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Description of key information

Human data on local irritation/corrosion are not available. 
In a primary dermal irritation study comparable to OECD Guideline very slight erythema was observed in one animal 1 hour after exposure and in 2/3 animals after 24 hours and was fully reversible within 48 hours after exposure. No edema was observed. This result was supported by a comparable test with a diluted testsubstance and by irritation results form the acute dermal toxicity study.
The results of a Low Volume Eye Test) study comparable to OECD Guideline 405 give no evidence of an eye irritating potential of MDEA-Esterquat C16-18 and C18 unsatd.. This result is supported by observations made with a similar substance. Mild conjunctival redness and chemosis (scores 1) were observed for the period of up to 24 hours after treatment and were fully reversible after the 48 hours.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-06-30 to 1992-07-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The study was conducted in compliance with the following GLP Regulations: GLP in Switzerland, Procedures and Principles, March 1986; OECD Principles of GLP, Paris, France, adopted May 12, 1981 and EPA, GLP Standards, Final Rule, U.S.A., Federal Register,
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diethyl ester dimethyl ammonium chloride (DEEDMAC, E-4429.01)
- Physical state: Solid
Species:
rabbit
Strain:
other: Chbb: NZW (SPF)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH
- Age at study initiation: 19 weeks
- Weight at study initiation: Male: 3.2 kg and Females: 3.1 - 3.3 kg
- Housing: Individually housed in stainless steel cages (size: 86 X 54 X 33 cm) equipped with feed hoppers and drinking water bottles
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, Batch 70/92 rabbit maintenance diet, ad libitum
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-3
- Humidity (%): 40-70 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 lux)/ 12 hours dark, music during the light period


IN-LIFE DATES: From: 1992-06-30 To: 1992-07-05
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 gm
- Concentration (if solution): Not applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of treatment / exposure:
Three Chbb: NZW (SPF) rabbits were dosed with 0.5 gm of Diethyl ester dimethyl ammonium chloride (DEEDMAC, E-4429.01). The test article was applied moistened with tap water to approximately 6 cm2 of the intact skin of the clipped area. It was covered with a 3.0 cm X 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm-tap water. The skin reaction was assessed at 1, 24, 48 and 72 hours after removal of the dressing, gauze patch and test article.
Observation period:
1, 24, 48 and 72 hours after removal of the dressing, gauze patch and test article.
Number of animals:
3 animals (one male and two females)
Details on study design:
TEST SITE
- Area of exposure: Approximately 6 cm2
- % coverage: Covered with a 3.0 cm X 3.0 cm patch of surgical gauze
- Type of wrap if used: The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin was flushed with lukewarm-tap water
- Time after start of exposure: 4 hours


SCORING SYSTEM: Erythema and escher scoring from0-4 with 0 = no erythema, 1= very slight erythema, 2 = well defined erythema, 3 = moderate to severe erythema, 4 = severe erythema to slight eschar formation.
Oedema scoring from0-4 with 0 = no oedema, 1= very slight oedema, 2 = slight oedema, 3 = moderate oedema, 4 = severe oedema.
Irritation parameter:
erythema score
Remarks:
Intact skin site
Basis:
animal: #1, #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin site
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
Intact skin site
Basis:
animal: #1, #2, #3,
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
PDII 0.33 at 1 hour for intact skin site
PDII 0.67 at 24 hours for intact skin site
PDII 0 at 48 and 72 hours for intact skin site
Other effects:
No corrosive effect occurred on the treated skin of any animal at each measuring interval

GHS Classification Evaluation

 Animal # Degree of erythema after...[observation time]              Degree of oedema after...[observation time]        GHS ClassificationØ 24/48/72 h>/= 2.3?  
   1h  24h  48h  72h  1h  24h  48h  72h  Erythema  Oedema
 40 (M)  1  1  0  0  0  0  0  0  No  No
         Ø 24/48/72 h =  0.33           Ø 24/48/72 h =  0      
 41 (F)  0  0  0  0  0  0  0  0  No  No
         Ø 24/48/72 h =  0           Ø 24/48/72 h =  0    
 42 (F)  0  1  0  0  0  0  0  0  No  No
          Ø 24/48/72 h =  0.33            Ø 24/48/72 h =  0    
Interpretation of results:
GHS criteria not met
Conclusions:
MDEA-Esterquat C16-18 and C18 unsatd. is slightly irritating to the skin of rabbits. The mean grades of skin reactions at 24, 48 and 72 h reading correspond to values classified as not irritant by theDirective 67/548/EEC as well as GHS Regulation EC No 1272/2008.
Executive summary:

In a primary dermal irritation study comparable to OECD guideline 404, 12 May 1981, three White New Zealand rabbits were dermaly exposed to 0,5 g  of MDEA-Esterquat C16-18 and C18 unsatd. undiluted for 4 hours to an intact area of approximately 6 cm² covered by a semi-occlusive dressing. Animals then were observed for 3 days.  Irritation was scored by the method of Draize 1;  24; 48 and 72 hours after exposure.

Very slight erythema was observed 1 h after exposure in one animal and in 2/3 animals at the 24 hour reading and was reversible within 48 hours after exposure. No oedema was observed.

The mean grades of skin reactions at 24, 48 and 72 h reading correspond to values classified as not irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.

When applied to the skin, the test article MDEA-Esterquat C16-18 and C18 unsatd. is classified as "not irritant" in this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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
Study period:
1986-03-17 to 1986-03-24
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)
Deviations:
yes
Remarks:
-10 mg solid dose instead of 100 mg as specfied by OECD 405 guidelines
GLP compliance:
yes
Specific details on test material used for the study:
- Diethylester dimethyl ammonium chloride
- Substance type: Waxy
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Buckmasters, Henham,Hartfordshire, England
- Age at study initiation: 10-14 weeks
- Weight at study initiation: 2.3-3.2 kg
- Housing: Metal cages with perforated floors
- Diet (e.g. ad libitum): SDS standerd Rabbit Diet,ad libitum
- Water (e.g. ad libitum): Tap water,ad libitum
- Acclimation period:Not given


ENVIRONMENTAL CONDITIONS
- Temperature (°C):19 °C
- Humidity (%): 30-70%
- Air changes (per hr): 19 air charges /hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light in each 24 hrs period.


IN-LIFE DATES: From:1986-03-17 To: 1986-03-24
Vehicle:
unchanged (no vehicle)
Controls:
other: Counter lateral eye.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mg, eye non rinsed
- Concentration (if solution): Not Applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): Not Applicable
- Concentration (if solution): Not Applicable
- Lot/batch no. (if required): Not Applicable
- Purity: Not Applicable
Duration of treatment / exposure:
4 seconds in Group 2 and 7 days in Group 1
Observation period (in vivo):
24, 48, 72 hrs, 4, and 7 days after instillation for Group I and Group 2.
Number of animals or in vitro replicates:
Group 1: 6 Rabbits (10 mg undiluted test material, non-rinsed),
Group 2: 3 Rabbits (10mg undiluted test material, rinsed 4 seconds after instillation)
Details on study design:
The test substance is placed directly on the cornea of rabbit eye

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Group 1 unwashed, Group 2 washing with 20 ml of lukewarm tap water.
- Time after start of exposure: 4 seconds in Group 2


SCORING SYSTEM: Draize Scoring system.


TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Remarks:
10 mg undiluted test material non-rinsed
Basis:
animal: #1 - #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
10 mg undiluted test material non-rinsed
Basis:
animal: #1 - #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
10 mg undiluted test material non-rinsed
Basis:
animal: #1 - #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Remarks:
10 mg undiluted test material non-rinsed
Basis:
animal: #1 - #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
10 mg undiluted test material rinsed group
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
10 mg undiluted test material rinsed group
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
10 mg undiluted test material rinsed group
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
10 mg undiluted test material rinsed group
Basis:
animal: #1, #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Remarks:
10 mg undiluted test material rinsed group
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The eyes of two respective group of 6 and 3 rabbits were instilled with 10 mg of undiluted test substance. The eyes of the first group of 6 rabbits were not rinsed and the second group of 3 rabbits were rinsed. No ocular irritation was observed in the non-rinsed group of 6 rabbits 24 hours after instillation. Mild conjunctival redness (overall ocular irritation score was 0.67 at 24 hours) was observed in the eyes of 2/3 rabbits in the 10 mg rinsed group that cleared by 48 hours.
Other effects:
None observed.

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test group 1 (not rinsed)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

-

-

-

-

24 h

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

48 h

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

72 h

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

Average 24h, 48h, 72h

0

0

0

0

Area effected

 

 

 

 

Maximum average score (including area affected, max 110)

 

 

 

 

Reversibility*)

C

C

C

C

Average time (unit) for reversion

 

 

 

 

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test group 2 (rinsed)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

-

-

-

-

24 h

0/0/0

0/0/0

1/0/1

0/0/0

48 h

0/0/0

0/0/0

0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0

0

0.33/0/0.33

0

Area effected

 

 

 

 

Maximum average score (including area affected, max 110)

 

 

 

 

Reversibility*)

C

C

C

C

Average time (unit) for reversion

 

 

 

 

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
study cannot be used for classification
Conclusions:
No occular irritation was observed in the non-rinsed group.
A very slight irritation was observed untill the 24 hour reading with max. scores of 1 for conjunctivae. All symptomes were reversible at the 48 hour reading.
Executive summary:

In a primary eye irritation study comparable to OECD guideline 405,10 mg of MDEA-Esterquat C16-18 and C18 unsatd. was directly applied onto the cornea of one eye of six young adult New Zealand rabbits each and observed for 7 days. A subgroup of 3 additional rabbits was treated in the same matter, but eyes were rinsed 4 sec. after instillation of test substance.

Animals then were observed for 7 days.  Irritation was scored by the method of Draize.

In the main group no eye irritation was observed, all readings were zero. Mild conjunctival redness (score 1) was observed in 2/3 rabbits of subgroup (rinsed group)after 24 hours and was reversible within 48 hours.

 

No information on content of active ingredient of the test substance in this study report. However, according to producer information test substance has 80 % a.i.

 

In this study, MDEA-Esterquat C16-18 and C18 unsatd. is not an eye irritant.

 

Due to the low volume applied, the results of this study are not adequate for classification and labelling purposes.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1993-07-05 to 1993-07-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
- Name of test material (as cited in study report): BFA-base E 4708.01
- Diethyl ester dimethyl ammonium chloride
- Substance type: Waxy
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH
- Age at study initiation: 15 weeks
- Weight at study initiation: Male: 2.6 kg; Females: 2.6-2.7 kg
- Housing: Individually in stainless steel cages (size: 120 X 52 X 60 cm) equipped with feed hoppers and drinking water bottles
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, Batch 77/93 rabbit maintenance diet, ad libitum
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum
- Acclimation period: 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 degrees C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/ 12 hours dark, music during the light period


IN-LIFE DATES: From: 1993-07-05 To: 1993- 07-12
Vehicle:
unchanged (no vehicle)
Controls:
other: Counter lateral eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg, eye non rinsed
- Concentration (if solution): Not applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of treatment / exposure:
100 mg of the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article.
Observation period (in vivo):
1, 24, 48 and 72 hours after instillation
Number of animals or in vitro replicates:
3 rabbits (1 male and 2 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed
- Time after start of exposure: Not applicable


SCORING SYSTEM: according to Draize


TOOL USED TO ASSESS SCORE: hand-slit lamp 30 SL/M and a Varta Cliptrix diagnostic-lamp
Irritation parameter:
cornea opacity score
Remarks:
100 mg undiluted test material non-rinsed
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
100 mg undiluted test material non-rinsed
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
100 mg undiluted test material non-rinsed
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
100 mg undiluted test material non-rinsed
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Remarks:
100 mg undiluted test material non-rinsed
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The left eyes of a group of 3 rabbits were instilled with 100mg of undiluted test substance. The eyes were not rinsed. Mild conjuctival redness was observed in the eyes of 3/3 and 2/3 animals at the 1 hour reading and 24 hours, respecitvly that cleared by 48 hours. CHemosis was observed in the eyes of 2/3 animals at 1 hour reading which also cleared by 48 hours.
Other effects:
Normal weight gains and no clinical signs were observed during study.

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

1/1/1

1/1/0

24 h

0/0/0

0/0/0

0/1/1

0/0/0

48 h

0/0/0

0/0/0

0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0

0

0/0.33/0.33

0

Area effected

Maximum average score (including area affected, max 110)

Reversibility*)

C

C

C

C

Average time (unit) for reversion

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
GHS criteria not met
Conclusions:
A very slight irritation was observed untill the 24 hour reading with max. scores of 1 for conjunctivae and chemosis. All symptomes were reversible at the 48 hour reading.
Executive summary:

In a primary eye irritation study according to OECD guideline 405, 12 May 1981, 100 mg of a MDEA-Esterquat C16-18 and C18 unsatd. with the same structure but a different distribution of the fatty acid moiety which contains a higher amount of unsaturated C18´ (Iodine Value 50) was instilled into the conjunctival sac of the left eye of young adult New Zealand white rabbits, 1male and 2 female. Animals then were observed for 72 hours.  Irritation was scored by the method of Draize. Mild conjunctival redness (score 1) was observed in 3/3 rabbits after 1 hour and was present in 2/3 animals at the 24 hour reading. Reversibility was shown within 48 hours. Chemosis (score 1) was observed in 2/3 rabbits and was reversible within 24 hours.

In this study the mean grades of ocular reactions at 24, 48 and 72 h after instillation were lower than the values classified as irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.

When administered to the eye, the test article MDEA-Esterquat C16-18 and C18 unsatd. (Iodine value 50) is classified as "non-irritant".

 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a primary dermal irritation study comparable to OECD Guideline 404 (24 April 2002), three White New Zealand rabbits were dermally exposed to 0.5 g of undiluted MDEA-Esterquat C16-18 and C18 unsatd. An intact skin area of approximately 6 cm² was covered by a semi-occlusive dressing for a duration of 4 hours. Animals were observed for 3 days. Irritation was scored using the method of Draize at the following timepoints: 1; 24; 48 and 72 hours after exposure.

Very slight erythema was observed in one animal 1 hour after exposure and in 2/3 animals after 24 hours and was fully reversible within 48 hours after exposure. No edema was observed.

In an additional study comparable to OECD Guideline 404 (24 April 2002), three White New Zealand rabbits were dermally exposed to 0.4 mL of MDEA-Esterquat C16-18 and C18 unsatd. 32 % of a.i. diluted in corn oil was administered to an intact and abraded skin area of approximately 2.5 cm² each under an occlusive dressing for a duration of 4 hours. Animals were observed for 3 days. Irritation was scored by the method of Draize at the following time points: 4.5; 24 and 72 hours after exposure.

Abraded and intact skin areas showed exactly the same scores. Very slight erythema was observed 4.5 h after exposure in all three animals. It was still apparent in 2/3 animals at the 24 hour reading and was fully reversible within 72 hours after exposure. No edema was observed.

Due to the very detailed description of irritation scores in the acute dermal toxicity study, additional data on the irritation endpoint were available. In an acute dermal toxicity study (comparable to OECD Guideline 402), groups of 3 male and 3 female New Zealand White rabbits were exposed dermally to MDEA-Esterquat C16-18 and C18 unsatd. (40 % a.i.) in oleum arachidis. Treatment lasted for 24 hours under an occlusive dressing. The applied dose of 2000 mg/kg bw resulted in an average concentration of 36 mg/cm² (assumed density 1; area of 10 x 15 cm).

Slight (1) to moderate (2) erythema and mainly moderate (2) edema with partly decreased intensity were observed at the treatment sites from 24 hours up to the 72 hours after treatment and were fully reversible within 7 days. The mean score were 1.3 for erythema and 1.75 for edema (after 24 and 72 hours). The applied scores of 1 and 2 for erythema and edema were comparable to the scores of the Draize method.

Furthermore an in vitro skin irritation study according to OECD Guideline 439 (In Vitro Skin Irritation) (22 July 2010) and EU method B.46 (In vitro skin irritation: reconstructed human epidermis model test) (20 July 2012) is available. 10.0 to 11.7 mg MDEA-Esterquat C16-18 and C18 unsatd. (100% a.i.) were applied in triplicates for 15 min to a three-dimensional human epidermis model (EPISKIN Small Model (EPISKIN-SM, 0.38 cm², Batch no.: 12-EKIN-047)). After 15 minutes exposure at room temperature, the tissues were washed with phosphate buffered saline to remove residual test substance. Subsequently the skin tissues were incubated for 43 h at 37°C. Cytotoxicity (irritancy) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

Positive (5% SDS) and negative (PBS) control gave the appropriate responses.

The relative mean tissue viability obtained after 15 minutes treatment with MDEA-Esterquat C16-18 and C18 unsatd. compared to the negative control tissues was 108%. Since the mean relative tissue viability for the test substance was above 50%, MDEA-Esterquat C16-18 and C18 unsatd. is considered to be not irritating.

Eye irritation

In a primary eye irritation LVET (Low Volume Eye Test) study comparable to OECD Guideline 405 (24 April 2002), 10 mg of MDEA-Esterquat C16-18 and C18 unsatd. was directly applied to the cornea of one eye of six young adult New Zealand White rabbits. Reactions were observed for 7 days afterwards. Irritation was scored by the method of Draize.

No eye irritation was observed, all readings were zero. No information on quantity of active ingredient contained in the test substance was given in this study report. However, according to information given by the producer, the test substance contained 80 % of a.i. (in isopropanol).

Additional data exist for a substance with the same structure but a different distribution of the fatty acid moiety which contains a higher amount of unsaturated C18, in particular, a primary eye irritation study is available according to OECD Guideline 405 (12 May 1981). 100 mg of MDEA-Esterquat C16-18 and C18 unsatd. (Iodine value of 50 instead of 25, the highest value for the submitted substance) was instilled into the conjunctival sac of the left eye of 3 young adult New Zealand White rabbits, 1male and 2 females. Animals were then observed for 72 hours. Irritation was scored by the method of Draize.

Mild conjunctival redness (score 1) was observed in 3/3 rabbits after 1 hour and was still present in 2/3 animals at the 24 hour reading. Full reversibility was shown within 48 hours. Chemosis (score 1) was observed in 2/3 rabbits and was fully reversible within 24 hours.

Following the Integrated Testing Strategy (ITS) according to Guidance on information requirements and chemical safety assessment, Endpoint specific guidance, Chapter R. 7.2.6 there is sufficient information available to proceed with classification and labelling using a weight of evidence approach. According to this guidance, for existing substances, the use of methods other than those specified in Annex V of Directive 67/548/EEC, or corresponding OECD methods, such as LVET (Griffith et al., 1980) may be accepted on a case-by-case basis.

The low volume eye test (LVET) is an alternative to the standard Draize eye irritation method. In contrast to the OECD Guideline 405, 10 µl/mg of test substance is directly applied to the cornea. Except for these two modifications, the methods are identical including the scoring method and data interpretation.

The LVET is an approved ASTM method (Standard test method for evaluation of eye irritation in Albino Rabbits E 1055-99) and has been widely used for detergent and cleaning preparations. The method is judged to be suitable to demonstrate toxicological effects on man of substances potentially hazardous to the eye (Freeberg et al. 1984).

Especially for detergent and cleaning preparations, the LVET is considered to be the best available predictor of effects on the human eye (ECETOC monograph 32, 2002). The acceptance of the LVET by national and international regulatory bodies and a further update of OECD Guideline 405 are under investigation. A retrospective validation study performed by ECVAM will shortly be peer-reviewed by the ESAC (Grindon et al. 2008).

MDEA-Esterquat C16-18 and C18 unsatd. is a cationic surfactant which is used as a fabric conditioner and therefore the substance fits exactly into the domain of applicability of detergent and cleaning products. In this context the results of the Low Volume Eye Test are of prime importance for the weight of evidence approach. Additional results are available from an eye irritation study according to OECD Guideline 405 with a structurally identical substance differing only in the fatty acid moiety. As compared to the one submitted for registration, this substance contains four times the amount of the unsaturated fatty acid moiety with the chain length of C18. Due to the higher amount of the unsaturated fatty acid moiety present in this substance, the hazard prediction derived from this study is more likely to be an over- than an underestimation.

The results of the LVET give no evidence of an eye irritating potential of MDEA-Esterquat C16-18 and C18 unsatd. This is supported by observations made with a similar substance. Mild conjunctival redness and chemosis (scores 1) were observed for the period of up to 24 hours after treatment and were fully reversible after the 48 hours.

Respiratory irritation

No data on the respiratory irritation of MDEA-Esterquat C16-18 and C18 unsatd. is available.

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.


Justification for classification or non-classification

When applied to the skin, the test article MDEA-Esterquat C16-18 and C18 unsatd.  caused slight irritation. The mean scores of skin reaction in all studies correspond to values which do not require the test substance to be classified as irritant according to GHS Regulation EC No 1272/2008 and labelling is not necessary.

The results of both eye irritation studies performed with MDEA-Esterquat C16-18 and C18 unsatd.  indicate that there is no need for classification as “eye irritant” according to GHS Regulation EC No 1272/2008. Therefore no labelling is required.