2-hexyldecanoic acid [4-(6-tert-butyl-7-chloro-1H-pyrazolo[1,5-b][1,2,4]triazol-2-yl)phenylcarbamoyl]methylester

Endpoint summary

Description of key information

Skin (OECD 404): not irritating
Eye (OECD 405): not irritating

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:

12 - 22 Aug 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

adopted august 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), adopted Nov 2000

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually in cages with perforated floors (Scanbur, Denmark)
- Diet: standard laboratory diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin), approximately 100 g per day, pressed hay was provided twice a week
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.4 - 22 (actual range)
- Humidity (%): 48 - 89 (actual range)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: watery ethanol (50% v/v)

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

VEHICLE
- Amount(s) applied: 0.5 g test substance was moistened with 0.5 mL vehicle prior to application
- Concentration (if solution): 50 % (v/v)

Duration of treatment / exposure:

4 hours

Observation period:

14 days
Reading time point: 1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm², dorsal area
- Type of wrap if used: metalline patch mounted on micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: using water and vehicle
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: erythema was only noted at the edges of the application area

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of animal #2 and #3

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

1/3 animals had very slight erythema at the edges of the application area. The skin irritation in this animal had completely resolved within 48 hours after exposure. No edema was noted.

Other effects:

No other effects were observed.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

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:

18 - 28 Aug 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

adopted August 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Nov 2000 including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually in cages with perforated floors (Scanbur, Denmark)
- Diet: standard laboratory rabbit diet (Charles River Maintenance Diet for Rabbits, Altromin) 100 g per day; pressed hay was provided twice per week
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.4 - 23.2 (actual range)
- Humidity (%): 40 - 96 (actual range)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 35.9 mg (35.6 - 36.0 mg) (corresponding to a volume of approximately 0.1 mL)

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

72 hours
Reading time points: 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Draize Scoring System

TOOL USED TO ASSESS SCORE: hand-slit lamp, fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of animal #1 and #2

Time point:

other: mean over 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 hours

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Instillation of 35.9 mg test substance into one eye of three rabbits each resulted in irritation of the conjunctivae which was seen as mild redness and mild-moderate chemosis in 3/3 rabbits at the 1-hour reading time point. 1/3 animals had a slight discharge 1 hour after application. 24 hours after application mild redness of the conjunctivae was still visible in all animals. This irritation had completely resolved within 48 hours in 2/3 animals and within 72 hours in 1/3 animal. 1 hour after application remnants of the test substance were still visible in all tested eyes.

Table 1. Results of eye irritation study. 

Rabbit #	Time [h]	conjunctivae		iris	cornea		conjunctivae		iris	cornea
		redness	swelling				redness	swelling
1	1	1	2	1	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0	Time to reversion	48.0	24.0	0.0	0.0
2	1	1	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0	Time to reversion	48.0	24.0	0.0	0.0
3	1	2	1	0	0
	24	1	0	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	0.67	0.0	0.0	0.0	Time to reversion	72.0	24.0	0.0	0.0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study assessing the skin irritation potential of 2-hexyldecanoic acid [4-(6-tert-butyl-7-chloro-1H-pyrazolo[1,5-b][1,2,4]triazol-2-yl)phenylcarbamoyl]methylester (UM-235) was performed according to OECD 404 (Teunissen, 2003b). 0.5 g test substance was, due to its insolubility in water, moistened with watery ethanol (50 % v/v) to ensure close contact with the skin and applied to the clipped skin of New Zealand White rabbits, under semi-occlusive conditions for 4 hours. There was only very slight erythema seen (Score 1 on a scale of 4) at the edge of the application site in 1/3 animals which had resolved within 48 hours. No edema was seen in any animals at any reading time point.

In the acute dermal toxicity study, UM-235 was administered to rats in a limit test performed according to OECD 402 (Hooiveld, 2004a). A single dose of 2000 mg/kg bw of the test substance dissolved in propylene glycol was applied to the shaved skin of rats under semi-occlusive conditions and left for 24 hours. Erythema (score 1 of 4), scales and/or scabs were noted at the treated skin area of all 5 female animals after removal of the dressing. The erythema had cleared completely in all animals by Day 9. The scales/scabs were still visible in one animal at terminal sacrifice on Day 14.

The skin irritation study, performed according to the standard guidelines (4 -hour exposure under semi-occlusive conditions) and using watery ethanol to moisten the substance did not result in skin irritation. The longer exposure period (24 h) employed in the acute dermal toxicity study shows that even under more severe conditions the test substance does not cause skin irritation that leads to a classification. Therefore, UM-235 is considered not to be a skin irritant.

To evaluate the eye irritation potential of UM-235, a study was performed according to OECD guideline 405 (Teunissen, 2003c). 35.9 mg (weight corresponding to 0.1 mL) was instilled into one eye of 3 New Zealand White rabbits each, without washing. Some test substance was still observed in the eye 1 hour after instillation. The irritating effect was assessed 1, 24, 48 and 72 hours after the treatment.

Instillation of the test substance resulted in irritation of the conjunctivae, which was seen as redness, chemosis and discharge. All animals showed chemosis and discharge (score 1 in 2/3, score 2 in 1/3) only 1 hour after application. Redness was still visible for all animals 24 hours after instillation into the eye (score 1). The irritation had completely resolved within 2 days in 2 animals and within 3 days in the other animal. Iridial irritation (score 1) was observed in one animal and had resolved within 24 hours. No corneal opacity was observed. Based on this study, UM-235 is not considered to be an eye irritant.

Justification for selection of skin irritation / corrosion endpoint:
There is only one study available.

Justification for selection of eye irritation endpoint:
There is only one study available.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.