Registration Dossier
Registration Dossier
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EC number: 701-177-3 | CAS number: -
Endpoint summary
Administrative data
Description of key information
Skin corrosion in vitro (OECD 431): not corrosive
Skin irritation in vivo (OECD 404, rabbit): irritating
Eye irritation in vivo (OECD 405, rabbit): serious eye damage
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 09 Dec 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- human
- Strain:
- other: reconstructed human epidermis EST-200
- Details on test animals or test system and environmental conditions:
- TEST SKIN MODEL
- Source: MatTek Corporation, Ashland, USA
- Before the start of the test, the skin models were pre-incubated for 1 h under culture conditions (5% CO2, 37 °C) with assay medium. The medium was changed and the test and reference substances were applicated (50 µL/insert) onto the skin model.
ENVIRONMENTAL CONDITIONS (Incubator)
- Temperature (°C): 37
- CO2 gas concentration (%): 5 - Type of coverage:
- open
- Preparation of test site:
- other: intact reconstructed human epidermis
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: concurrent negative control tissue treated with distilled water
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.05 mL (ca. 83 µL/cm²) - Duration of treatment / exposure:
- 3 min and 1 h
- Observation period:
- Not applicable
- Number of animals:
- Not applicable. Tests were performed in triplets for each treatment duration.
- Details on study design:
- TEST SITE
- Area of exposure: 0.6 cm²
REMOVAL OF TEST SUBSTANCE
- Washing (if done): after the incubation periods, the inserts were washed carefully
- Time after start of exposure: 3 min and 1 h
CELL VIABILITY MEASUREMENTS
- Method: MTT assay
- Details on method used: after exposure to the test substance, the skin model was incubated with MTT solution for 3 h. Thereafter, the inserts were washed 3 times with PBS. For viability testing, the inserts were placed in new 24-well plates and the extraction of blue formazan was performed in the extraction solution on a shaker for 120 min (120 U/min) at room temperature. For determination of cell viability, the solution was homogenized and 3 x 200 µL were inserted into a 96 well plate. The absorption was measured in duplicates at 570 nm in a plate reader. - Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 min
- Value:
- 72
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60 min
- Value:
- 25
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Interpretation of results:
- other: not corrosive
- Conclusions:
- There is regulatory acceptance in the EU that a substance can be considered corrosive (Skin cor. 1, 1A, 1B/C) based on a positive result in the Reconstructed human epidermis test method (in vitro skin corrosion). A negative in vitro corrosivity response is not conclusive with respect to non-classification or classification as a skin irritant and therefore requires further evaluation and/or data generation.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25 Mar - 09 Aug 1991
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- lack of test material details
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- lack of test material details
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Bancel (Albon, France)
- Age at study initiation: adult
- Weight at study initiation: 2.4-2.65 kg
- Housing: animals were housed individually in polystyrene cages, with perforated flooring.
- Diet: approximately 150 g per animal per day of complete pelleted rabbit maintenance diet (U.A.R. formula 112, U.A.R. Villemoisson, Orge, France)
- Water: softened and filtered mains drinking water, ad libitum
- Acclimation period: at least 21 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 21-59
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: untreated sites of the same animal served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL - Duration of treatment / exposure:
- 4 h
- Observation period:
- 14 days
Reading time points: 1, 24, 48 and 72 h and 7 and 14 days - Number of animals:
- 6 males
- Details on study design:
- TEST SITE
- Area of exposure: 6 cm² on the back and the flanks of the animal
- Type of wrap if used: The treated skin was covered with a square of 8-layer thick Codex hydrophilic gauze with an identical surface area and held in place by means of a semi-occlusive dressing (perforated adhesive tape applied onto a band of crepe gauze).
-Other: during exposure, animals were immobilised in restraining boxes.
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- erythema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- erythema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- erythema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- edema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- edema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritant / corrosive response data:
- Absence of hair on the whole application area was observed in all animals.
- Other effects:
- All test animals showed burnt aspect of the skin from less than one quarter of the application area (4/6), about one quarter (1/6) to the whole application area (1/6), after 24 and 48h. At the 72 h reading time point all animals showed slight dryness of the skin at the application site.
Slight desquamation of the epidermis on the application area was observed in 2/6 animals and severe desquamation in 3/6 animals after 7 days. At this time point all animals showed slight dryness of the skin on the application area. Furthermore, at 7 days one animal showed burnt aspect on the whole application area. After 14 days absence of hair on the whole application area was apparent in all animals. - Interpretation of results:
- other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 09 Mar - 16 Mar 1981
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- other: Proposed Guidelines of the United States Environmental Agency (EPA) § 163.81-5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- occlusive dressing and limited data on test material.
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Housing: animals were housed individually in metal cages.
- Diet: standard rabbit food - NAFAG, No. 814 (Gossau SG), ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Photoperiod (hrs dark / hrs light): 10/10 - Type of coverage:
- occlusive
- Preparation of test site:
- other: shaved and abraded
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: untreated sites of the same animal served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.5 mL - Duration of treatment / exposure:
- 24 h
- Observation period:
- 7 days
Reading time points: 24, 48, 72 h and 4 and 7 days - Number of animals:
- 3 males and 3 females
- Details on study design:
- TEST SITE
- Area of exposure: approx. 2.5 cm by 2.5 cm on the back and the flank of the animal
- Type of wrap if used: the treated skin was covered with a gauze patch. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- mean
- Remarks:
- out of all 6 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 2.9
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- out of all 6 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 2.33
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- other: necrosis
- Basis:
- other: all animals
- Time point:
- other: 72 h
- Reversibility:
- not reversible
- Remarks on result:
- other: slight necrosis and hardened skin observed at the 72 h reading time point after 24 h exposure
- Irritant / corrosive response data:
- Results of the skin irritation study on intact skin are given in Table 1 under "Any other information on results incl. tables". On abraded skin, erythema effects were identical in all animals to the results on intact skin at all reading time points. Oedema scores on abraded skin were more pronounced in single animals. However, the scores for oedema formation on abraded skin did not exceed moderate oedema and were similar to the scores on intact skin at the 7 day observation time point.
- Interpretation of results:
- other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Referenceopen allclose all
Table 1. Results of the MTT assay.
Test substance |
Tissue |
OD |
Cell viability (% of negative control) |
||||
Value 1 |
Value 2 |
Value 3 |
Mean |
Mean (tissue 1+2) |
|||
Incubation time 3 min |
|||||||
Negative control |
1 |
2.007 |
1.993 |
2.010 |
2.003 |
2.031 |
100 |
2 |
2.067 |
2.032 |
2.074 |
2.058 |
|||
Test substance |
1 |
1.263 |
1.250 |
1.292 |
1.268 |
1.454 |
72 |
2 |
1.638 |
1.635 |
1.648 |
1.640 |
|||
Positive control |
1 |
0.545 |
0.527 |
0.533 |
0.535 |
0.485 |
24 |
2 |
0.438 |
0.431 |
0.436 |
0.435 |
|||
Incubation time 60 min |
|||||||
Negative control |
1 |
1.841 |
1.848 |
1.853 |
1.847 |
1.755 |
100 |
2 |
1.687 |
1.640 |
1.658 |
1.662 |
|||
Test substance |
1 |
0.481 |
0.457 |
0.461 |
0.466 |
0.445 |
25 |
2 |
0.426 |
0.422 |
0.421 |
0.423 |
|||
Positive control |
1 |
0.168 |
0.163 |
0.191 |
0.174 |
0.213 |
12 |
2 |
0.251 |
0.250 |
0.252 |
0.251 |
|||
OD: optical density
Table 1. Results of skin irritation study.
Observation time |
Rabbit no. |
||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
||||||||
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
||
1 h |
2 |
2 |
2 |
1 |
2y |
2 |
2 |
2 |
2 |
0 |
2 |
0 |
|
24 h |
2y |
2 |
2y |
2 |
4u |
2 |
4x |
3 |
2y |
1 |
2y |
1 |
|
48 h |
2y |
2 |
2y |
1 |
4us |
2 |
4x |
3 |
2y |
2 |
2y |
1 |
|
72 h |
4xs |
3 |
2ys |
2 |
4us |
2 |
4xs |
3 |
2ys |
3 |
2ys |
1 |
|
Mean value 24 + 48 + 72 h |
2,67 |
2,33 |
2,00 |
1,67 |
4,00 |
2,00 |
4,00 |
3,00 |
2,00 |
2,00 |
2,00 |
1,00 |
|
S: Slight dryness of the skin to the application area.
u: Burnt aspect on the whole application area.
x: Burnt aspect on about one quarter of the application area.
y: Burnt aspect on a surface less than one quarter of the application area.
Table 2. Results of skin irritation study after 7 and 14 days.
Observation time |
Rabbit no. |
||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
||||||||
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
||
7 days |
4usd |
2 |
2ysD |
1 |
2Ts |
1 |
4xsD |
1 |
2ds |
1 |
2DTs |
0 |
|
14 days |
0T |
0 |
0T |
0 |
0T |
0 |
0T |
0 |
0T |
0 |
0T |
0 |
|
D: Severe desquamation of the epidermis to the application area.
T: Absence of hair on the whole application area.
d: Slight desquamation of the epidermis to the application area.
s: Slight dryness of the skin to the application area.
u: Burnt aspect on the whole application area.
x: Burnt aspect on about one quarter of the application area.
y: Burnt aspect on a surface less than one quarter of the application area.
Table 1. Results of skin irritation study (intact skin).
Observation time |
Rabbit no. |
|
||||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
|
||||||||||
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
|
||||
24 h |
2 |
2 |
2 |
3 |
3 |
3 |
3 |
3 |
3 |
2 |
3 |
2 |
|
|||
48 h |
2 |
2 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
2 |
3 |
2 |
|
|||
72 h |
3 |
2 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
2 |
|
|||
4 days |
3 |
2 |
3 |
2 |
3 |
2 |
3 |
2 |
3 |
2 |
3 |
2 |
|
|||
7 days |
3 |
2 |
3 |
2 |
3 |
2 |
3 |
2 |
3 |
2 |
3 |
2 |
|
|||
Mean value 24 + 48 + 72 h |
2,60 |
2,00 |
2,80 |
2,60 |
3,00 |
2,60 |
3,00 |
2,60 |
3,00 |
2,20 |
3,00 |
2,00 |
|
|||
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- other: US-EPA § 163.81-4, “Primary eye irritation study”, Federal Register, Vol 43, No. 163, August 22, 1978
- Deviations:
- yes
- Remarks:
- lack of test material details, observation period only 7 days
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Housing: animals were housed individually in metal cages
- Diet: standard rabbit food - NAFAG, No. 814 (Gossau SG), ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 10/10 - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: the untreated eye served as control
- Amount / concentration applied:
- 0.1 mL
- Duration of treatment / exposure:
- 24 h
- Observation period (in vivo):
- 7 days
Reading time points: 1, 2, 3, 4 and 7 days - Number of animals or in vitro replicates:
- 3 males and 3 females
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing: in 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 mL of physiological saline.
- Time after start of exposure: 30 seconds
SCORING SYSTEM: Draize scoring system and primary irritation index
TOOL USED TO ASSESS SCORE: hand-slit lamp - Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- out of all 3 animals without rinsing
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- out of all 6 animals
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 3.7
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days
- Irritant / corrosive response data:
- The individual results of the eye irritation test after 24, 48 and 72 h are listed in Table 1. In general, rinsing of the eye following instillation was of low or no effect (see Table 1 under "Any other information on results incl. tables").
Cornea: After 4 days scattered or diffuse area in 3/6 animals and easily discernible translucent areas 3/3 animals were observed. After 7 days 2/6 animals showed scattered or diffuse area and 4/6 animals showed easily discernible translucent areas.
Iris: After 4 days 1/6 animals and after 7 days 2/6 animals (all from the group without rinsing) showed folds above normal, congestion, swelling, circumcornea injection (any or all of these or combination of any thereof) iris still reacting to light.
Conjunctivae:Redness: All animals showed diffuse beefy redness after 4 and 7 days. After 4 days obvious swelling with partial eversion of lids was observed in 4/6 animals and swelling with lids about half closed in 2/6 animals (group without rinsing). After 7 days in all animals obvious swelling with partial eversion of lids was still apparent.
Discharge: After 4 days, discharge with moistening of the lids and hairs just adjacent to lids was observed in 4/6 animals, discharge with moistening of the lids and hairs, and considerable area around the eye was observed in 1 animal of the group without rinsing. In 1 animal (rinsing group) only slight discharge was observed. After 7 days, 2/6 animals showed slight discharge, and 3/6 animals still moderate and 1 animal (without rinsing group) discharge with moistening of the lids and hairs, and considerable area around the eye. - Other effects:
- No further local or systemic effects were reported.
- Interpretation of results:
- other: Eye damage 1, H318. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
- Conclusions:
- In the present study irreversible effects within a shorter observation period were observed in all animals. Classification as Eye damage, Cat. 1, was based on an expert judgement considering a worst case assumption.
Reference
Table 1. Results of eye irritation study.
Rabbit # |
Time [h] |
conjunctivae |
|
iris |
cornea |
redness |
swelling |
||||
407 |
24 |
3 |
3 |
0 |
1 |
48 |
3 |
3 |
0 |
1 |
|
72 |
3 |
3 |
0 |
1 |
|
average |
3,0 |
3,0 |
0,0 |
1,0 |
|
408 |
24 |
3 |
3 |
0 |
1 |
48 |
3 |
4 |
0 |
1 |
|
72 |
3 |
4 |
0 |
2 |
|
average |
3,0 |
3,7 |
0,0 |
1,3 |
|
409 |
24 |
3 |
3 |
0 |
1 |
48 |
3 |
3 |
0 |
1 |
|
72 |
3 |
3 |
0 |
2 |
|
average |
3,0 |
3,0 |
0,0 |
1,3 |
|
410 rinsed |
24 |
3 |
3 |
0 |
1 |
48 |
3 |
2 |
0 |
1 |
|
72 |
3 |
2 |
0 |
2 |
|
average |
3,0 |
2,3 |
0,0 |
1,3 |
|
411 rinsed |
24 |
3 |
3 |
0 |
1 |
48 |
3 |
2 |
0 |
1 |
|
72 |
3 |
2 |
0 |
1 |
|
average |
3,0 |
2,3 |
0,0 |
1,0 |
|
412 rinsed |
24 |
3 |
3 |
0 |
1 |
48 |
3 |
2 |
0 |
1 |
|
72 |
3 |
2 |
0 |
2 |
|
average |
3,0 |
2,3 |
0,0 |
1,3 |
|
|
Time [h] |
conjunctivae |
Iris |
cornea |
|
|
redness |
swelling |
|
|
|
average |
24 |
3,00 |
3,00 |
0,00 |
1,00 |
48 |
3,00 |
2,67 |
0,00 |
1,00 |
|
72 |
3,00 |
2,67 |
0,00 |
1,67 |
|
24+48+72 |
3,00 |
2,78 |
0,00 |
1,22 |
|
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irreversible damage)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation
The skin irritation properties of N-methyl-N-(C18-(unsaturated)alkanoyl)glycine (EC No. 701-177-3) have been investigated in several in vitro and in vivo studies.
The in vitro skin corrosion properties were tested in a study according to OECD guideline 431 under GLP conditions using the reconstructed human epidermis EST-200 assay (Frey-Tox, 2005). In the study, the tissues were treated with the unchanged test material for exposure periods of 3 and 60 min. Positive and negative controls were included in the study and gave the expected results. The test substance decreased the cell viability in comparison to the control to 72% after 3 min and to 25% after 60 min of incubation. The cell viability after 3 min exposure was greater than 50% and the cell viability after 1 h exposure was greater than 15%. Thus, the test material is considered to be non-corrosive under the experimental conditions to reconstructed human epidermis in-vitro.
Furthermore, the skin irritating properties were tested in an in vivo study according to OECD guideline 404 (Hazleton, 1991). In the study, 6 male New Zealand White rabbits were exposed to the unchanged test substance onto the shaved skin for 4 h using a semiocclusive dressing. The treated skin was observed and evaluated at 1, 24, 48 and 72 h and 7 and 14 days post-application. At the 24, 48 and 72 h reading time point, well defined erythema to severe erythema to slight eschar formation were observed within the animals (mean erythema score out of all 6 animals = 2.89). Furthermore, oedema formation was observed in all animals (mean oedema score out of all 6 animals = 2.0). The authors described, that all animals showed burnt aspects and slight dryness of the skin at the application site at the 72 h reading time point. After 14 days, erythema and oedema formation was fully reversible. However, absence of hair on the whole application area was apparent in all animals.
In addition, the skin irritation properties were also investigated in an in vivo study according to the Proposed Guidelines of the United States Environmental Agency (EPA) § 163.81-5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978 (Ciba Geigy, 1981a). In the study, 3 male and 3 female New Zealand white rabbits were exposed to the unchanged test substance applied to the shaved and abraded skin for 24 h using an occlusive dressing. The treated skin was observed and evaluated at 24, 48 and 72 h and 4 and 7 days post-application. All animals showed well defined erythema to moderate to severe erythema at all reading time points. The mean erythema score out of all 6 animals over 24, 48 and 72 h was 2.9 with all animals showing an individual mean score ≥ 2.3. The mean oedema score out of all 6 animals over all time points was 2.33. Erythema and oedema were not fully reversible in all animals after 7 days. Furthermore, slight necrosis and hardened skin was observed at the 72 h reading time point.
Conclusion on skin irritation/corrosion
In summary, N-methyl-N-(C18-(unsaturated)alkanoyl)glycine (EC No. 701-177-3) was considered to be non-corrosive in an in vitro skin corrosion test but revealed irritating effects in one study performed according to OECD 404. In the available non-guideline study (Ciba Geigy, 1981a), irreversible effects were observed. This finding is possibly related to the shorter observation period of 7 days and the occlusive dressing. Regarding the calculated mean scores in this study, the test material is not considered to produce irreversible effects on the skin but rather irritating effects which would be reversible after a longer observation period. In conclusion, all available data indicate that the test substance is skin irritating.
Eye irritation
The eye irritation properties of N-methyl-N-(C18-(unsaturated)alkanoyl)glycine (EC No. 701-177-3) were tested in a study performed according to US-EPA § 163.81 -4, “Primary eye irritation study”, Federal Register, Vol 43, No. 163, August 22, 1978 (Ciba Geigy, 1981b). In a group of 3 male and 3 female New Zealand white rabbits, 0.1 mL of the unchanged test substance was applied into one eye, in a single application without washing in 3 animals and with washing in the remaining 3 animals. The eyes were observed and reactions were evaluated 24, 48 and 72 h and 4 and 7 days after instillation. In the study, rinsing of the eye following instillation was of low or no effect. No effects on iris were noted in any animal. Corneal opacity ≥ 1 was seen in the mean over 24, 48 and 72 h in all animals and was not fully reversible within 7 days. All animals showed diffuse beefy redness of the conjunctivae resulting in a mean conjunctivae score out of all 6 animals over 24, 48 and 72 h of 3. Chemosis with a mean score of 2.78 out of all 6 animals over 24, 48 and 72 h was not fully reversible within 7 days, either. After 7 days, in all animals obvious swelling with partial eversion of lids and discharge in various degrees were still apparent. No further local or systemic effects were reported. In the present study irreversible effects within an observation period of 7 days were observed in all animals. Thus, the test substance is considered to induce serious eye damage.
Justification for classification or non-classification
The available in vitro and in vivo data on skin irritation with N-methyl-N-(C18-(unsaturated)alkanoyl)glycine (EC No. 701-177-3) meet the classification criteria for Skin Irrit. 2 (H315) according to Regulation (EC) No. 1272/2008 (CLP). The available data on eye irritation meet the classification criteria for Eye Damage 1 (H318) according to Regulation (EC) No. 1272/2008 (CLP).
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