
mean
Time point:
24 h
Score:
1.17
Max. score:
2
Irritation parameter:
iris score
Remarks:
washed
Basis:
mean
Time point:
24 h
Score:
0.33
Max. score:
1
Irritation parameter:
chemosis score
Remarks:
unwashed
Basis:
mean
Time point:
24 h
Score:
4
Max. score:
4
Irritation parameter:
chemosis score
Remarks:
washed
Basis:
mean
Time point:
24 h
Score:
4
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
redness/unwashed
Basis:
mean
Time point:
24 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness/washed
Basis:
mean
Time point:
24 h
Score:
2.67
Max. score:
3
Irritation parameter:
cornea opacity score
Remarks:
unwashed
Basis:
mean
Time point:
48 h
Score:
2.5
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
cornea opacity score
Remarks:
washed
Basis:
mean
Time point:
48 h
Score:
1.33
Max. score:
2
Irritation parameter:
iris score
Remarks:
unwashed
Basis:
mean
Time point:
48 h
Score:
1.17
Max. score:
2
Irritation parameter:
iris score
Remarks:
washed
Basis:
mean
Time point:
48 h
Score:
0.33
Max. score:
1
Irritation parameter:
chemosis score
Remarks:
unwashed
Basis:
mean
Time point:
48 h
Score:
4
Max. score:
4
Irritation parameter:
chemosis score
Remarks:
washed
Basis:
mean
Time point:
48 h
Score:
4
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
redness/unwashed
Basis:
mean
Time point:
48 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness/washed
Basis:
mean
Time point:
48 h
Score:
2.67
Max. score:
3
Irritation parameter:
cornea opacity score
Remarks:
unwashed
Basis:
mean
Time point:
72 h
Score:
3
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
washed
Basis:
mean
Time point:
72 h
Score:
1.33
Max. score:
2
Irritation parameter:
iris score
Remarks:
unwashed
Basis:
mean
Time point:
72 h
Score:
1.17
Max. score:
2
Irritation parameter:
iris score
Remarks:
washed
Basis:
mean
Time point:
72 h
Score:
0.33
Max. score:
1
Irritation parameter:
chemosis score
Remarks:
unwashed
Basis:
mean
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Remarks:
washed
Basis:
mean
Time point:
72 h
Score:
3.67
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
redness/unwashed
Basis:
mean
Time point:
72 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness/washed
Basis:
mean
Time point:
72 h
Score:
3
Max. score:
3
Irritation parameter:
cornea opacity score
Remarks:
unwashed
Basis:
mean
Time point:
7 d
Score:
3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Remarks:
washed
Basis:
mean
Time point:
7 d
Score:
2
Max. score:
3
Irritation parameter:
iris score
Remarks:
unwashed
Basis:
mean
Time point:
7 d
Score:
1.5
Max. score:
4
Irritation parameter:
iris score
Remarks:
washed
Basis:
mean
Time point:
7 d
Score:
1.33
Max. score:
2
Irritation parameter:
chemosis score
Remarks:
unwashed
Basis:
mean
Time point:
7 d
Score:
3.83
Max. score:
4
Irritation parameter:
chemosis score
Remarks:
washed
Basis:
mean
Time point:
7 d
Score:
1.67
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness/unwashed
Basis:
mean
Time point:
7 d
Score:
2.83
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness/washed
Basis:
mean
Time point:
7 d
Score:
2
Max. score:
3
Irritation parameter:
other: rabbits with unwashed eyes were sacrificed at day 14. All animals showed keratinitis.
Time point:
14 d
Remarks on result:
other: rabbits with unwashed eyes were sacrificed at day 14. All animals showed keratinitis.
Irritation parameter:
cornea opacity score
Remarks:
washed
Basis:
mean
Time point:
14 d
Score:
0.67
Max. score:
1
Irritation parameter:
iris score
Remarks:
washed
Basis:
mean
Time point:
14 d
Score:
0.67
Max. score:
1
Irritation parameter:
chemosis score
Remarks:
washed
Basis:
mean
Time point:
14 d
Score:
0.33
Max. score:
1
Irritation parameter:
conjunctivae score
Remarks:
redness/washed
Basis:
mean
Time point:
14 d
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Remarks:
washed
Basis:
mean
Time point:
21 d
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Remarks:
washed
Basis:
mean
Time point:
21 d
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Remarks:
washed
Basis:
mean
Time point:
21 d
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
At 24 hours, all the animals’ corneas showed lesions and the eyes were severely irritated. The eye of the unwashed group of animals never recovered and by day 14 were completely keratinized. The eyes of the washed group of rabbits were completely normal by day 21.
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Undiluted AEPD was found to be severly irritating to eyes. The unwashed eyes were permenently damaged by day 14. Washing the material from the eye prevented irreversible damage (eyes normal at day 21), however the material was still severly irritating. The substance needs to be classified as Category 2a (H319, severe eye irritation) under the CLP/GHS Regulation (EC) No 1272/2008.
Executive summary:

2-Amino-2-ethyl-1,3-propanediol or AEPD (P-1050) was tested in rabbits to determine the eye irritation potential of the product. At 24 h, all the animals’ corneas showed lesions and the eyes were severely irritated. The eyes of the unwashed group of animals never recovered and by day 14 were completely keratitised, and the animals were sacrificed. The organs in all the animals were normal. The eyes of the washed group of animals showed improvement by day 14 and were completely normal by day 21. One of the rabbits in the unwashed group died on day 8 of the test, and the post mortem examination showed that the animal was suffering from severe diarrhea; the death was not related to the treatment.

In conclusion, undiluted AEPD was found to be severly irritating to eyes. The unwashed eyes were permenently damaged by day 14. Washing the material from the eye prevented irreversible damage (eyes normal at day 21), however the material was still severly irritating. The substance needs to be classified as Category 2a (H319, severe eye irritation) under the CLP/GHS Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

Several skin irritation studies with 2 -amino-2 -ethyl-1,3-propanediol (AEPD) are available. AEPD is a highly alkaline substance; the pH of a 1% solution is 11.18 and of the 100% substance 11.78. In a reliable study performed by Parekh (1982d) on rabbits, 0.5 mL of the test substance was applied to shaved skin and covered with an occlusive dressing for 24 hours. The test substance caused slight erythema and moderate to severe oedema on all the exposed skin sites within 24 hours. The effects were fully reversible within 72 hours in 5/6 animals and within 7 days in all animals tested. Under the conditions of this study (24 h exposure) the test substance showed a skin irritating potential. Parekh performed an additional, reliable study (1982c) to assess the specific skin corrosion potential of the test substance in rabbits. The skin on the back of the animals was shaved and 0.5 mL of the test substance applied and covered with an occlusive dressing for 4 hours. The skin was then cleaned and examined. No erythema or oedema was observed in any of the animals 24 and 48 hours after exposure ended. Several other studies are also available. Sausaman (1975) reported that the test substance had a slight irritating effect in rabbits, with an overall irritation score of 1.37. In a study by Power (1974) the test substance is reported to be non-corrosive to the skin of rabbits. Machle (1941) assessed the potential skin irritating effect of AEPD in rabbits. A sample was applied to the shaved skin of a rabbit in 2 doses, 30 minutes apart, with an exposure time of 30 to 60 minutes. The rabbit was treated daily for 10 days. No skin irritating effects were observed during the study period. Taking all the available data into account, AEPD is not considered to be skin-irritating.

Eye irritation:

In a reliable study 0.1 mL AEPD was instilled into the eye of rabbits, after which the eye was either rinsed after 20 -30 seconds or not rinsed at all (Parekh, 1982). 24 hours after exposure, the corneas of the exposed eyes of all animals showed lesions and were severely irritated. Severe conjunctivae and chemosis were observed until 72 hours after exposure. The effects on the rinsed eyes were completely reversed by day 21, while the eyes that were not rinsed were completely keratinized by day 14.

In the second study, Sausaman (1974) reported that the test substance was corrosive to the rabbit eye, citing a maximum mean total score of 73.8. Taking the available data into account, AEPD is considered to have a corrosive effect on the eye.


Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on skin irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

The available data on eye irritation of the test substance meet the criteria for classification as Category 1 (H318) according to Regulation (EC) 1272/2008 and as Xi, R41 according to Directive 67/548/EEC.