Quaternary ammonium compounds, C18-22 (even numbered) alkyltrimethyl, chlorides; Docosyltrimethylammonium chloride; C18-22 TMAC

Endpoint summary

Description of key information

Based on the results of the read across in vivo skin and eye irritation studies on read across substance, the test substance, C18-22TMAC, is considered as irritating to skin and causes serious damage to eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From March 18, 2008 to April 22, 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (2000) including the most recent partial revisions

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 7 - 13 weeks old
- Weight at study initiation: 1492-2366 g
- Housing: Individually in labelled cages with perforated floors (dimensions 56x44x37.5 cm)
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay was provided at least three times a week.
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 - 21.4
- Humidity (%): 44 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: moistened with water

Controls:

not required

Amount / concentration applied:

TEST SUBSTANCE
- Amount(s) applied (volume or weight with unit): 500 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

14 d

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm
- % coverage: 100
- Type of wrap if used: mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage


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


SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Remarks:

Mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

edema score

Remarks:

Mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

erythema score

Remarks:

Mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

erythema score

Remarks:

Mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

other: on day 7 reached score 4

Irritation parameter:

erythema score

Remarks:

Mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

erythema score

Remarks:

Mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

other: on day 7 reached score 4

Irritant / corrosive response data:

Four hours exposure to 0.5 g of the test substance resulted in moderate to severe or severe erythema and very slight or slight oedema in the treated skin-areas of the three rabbits. In all animals, the observed erythema was scattered at 48 and/or 72 h after exposure. Fissuring of the skin was noted at 7 days after exposure in two animals and these animals showed scaliness at 7 and 14 days after exposure and bald skin at 14 days after exposure. The other animal showed scaliness at 7 days after exposure. The skin irritation had resolved within 14 days after exposure, except for scaliness and bald skin in two animals. There was no evidence of a corrosive effect on the skin.

Other effects:

No staining of the treated skin by the test substance was observed and no test substance remnants were seen. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Animal		778^1				757				803
Time after exposure		Erythema	Oedema	comments		Erythema	Oedema	comments		Erythema	Oedema	comments
1 hour		2	1			1	1			2	1
24 hours		3	1			2	2			2	1
48 hours		3	1	v		2	2			2	1	v
72 hours		3	1	v		3	1	v		2	0	l,v
7 days		4	-	g,l		1	1	l		4	-	g,l
14 days		0	0	h,l		0	0			0	0	h,l

¹Sentinel.

 

Comments:

-.      No scoring possible due to fissuring of the skin

g.     Fissuring of the skin.

h.     Bald skin.

l.      Scaliness.

v.     Scattered erythema.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Based on the results of the read across study, the test substance is considered to be irritating to skin.

Executive summary:

A study was conducted to determine the skin irritation / corrosion of the read across substance, C20 -22 TMAC (active: 97.8%), according to OECD Guideline 404 and EU Method B.4, in compliance with GLP.

In the study, 0.5 g of the read across substance moistened with water was applied under semi-occlusive patches to the shaved dorsal area of three rabbits. The test sites were examined for evidence of primary irritation and scored according to Draize method. Following 4 h exposure to 0.5 g of the test substance resulted in moderate to severe or severe erythema and very slight or slight oedema in the treated skin-areas of the three rabbits. In all animals, the observed erythema was scattered at 48 and/or 72 h after exposure. Fissuring of the skin was noted at 7 d after exposure in two animals and these animals showed scaliness at 7 and 14 d after exposure and bald skin at 14 d after exposure. The other animal showed scaliness at 7 d after exposure. The skin irritation had resolved within 14 d after exposure, except for scaliness and bald skin in two animals.No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of test substance to the intact rabbit skin. No staining of the treated skin by the read across substance was observed and no read across substance remnants were seen. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Under the study conditions, the read across substance was considered to be irritating to rabbit skin following 4 h of exposure (Stitzinger, 2008). Based on the results of the read across study, similar skin irritation potential is expected for the test substance, C18-22 TMAC.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From April 23, 2008 to April 24, 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 to due to RA

Justification for type of information:

Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The body weight of the animal was not determined after sacrifice. Evaluation: Sufficient data was available to assess the possible irritation or corrosion potential of the test substance. The study integrity was not adversely affected by the deviations.

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The body weight of the animal was not determined after sacrifice. Evaluation: Sufficient data was available to assess the possible irritation or corrosion potential of the test substance. The study integrity was not adversely affected by the deviations.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

The body weight of the animal was not determined after sacrifice. Evaluation: Sufficient data was available to assess the possible irritation or corrosion potential of the test substance. The study integrity was not adversely affected by the deviations.

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2000) including the most recent partial revisions

Deviations:

yes

Remarks:

The body weight of the animal was not determined after sacrifice. Evaluation: Sufficient data was available to assess the possible irritation or corrosion potential of the test substance. The study integrity was not adversely affected by the deviations.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 2215 g
- Housing: Individually in labeled cages with perforated floors (dimensions 56x44x37.5 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay was provided at least three times a week
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 – 21.3
- Humidity (%): 45 - 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye remained untreated and served as the reference control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 64.9 mg (volume of approx. 0.1mL)

Duration of treatment / exposure:

24 h

Observation period (in vivo):

1 and 24 hours after instillation of the test substance

Number of animals or in vitro replicates:

1 (male)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

Within 24 h

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 24 h

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 1 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal #1

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

other: 1 h

Score:

3

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

24 h

Score:

3

Reversibility:

not reversible

Remarks:

within 24 h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Instillation of approximately 65 mg of the test substance (a volume of approximately 0.1 mL) into an eye of one rabbit resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (100% of the corneal area). Iridial irritation grade 1 was observed and the irritation of the conjunctivae consisted of redness, chemosis and discharge. Grey/white discoloration of the eyelids and nictating membrane (a sign of necrosis) was noted. Erythema and oedema of the outside of the eyelids was noted. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons immediately after the 24 hours observation and the two further rabbits assigned to the study were not treated.

Other effects:

Remnants of the test substance were present in the eye on Day 1. No staining of (peri) ocular tissues by the test substance was observed. No symptoms of systemic toxicity were observed in the animal until the animal was sacrficed due to severe ocular effects.

Interpretation of results:

other: Eye Damage 1 (causes serious eye damage) based on CLP criteria

Conclusions:

Based on the results of the read across study, the test substance was considered to be causes serious eye damage to rabbit eyes.

Executive summary:

A study was conducted to determine the eye irritation/corrosion of the read across substance, C20-22 TMAC (active: 97.8%), according to OECD Guideline 405 and EU Method B.5, in compliance with GLP. In the study, 65 mg (volume of approx. 0.1mL) of the test substance was instilled into an eye of one rabbit. The test sites were examined for evidence of irritation and scored according to Draize method. Observations were made 1 and 24 h after instillation. Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (100% of the corneal area). Iridial irritation grade 1 was observed and the irritation of the conjunctivae consisted of redness, chemosis and discharge. Grey/white discoloration of the eyelids and nictating membrane (a sign of necrosis) was noted. Erythema and oedema of the outside of the eyelids was noted. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons immediately after the 24 h observation and the two further rabbits assigned to the study were not treated. Under the study conditions, the test substance was considered to be causes serious eye damage to rabbit eye (Stitzinger, 2008). Based on the results of the read across study, similar irritation potential is expected for the test substance, C18-22 TMAC.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

A study was conducted to determine the skin irritation / corrosion of the read across substance, C20 -22 TMAC (active: 97.8%), according to OECD Guideline 404 and EU Method B.4, in compliance with GLP.

In the study, 0.5 g of the read across substance moistened with water was applied under semi-occlusive patches to the shaved dorsal area of three rabbits. The test sites were examined for evidence of primary irritation and scored according to Draize method. Following 4 hexposure to 0.5 g of the test substance resulted in moderate to severe or severe erythema and very slight or slight oedema in the treated skin-areas of the three rabbits. In all animals, the observed erythema was scattered at 48 and/or 72 h after exposure. Fissuring of the skin was noted at 7 d after exposure in two animals and these animals showed scaliness at 7 and 14 d after exposure and bald skin at 14 d after exposure. The other animal showed scaliness at 7 d after exposure. The skin irritation had resolved within 14 d after exposure, except for scaliness and bald skin in two animals.No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of test substance to the intact rabbit skin.No staining of the treated skin by the read across substance was observed and no read across substance remnants were seen. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Under the study conditions, the read across substance was considered to be irritating to rabbit skin following 4 h of exposure (Stitzinger, 2008).Based on the results of the read across study, similar skin irritation potential is expected for the test substance, C18-22 TMAC.

Eye:

A study was conducted to determine the eye irritation/corrosion of the read across substance, C20-22 TMAC (active: 97.8%), according to OECD Guideline 405 and EU Method B.5, in compliance with GLP. In the study, 65 mg (volume of approx. 0.1mL) of the test substance was instilled into an eye of one rabbit. The test sites were examined for evidence of irritation and scored according to Draize method. Observations were made 1 and 24 h after instillation. Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (100% of the corneal area). Iridial irritation grade 1 was observed and the irritation of the conjunctivae consisted of redness, chemosis and discharge. Grey/white discoloration of the eyelids and nictating membrane (a sign of necrosis) was noted. Erythema and oedema of the outside of the eyelids was noted. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons immediately after the 24 h observation and the two further rabbits assigned to the study were not treated. Under the study conditions,the test substance was considered to be causes serious eye damage to rabbit eye (Stitzinger, 2008). Based on the results of the read across study, similar irritation potential is expected for the test substance, C18-22 TMAC.

Overall, based on the results of the read across studies, the test substance, C18-22TMAC, is considered as irritating to skin and causes serious damage to eyes.

Justification for classification or non-classification

Skin irritation:

Based on the results of the read across in vivo study, the test substance, C18-22 TMAC, is considered to warrant 'Skin Irrit.2: H315 - Causes skin irritation' classification, according to the EU CLP criteria (Regulation 1272/2008/EC).

Eye irritation:

Based on the results of read across in vivo study, the test substance, C18-22 TMAC, is considered to warrant 'Eye damage. 1: H318 - Causes serious eye damage’classification according to the EU CLP criteria (Regulation 1272/2008/EC).