Reaction products of N6,N6'-hexane-1,6-diylbis[N2,N4-dibutyl-N2,N4,N6-tris(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,5-triazine-2,4,6-triamine] and allylbromide, subsequently reacted with ethaneperoxoic acid, hydrogenated

Endpoint summary

Description of key information

The substance was found to cause slight reversible effects on conjunctivae (OECD 405, GLP).

The substance itself was found to cause slight reversible erythema (OECD 404, GLP).

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:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

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: Envigo RMS GmbH, Germany
- Age at study initiation: 6 - 8 months
- Weight at study initiation: 3.02 kg – 3.94 kg
- Housing: Single cages
- Diet ad libitum
- Water ad libitum
- Acclimation period: Acclimatization for at least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 13 July 2017 To: 24 Aug 2017

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

The solid test item was minimally moistened with a suitable amount of highly deionized water to guarantee skin contact immediately before test item application .

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

single treatment

Observation period:

up to 14 days

Number of animals:

3

Details on study design:

The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and in weekly intervals until disappearance of effects (latest on day 14).

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: no indication of edema at any observation time point

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 7 days

Table: Readings of erythema and edema in individual animals

(for animals 2 and 3, the study was discontinued after 3 days since animals were free of findings)

Readings	Animal no	Erythema	Edema
0h	1	0	0
0h	2	1	0
0h	3	1	0
1h	1	0	0
1h	2	1	0
1h	3	1	0
24h	1	1	0
24h	2	1	0
24h	3	1	0
48h	1	1	0
48h	2	0	0
48h	3	1	0
72h	1	1	0
72h	2	0	0
72h	3	0	0
7 days	1	0	0
7 days	2	-	0
7 days	3	-	0
Mean 24/48/72h	1	1	0
Mean 24/48/72h	2	0.3	0
Mean 24/48/72h	3	0.7	0
Mean		0.7	0.0

Interpretation of results:

GHS criteria not met

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:

2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

October 02, 2012

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability of the test substance under storage conditions over the test period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: November 02, 2020
Storage conditions: Room temperature
Physical state/ color: Solid / rose

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Envigo CRS (Switzerland) Limited
- Age at study initiation: Approx. 3 months
- Weight at study initiation: 2.55 kg – 2.86 kg
- Housing: Single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL bulk volume (about 25 mg of the comminuted test item)

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

Scorings on 1, 24, 48 and 72 h after application and on study day 7.

Number of animals or in vitro replicates:

3

Details on study design:

1 hour before application with buprenorphine (0.01 mg/kg s.c.). Additional injections of analgesics were not necessary due to the minimal ocular reactions observed.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: 24h

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp (24h), fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

3

Reversibility:

fully reversible within: 7 days

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Eye irritation in vivo (OECD 405, GLP)

The potential of the test material to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL bulk volume (about 25 mg) of the undiluted test item to one eye of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About, and not less than 24 hours after application, the eye was rinsed with tap water.

The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and on study day 7 at the latest. Additional eye examinations were performed at 24 and 48 h after application with the instillation of a fluorescein solution. Due to absence of detectable lesions following fluorescein instillation, all subsequent readings were performed without the aid of fluorescein.

Slight conjunctival redness (grade 1), slight conjunctival chemosis (grade 1) and slight discharge (grade 1) were observed. The ocular reactions were reversible in one animal within 72 hours and in two animals within 7 days after application. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity and for iris lesions, 0.7, 1.0 and 1.0 for redness of the conjunctiva and 0.0, 0.0 and 0.3 for chemosis.

 

Skin irritation in vivo (OECD 404, GLP)

The potential to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 g of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal, supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and on study day 7. Very slight erythema (grade 1) were recorded during the course of the study

The cutaneous reactions were reversible in two animals within 72 hours and in one animal within 7 days after removal of the patch.

Mean scores over 24, 48 and 72 hours for each animal were 1.0, 0.3 and 0.7 for erythema and 0.0, 0.0 and 0.0 for edema.

 

Comment on the local effects observed during the acute dermal toxicity study in rats (OECD 402,GLP):

For the acute dermal toxicity study, the substance was applied as a solution in oil at a higher dose and onto a larger surface for a longer period (24h versus 4h). If compared to the pure, insoluble form, uptake in the skin is more likely in the dissolved form with oil as carrier. Under these conditions, significant and prolonged redness (erythema) and slight edema were observed.

 

Justification for classification or non-classification

The available experimental test data on eye and skin irritation are reliable and suitable for classification purposes under Regulation 1272/2008. A GLP-compliant OECD 405 and 404 study is available for eye and skin irritation, respectively. The scores for the test item treated tissues were below the thresholds for classification as an irritant based on GHS criteria. 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.