[No public or meaningful name is available]

Endpoint summary

Description of key information

Based on the available data, it can be concluded that the available data on skin irritation from the source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C16-18 and C18 unsatd., and MDIPA-Esterquat C18 unsatd. can be applied to the target substance MDEA-Esterquat C18 unsatd. The results obtained with the source substance MDIPA-Esterquat C18 unsatd. are considered the most relevant for the target substance. Therefore, MDEA-Esterquat C18 unsatd. is considered to be irritating to skin (Category 2) and classified as Eye Damage 1 (Category 1).

 

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological and ecotoxicological properties because they share structural similarities with common functional groups: quaternary amines, esters, and fatty acid chains varying in their length and degree of (un)saturation. Moreover, the fatty acid chains are chemically simple structures which have no structural alerts for toxicity, and which are closely related to substances of known low toxicity (i.e. stearic acid, oleic acid, linoleic acid, linolenic acid). Furthermore, the substances can be expected to have comparable breakdown products (MDEA or MDIPA and long chain fatty acids).

This read-across hypothesis corresponds to scenario 2 - different compounds have qualitatively and quantitatively the same type of effects - of the read-across assessment framework i.e. properties of the target substance MDEA-Esterquat C18 unsatd. are predicted to be similar to those of the source substances MDIPA Esterquat C18 unsatd., MDEA-Esterquat C16-18 and C18 unsatd. and MDIPA-Esterquat C16-18 and C18 unsatd.

Therefore, read-across from the available physicochemistry, toxicity and ecotoxicity studies with the source substances MDIPA Esterquat C18 unsatd., MDEA-Esterquat C16-18 and C18 unsatd. and MDIPA-Esterquat C16-18 and C18 unsatd. are considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance MDEA-Esterquat C18 unsatd., in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
please refer to read-across justification attached to Iuclid section 13

3. ANALOGUE APPROACH JUSTIFICATION
please refer to read-across justification attached to Iuclid section 13

4. DATA MATRIX
please refer to read-across justification attached to Iuclid section 13

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation / corrosion parameter:

% tissue viability

Value:

82.7

Negative controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological and ecotoxicological properties because they share structural similarities with common functional groups: quaternary amines, esters, and fatty acid chains varying in their length and degree of (un)saturation. Moreover, the fatty acid chains are chemically simple structures which have no structural alerts for toxicity, and which are closely related to substances of known low toxicity (i.e. stearic acid, oleic acid, linoleic acid, linolenic acid). Furthermore, the substances can be expected to have comparable breakdown products (MDEA or MDIPA and long chain fatty acids).

This read-across hypothesis corresponds to scenario 2 - different compounds have qualitatively and quantitatively the same type of effects - of the read-across assessment framework i.e. properties of the target substance MDEA-Esterquat C18 unsatd. are predicted to be similar to those of the source substances MDIPA Esterquat C18 unsatd., MDEA-Esterquat C16-18 and C18 unsatd. and MDIPA-Esterquat C16-18 and C18 unsatd.

Therefore, read-across from the available physicochemistry, toxicity and ecotoxicity studies with the source substances MDIPA Esterquat C18 unsatd., MDEA-Esterquat C16-18 and C18 unsatd. and MDIPA-Esterquat C16-18 and C18 unsatd. are considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance MDEA-Esterquat C18 unsatd., in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
please refer to read-across justification attached to Iuclid section 13

3. ANALOGUE APPROACH JUSTIFICATION
please refer to read-across justification attached to Iuclid section 13

4. DATA MATRIX
please refer to read-across justification attached to Iuclid section 13

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

iris score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 - 14 d

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the available data, it can be concluded that the available data on eye irritation from the source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C16-18 and C18 unsatd., and MDIPA-Esterquat C18 unsatd. can be applied to the target substance MDEA-Esterquat C18 unsatd. The results obtained with the source substance MDIPA-Esterquat C18 unsatd. are considered the most relevant for the target substance. Therefore, MDEA-Esterquat C18 unsatd. is classified as Eye Damage 1.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological and ecotoxicological properties because they share structural similarities with common functional groups: quaternary amines, esters, and fatty acid chains varying in their length and degree of (un)saturation. Moreover, the fatty acid chains are chemically simple structures which have no structural alerts for toxicity, and which are closely related to substances of known low toxicity (i.e. stearic acid, oleic acid, linoleic acid, linolenic acid). Furthermore, the substances can be expected to have comparable breakdown products (MDEA or MDIPA and long chain fatty acids).

This read-across hypothesis corresponds to scenario 2 - different compounds have qualitatively and quantitatively the same type of effects - of the read-across assessment framework i.e. properties of the target substance MDEA-Esterquat C18 unsatd. are predicted to be similar to those of the source substances MDIPA Esterquat C18 unsatd., MDEA-Esterquat C16-18 and C18 unsatd. and MDIPA-Esterquat C16-18 and C18 unsatd.

Therefore, read-across from the available physicochemistry, toxicity and ecotoxicity studies with the source substances MDIPA Esterquat C18 unsatd., MDEA-Esterquat C16-18 and C18 unsatd. and MDIPA-Esterquat C16-18 and C18 unsatd. are considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance MDEA-Esterquat C18 unsatd., in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
please refer to read-across justification attached to Iuclid section 13

3. ANALOGUE APPROACH JUSTIFICATION
please refer to read-across justification attached to Iuclid section 13

4. DATA MATRIX
please refer to read-across justification attached to Iuclid section 13

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

in vitro irritation score

Run / experiment:

20%

Value:

52.59

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on the available data, it can be concluded that the available data on eye irritation from the source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C16-18 and C18 unsatd., and MDIPA-Esterquat C18 unsatd. can be applied to the target substance MDEA-Esterquat C18 unsatd. The results obtained with the source substance MDIPA-Esterquat C18 unsatd. are considered the most relevant for the target substance. Therefore, MDEA-Esterquat C18 unsatd. is classified as Eye Damage 1.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No experimental data are available for the target substance MDEA-Esterquat C18 unsatd. However, skin and eye irritation studies are available for the structurally related source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C16-18 and C18 unsatd., and MDIPA-Esterquat C18 unsatd. 

A justification for read-across is attached to Iuclid section 13.

 

Skin irritation

MDEA-Esterquat C16-18 and C18 unsatd. 

In a primary dermal irritation study comparable to OECD guideline 404, 12 May 1981, three White New Zealand rabbits were dermally exposed to 0,5 g of MDEA-Esterquat C16-18 and C18 unsatd. undiluted for 4 hours (intact skin, semi-occlusive). 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. MDEA-Esterquat C16-18 and C18 unsatd. is classified as "not irritant" in this study.

 

In a dermal irritation study according to OECD Guideline 439 (In Vitro Skin Irritation), 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. 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 42 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. 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.

 

MDIPA-Esterquat C16-18 and C18 unsatd.

In a dermal irritation study performed in accordance with 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), MDIPA-Esterquat C16-18 and C18 unsatd. (100% a. i.) was applied to the three-dimensional human epidermis model tissue (EPISKIN Small Model (EPISKIN-SM, 0.38 cm², Batch no.: 12-EKIN-039) for an exposure period of 15 minutes. The number of replicate tissues was three). The test substance was heated in advance to approximately 50°C to soften the waxy substance. To achieve optimal contact with the tissue without causing mechanical damage, the test substance was applied using a cotton swab. The exact amount of test substance applied to cover the entire skin surface could not be determined using this method. Since optimal contact was obtained using this method this deviation has no impact on the study integrity. After 15 minutes exposure at room temperature, the tissues were washed with phosphate buffered saline pre-warmed to approximately 50°C, and residual test substance was carefully removed using a spatula. Subsequently the tissue constructs were incubated for 42 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.

The relative mean tissue viability obtained after 15 minutes treatment with MDIPA-Esterquat C16-18 and C18 unsatd. compared to the negative control tissues was 114%. Since the mean relative tissue viability for the test substance was above 50%, MDIPA-Esterquat C16-18 and C18 unsatd. is identified to be not irritating.

 

In a primary dermal irritation study according to OECD guideline 404, young adult New Zealand White rabbits were dermally exposed to 0.5% of a 30% dispersion of MDIPA-Esterquat C16-18 and C18 unsatd. in water for 3 min, 1 h and 4 h to an area of 2 cm x 3 cm. Animals then were observed for 14 days.  Irritation was scored by the method of Draize.

A 3-minute exposure resulted in very slight oedema and/or erythema immediately after exposure in the treated skin area of the three rabbits.

A 1-hour exposure resulted in well-defined to severe erythema and very slight to severe oedema in the treated skin area of the three rabbits. For two rabbits, erythema was scattered in nature at 7 days or between 24 hours and 7 days after exposure, and for one of these animals erythema was noted at the edges of the application area at 7 days after exposure. Fissuring and reduced flexibility of the skin was observed for one animal at 7 days after exposure. Scaling was observed on the treated skin site for all animals at 7 and/or 14 days after exposure, being present on the edges of the application area for one of the animals at 14 days after exposure.

A 4-hour exposure resulted in severe erythema and moderate or severe oedema in the treated skin area of the three rabbits. The maximum grade for erythema was generally achieved at 72 hours and/or 7 days after exposure. At 14 days after exposure, edema had resolved and erythema remained present for two animals at well-defined grade. For one rabbit erythema was scattered in nature and present at the edges of the application area at 7 days after exposure. All animals showed reduced flexibility of the skin at 72 hours after exposure, and a bald skin with scaliness at 14 days after exposure. For one of these animals, scaling and bald skin was primarily present on the edges of the application area. Fissuring of the skin and yellow-brown superficial scabs were noted for two animals at 7 days after exposure, due to which oedema could not be scored.

The mean 24, 48 and 72 hours value irritation scores after 4 hours of exposure were 3.0/2.7/3.0 for erythema and 4.0/2.3/3.7 for edema.

Sticky remnants of the test substance were present on all treated skin sites in all animals on Day 1.

 

One rabbit showed a pronounced inflammatory cell infiltrate in the 4 hour treated skin area consisting of a moderate lymphocytic infiltrate, a slight macrophage infiltrate with the presence of multinucleated giant cells containing hair debris (likely related to the clipping) and slight epidermal thickening. The minimal heterophilic or lymphocytic infiltrate observed in the other treated skin sites remained within the background pathology range.

The other two rabbits showed minimal inflammatory lesions consisting of a minimal lymphocytic and/or heterophilic infiltrate of the dermis in the skin sites treated for 3 minutes, one hour and four hours. The nature and incidence of these findings showed no apparent relation to the duration of treatment and remained within the background pathology range.

No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period and at histopathological examination of the treated skin sites, indicating that no corrosion of the skin had occurred by dermal application of the test itemn to the intact rabbit skin.

Skin reactions (well-defined erythema, bald skin and/or scaliness) remained present in all animals up to the end of the 14-day observation period following a 4-hour exposure duration.

Histopathology showed a pronounced inflammatory cell infiltrate in the 4-hour treated skin site of one of the rabbits.

There were no signs of corrosion in any of the skin samples examined.

In this study, based on mean value scores for erythema and edema and taking into account reversibility criteria, MDIPA-Esterquat C16-18 and C18 unsatd. (30% dispersion in water) is a dermal irritant.

MDIPA Esterquat C18 unsatd.

In a primary dermal irritation study according to OECD guideline young adult New Zealand White, CRL:KBL (NZW) rabbits (2 female, 1 male) were dermally exposed to 0.5 mL of undiluted MDIPA Esterquat C18 unsatd. (100% a.i.) for 4 hours. Well-defined to moderate erythema and slight to moderate edema (grade 2 or 3) was observed within 72 hours after patch removal in all three animals. 7 days after patch removal very slight to slight erythema and edema (grading 1 or 2) was observed and 14 days after patch removal very slight erythema (grade 1) was still existent in all animals. 21 days after application all three animals were without any sign of skin irritation.

Additionally, strong desquamation and atrophy of the skin was observed in all three animals beginning on day 7. These skin reactions declined with time as well. Grade 1 atrophy was still present in one animal on day 21.

Mean erythema scores from observations at 24, 48 and 72 h after patch removal were >/=2.3 for 2/3 animals; mean edema scores were >/=2.3 for all three animals. In this study MDIPA Esterquat C18 unsatd. was irritating to the skin.

 

In a dermal irritation study according to OECD Guideline 439 (In Vitro Skin Irritation, 30 µL MDIPA Esterquat C18 unsatd. (100% a.i.) was applied in triplicates for 60 min to a three-dimensional human epidermis model (EpiDerm EPI-200-SIT, MatTek Corporation).

After 60 minutes exposure at 37°C, the tissues were rinsed 15 times with phosphate buffered saline to remove residual test substance. Subsequently the skin tissues were incubated for 42 ± 2 h at 37°C.

Cytotoxic (irritancy) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

The relative mean tissue viability obtained after 60 minutes treatment with MDIPA Esterquat C18 unsatd. compared to the negative control tissues was 82.7 ± 1.5%. Since the mean relative tissue viability for the test substance was above 50%, MDIPA Esterquat C18 unsatd. is considered to be not irritating.

 

Conclusion

Based on the available data, it can be concluded that the available data on skin irritation from the source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C16-18 and C18 unsatd., and MDIPA-Esterquat C18 unsatd. can be applied to the target substance MDEA-Esterquat C18 unsatd. The results obtained with the source substance MDIPA-Esterquat C18 unsatd. are considered the most relevant for the target substance. Therefore, MDEA-Esterquat C18 unsatd. is considered to be irritating to skin (Category 2).

 

Eye irritation

MDEA-Esterquat C16-18 and C18 unsatd

In a primary eye irritation study according to OECD guideline 405 100 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, 1 male and 2 females. 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. When administered to the eye, the test article MDEA-Esterquat C16-18 and C18 unsatd. (Iodine value 50) is classified as non-irritant.

 

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

 

MDIPA-Esterquat C16-18 and C18 unsatd.

For the assessment of the eye irritation potential of MDIPA-Esterquat C16-18 and C18 unsatd. Data from an Isolated Chicken Eye (ICE) test are available This in vitro study was performed in accordance with OECD Test Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage).

Approximately 7 weeks old chickens (obtained from slaughter animals for human consumption) were used as eye-donors. A total of 7 eyes were selected for testing: 3 for the test substance, 3 for the positive control (5 % (w/v) Benzalkonium Chloride (BAC) and 1 for the negative control (physiological saline).

The isolated chicken eyes were exposed to a single application of 30 µL of the test sample for 10 seconds followed by a 20 mL saline rinse. Three main parameters were measured to disclose possible adverse eye effects: corneal thickness (expressed as corneal swelling), corneal opacity and fluorescein retention of damaged epithelial cells.  

MDIPA-Esterquat C16-18 and C18 unsatd. tested neat caused slight corneal swelling (mean swelling of 9%), moderate corneal opacity (mean score of 2) and slight to moderate fluorescein retention (mean score of 1.5). In addition, the top-layer of epithelium had a vesicular appearance. The calculated Irritation Index was 79. Microscopic examination of the corneas treated with the test substance revealed very slight erosion of the epithelium only. No abnormalities of the stroma and endothelium were observed.

According to the classification schemes identified within the ICE test protocol, MDIPA-Esterquat C16-18 and C18 unsatd. is classified as Category 2, Irritating to eyes. It is recognized that the prediction models adopted in the OECD Test Guideline 438 are foridentifying i) chemicals inducing serious eye damage and ii) chemicals not requiring classification for eye irritation or serious eye damage. However, further support for identification of MDIPA-Esterquat C16-18 and C18 unsatd. tested neat in this ICE study as a Category 2 irritant is derived from histopathology examination within the ICE test.

 

For the assessment of the eye irritation potential of MDIPA-Esterquat C16-18 and C18 unsatd. data from an Isolated Chicken Eye (ICE) test are available. This in vitro study was performed in accordance with OECD Test Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage).

Approximately 7 weeks old chickens (obtained from slaughter animals for human consumption) were used as eye-donors. A total of 7 eyes were selected for testing: 3 for the test substance, 3 for the positive control (5 % (w/v) Benzalkonium Chloride (BAC) and 1 for the negative control (physiological saline).

The isolated chicken eyes were exposed to a single application of approx. 30 µL of the test sample for 10 seconds followed by a 20 mL saline rinse. Three main parameters were measured to disclose possible adverse eye effects: corneal thickness (expressed as corneal swelling), corneal opacity and fluorescein retention of damaged epithelial cells.

MDIPA-Esterquat C16-18 and C18 unsatd. tested neat caused caused slight corneal swelling (mean swelling of 7%), severe opacity (mean score of 3.0) and moderate or severe fluorescein retention (mean score of 2.3). The calculated Irritation Index was 113. Microscopic examination of the corneas treated with the test item revealed very slight erosion and very slight vacuolation (top region) of the epithelium.

According to the classification schemes identified within the ICE test protocol, MDIPA-Esterquat C16-18 and C18 unsatd. is classified as Category 2, Irritating to eyes. It is recognized that the prediction models adopted in the OECD Test Guideline 438 are foridentifying i) chemicals inducing serious eye damage and ii) chemicals not requiring classification for eye irritation or serious eye damage. However, further support for identification of MDIPA-Esterquat C16-18 and C18 unsatd. tested neat in this ICE study as a Category 2 irritant is derived from histopathology examination within the ICE test.

 

MDIPA Esterquat C18 unsatd.

In a primary eye irritation study according to OECD guideline 405 0.1 mL of MDIPA Esterquat C18 unsatd. (20% in olive oil) was instilled into the conjunctival sac of the right eye of 2 male New Zealand White rabbits. The contralateral eye was treated with 0.1 mL olive oil as vehicle control. The eyes were not rinsed after application. Animals were then observed for 21 days.  Irritation was scored by the method of Draize.

No corneal or iridial effects were noted in the vehicle control, only minimal conjunctival irritation was noted in both treated eyes one hour after treatment. Both eyes appeared normal at the 24 h observation. The test substance produced scattered or diffuse corneal opacity (grade 1) in one eye one hour after treatment and in both treated eyes for up to 7 days. Vascularisation with a localised ingrowth of vessels at the lower edge of the cornea, was noted in one treated eye at the 14 and 21 d observations. Iridial inflammation (grade 1) was observed, which was reversible within 7 or 14 days.

Moderate conjunctival irritation (grade 2 redness and grade 2 chemosis) was noted in both treated eyes. This was reversible in one animal within 14 d. But minimal conjunctival irritation (grade 1 redness) was still present in one treated eye at the 14 d observation.

One treated eye appeared normal at the 14 d observation. The corneal vascularisation observed in one treated eye was considered to be irreversible. Thus, a 20% dilution of MDIPA Esterquat C18 unsatd. in olive oil produced irreversible effects to the eye and thus has to be classified as Category 1 (irreversible effects on the eye).

 

This in vitro study was performed to assess them corneal irritation and damage potential of MDIPA Esterquat C18 unsatd. (20% in olive oil) by means of the BCOP assay using fresh bovine corneae according to OECD guideline 437.

The corneae were incubated with the test substance and controls for 10 min. After rinsing with saline, the corneae were incubated for another 2 h at 32±1°C. The test was performed in triplicates. Opacity and permeability were determined. The in vitro irritancy score (IVIS) were calculated as mean opacity value + (15 x mean OD490 value); a substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant.

A 20% dilution of the test substance in olive oil caused an increase of the corneal opacity and permeability. The calculated mean in vitro irritation score was 52.59.

The positive control (2-Ethoxyethanol) increased the opacity and permeability of the corneae in both experiments (mean in vitro irritation score 65.46 (1st experiment) and 76.72 (2nd experiment)). 

With the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed in both experiments (mean in vitro irritation score 0.65 (1st experiment) and 0.21 (2nd experiment)). The solvent control olive control did not show relevant effects. The irritation score was 0.65.

Since the mean in vitro irritancy score of the test substance was <55.1, a 20% dilution of MDIPA Esterquat C18 unsatd. in olive oil is considered to not be severely irritating/ corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in this report.

 

This in vitro study was performed to assess the corneal irritation and damage potential of MDIPA Esterquat C18 unsatd. (100% a.i.) by means of the BCOP assay using fresh bovine corneae according to OECD guideline 437.

The corneae were incubated with the test substance and controls for 10 min. After rinsing with saline, the corneae were incubated for another 2 h at 32±1°C. The test was performed in triplicates. Opacity and permeability were determined. The in vitro irritancy score (IVIS) were calculated as mean opacity value + (15 x mean OD490 value); a substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant. 

The test item caused an increase of the corneal opacity and permeability. The calculated mean in vitro score was 99.30.

The positive control (2-Ethoxyethanol) increased the opacity and permeability of the corneae (mean in vitro score 56.02) corresponding to a classification as corrosive to the eye. With the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed (mean in vitro score 0.00).

Since the mean in vitro irritancy score of the test substance was >55.1, MDIPA Esterquat C18 unsatd. is considered to be severely irritating/ corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in this report.

 

MDIPA Esterquat C18 unsatd. (100% a.i.) was tested in the hen's egg chorioallantoic membrane test (HET-CAM), an accepted alternative method to the Draize test, to evaluate the acute irritation potential. The potential to cause irritation upon first contact with eyes or mucous membranes was assessed by application of the test substance onto the chorioallantoic membrane (CAM) of 6 fertilised and incubated eggs (strain SPAFAS).

200 µL of the test substance, negative (tap water) and positive (5% Texapon ASV 70 Special) control were applied onto the membrane. Observations for vascular injection, haemorrhage and coagulation were made after 30 seconds, 2 and 5 minutes.

Application of the negative control onto the CAM showed no effects; the irritation index was 0.0 of 21 total possible scores. Treatment with the positive control resulted in an irritation index of 10.3 of 21 total possible scores.  

Treatment with the test substance resulted in the appearance of haemorrhage on the CAM of 5 eggs 5 minutes post application and in the appearance of coagulation on the CAM of 4 eggs 2 minutes and of 2 eggs 5 minutes post application. No other effect was detected after treatment (8.8 scores of total 21 possible scores). No other effect was detected after treatment.

Thus, the test substance was graded as moderately irritating according to the evaluation scheme.

 

Conclusion

Based on the available data, it can be concluded that the available data on eye irritation from the source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C16-18 and C18 unsatd., and MDIPA-Esterquat C18 unsatd. can be applied to the target substance MDEA-Esterquat C18 unsatd. The results obtained with the source substance MDIPA-Esterquat C18 unsatd. are considered the most relevant for the target substance. Therefore, MDEA-Esterquat C18 unsatd. is classified as Eye Damage 1 (Category 1).

Justification for classification or non-classification

Based on relevant, reliable and adequate data MDEA Esterquat C18 unsatd. is classified as Skin irritation Category 2 and Eye Damage 1 (Category 1) according to the CLP Regulation (EC) No 1272/2008.