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Diss Factsheets

Administrative data

Description of key information

Skin irritation / corrosion (in vivo, OECD 404): irritating


Conclusion based on data  with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8).


 


Eye irritation: serious eye damage


Conclusion based on data  with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) and considering all available data on eye irritation in the Alkyl Ether Sulfate (AES) category in a Weight-of-Evidence approach.


Specific Concentration Limits (SCL):


5% - <10% Eye Irrit. 2, H319


< 5% No Classification

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
Study period:
7 Jun - 19 Jul 1994
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:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Certifying authority: Central Veterinary Public Health Inspectorate, Rijswijk, NL
Species:
rabbit
Strain:
New Zealand White
Remarks:
SPF-Quality
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, NL
- Age at study initiation: 13 - 15 weeks
- Weight at study initiation: 2382 - 2833 g
- Housing: individually in labelled cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen, NL).
- Diet: standard rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, NL); approximately 100 g per day. In addition, hay (BMI, Helmond, NL) provided once per week.
- Water: tap water diluted with decalcified water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
3 x 0.5 g
Duration of treatment / exposure:
3 min, 1 h and 4 h
Observation period:
21 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Approximately 24 h prior to treatment, the dorsal fur was shaved with electric clippers, exposing an area of approximately 150 sqcm (10 x 15 cm^2).
- Type of wrap if used: Scotchpak-Non-Woven patches of 2 x 3 cm each mounted on separate Micropore tapes. Each dressing was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: the remaining test substance was removed using firstly a tissue moistened with tap water and subseuqently a dry tissue.
- Time after start of exposure: 3 min, 1 h or 4 h.

OBSERVATION TIME POINTS
In the first animal: 24, 48 and 72 h and 7, 14 and 21 days.
In the two other animals: 1, 24, 48 and 72 h and 7, 14 and 21 days.


SCORING SYSTEM:
- Method of calculation:
Erythema and eschar formation
No erythema = 0
Very slight erythema (barely perceptible) = 1
Well-defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beet redness)* = 4

* In case of signs of necrosis or corrosion (injuries in depth) preventing erythema reading, the maximum grade was given

Oedema formation
No oedema = 0
Very slight oedema (barely perceptible) = 1
Slight oedema (edges of area well defined by definite raising) = 2
Moderate oedema (raised approximately 1 mm) = 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure) = 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Very slight erythema was observed in the treated skin area immediately after the 3 min exposure. A gradual increase of the irritation was observed during the course of the study, resulting in severe erythema, moderate oedema and reduced flexibility of the skin after 72 h. After 7 days, the irritation had decreased and moderate to severe erythema, slight oedema and scaliness were observed in the bald skin area. The irrigation had completely resolved at termination (21 days after exposure)

Exposure for 1 h resulted in well -defined erythema immediately after exposure. The skin irration increased form day 2 onwards and after 72 h the maximum degree of irritation was observed, consisting of severe erythema and oedema and reduced flexibility of the skin. After 7 days moderate to severe erythema, slight oedema and scaliness were observe din a bald skin area. The bald skin persisted until 14 days after exposure. The irritation had completely resolved at termination.

Exposure for 4 h resulted in moderate to severe erythema and very slight oedema immediately after exposure. Fissuring of the skin, indicating superficial necrosis, reduced flexibility of the skin and severe erythema and oedema were noted after 72 h. after 7 days moderate to severe erythema, slight oedema and scaliness were observed in a bald skin area. The irritation had completely resolved within 21 days after exposure, however, the bald skin persisted at termination.

Exposure of two additional animals to the test substance for 4 h resulted in comparable irritation to the that observed in the first animal, when exposes for 4 h. Well – defined erythema without oedema and moderate to severe erythema and very slight oedema were observed in the two animals on day 1. After 72 h reduced flexibility, fissuring of the skin and severe erythema and oedema were apparent. The degree of irritation decreased thereafter and the irritation had completely resolved within 21 days after exposure. A bald skin was apparent from 14 days after exposure onwards and persisted at termination in the two animals.


PRIMARY IRRITATION INDEX
A primary irritation index of 6.7 (severely irritating) was calculated, using the scores of three animals, when the test substance was applied to the intact rabbit skin for 4 hours.
Other effects:
No symptoms of systemic toxicity were observed and no mortality occurred.

Table 1: Results of the skin irritation study

Observation time Rabbit no.
1 2 3
Erythema Edema Erythema Edema Erythema Edema
1 h 3 2 2 0 3 1
24 h 3 2 2 3 3 3
48 h 3 3 3 3 3 3
72 h 4 4 4 4 4 4
7 d 3 2 3 3 2 3
14 d 1 0 1 0 1 0
21 d 0 0 0 0 0 0
Mean value 24 + 48 + 72 h 2.80 3.00 3.00 3.33 3.00 3.33
Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study, the test substance induced erythema and oedema in the rabbits tested when exposed to 0.5 g test substance under semiocclusive conditions. For both erythema and oedema, the scores for all three animals were above the cut-off value of 2.3. However, erythema was fully reversible within 21 days and oedema within 14 days. Based on the obtained erythema and oedema scores, the test substance is concluded to be irritant to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
other: albino
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
No data
Number of animals:
No data
Irritant / corrosive response data:
No scores given.
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
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:
yes
Remarks:
only 72 h observation time
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: 4 clipped, 1 abraded, 1 normal
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72h
Score:
ca. 2.2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
ca. 1.4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h.
Irritant / corrosive response data:
Well-defined erythema was apparent at treated sites on both abraded and intact skin of all 6 rabbits after the 24-h period of exposure. Areas of necrosis were observed at the treated sites of one animal at this time. Slight oedema was noted at 5 abraded sites and 3 intact skin sites and very slight oedema was observed at 1 abraded site and 3 intact skin sites. Generally slight decline in the irritant response was apparent during the study. However, one animal, where necrosis had been noted on the treated skin, showed a marked increase in irritation at the skin sites. Severe erythema with eschar was observed at both treated sites and areas of necrosis remained.
Interpretation of results:
other: Skin Irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study, the test substance induced well-defined erythema and slight edema in the treated rabbits. Necrosis occurred in one case where irreversible skin damage was noted. The symptoms were not reversible within the 72 h observation period. however, it is unclear if symptoms would resolve within a longer observation period. The individual scores were below the cut-off value of 2.3 except in one case. Therefore, weighing all factores, the test substance was concluded to be irritant to skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
22 Nov - 16 Dez 1985
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:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb:HM/Fa
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, DE
- Weight at study initiation: 2428 - 2508 g
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
21 days
Number of animals:
5 males
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: linen wrap, covered in a plastic wrap, fixated with adhesive tape and secured with acrylastic tape to achieve an occlusive wrapping

OBSERVATION TIME POINTS
1, 24, 48, 72, 96 and 168 h and 8, 10, 14, 17 and 21 days after removal of wrapping

SCORING SYSTEM:
- Method of calculation: Draize criteria
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 17 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Directly after removal of the wrapping, slight erythema and minimal oedema were noted, which intensified over the first 2 - 3 days and resolved afterwards (completely by Day 17).

Table 1: Results of the skin irritation study































































































































































Observation timeRabbit no.
123 45
ErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdema
1 h1010100000
24 h2021321032
48 h2142420042
72 h4343430041
96 h4243430041
7 d2010200010
10 d1020200000
17 d0000000000
21 d0000000000
Mean value 24 + 48 + 72 h2.141.333.332.003.402.330.140.002.291.67
Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study, treatment of male rabbits with the test substance resulted in erythema and slight oedema which were reversible within the 21 day observation period. 3 animals had scores for erythema and/or oedema which were at or above the cut-off value of 2.3. Based on these achieved scores, the test substance is concluded to be irritating to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting 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)
Version / remarks:
adopted in 1981
Deviations:
yes
Remarks:
only 8 days observation period
GLP compliance:
no
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb-SPF
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, Biberach, DE
- Weight at study initiation: 2.0 - 2.1 kg
- Diet: K4 rabbit diet (Ssniff Spezialfutter GmbH, Soest, DE); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
8 days
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: ca. 6 cm^2
- Type of wrap if used: 2.5 x 2.5 cm gauze wrap covered with a polyethylene foil (6 x 6 cm). The application site was then fixated using an elastic tape.

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h and 6 and 8 days.

SCORING SYSTEM:
- Method of calculation: according to OECD test guideline
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
For individual animal responses, please refer to table 1 under "Any other information on results incl. tables."
In one animal, slight eschar was observed at time point 48, and eschar was also present at 72 h, but not anymore thereafter.

Table 1: Results of the skin irritation study





















































































Observation timeRabbit no.
123
ErythemaEdemaErythemaEdemaErythemaEdema
1 h101010
24 h001010
48 h000010
72 h000010
6 d000000
8 d000000
Mean value 24 + 48 + 72 h0.000.000.330.000.750.00
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo skin irritation study, the test substance did only induce very weak erythema (mean score: 0.4 out of 4) which was fully reversible within the 8 - day observation period. No oedema was observed in the test animals. Based on the results of the study, the test substance was concluded not to be irritating to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting 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:
yes
Remarks:
exposure time, skin preparation procedures (skin not intact), number of animals used, occlusive conditions
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: clipped; and abraded (see any other information on materials and methods, incl. tables)
Vehicle:
other: undiluted on one site and diluted in distilled water (5 % v/v) on another site.
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
72 h
Observation time points: 24 h and 72 h
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Remarks:
undiluted score
Time point:
24/48/72 h
Score:
ca. 2.2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h; 48 h value was extrapolated
Irritation parameter:
edema score
Basis:
mean
Remarks:
undiluted score
Time point:
24/48/72 h
Score:
ca. 1.6
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h; 48 h value was extrapolated
Irritant / corrosive response data:
For individual animal responses (undiluted scores), please refer to Tables 1 and 2 under "Any other information on results incl. tables."

RESULTS FOR DILUTED SUBSTANCE (5% v/v in water)
Erythema mean scores (intact and abraded skin, 24 and 72 h time points) were ca. 1 (max. 4).
Oedema mean scores (intact and abraded skin, 24 and 72 h time points) were ca. 0.3 (max. 4).

Table 1: Results of the skin irritation study

































































Observation timeRabbit no.
123456
ErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdema
24 h212122322222
48 hNo experimental data available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption)
72 h212122213222

 


Table 2: Calculation of mean scores

















































 Rabbit no.
123456
ErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdemaErythemaEdema
Mean value 24 + 48 + 72 h*2.001.002.001.002.002.002.671.672.332.002.002.00
 

*No 48 h data are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h).


Only scores for intact skin were reported and used for classification.

Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study in rabbits, the test substance induced erythema and edema which were not fully reversible within the 72 hour observation period, however it is unclear whether symptoms would resolve within a longer observation period. The reactions to the diluted substance were milder than for the undiluted one. The scores were below the cut-off value of 2.3 for the undiluted substance. Weighing all factors together and applying a precautionary appraoch, the test substance is concluded to be irritant to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting 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:
yes
Remarks:
Observation period is only 6 days.
GLP compliance:
no
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb:SPF
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
6 days
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
All scores were 0 in all animals at all relevant time points. Erythema grade 1 was noted in 2 animals 1 h after removal of the dressing. No other reactions occurred.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo skin irritation study in rabbits, the test substance did not lead to any irritation reactions, i.e. erythema or oedema, on the skin of the animals. Therefore, it is concluded that the test substance is not irritating to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
29 Jul - 12 Aug 1986
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:
yes
Remarks:
only 14 days observation period
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb-SPF
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, Biberach, DE
- Weight at study initiation: 2.38 - 2.52 kg
- Housing: individually in stainless steel cages
- Diet: K4 rabbit diet (Ssniff Spezialfutter GmbH, Soest, DE); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
clipped
Remarks:
dorsal area: 10 x 10 cm
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: ca. 6 cm^2
- Type of wrap if used: 2.5 x 2.5 cm gauze wrap covered with a polyethylene foil (6 x 6 cm). The application site was then fixated using an elastic tape.

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h and 6, 8, 10 and 14 days

SCORING SYSTEM:
- Method of calculation: according to OECD test guideline
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Observation period lasted only 14 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
For individual animal responses, please refer to Table 1 under "Any other information on results incl. tables."

Table 1: Results of the skin irritation study


 




























































































Observation timeRabbit no.
123
ErythemaEdemaErythemaEdemaErythemaEdema
1 h222322
24 h222423
48 h323334
72 h323334
6 dEscharEscharEschar
8 dEscharEscharEschar
10 dEscharEscharEschar
14 d0-EscharEschar
Mean value 24 + 48 + 72 h2.672.002.673.332.673.67
Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study, the test substance induced erythema and oedema when applied onto rabbit skin under occlusive conditions for an exposure period of 4 h. The cut-off value of 2.3 was exceeded in all three animals. Based on the obtained scores for erythema and oedema, the test substance was concluded to be irritating to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
26 Nov - 17 Dec 1985
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)
Version / remarks:
adopted in 1981
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
30, 60 min, 24, 48 and 72 hours and 7, 14 and 21 days.
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
For details on individual animal responses, please refer to Table 1 under "Any other information on results incl. tables."

Table 1: Results of the skin irritation study






























































































Observation timeRabbit no.
123
ErythemaEdemaErythemaEdemaErythemaEdema
1 h101010
24 h101010
48 h203031
72 h303031
7 d102020
14 d001010
21 d000000
Mean value 24 + 48 + 72 h1.400.002.330.002.250.67

 

Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study in rabbits, the test substance induced erythema and slight oedema after exposure under semi-occlusive conditions for 4 hours. All symptoms of irritation were fully reversible within the 21 h observation period. Strictly speaking, the cut-off value of 2.3 was reached in two animals (2.33 and 2.25, respectively). Applying a precautionary approach, the test substance was concluded to be irritant to skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
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)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb:HM
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, Biberach, DE
- Age at study initiation: approx. 15 months
- Weight at study initiation: approx. 2740 g
- Diet: K4 rabbit diet (Ssniff GmbH, Soest, DE); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Remarks:
1/10 mm
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
3 x 0.5 g
Duration of treatment / exposure:
3 min, 1 h and 4 h
Observation period:
21 days
Number of animals:
1 male
Details on study design:
TEST SITE
- Type of wrap if used: Hansapor steril (6 cm^2), BDP hypoallergenic adhesive air- and vapor permeable gauze bandage: Fixomull stretch, BDF.

REMOVAL OF TEST SUBSTANCE
- Washing: tissue moistened with tap-water and subsequently wiping with a dry tissue
- Time after start of exposure: 3 min, 1 or 4 h

OBSERVATION TIME POINTS
1, 24, 48, 72 h and 7, 14, 21 days.

SCORING SYSTEM:
- Method of calculation: according to test guideline
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 h exposure time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 h exposure time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
3-minute patch (left flank):
No erythema and edema were observed at the application area during 72 h of observation. Below the application area, weak erythema and edema were observed 48 and 72 hours after application. At the 7 day observation, eschar was found at this area.

1 hour patch (right flank, caudal):
No erythema and edema after 1 hour and only a brownish discoloration was observed. Slight erythema, weak edema and a brownish discoloration were observed after 25 hours. Weak erythema and edema with a slight brownish discoloration were observed after 48 hours. Moderate erythema, weak edema and a brownish discoloration were observed after 72 hours. Up to 21 days the reactions of the skin were irreversible. Eschar was observed after 7 days. After 14 days the skin was shiny. An intense growth of hair and a thickening of skin at the application area were observed after 21 days.

4 hour patch (right flank, cranial):
Slight erythema, no edema and a brownish skin were observed after 1 hour. Weak to severe erythema, moderate edema and a slight brownish discoloration were observed 24 to 72 hours. Up to 21 days the reactions of the skin were irreversible. A necrosis and brownish discoloration were observed after 7 days. After 14 days the necrosis was peeled off in its whole thickness as a coherent piece of skin. This new skin was thickened. After 21 days, thickening of the treated skin and an intense growth of hair were observed.

Table 1: Results of the skin irritation study





































































































Observation time3 min expsoure1 h exposure4 h exposure
       
 ErythemaEdemaErythemaEdemaErythemaEdema
1 h000010
24 h001223
48 h0 (2)0 (2)2243
72 h0 (2)0 (2)3233
7 dreversiblereversibleirreversibleirreversibleirreversibleirreversible
14 dreversiblereversibleirreversibleirreversibleirreversibleirreversible
21 dreversiblereversibleirreversibleirreversibleirreversibleirreversible
Mean value 24 + 48 + 72 h002233

() = outside, below the application area

Interpretation of results:
other: Skin Dam. 1, H314. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study in rabbits, the test substance induced erythema and edema which were irreversible within 21 days. Based on the results of the 4 hour exposure patch, the test substance was concluded to be corrosive to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Only 7 days observation period, 6 instead of 3 animals tested
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: “Padre Antonio” center - Mariano Comense (CO), IT
- Weight at study initiation: 2000 - 3000 g
- Diet: Pelleted complete diet; ad libitum
- Water: Filtered tap water; ad libitum
- Acclimation period: 1 week
- Cages: Stainless steel cages model 1472 (Tecniplast - Varese)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 8
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 h
Observation period:
7 days
Reading timepoints: 24, 48, 72 h and 5 and 7 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap used: The test material was applied to a gauze pad which was hold in place by an adhesive tape. The gauze pad was further hold in place and secured by wrapping the hole trunk with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: With water or adequate solvent
- Time after start of exposure: 4 h

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: The observation period was only 7 days.
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: The observation period was only 7 days.
Irritant / corrosive response data:
Based on the individual scores no classification for skin irritation is needed. However, it is unknown if the scores are reversible within 14 days as requested in the OECD Guideline 404 for a negative outcome. Using the worst case apporach and assuming the effects to be irreversible a classification is required. Please refer to Table 1 under "Any other information on results incl. tables" for details on the achieved scores.

Table 1. Results of the skin irritation study





























































































































Observation time



Rabbit No



1



2



3



4



5



6



E



O



E



O



E



O



E



O



E



O



E



O



24 h



2



2



2



2



1



1



1



1



1



2



2



2



48 h



2



2



2



2



1



1



1



1



1



2



2



2



72 h



2



2



2



2



1



1



1



1



1



2



2



2



5 d



2



2



2



2



1



1



1



1



1



2



2



2



7 d



2



2



2



2



1



1



1



1



1



2



2



2



24, 48, 72 h mean



2



2



2



2



1



1



1



1



1



2



2



2



Mean of all six animals: E = 1.50; O = 1.67



E: Erythema. O: Oedema


 

Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin irritation study in rabbits, the test substance induced slight erythema and oedema which were not fully reversible within the 7-day observation period. Based on the individual scores no classification for skin irritation is needed. However, it is unknown if the scores are reversible within 14 days as requested in the OECD Guideline 404 for a negative outcome. Using the worst case apporach and assuming the effects to be irreversible, a classification is required.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
water
Controls:
not required
Amount / concentration applied:
Amount: 0.1 mL
Concentration: 20% (5.4% a.i.)
Duration of treatment / exposure:
single administration without washing
Observation period (in vivo):
7 days
Observation time points: 1, 24, 48 and 72 h after administration
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Cornea and iris were normal.
Conjunctiva redness and swelling appeared after 60 minutes. Swelling disappeared in part in 2 animals after 24 hours and in all after 7 days. Redness disappeared completely after 24 hours.
For individual animal responses, please refer to Table 1 under "any other information on results incl. tables."

Table 1: Results of the eye irritation study

 

Rabbit # Time conjunctivae   iris cornea
redness swelling
1 1 h 3 1 0 0
24 h 2 0 0 0
48 h 1 0 0 0
72 h 1 0 0 0
7 d 0 0 0 0
average 1.3 0.0 0.0 0.0
2 1 h 3 1 0 0
24 h 3 0 0 0
48 h 1 0 0 0
72 h 1 0 0 0
7 d 0 0 0 0
average 1.7 0.0 0.0 0.0
3 1 h 3 1 0 0
24 h 2 0 0 0
48 h 0 0 0 0
72 h 0 0 0 0
7 d 0 0 0 0
average 0.5 0.0 0.0 0.0
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo eye irritation study in rabbits, the test substance produced weak irritation symptoms in the conjunctiva of the tested animals. The reactions were fully reversible within 7 days. Based on the obtained scores which were below the cut-off values for a positive response, the test substance was concluded not to be irritant to the eye.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
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)
Deviations:
yes
Remarks:
Observation period lasted only 72 h.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
According to Guideline.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
single application
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): for one part of the study, the eyes were washed with 20 ml of distilled water at 38 °C
- Time after start of exposure: 5 s
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h.
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.4
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.9
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Observation period lasted only 72 h.
Irritant / corrosive response data:
For individual animal responses (unrinsed exposure), please refer to Table 1 under "any other information on results incl. tables."

Table 1: Results of the eye irritation study














































































































































































































































Rabbit #Time [h]conjunctivae iriscornea
rednessswelling
1241011
480000
720000
average0.30.00.50.5
2242111
482211
721111
average1.71.31.01.0
3242211
482200
720000
average1.31.30.30.3
4241110.5
480000
720000
average0.30.30.30.2
5242211
482211
720000
average1.31.30.70.7
6241100.5
480000
720000
average0.30.30.00.2
  
Time [h]conjunctivae iriscornea
 rednessswelling  
average
score
241.501.170.830.83
481.001.000.330.33
720.170.170.170.17
24+48+720.890.780.440.44

The response "dull" for cornea was translated to a score of 0.5.


Only scores of the unrinsed animals were reported and used for classification.

Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo eye irritation study, the test substance was assessed for its irritant effects on the eyes of rabbits. Indeed only one animal shows irreversible effects at the end of the observation period of only 72 h. It remains unclear whether the effects would resolve within a longer observation period. Generally, all scores were very mild. Weighing all factors it is concluded that the test substance is irritating to the eye.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
20 May - 10 Jun 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb-SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, Biberach, DE
- Weight at study initiation: 1.8 - 2.3 kg
- Housing: individually in stainless steel cages
- Diet: K4 rabbit diet (Ssniff Spezialfutter GmbH, Soest, DE); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
single application
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: warm physiological saline solution
- Time after start of exposure: 72 h

SCORING SYSTEM: Draize (1959)

TOOL USED TO ASSESS SCORE: fluorescein/slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.8
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
For details on individual animal responses, please refer to Table 1 under "Any other information on results incl. tables."

Table 1: Results of the eye irritation study

Rabbit # Time conjunctivae   iris cornea
redness swelling
1 1 h 2 1 0 1
24 h 3 1 1 1
48 h 3 1 1 2
72 h 3 1 0 2
6 d 3 0 0 1
8 d 1 0 0 1
10 d 1 0 0 1
13 d 1 0 0 1
17 d 0 0 0 0
21 d 0 0 0 0
average 3.0 1.0 0.7 1.7
2 1 h 2 1 1 1
24 h 3 1 1 1
48 h 3 1 1 1
72 h 3 1 0 1
6 d 2 0 1 2
8 d 2 0 0 2
10 d 2 0 1 2
13 d 2 0 1 2
17 d 0 0 1 2
21 d 0 0 1 2
average 3.0 1.0 0.7 1.0
3 1 h 2 1 1 1
24 h 3 1 1 1
48 h 3 1 1 1
72 h 3 1 1 2
6 d 3 1 1 2
8 d 3 0 1 2
10 d 3 0 1 2
13 d 3 0 1 2
17 d 0 0 1 3
21 d 0 0 1 2
average 3.0 1.0 1.0 1.3
Interpretation of results:
other: Eye Dam. 1, H318. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo eye irritation study, the test substance caused irritation in cornea, iris and conjunctiva, as well as chemosis in all three tested rabbits. The damage in cornea and iris was irreversible in two animals, while the effects in conjunctiva and chemosis were reversible within the 21-day observation period. Based on the irreversibility of the effects in two animals, the test substance is concluded to be damaging to the eye.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
03 - 16 Jun 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
yes
Remarks:
observation time only 6 days
GLP compliance:
no
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb-SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, Biberach, DE
- Weight at study initiation: 2.2 - 2.6 kg
- Housing: individually in stainless steel cages
- Diet: K4 rabbit diet (Ssniff Spezialfutter GmbH, Soest, DE); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
water
Controls:
not required
Amount / concentration applied:
Amount: 0.1 mL
Concentration: 1%
Duration of treatment / exposure:
single application
Observation period (in vivo):
6 days
Observation time points: 1, 24, 48, 72 h and 6 days
Number of animals or in vitro replicates:
3 (2 males and 1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: warm physiological saline solution
- Time after start of exposure: 72 h

SCORING SYSTEM: Draize (1959)

TOOL USED TO ASSESS SCORE: fluorescein and eye-lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.56
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.11
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
For details on individual animal responses, please refer to Table 1 under "Any other information on results incl. tables"

Table 1: Results of the eye irritation study

Rabbit # Time conjunctivae   iris cornea
redness swelling
1 1 h 2 0 0 0
24 h 1 0 0 0
48 h 0 0 0 0
72 h 0 0 0 0
6 d 0 0 0 0
average 0.3 0.0 0.0 0.0
2 1 h 2 0 0 0
24 h 1 0 0 0
48 h 0 0 0 0
72 h 0 0 0 0
6 d 0 0 0 0
average 0.3 0.0 0.0 0.0
3 1 h 1 0 0 0
24 h 2 1 0 0
48 h 1 0 0 0
72 h 0 0 0 0
6 d 0 0 0 0
average 0.8 0.3 0.0 0.0
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo skin irritation study in the rabbit, the test substance induced only very weak irritation symptoms in conjunctiva and chemosis, which were fully reversible within 72 hours. Therefore, it is concluded that the test substance is not irritating to the eye.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
not reported
Number of animals or in vitro replicates:
not reported
Irritation parameter:
other: Result section states "R41".
Time point:
24/48/72 h
Remarks on result:
positive indication of irritation

Result section states classification as "R41" (risk of serious eye damage)

Interpretation of results:
other: Eye damage 1, H318. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no anaesthetics used more than 1 (2) animal(s) used
GLP compliance:
no
Species:
rabbit
Strain:
Himalayan
Remarks:
Chbb:HM/Fa
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, DE
- Weight at study initiation: 2092.5 - 2477.5 g
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
single application
Observation period (in vivo):
21 days
Observation time points: 1, 6, 24, 48, and 72 h as well as 7, 10, 14, 17 and 21 days after administration
Number of animals or in vitro replicates:
4
Details on study design:
SCORING SYSTEM: Draize (1959)

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.8
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Treatment with fluorescein yielded mean values of 93.75 at the time point of 24 h after administration, and 15.00 at the time point of 21 days after application.
For details on individual animal responses, please refer to Table 1 under "any other information on results incl. tables."

Table 1: Results of the eye irritation study

 

Rabbit # Time conjunctivae   iris cornea
redness swelling
1 1 h 1 2 0 0
6 h 2 2 0 1
24 h 3 1 0 1
48 h 3 1 0 1
72 h 2 1 0 1
7 d 2 1 0 1
10 d 1 0 0 1
14 d 1 0 0 0
17 d 0 0 0 0
21 d 0 0 0 0
average 2.7 1.0 0.0 1.0
2 1 h 1 1 0 1
6 h 2 1 0 1
24 h 3 1 0 1
48 h 3 1 0 1
72 h 3 1 0 1
7 d 1 0 0 1
10 d 1 0 0 1
14 d 0 0 0 1
17 d 0 0 0 1
21 d 0 0 0 1
average 3.0 1.0 0.0 1.0
3 1 h 1 1 0 1
6 h 1 2 0 1
24 h 3 1 0 1
48 h 3 1 0 1
72 h 3 1 0 1
7 d 3 1 0 1
10 d 3 1 0 1
14 d 2 0 0 1
17 d 2 0 0 1
21 d 2 0 0 1
average 3.0 1.0 0.0 1.0
4 1 h 1 2 0 1
6 h 1 2 0 1
24 h 2 1 0 1
48 h 3 1 0 1
72 h 2 1 0 1
7 d 1 0 0 1
10 d 1 0 0 0
14 d 1 0 0 0
17 d 1 0 0 0
21 d 0 0 0 0
average 2.3 1.0 0.0 1.0

Average values refer to the time points 24/48/72 h.

Interpretation of results:
other: Eye Dam. 1, H318. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo eye irritation study the test substance induced irritation in the cornea and conjunctiva. In one animal, reactions in cornea and conjunctiva (redness) were not fully reversible within the 21-day observation period. Based on the irreversibility of the effects in one test animal, the test substance is considered damaging to the eye.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, DE
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.4 - 3.8 kg
- Housing: individually, battery-housing
- Diet: Altromin 2123 rabbit diet (Altromin, DE); ad libitum. Additionally, 15 g hay daily
- Water: deionized, chlorinated water available via automated drinking bottles; ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
14 days
Observation time points: 1, 24, 48, and 72 h, as well as after 7 and 14 days.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: with warm (37°C) physiological saline solution
- Time after start of exposure: 24 h and at all other observation times where discharge was noted.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.8
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.9
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
For individual animal responses, please refer to Table 1 under "any other information on results incl. tables."

Table 1: Results of the Eye irritation study

 

Rabbit # Time conjunctivae   iris cornea
redness swelling
1 1 h 3 3 1 1
24 h 3 1 1 1
48 h 3 1 0 1
72 h 2 0 0 1
7 d 0 0 0 0
14 d - - - -
average 2.7 0.7 0.3 1.0
2 1 h 3 2 1 1
24 h 3 3 1 1
48 h 3 3 1 1
72 h 3 2 1 2
7 d 2 1 0 1
14 d 0 0 0 0
average 3.0 2.7 1.0 1.3
3 1 h 3 3 1 1
24 h 3 3 1 1
48 h 2 2 1 1
72 h 3 2 1 1
7 d 2 1 0 1
14 d 0 0 0 0
average 2.0 1.6 0.6 0.8
Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo eye irritation test in rabbits, the test substance induced eye irritation in the cornea, iris, conjunctiva and chemosis, which were fully reversible within 14 days. In at least 2 animals, a positive response was observed, i.e. the cut-off value of 1 (cornea and/or iris) or 2 (conjunctival redness and/or chemosis) were reached or exceeded.Based on the obtained scores and positive responses in at least 2 animals, it was concluded that the test substance (at 27% a.s.) is irritant to the eye.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
07 Jun - 12 Jul 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, DE
- Weight at study initiation: 3.1 - 3.4 kg
- Housing: individually in cages arranged in a battery
- Diet: Altromin 2123 maintenance diet for rabbits (Altromin GmbH, DE); ad libitum
- Water: water from automatic water dispensers; ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: warm isotonic saline (37°C)
- Time after start of exposure: 24 after application and at all other examination times when the treated eyes still showed discharge

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.8
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
No individual values were given.
The mean values per animal are depicted in Table 1 under "Any other information on results incl. tables."
Mean of 24/48/72 h observation time points animal #1 animal #2 animal #3
Corneal opacity 1.0 1.0 1.7
Iris 0.7 0.7 1.0
Conjunctival redness 3.0 2.7 2.7
Chemosis 2.3 2.3 2.3
Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo eye irritation study in rabbits, the test substance induced irritant reactions in the cornea, iris, conjunctiva and chemosis. The effects were fully reversible within the 21-day observation period. In at least 2 animals, a positive response was observed, i.e. the cut-off value of 1 (cornea and/or iris) or 2 (conjunctival redness and/or chemosis) were reached or exceeded. Based on the obtained scores, the test substance (at 27% a.s) is concluded to be irritant to the eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion


Data on skin irritation / corrosion are available for alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) as well as several member substances of the Alkyl Ether Sulfates (AES) category.


 


Studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8)


There are 11 studies on skin irritation / corrosion available. A study performed according to OECD guideline 404 under GLP conditions is identified as key study, representing the endpoint skin irritation (BASF, 1994a). In the key study, three New Zealand White rabbits were exposed to the unchanged test substance (70% purity). The animals were examined for any abnormality prior to the test substance administration, with a special emphasis on the skin to be treated. Animals were observed for viability/mortality and general signs of toxicity twice daily. The body weight was recorded on the day of treatment, prior to application. About 24 h prior to treatment, the dorsal fur was shaved with electric clippers, exposing an area of approx. 10 x 15 cm2. Whenever necessary, the skin areas concerned were re-shaved at least 3 h before observations, to facilitate scoring. A first animal was subjected to three treatments with 0.5 g unchanged test substance with three different exposure times (1 min, 1 h and 4 h) with an occlusive dressing (Scotchpak-Non-Woven patches of 2 x 3 cm each mounted on separate Micropore tapes). Each dressing was wrapped around the abdomen and secured with Coban elastic bandage. The remaining test substance was removed using first a tissue moistened with tap water and subsequently a dry tissue. The animals' contralateral flank served as concurrent control. Two other animals were treated 3 weeks later with a single dose of 0.5 g for an exposure period of 4 h in a similar way. Observation time points for scoring were 24, 48 and 72 h and 7, 14 and 21 days for the first animal and 1, 24, 48 and 72 h and 7, 14 and 21 days for the two additional animals. Scoring was performed according to the Draize scheme.


Very slight erythema was observed in the treated skin area immediately after the 3 min exposure. A gradual increase of the irritation was observed during the study, resulting in severe erythema, moderate oedema and reduced flexibility of the skin after 72 h. After 7 days, the irritation had decreased and moderate to severe erythema, slight oedema and scaliness were observed in the bald skin area. The irritation had completely resolved at termination (21 days after exposure). Exposure for 1 h resulted in well -defined erythema immediately after exposure. The skin irritation increased from day 2 onwards and after 72 h the maximum degree of irritation was observed, consisting of severe erythema and oedema and reduced flexibility of the skin. After 7 days moderate to severe erythema, slight oedema and scaliness were observed in the bald skin area. The bald skin persisted until 14 days after exposure. The irritation had completely resolved at termination. Exposure for 4 h resulted in moderate to severe erythema and very slight oedema immediately after exposure. Fissuring of the skin, indicating superficial necrosis, reduced flexibility of the skin and severe erythema and oedema were noted after 72 h. After 7 days moderate to severe erythema, slight oedema and scaliness were observed in the bald skin area. The irritation had completely resolved within 21 days after exposure; however, the bald skin persisted at termination. Exposure of the two additional animals to the test substance for 4 h resulted in comparable irritation to the that observed in the first animal, when exposes for 4 h. Well-defined erythema without oedema and moderate to severe erythema and very slight oedema were observed in the two animals on day 1. After 72 h reduced flexibility, fissuring of the skin and severe erythema and oedema were apparent. The degree of irritation decreased thereafter, and the irritation had completely resolved within 21 days after exposure. A bald skin patch was apparent from 14 days after exposure onwards and persisted until termination in the two animals. No symptoms of systemic toxicity were observed in any animal and no mortality occurred. Based on the obtained erythema and oedema scores, alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) is concluded to be irritant to the skin.


A total of 10 additional in vivo studies is available that support the findings of the key investigation. The supporting studies were performed with several different concentrations of alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) and are further evaluated below in the context of all available studies in the AES category.


 


Studies in the AES category


Studies on skin irritation / corrosion, including those performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), are available for the following AES substances:


 


Table 1: Database on skin irritation / corrosion in the Alkyl Ether Sulfates (AES) category




































































































































































CAS / EC Nos.



Substance



Study or Report No.



Study protocol (adopted in)



Concentration in test material [%]



Hazard conclusion



‘Linear’ subgroup



1471312-55-6 / 939-523-2



Alcohols, C8-10, ethoxylated, sulfates, sodium salts



121484



OECD 439



100



Irritating or corrosive



122043



OECD 431 (EpiDerm)



100



Not corrosive



68585-34-2 / 500-223-8



Alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts



000504/1



Similar OECD 404



68



Irritating



82-003E



Similar OECD 404



25



Irritating



82-003B



Similar OECD 404



25 - 30



Irritating



A/S/12431



Similar OECD 404



70



Irritating



18957



OECD 404



58.5



Irritating



4299



Similar OECD 404



10



Not irritating



4306



Similar OECD 404



1



Not irritating



68891-38-3 / 500-234-8



Alcohols, C12-14, ethoxylated, sulfates, sodium salts



R9400637



OECD 404



70



Irritating



TBD860073



Similar OECD 404



25



Irritating



3108



Similar OECD 404



28



Not irritating



2976



Similar OECD 404



70



Irritating



000504/1



Similar OECD 404



68



Irritating



3116



Similar OECD 404



1



Not irritating



R9400325



OECD 404



70.1



 Corrosive



256/8409



Similar OECD 404



70



Irritating



R9600430



OECD 404



27



Irritating



86498D/UGF 17/SE



Similar OECD 404



70



Irritating



Hoe88.0919



Similar OECD 404



69



Irritating



174450-50-1 / 605-725-1



Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts



2397



OECD 404



83.8



Irritating



Mixed branched & linear’ subgroup



160901-28-0 / 500-465-4



Alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts



219-7703



Similar OECD 404



30



Irritating



 


Evaluation of skin irritation / corrosion as observed in studies


The concentration of AES substances in the test materials used in the skin irritation / corrosion studies varies from 1% to approx. 100%. Tested AES substances induced mostly moderate to severe erythema and oedema at concentrations above 25%. Irritation symptoms started to occur immediately after removal of the test substance and were usually reversible within the 21-day observation period of the respective studies. However, since in some studies observations were made for a period less than the maximum of 21 days, skin effects were still observed at the termination of most of these studies. AES concentrations ≤ 10% did not cause irritation (studies 4299 and 4306 with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts, CAS No. 68585-34-2, EC No. 500-223-8). The only exception to this finding was one of the in vivo studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8, study No. 3108) in which the substance was tested at a concentration of 28% and induced only very weak erythema which was fully reversible within the 8-day observation period. No oedema was observed in this study. The reason for this deviation from the general observation is unknown. In some studies, the exposure period was 24 h and/or an occlusive cover was used. Only one of the available studies revealed a corrosive potential (study no. R9400325 performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts. All other available studies indicate a potential to induce irritation. The reason for the corrosion found in study R9400325 is unknown. However, since it is the only study in the database of the category, it is considered not to contradict the overall conclusion of skin irritation for AES substances. The main findings of the in vivo studies are supported by the available in vitro assays performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2). The combined results of the in vitro studies provide evidence for an irritating (but not corrosive) potential.


The WoE analysis based on the in vitro and in vivo studies indicates that AES substances in general exhibit a potential to induce skin irritation. This finding applies to all AES substances in the category, whether they belong to the ‘linear’, ‘unsaturated’ or ‘mixed branched & linear’ subgroups and it is fully supported by the OECD QSAR Toolbox profiling. The outcome of this overall WoE evaluation is used for the hazard assessment and to conclude on classification and labelling of all AES substances in the category. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the skin irritation / corrosion potential of the substances in the AES category, please refer to the category justification attached to the category object.


 


Eye irritation


Data on eye irritation are available for alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) as well as several member substances of the Alkyl Ether Sulfates (AES) category.


There are eight in vivo studies on eye irritation available for alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) all of which exhibit minor or major deficiencies when compared to the requirements of the newest version of OECD guideline 405. However, none of the studies are considered to be invalid. Therefore, all the studies are accounted for in a Weight-of-Evidence approach. Since there are in vivo eye irritation studies available also for several other members of the AES category, the studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) are also used to assess the endpoint for the complete category, i.e. for those AES substances lacking own data with respect to eye irritation. Due to the high number, the studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) are not discussed in detail here. Instead, an assessment of of eye irritation potential based on all available studies in the AES category, incl. those with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) is provided.


Studies on eye irritation, including those performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), are available for the following AES substances:


 


Table 2: Database on eye irritation in the Alkyl Ether Sulfates (AES) category























































































































































CAS / EC Nos.



Substance



Study or Report No.



Study protocol (adopted in)



Concentration in test material [%]



Hazard conclusion based on study report



‘Linear’ subgroup



68585-34-2 / 500-223-8



Alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts



4298



Similar OECD 405



10



Serious eye damage



97/10197-2



OECD 405



27



Not irritating



RE80/159A



Similar OECD 405



58



Irritating



28366



Similar OECD 405



69



Irritating



4288



Similar OECD 405



25



Irritating



4307



Similar OECD 405



24.3



Irritating



4308



Similar OECD 405



1



Not irritating



A/E/12323



Similar OECD 405



70



Not irritating



97/9690-2



OECD 405



27



Irritating



82-003C



Similar OECD 405



25 - 30



Irritating



82-003F



Similar OECD 405



Not specified



Irritating



19970



OECD 405



60



Serious eye damage



68891-38-3 / 500-234-8



Alcohols, C12-14, ethoxylated, sulfates, sodium salts



TBD890310



OECD 405



25



Serious eye damage



3109



Similar OECD 405



28



Serious eye damage



3117



Similar OECD 405



1



Not irritating



261/8409



Similar OECD 405



70



Irritating



Hoe88.1081



OECD 405



70



Serious eye damage



R9600431



OECD 405



27 - 28



Irritating



R9900359



OECD 405



27 - 28



Irritating



97/10197-2



OECD 405



5.4



Not irritating



174450-50-1 / 605-725-1



Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts



2398



OECD 405



83



Serious eye damage



 


Evaluation of eye irritation as observed in studies


The concentration of AES substances in the tested materials ranges from 1% in the studies with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8) and alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) to 83% applied in the study with alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1). Most of the studies were performed with AES concentrations between 25% and 70%. Concentrations at or above 10% generally induce moderate to severe irritant responses in conjunctiva, iris and cornea and cause chemosis. Some studies were terminated while effects were still observed in one or several animals. Since the observation periods applied in the different studies were not always as defined in the current OECD guideline 405, a concluding evaluation with respect to the reversibility of effects could not always be made and a case-by-case evaluation was made to reach a hazard conclusion. The exceptions to the general finding of irritating / damaging properties at concentrations > 10% are the studies 97/10197-2 and A/E/12323 with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8). These studies resulted in ‘not irritating’ at concentrations of 27% and 70%, respectively. The reason for the deviation of the general irritating / damaging properties is not known. However, the studies contribute only to a minor extent to the hazard assessment of the whole AES category.


In the following studies severe eye damage was observed: 4298 (10% concentration) and 19970 (60% concentration) with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8), as well as TBD890310, 3109, and Hoe88.1081 with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) at concentrations of 25%, 28%, and 70%, respectively. There is no clear trend in the available data between the concentration of a substance and the severity of eye effects (measured as chemosis, and reaction in conjunctivae, cornea, and iris) and it is therefore not possible to predict when eye irritation turns into serious eye damage. Therefore, all AES substances at concentrations ≥ 10% are considered to induce serious eye damage. The studies 4308 with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8) and 3117 with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) clearly demonstrate that highly diluted AES substances are not irritating anymore. Based on the fact that most of the available studies revealed an eye irritating rather than an eye damaging potential and that the lowest concentration inducing eye damage is 25%, it is considered justifiable to define a cut-off concentration for eye damage of 10%. Therefore, a cut-off value for the induction of severe eye damage is set at a concentration of ≥ 10% for all AES substances in the category. The cut-off value for inducing irritation is set at a concentration of ≥ 5%.


In conclusion, the WoE analysis based on all available studies on eye irritation indicates that AES substances generally exhibit a potential to induce severe eye damage at concentration ≥ 10%, eye irritation in the concentration range 5 - 10% and no irritation < 5%. This finding applies to all AES substances in the category, whether they belong to the ‘linear’, ‘unsaturated’ or ‘mixed branched & linear’ subgroups and it is fully supported by the OECD QSAR Toolbox profiling. The outcome of this overall WoE evaluation is used for the hazard assessment and to conclude on classification and labelling for all AES substances in the category. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the skin irritation / corrosion potential of the substances in the AES category, please refer to the category justification attached to the category object.


 


Data on counter ions


The counter ions Na+, Mg2+ and NH4+ are not associated with an irritating or corrosive potential. They have no effect on the irritation / corrosion potential of the substances in the AES category.


In vivo studies on skin and eye irritation with alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) revealed an irritating and corrosive potential, respectively. Since skin irritation and eye damage have been identified for all members of the AES category - either based on experimental data or predicted for those AES substances lacking own data - the impact of triisopropanolamine (TIPA) has already been accounted for.


For a detailed evaluation of a potential effect of the counter ions on the toxicological profiles of the AES member substances, please refer to the category justification attached to the category object.

Justification for classification or non-classification

The available data on skin and eye irritation obtained with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008. The substance is classified for skin and eye irritation as Skin Irrit. 2, H315, and Eye Damage 1, H318, respectively.