Fatty acids, C14-18 and C16-18-unsatd., 2-phenoxyethyl esters, maleated

Endpoint summary

Description of key information

Skin irritation/corrosion rabbit, 24 hour occlusive treatment of intact or abraded skin with neat test substance (as received from the sponsor):
Intact and abraded skin:     At each observation time point (0 and 48 h and 6 d post patch removal) no erythema and no edema reaction in each of 5 animals.
Eye irritation, rabbit; treatment with neat test substance (as received from the sponsor):
Mean irritation score 24, 48 and 72 h for each of 6 animals:
0.0 for corneal opacity; 0.0 for iris lesion; 2.0 for redness of conjunctivae; 1.7 to 2.7 for oedema of conjunctivae (chemosis); 1.7 for lacrimation.
Findings and gradings similar to these were recorded from 1 to 8 h post instillation and all were fully reversible, as from 5 to 6 days post instillation each treated eye was free from ocular findings.
(Local lymph node assay, mouse (Endpoint study record "7.4.1 Skin sensitisation - LLNA_mouse_GAH0129):
Group Mean Stimulation Index (SI) = 1.0, 33.9, 45.1 and 59.9 at test substance concentrations of 0 % (vehicle control), 10, 25 and 50% w/v, respectively.
Conclusion: Classification and labelling as
"irritant (Xi)" and  "may cause sensitisation by skin contact (R43)" [DIRECTIVE 67/548/EEC] and
“Category 1” (Warning: May cause an allergic skin reaction)" [REGULATION (EC) 1272/2008]).

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a contract research organization. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (e.g. due to limited reporting).

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

of 1981

Deviations:

yes

Remarks:

Skin examination 0 h, 48 h and 6 days after patch removal

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Number: 5 animals,
- Average bodyweight: 3 kg
- Housing: Individual housing in cages.
- Diet: Commercially available standard laboratory diet for rabbits ( Altromin, Lage, Germany).
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS

Room temperature kept constant at 18±2°C, the relative humidity at 50-60%. 12 hours illumination per day.

Type of coverage:

occlusive

Preparation of test site:

other: abraded versus only shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL of neat test substance was administered to the skin by means of a "2.5 cm2" cellulose patch.*

* Comment by the data submitter:
There is no indication in the report, whether the size of treated skin patches was inadvertently stated as only "2.5 cm2" in reality having been sized 2.5 cm x 2.5 cm (i.e. ca. 6 cm2) or whether, contrarily to the cited OECD 404 test guideline, the size of the treated skin patches was really confined to only 2.5 cm2. Regardless whether the treated skin patch was ca. 6 cm2 or only 2.5 cm2, the study results are considered to be valid for assessment.

Duration of treatment / exposure:

24 hours

Observation period:

7 days (i.e. the final observation time point was 6 days post patch removal)

Number of animals:

5

Details on study design:

TEST SITE PREPARATION

Samples of 0.5 mL of the neat test substance were applied to the shaved intact and to shaved and then abraded skin of albino rabbits by means of cellulose patches. Patches were fixed with leucoplast and the whole trunk of each animal was enwrapped by a rubber cloth during the 24 hour treatment period, in order to delay evaporation of substances. From the coverage of the whole animal trunk (patches inclusive) with rubber cloth occlusive treatment was concluded by the data submitter, although the report did not specify whether this coverage was considered to be occlusive or semi-occlusive.

Two untreated skin sites (one of shaved intact skin and one of shaved and then abraded skin) served as controls. Only skin reactions different to controls were graded as positive skin reactions.


TREATMENT PERIOD AND REMOVAL OF TEST SUBSTANCE

Occlusive treatment lasted 24 hours. Then the dressings were removed. There was no mentioning in the report that exposed skin patches were cleaned from residual test substance after treatment.

TIME POINTS OF SKIN EVALUATION:

The treated skin patches were evaluated 24 and 72 hours and 7 days post application (i.e. immediately and 48 hours and 6 days post patch removal). The scoring system for the grading of skin reactions is listed in Table 1 (next field below).

Irritation parameter:

erythema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0

Max. score:

4

Reversibility:

other: erythema formation was not evident

Remarks on result:

other: Neat test substance administered to intact skin for 24 hours

Irritation parameter:

edema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0

Max. score:

4

Reversibility:

other: edema formation was not evident

Remarks on result:

other: Neat test substance administered to intact skin for 24 hours

Irritation parameter:

erythema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0

Max. score:

4

Reversibility:

other: erythema formation was not evident

Remarks on result:

other: Neat test substance administered to abraded skin for 24 hours

Irritation parameter:

edema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0

Max. score:

4

Reversibility:

other: edema formation was not evident

Remarks on result:

other: Neat test substance administered to abraded skin for 24 hours

Irritant / corrosive response data:

In each animal, shaved intact skin patches treated with neat test substance and shaved abraded skin patches treated with neat test substance were free from erythema, scab or edema formation at any observation time point of the study.

Other effects:

None

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a contract research organization. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (e.g. due to limited reporting).

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

of 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

other: Tattooed New Zealands (albino rabbit)

Details on test animals or tissues and environmental conditions:

- Number: 6 animals,
- Bodyweight: 2.8 to 3.2 kg
- Housing: Individual housing in cages.
- Diet: Commercially available standard laboratory diet for rabbits ( Altromin, Lage, Germany).
Prior to dosing the animals were starved for 16 hours.
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS

Room temperature kept constant at 18±2°C, the relative humidity at 50-60%. 12 hours illumination per day.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml of undiluted liquid test substance was administered into the conjunctival sac of one eye per rabbit. The contralateral eye remained untreated to serve as a control.

Duration of treatment / exposure:

There was no mentioning in the report that eyes were rinsed after treatment. Consequently the treatment/exposure period was equivalent to the entire observation period following administration, which was 7 days, or lasted until removal of the test material by physiological mechanisms, whichever happened sooner.

Observation period (in vivo):

7 days (i.e. the final observation time point was 7 days post instillation)

Number of animals or in vitro replicates:

6 adult rabbits

Details on study design:

Before and after the test the eyes were evaluated for occular lesions using ultraviolet light.

The numerical scoring system listed in Table 1 in the field below was adopted. Time points of evaluation were: Pretest (prior to treatment), 1, 2, 4, 8, 24, 48, 72 and 96 hours after administration and daily thereafter until 7 days after administration. Grades attained at 24, 48 and 72 hours after administration were included in the mean gradings of ocular lesions used for eye irritation/corrosion classification.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: Corneal irritation or opacity was not evident during the study

Irritation parameter:

iris score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

other: Iridal changes were not evident during the study

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #4

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #5

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #6

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

2.2

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #4

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #5

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #6

Remarks:

mean over 3 time points

Time point:

other: 24, 48, 72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

other: lacrimation score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

Corneal and iridic lesions were not evident throughout the study. Conjunctival redness, grade 2, was seen in all treated eyes until 72 hours post instillation, declining in severity thereafter and having completely disappeared in all animals by 5 to 6 days post instillation. Chemosis, grade 2 or 3, was seen in all treated eyes until 48 or 72 hours post instillation, declining in severity thereafter and having completely disappeared in all animals by 5 days post instillation. In addition, lacrimation, grade 1 or 2 was recorded in all treated eyes until 72 hours post instillation. As from 5 to 6 days post instillation, each treated eye was free from ocular findings.

Other effects:

There was no mentioning of any other effects in the report.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Effects on eye irritation: irritating

Justification for classification or non-classification

In view of the absence of any effects on shaved intact and abraded skin treated for 24 hours with neat WS400109, classification regarding skin irritation or corrosion according to EU classification rules [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008] is not necessary.

The incidence and severity of chemosis and conjunctival redness attained in the in vivo eye irritation study necessitates classification of WS400109 as "irritant (Xi)" and "irritating to eyes (R36) [DIRECTIVE 67/548/EEC] and as “Category 2 (irritating to eyes)" [REGULATION (EC) 1272/2008].