Propanoic acid, 2-[4-[4,6-bis([1,1'-biphenyl]-4-yl)-1,3,5-triazin-2-yl]-3-hydroxyphenoxy]-, isooctyl ester

Endpoint summary

Description of key information

The irritation potential of the test item was assessed by application onto skin (OECD guideline 404, GLP) or installation into eyes of rabbits (OECD guideline 405, GLP). Skin reactions were not observed. Treatment of eyes caused mild, transient conjunctival irritation (redness) which resolved within post observation period. The substance is not considered to be irritating to skin or eyes.

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:

29-Nov-2002 to 13-Dec-2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline test, GLP compliance

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted on 17th July 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

adopted in August 1998

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 UK Ltd, Bicester, Oxon, England
- Age at study initiation: at least 12 weeks
- Weight at study initiation: 2.77 - 3.18 kg
- Housing: individually in stainless steel cages with perforated floors
- Diet: each rabbit was offered 125 g of a standard laboratoty rabbit diet (Special Diet Services TANRAB (P) SQC pellet) per day; dietary supplement of hay
- Water: drinking water was provided ad libitum
- Acclimation period: at least 46 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C
- Humidity: 40-70%
- Photoperiod : 12 hours dark / 12 hours light

IN-LIFE DATES: not indicated

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: a control gauze patch was applied to the contralateral flank

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

Examination of the treated skin was made on removal of the dressings (for 3 minute or one hour exposures) and aproximately 1, 24, 48 and 72 hours later

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 25 mm x 25 mm
- Type of wrap if used: cotton wool and "Tubigrip" elasticated bandage dressing (semi-occlusive)

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm water (30-40°C) . The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

SCORING SYSTEM: The skin reactions were evaluated according to the OECD scoring system.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No dermal reaction was observed in any animal throughout the duration of the study.

Other effects:

No other effects observed.

Interpretation of results:

GHS criteria not met

Conclusions:

Application of the test substance onto skin did not provoke any skin reaction. The substance is therefore not considered to be irritating to skin.

Executive summary:

A GLP-compliant Acute dermal irritation/corrosion study according to OECD TG 404 was performed to assess the skin irritation potential of the test substance to the rabbit. Three rabbits received a single four hour, semi-occlusive, dermal administiation of approximately 0.5g of the test substance (moistened with water) and were observed for four days. No dermal reaction was observed in any animal throughout the duration of the study. The means of scores for oedema and erythema at approximately 24, 48 and 72 hours after administration, were 0 for each animal. As a result, the substance is not considered to be irritating to skin.

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:

12-Dec-2002 to 02-Jan-2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD test guideline 405)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted on 24th February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: at least 8 weeks
- Weight at study initiation: 2.75-3.17 kg
- Housing: individually in stainless steel cages with perforated floors
- Diet: 125 g of a standard laboratoty rabbit diet per day. A dietary supplement of hay was given during the acclimatisation period until at least two days prior to dose instillation.
- Water: drinking water was provided ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16-20 °C
- Humidity: 40-70%
- Photoperiod 12 hours dark / 12 hours light

IN-LIFE DATES: not indicated

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 70 mg (corresponding to a volume of 0.1 mL based on specific gravitiy)

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

8 days. Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours and eight days after treatment.

Number of animals or in vitro replicates:

three male

Details on study design:

SCORING SYSTEM: The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992.

TOOL USED TO ASSESS SCORE: ophthalmoscope/pencil beam torch

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Injection of the conjunctival blood vessels or a crimson-red conjunctival appearance with or without very-slight discharge was evident in all animals one hour after instillation. Conjunctival injection or a crimson-red conjunctival appearance was apparent in two animals during the next three days. One animal was overtly normal 24 hours after instillation, the remaining two were overtly normal after one week.

Other effects:

- Lesions and clinical observations: There was no sign of toxicity or ill health in any rabbit during the observation period.
- Ophthalmoscopic findings: not determined
- Histopathological findings: not determined
- Effects of rinsing or washing: not applicable
- Other observations: Instillation of the test substance gave rise to practically no or a slight initial pain response.

Interpretation of results:

GHS criteria not met

Conclusions:

Installation into the eyes of rabbits caused mild, transient conjunctival irritation which resolved within the post observation period. The substance is therefore not considered to be irritating to eyes.

Executive summary:

A GLP-compliant Acute eye irritation/corrosion study according to OECD TG 405 was performed to assess the eye irritation potential of the test substance to the rabbit. Three rabbits were each administered a single ocular dose of a volume of 0.1 ml of the test substance weighing approximately 70 mg and observed for eight days after instillation. Injection of the conjunctival blood vessels or a crimson-red conjunctival appearance with or without very-slight discharge was evident in all animals one hour after instillation. Conjunctival injection or a crimson-red conjunctival appearance was apparent in two animals during the next three days. One animal was overtly normal 24 hours after instillation, the remaining two were overtly normal after one week. Instillation of the test substance gave rise to practically no or a slight initial pain response. As only mild, transient conjunctival irritation which resolved within the post observation period was observed, the substance is not considered to be irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Procedure and observation

Three rabbits received a single four hour, semi-occlusive, dermal administiation of approximately 0.5g of the test substance (moistened with water) and were observed for four days. No dermal reaction was observed in any animal throughout the duration of the study. The means of scores for oedema and erythema at approximately 24, 48 and 72 hours after administration, were 0 for each animal.

Three rabbits were each administered a single ocular dose of a volume of 0.1 ml of the test substance weighing approximately 70 mg and observed for eight days after instillation. Conjunctival irritation (redness) was observed in all animals 1h after installation. All symtopms resolved latest on day 8 of the post observation period.

 

Conclusion

Application of the substance onto skin did not provoke any skin reaction. Installation into the eyes of rabbits caused mild, transient conjunctival irritation which resolved within the post observation period. The substance is therefore not considered to be irritating to skin or eyes.

Justification for classification or non-classification

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. A GLP-compliant OECD 404 study is available for skin irritation. A GLP-compliant OECD 405 study is available for eye irritation. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.