Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides

Endpoint summary

Description of key information

The irritation property of the registration substance was investigated according to the guideline OECD 404. Three rabbits were treated. Erythema of up to the score 4 and oedema of up to the score 2 were observed, which were reversible by end of the observation period of 14 days. Two animals exhibited scaliness and bald skin at the end of the observation period. The registration substance is to be classified as irritant based on the obtained results.

 

The eye irritation/corrosion of the registration substance was investigated according to the guideline OECD 405. A sample of 65 mg of the registration substance moistured with water (a volume of 0.1 ml) was applied into an eye of one rabbit. Within 24 hours signs of severe ocular lesions was noted. (discoloration of the eyelied, nictating membrane, changes of the outside of the eyelieds). For the ethical reasons the animal was sacrified and the two further rabbits assigned to the study were not treated. The registration substance is to be classified as having irreversible effects on the eye, Cat 1.

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:

18.03.2008-22.04.2008

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

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:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

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:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

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) based on GHS criteria

Conclusions:

The irritation property of the registration substance was investigated according to the guideline OECD 404. The registration substance is to be classified as irritant based on the obtained results.

Executive summary:

The irritation property of the registration substance was investigated according to the guideline OECD 404. Three rabbits were treated. Erythema of up to the score 4 and oedema of up to the score 2 were observed, which were reversible by end of the observation period of 14 days. Two animals exhibited scaliness and bald skin at the end of the observation period. The registration substance is to be classified as irritant based on the obtained results.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23.04.2008-24.04.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

1male

Details on study design:

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

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

not determinable

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:

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

Conclusions:

The eye irritation/corrosion of the registration substance was investigated according to the guideline OECD 405. Signs of severe ocular lesions were found within 24hours after the single treatment of an eye of one rabbit. The registration substance is to be classified as having irreversible effects on the eye, Cat 1.

Executive summary:

The eye irritation/corrosion of the registration substance was investigated according to the guideline OECD 405. A sample of 65 mg of the registration substance moistured with water (a volume of 0.1 ml) was applied into an eye of one rabbit. Within 24 hours signs of severe ocular lesions was noted. (discoloration of the eyelied, nictating membrane, changes of the outside of the eyelieds). For the ethical reasons the animal was sacrified and the two further rabbits assigned to the study were not treated. The registration substance is to be classified as having irreversible effects on the eye, Cat 1.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The irritation property of the registration substance was investigated according to the guideline OECD 404. The registration substance is to be classified as irritant, Cat 2 based on the obtained results.

The eye irritation/corrosion of the registration substance was investigated according to the guideline OECD 405. Signs of severe ocular lesions were found within 24hours after the single treatment of an eye of one rabbit.  The registration substance is to be classified as having irreversible effects on the eye, Cat 1.