C8-18 alkylampho(di)propionates

Endpoint summary

Description of key information

In 4 in vivo studies performed before the adoption of OECD 404, the skin irritation potential of the substance and of solutions of the substance was investigated. The only effect that was reported was slight erythema directly after patch removal, which reversed within 48 hours.
In 7 in vivo studies, performed similar to OECD 405 (1981), the eye irritation potential of the substance and of solutions of the substance was investigated. As reversibility could not be observed in all animals, the substance should be classified according to Regulation EC 1272/2008 with category 1, H318 "Causes serious eye damage". Based on the results obtained with solutions of the substance, ≤ 43% solutions of the substance (solid content ≤ 16%) do not need to be classified for eye irritation according to the criteria of the CLP Regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

June 15, 1988 - June 29, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study has been performed similar to OECD 405 (1981) and according to GLP principles. However, as the observation period stopped on day 7, the reversibility could not be fully assessed.

Qualifier:

according to guideline

Guideline:

other: modification of the Code of Federal Regulations 1500-42 (1985)

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

yes

Remarks:

the observation period of only 7 days instead of up to 21 days was not sufficient to evaluate the reversibility or irreversibility of the effects observed, and the ocular lesions were not scored 1 hour after installation

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA, USA
- Age at study initiation: no data (but reported to be young adults)
- Weight at study initiation: 2.30 - 2.62 kg
- Housing: suspended wire mesh cages
- Diet: Purina rabbit pellets (ad libitum)
- Water: ad libitum
- Acclimation period: minimum period of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 72 ± 5 degrees F (22.2 ± 5 °C)
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark/12 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated left eye served as the control

Amount / concentration applied:

TEST MATERIAL (applied as such)
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Not applicable (the eyes were not rinsed)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 (2 females and 1 male)

Details on study design:

REMOVAL OF TEST SUBSTANCE: not applicable
SCORING SYSTEM: similar to OECD 405
TOOL USED TO ASSESS SCORE: no data

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 3d

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 2d

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 4d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 4d

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

not fully reversible within: 7d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 2d

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 7d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritant / corrosive response data:

See section "Any other information on results incl. tables"

Other effects:

See section "Any other information on results incl. tables"

Animal number and sex	Parameter	Hours after instillation			Days after instillation
		24	48	72	4	7
7907 Male	Cornea (opacity)	1	1	0	0	0
	Cornea (area)	1	1	0	0	0
	Iris	1	0	0	0	0
	Conjunctivae (redness)	2	1	1	0	0
	Conjunctivae (chemosis)	2	1	1	0	0
	Conjunctivae (discharge)	2	1	0	0	0
7908 Female	Cornea (opacity)	2	2	2	2	2
	Cornea (area)	not scored
	Iris	1	1	1	0	1
	Conjunctivae (redness)	3	3	2	1	2
	Conjunctivae (chemosis)	2	2	1	1	2
	Conjunctivae (discharge)	2	2	1	1	2
7909 Female	Cornea (opacity)	2	2	2	1	0
	Cornea (area)	2	2	1	1	0
	Iris	1	0	0	0	0
	Conjunctivae (redness)	2	2	1	1	0
	Conjunctivae (chemosis)	2	1	1	1	0
	Conjunctivae (discharge)	2	2	1	0	0

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study, performed similar to OECD 405 (1981) and according to GLP principles, the substance (solid content 38-40%) is classified as causing serious eye damage (Category 1) according to the criteria of the CLP Regulation.

Executive summary:

The substance was tested for acute ocular irritation in 2 females and 1 male New-Zealand White rabbits, similar to OECD 405 and according to GLP principles. The test material (solid content: 38-40%), was instillated as such in a single dose of 0.1 ml into the conjunctival sac of the right eye of each animal. The left eye remained untreated and served as a control. The eyes were not rinsed. Ocular examinations were performed 24, 48, 72 hours and 4 and 7 days after the instillation. Grade 2 corneal opacity was observed in 2 animals at 24 hours, lasting up to 72 hours in 1 animal. It persisted in the other animal throughout the 7 day observation period. In this same animal, conjunctival redness (grade 1, 2 and 3), conjunctival chemosis (grade 1 and 2) and iris inflammation (grade 1) persisted also throughout the observation period. In the other 2 animals the effects (grade 1 and 2) reversed within the observation period. As reversibility could not be observed in 1 animal in this study, the substance should be classified according to Regulation EC 1272/2008 with category 1, H318 "Causes serious eye damage".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In 4 in vivo studies performed according to Code of Federal Regulations 21, Part 191.1 (g) (2), 191.11, before the adoption of OECD 404, the skin irritation potential of the substance and of solutions of the substance was investigated. The rabbits were exposed to 0.5 mL of test material as is (2 studies) or to 0.5 mL of dilutions of test material (2 studies) for 24 hours under occlusive conditions. The only effect that was reported was slight erythema directly after patch removal, which reversed within 48 hours.

As the conditions under which the studies were performed were more severe than prescribed by OECD 404 (24 hours occlusive exposure instead of 4 hours semi-occlusive exposure), the studies are regarded as reliable information for assessing the skin irritation hazard of the substance and an additional study for investigating the skin irritation potential of the substance is not regarded to be needed. Although there is no study available for the substance performed according to a method referred to in REACH article 13(3), it is considered justified to conclude based on the existing data and a weight of evidence approach that further testing is not scientifically necessary, as when the available studies are compared with the in vivo method referred to in REACH article 13(3):

- The exposure duration was longer (24 hours instead of 4 hours)

- The exposure condition was more severe (occlusive instead of semi-occlusive)

- The skin was abraded

- There were little or no effects observed, that reversed within the observation period, making it questionable whether performing more effect readings would have been of any use for classification purposes according to the CLP Regulation (as the observed effects were reversed within 48 hours).

In addition, there is no specific alert or concern raised in the existing data or uncertainty on the scores reported that would require further investigation.

Eye irritation

In 7 in vivo studies, performed similar to OECD 405 (1981), the eye irritation potential of the substance as registered (in 3 studies) and of aqueous dilutions of the substance was investigated (in 4 studies). In the 3 studies with the undiluted substance, the intensity of effects were always below the criteria of severe effects, however reversibility could not be observed in all animals due to the limited observation period after exposure (observation period stopped on day 7 in 2 studies, or 72 hours in 1 study).

Based on the results obtained with solutions of the substance, ≤ 43% solutions of the substance (solid content ≤ 16%) do not need to be classified for eye irritation according to the criteria of the CLP Regulation.

Justification for selection of skin irritation / corrosion endpoint:
As the endpoint conclusion is based on a weight of evidence approach, no study has been selected.

Justification for selection of eye irritation endpoint:
The key study

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation

As in 4 in vivo studies only slight erythema directly after patch removal was reported, which reversed within 48 hours, the substance does not need to be classified for skin irritation in accordance with the CLP Regulation.

Based on the limited reactions observed in the available studies with the aqueous solutions, the solid (surfactant) fraction is not expected to be a skin irritant.

Eye irritation

As in the 3 in vivo studies with the undiluted substance the full reversibility could not be demonstrated in all animals during the observation period, a worst-case classification is applied and the substance is classified according to Regulation EC 1272/2008 with category 1, H318 "Causes serious eye damage".

Based on the results obtained in the 4 in vivo studies with dilutions of the substance, ≤ 43% solutions of the substance (solid content ≤ 16%) do not need to be classified for eye irritation according to the criteria of the CLP Regulation.

The substance is considered cat.1, H318 "Causes serious eye damage" for concentrations ≥ 40% (rounded value).