Hexadecyl(2-hydroxyethyl)dimethylammonium dihydrogen phosphate

Endpoint summary

Description of key information

Skin irritation: irritating
- OECD 404, irritating
- EPA guideline study, irritating
Eye irritation:
- EPA guideline study: risk of serious damage to eyes (R 41)

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- SPF
- Animal supplier: Dr. K. Thomae GmbH, Biberach
- Acclimatization period: at least one week
- Young adult animals were used; mean body weight females 3.74 kg, male 3.62 kg
- Singly housing in stainless steel wire mesh cages with grating, floor area: 3000 cm2.
- No bedding in the cages, dawdust in the waste trays
- The animals were identified via ear tattoo.
- The rabbits were housed in fully air-conditioned rooms with a room temperature of 20 - 24°C and a relative humidity of 30 - 70%. The day/night rhythm was 12 h light and 12 h darkness.
- The animals were offered a standardized animal laboratory diet (about 130 g/animal/day) as well as tap water (about 250 ml/animal/day).

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

The test patches (2.5 x 2.5 cm) were moistened with a dose of 0.5 ml.

Duration of treatment / exposure:

4 hours

Observation period:

15 days

Number of animals:

3

Details on study design:

At least 24 hours before study start, the fur of the rabbits was removed by clipping the dorsal of the trunk of the animals. Only animals with healthy intact skin have been used.
Weight determination: shortly before application
The test substance was applied in a singly dose ot the intract untreated skin. The test patch was secured in position with a semiocclusive dressing. The test substance was removed at the end of the application period with Lutrol and Lutrol/water (1:1).
Application site: upper third of the back or flanks
Readings: 1 h, 24 h, 48 h, 72 h, 8 d and 15 d after removal of the test patch
A check was for general observations and dead resp. moribund animals was made twice each working day and once on weekends and on public holidays.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

3.3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Slight erythema still visible, scaling observed in all animals on day 15.

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

2.1

Max. score:

4

Reversibility:

fully reversible within: 15 d

Irritant / corrosive response data:

Erythema mean values per animal (24-72h):
1) 3.7
2) 2.7
3) 3.7

Edema mean values per animal (24-72h):
1) 3.0
2) 1.3
3) 2.0

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions chosen the test item gives indication of an irritant property to the skin.

Executive summary:

The potential of the test item to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 white New Zealand rabbits for 4 hours under semi-occlusive dressing.

The average score (24 to 72 h) for irritation was calculated to be 3.3 for erythema and 2.1 for edema. Signs of skin irritation (such as edema) were reversible within 15 days after removal of the patches, while erythema and scaling were still present at study termination. Symptoms observed indicate an irritant property of the test item to the 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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable study report

Principles of method if other than guideline:

based on the Proposed Guidelines of the United States Environmental Protection Agency (EPA), § 163.81-5 "Primary eye irritation study", Fed. Reg. 43, No. 163, 1978

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Initial body weight range: 2 - 3 kg
- Animal identification: ear numbers
- The animals were housed individually in metal cages.
- The animal room was air-conditioned: room temperature 22 +/- 3°C, relative humidity 55 +/- 15%, 12 h light and 12 h darkness, approx. 15 air changes per hour.
- Adaptation period: 4 days
- The animals were offered a standardized animal laboratory diet and water ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 (3 males, 3 females)

Details on study design:

- The test material in an amount of 0.1 ml was inserted in the conjunctival sac of the left eye of the rabbits and the lids were gently closed for 15 seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after the treatment the treated eye was flushed with 10 ml of sterile physiological saline.
- The eye irritation was assessed with a slit-lamp at 24, 48, 72 hours and 4 and 7 days after treatment and was scored for each iridividual rabbit.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: unrinsed eye

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: rinsed eye

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: unrinsed and rinsed eye

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: unrinsed and rinsed eye

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: unrinsed eye

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: rinsed eye

		Redness				Chemosis				Opacity				Iris
Animal		24 h	48 h	72 h	Mean	24 h	48 h	72 h	Mean	24 h	48 h	72 h	Mean	24h	48 h	72 h	Mean
1	Unrinsed (male)	3	3	3	3.0	3	3	3	3.0	1	1	1	1.0	1	1	1	1.0
2		3	3	3	3.0	3	3	3	3.0	2	2	2	2.0	1	1	1	1.0
3		3	3	3	3.0	3	3	2	2.7	1	1	1	1.0	1	1	1	1.0
4	Rinsed (female)	3	3	3	3.0	3	2	2	2.3	1	1	1	1.0	1	1	1	1.0
5		3	3	3	3.0	2	2	2	2.0	1	1	1	1.0	1	1	1	1.0
6		3	3	3	3.0	3	2	2	2.3	1	1	1	1.0	1	1	1	1.0

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study the test item was found to possibly cause irreversible effects on the eye.

Executive summary:

The test material was inserted in an amount of 0.1ml in the conjunctival sac of the left eye of six New Zealand White Rabbits. The right eye was not treated and served as negative control. In 3 of 6 animals approximately 30 seconds after the treatment the treated eye was flushed with 10 ml of sterile physiological saline. The eye irritation was assessed with a slit-lamp at 24, 48 and 72 hours and 4 and 7 days after treatment and was scored for each individual rabbit. Under the conditions of the present study the test item was found to possibly cause irreversible effects on the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The potential of the test item to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 white New Zealand rabbits for 4 hours under semi-occlusive dressing.

The average score (24 to 72 h) for irritation was calculated to be 3.3 for erythema and 2.1 for edema. Signs of skin irritation (such as edema) were reversible within 15 days after removal of the patches, while erythema and scaling were still present at study termination. Symptoms observed indicate an irritant property of the test item to the skin.

The supporting study was performed similar to the USA Federal Hazardous Substances Act (US-FHSA). The test substance was applied to 3 male and 3 female New Zealand white rabbits under occlussive conditions for 24 hours on intact and abraded skin.

The average score (24 to 72 hours) for erythema on intact skin was calculated to be 2.7 and 2.95 for edema. Signs of skin irritation were still present after 7 days of patch removal. Under the conditions of the present experiment the test item was found to cause marked irritation when applied to intact and abraded rabbit skin.

Eye irritation:

The test material was inserted in an amount of 0.1ml in the conjunctival sac of the left eye of six New Zealand White Rabbits. The right eye was not treated and served as negative control. In 3 of 6 animals approximately 30 seconds after the treatment the treated eye was flushed with 10 ml of sterile physiological saline. The eye irritation was assessed with a slit-lamp at 24, 48 and 72 hours and 4 and 7 days after treatment and was scored for each individual rabbit. Under the conditions of the present study the test item was found to possibly cause irreversible effects on the eye.

Justification for selection of skin irritation / corrosion endpoint:
Most reliable guideline study which is the basis for classification.

Justification for selection of eye irritation endpoint:
Most reliable guideline study which is the basis for classification.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is considered to be classified for eye irritation and for skin irritation under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EC.

 Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for eye irritation and for skin irritation under Regulation (EC) No 1272/2008, as amended for the fifth time in Directive EC 944/2013.

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