Docosyltrimethylammonium methyl sulphate

Endpoint summary

Description of key information

Skin irritation: The submission substance is rated as a skin irritant according to test results from a similar supporting substance:
In a guideline-compliant primary skin irritation/corrosion test in rabbits, a supporting substance caused moderate-to-severe or severe erythema and very slight or slight oedema. 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 the test substance to the intact rabbit skin. The supporting substance was irritating to rabbit skin.
Eye irritation: The submission substance is rated as an eye irritant according to test results from a similar supporting substance:
In a guideline-compliant acute eye irritation/corrosion study in rabbits, a supporting substance caused corneal opacity (maximum grade 2) with epithelial damage of 100% of the corneal area, iridial irritation grade 1, and irritation of the conjunctivae consisting of redness (grade 3), chemosis (grade 4) and discharge (grade 3) 24 hours after treatment. Signs of necrosis of the eyelids and nictating membrane were observed as grey/white discoloration. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons after 24 hours. The supporting substance caused irreversible effects on the rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

18.03.2008-22.04.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 404, EU B.4). For justification for read-across see chapter 1 of the chemical safety report.

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 MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams

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

Duration of treatment / exposure:

4 hours

Observation period:

14 days

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:

edema score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 hrs

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: Mean 24, 48 and 72 hrs

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: Mean 24, 48 and 72 hrs

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 hrs

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: on day 7 reached score 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: Mean 24, 48 and 72 hrs

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: Mean 24, 48 and 72 hrs

Score:

2

Max. score:

4

Reversibility:

fully reversible within: within 14 days

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 hours 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)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline-compliant primary skin irritation/corrosion test in rabbits, a supporting substance caused moderate-to-severe or severe erythema and very slight or slight oedema. 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 the test substance to the intact rabbit skin. The supporting substance was irritating to rabbit skin.

Executive summary:

A primary skin irritation/corrosion study with a supporting substance in the rabbit (4-hour semi-occlusive application) was carried out based on the following guidelines:

OECD No.404, "Acute Dermal Irritation/Corrosion" (2002)

EC, Council Directive 67/548/EEC, An.V, B.4 (2004), "Acute Toxicity: Dermal Irritation/ Corrosion"

USEPA, OPPTS 870.2500 (1998), Acute Dermal Irritation 

JMAFF Guidelines (2000) including the most recent partial revisions.

Three rabbits were exposed to 0.5 grams of the test substance, moistened with water, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 and 14 days after exposure.

Exposure to the supporting 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 hours 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.

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 the supporting substance to the intact rabbit skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

23.04.2008-24.04.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 405; EU B.5). For justification for read-across see chapter 1 of the chemical safety report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

see below

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

see below

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

see below

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

see below

Principles of method if other than guideline:

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 hours

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 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

other: 24 hours

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24 hours

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24 hours

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal #1

Time point:

other: 1 hour

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal #1

Time point:

other: 24 hours

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

other: 24 hours

Score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

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 severe tissue damage) 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:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline-compliant acute eye irritation/corrosion study in rabbits, a supporting substance caused corneal opacity (maximum grade 2) with epithelial damage of 100% of the corneal area, iridial irritation grade 1, and irritation of the conjunctivae consisting of redness (grade 3), chemosis (grade 4) and discharge (grade 3) 24 hours after treatment. Signs of tissue damage of the eyelids and nictating membrane were observed as grey/white discoloration. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons after 24 hours. The supporting substance caused irreversible effects on the rabbit eye.

Executive summary:

An acute eye irritation/corrosion study with a supporting substance in the rabbit was carried out according to the following guidelines:

OECD No.405 (2002) "Acute Eye Irritation / Corrosion"

EC, Council Directive 67/548/EEC, An. V,B.5, (2004) "Acute Toxicity: Eye Irritation / Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

JMAFF guidelines (2000) including the most recent partial revisions.

 A single sample of approximately 65 mg of supporting substance (a volume of approximately 0.1 ml) was instilled into an eye of one rabbit. Observations were made 1 and 24 hours 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 severe tissue damage) 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. 

Remnants of the test substance were present in the eye on Day 1.

Based on the degree of the ocular injury and observed necrosis, it was concluded that ocular corrosion had occurred by instillation of the supporting substance into the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A primary skin irritation/corrosion study with a supporting substance in the rabbit (4-hour semi-occlusive application) was carried out based on the following guidelines:

OECD No.404, "Acute Dermal Irritation/Corrosion" (2002)

EC, Council Directive 67/548/EEC, An.V, B.4 (2004), "Acute Toxicity: Dermal Irritation/ Corrosion"

USEPA, OPPTS 870.2500 (1998), Acute Dermal Irritation 

JMAFF Guidelines (2000) including the most recent partial revisions.

Three rabbits were exposed to 0.5 grams of the test substance, moistened with water, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 and 14 days after exposure.

Exposure to the supporting 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 hours 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.

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 the supporting substance to the intact rabbit skin.

Based on these results, the submission substance is rated as a skin irritant (cat. 2) like the supporting substance.

An acute eye irritation/corrosion study with a supporting substance in the rabbit was carried out according to the following guidelines:

OECD No.405 (2002) "Acute Eye Irritation / Corrosion"

EC, Council Directive 67/548/EEC, An. V,B.5, (2004) "Acute Toxicity: Eye Irritation / Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

JMAFF guidelines (2000) including the most recent partial revisions.

 A single sample of approximately 65 mg of supporting substance (a volume of approximately 0.1 ml) was instilled into an eye of one rabbit. Observations were made 1 and 24 hours 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 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. 

Remnants of the test substance were present in the eye on Day 1.

Based on the degree of the ocular injury, it was concluded that ocular corrosion had occurred by instillation of the supporting substance into the rabbit eye.

Based on these results, the submission substance is rated as causing serious eye damage (cat. 1) like the supporting substance.

Justification for selection of skin irritation / corrosion endpoint:
Reliable study for surrogate substance.

Justification for selection of eye irritation endpoint:
Reliable study for surrogate substance.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

In a guideline-compliant primary skin irritation/corrosion test in three rabbits with a supporting substance, the individual mean of scores 1, 2 and 3 days after treatment were 0.7, 1.0 and 1.7 for edema and 2.0, 2.7 and 3.0 for erythema. Therefore, the supporting substance was classified as R38 - Irritating to skin according to the criteria laid down in the EU Dangerous Substances Directive (67/548/) and as Category 2 H315: Causes skin irritation according to the criteria of the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Based on these results, the submission substance is rated as a skin irritant (cat. 2) like the supporting substance.

 

In a guideline-compliant acute eye irritation/corrosion study in rabbits, the supporting substance caused corneal opacity (maximum grade 2) with epithelial damage of 100% of the corneal area, iridial irritation grade 1, and irritation of the conjunctivae consisting of redness (grade 3), chemosis (grade 4) and discharge (grade 3) 24 hours after treatment. Grey/white discolorationof the eyelids and nictating membrane were observed. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons after 24 hours. Therefore, the supporting substance was classified as R41 - Risk of serious damage to eyes according to thecriteria laid down in the EU Dangerous Substances Directive (67/548/) and as Category 1 H318: Causes serious eye damage according to the criteria of the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Based on these results, the submission substance is rated as causing serious eye damage (cat. 1) like the supporting substance.

 

No conclusion on classification and labeling regarding respiratory tract irritation can be derived due to lack of data.