Phosphoric Acid, Esters with Alcohols, C11-14 iso, C13-rich

Endpoint summary

Description of key information

Irritation studies.

 

Skin: Category 1B (corrosive) based on GHS criteria

 

Studies for eye irritation and respiratory irritation were waived based on the findings of skin corrosivity.

 

The test material contains between 20 - 40% of the parent alcohol Alcohols, C11-14-iso-, C13-rich (EC 271-235-6). In consideration of this, in the REACH registration for that substance, it was not interpreted to be either a skin or eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

ANIMALS AND ANIMAL HUSBANDRY

- Rabbits were sourced from Kuiper Rabbitry, Gary, Indiana, USA and were approximately 8-10 weeks old.
- Animals were housed individually in stainless steel cages in a temperature, humidity and light controlled room.
- Rabbits were conditioned for at least three days prior to study initiation.
- Purina Rabbit Chow and water were available ad libitum.
- All animals used for the investigation were considered to be in good health at study initiation.

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

7 days

Number of animals:

6

Details on study design:

COMPOUND ADMINISTRATION

- Three intact sites were prepared on each of the six animals.
- A dose of 0.5 mL of the test article was applied to the occluded sites for contact periods of 3 minutes (site A), 1 hour (site B) and 4 hours (site C).
- At the conclusion of the individual contact periods, any remaining test material was wiped from the site.
- If necrosis was observed at the shorter contact periods the test was considered to be concluded and longer exposure times were not required.

CLINICAL OBSERVATIONS
- Observations for irritation, ulceration and necrosis were performed at the end of each contact period.
- Observations were repeated at 60 minutes for the 3 minute contact time.
- Observations were repeated at 24, 48 and 72 hours following test article application for the 1 and 4-hour contact times.
- Additional readings were continued up to Day 7 to confirm transport packing group
- Corrosion was considered to have resulted if the substance in contact with rabbit skin produced full thickness destruction or irreversible alteration of tissue.
- Tissue destruction was considered to have occurred if ulceration and/or necrosis was observed at any of the readings.
- Tissue destruction did not include merely sloughing of the epidermis, erythema, edema or fissuring.
- Scoring crieria used during evaluation of skin reactions are given in Table 2 (attached).

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 3 min

Score:

0

Max. score:

4

Reversibility:

other: not applicable site A

Remarks on result:

other: Animals 53, 54, 55, 56, 57 and 58

Irritation parameter:

erythema score

Basis:

mean

Remarks:

mean 3 min contact time

Time point:

other: 1 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable site A

Remarks on result:

other: not corrosive after 3 min contact time Animals 53, 54, 55, 56, 57 and 58

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 53 Necrosis reported at 7 d observation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 54 Score unchanged at 7 d observation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

I h contact time

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 55 Necrosis reported at 72 h observation

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 56 Score unchanged at 7 d observation

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 57 Score unchanged at 7d observation

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 58 Necrosis reported at 7 d observation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

- Data showing individual responses of each animal are attached.
- Occluded contact with the test material for three minutes produced no irritation and necrosis was not observed in any of the six animals.
- Occluded contact with the test material for one hour produced severe irritation and necrosis was observed in three of the six animals within 7 days.
- Occluded contact with the test material for four hours caused necrosis in all six animals.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

Occluded contact with the test item for one hour produced severe irritation (erythema scores at 24/4 8/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days.
On the basis of this study, the test material is found to be corrosive to skin.

Executive summary:

In a study performed in accordance with US D.O.T. regulations and OECD 404, the test item was applied to three prepared skin sites on New Zealand White rabbits under occluded conditions for 3 minutes, 1

hour and 4 hours. After the relevant contact period, any remaining test item was wiped from the site. After removal of patches and 24, 48 and 72 hours later, the test sites were examined for evidence of

primary irritation and scored for erythema. No effects were noted over a period of 60 minutes following contact with the test item for 3 minutes. However, occluded contact with the test item for one hour

produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days. On the basis of this study, the test material is found

to be corrosive to skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across hypothesis proposed is that the organism is not exposed to common compounds but rather, because of structural similarity, that different compounds have similar toxicological and fate properties. In this case the ECHA Read-Across Assessment Framework (RAAF) Scenario 2 is used.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source: Phosphoric Acid, C8-12 (even-numbered) linear Alkyl Esters [EC not yet assigned; CAS not assigned]
Target: Phosphoric Acid, Esters with Alcohols, C11-14 iso, C13-rich [EC not yet assigned; CAS not assigned]
3. ANALOGUE APPROACH JUSTIFICATION
The Source substance is classified as Corrosive 1B. The Target has a similar pH in solution, and is of a similar chainlength. It can be predicted that local effects to skin will be similar and that the Target may also be similarly classified.
4. DATA MATRIX
Please refer to attached justification.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

mean 3 min contact time

Time point:

other: 3 min

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Animals 53, 54, 55, 56, 57 and 58

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 min contact time

Time point:

other: 1 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: not corrosive after 3 min contact time Animals 53, 54, 55, 56, 57 and 58

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

1 h contact timw

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 53 Necrosis reported at 7 d observation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 54 Score unchanged at 7 d observation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 55 Necrosis reported at 72 h observation

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 56 Score unchanged at 7 d observation

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 57 Score unchanged at 7d observation

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

1 h contact time

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Animal 58 Necrosis reported at 7 d observation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Reference 3

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Reference 2

Endpoint:

eye irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin: Category 1B (corrosive) based on GHS criteria.

The test material contains between 20 - 40% of the parent alcohol Alcohols, C11-14-iso-, C13-rich (EC 271-235-6). In consideration of this, in the REACH registration for that substance, it was not interpreted to be either a skin or eye irritant.