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 did not cause adverse effects upon 14 -day gavage dosing with 1000 mg/kg bw. Therefore, it is not necessary to perform an additional study for acute oral toxicity with 2000 mg/kg bw. 

The substance was tested in the acute dermal toxicity study (OECD 402, GLP) using corn oil as vehicle. No mortality was observed, but there were local reactions which occurred with a time delay.

A study for acute inhalation was not performed because the substance is not handled in an inhalable form.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Clinical signs:

other: other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

1 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, 97633 Sulzfeld, Germany

- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: average 211 g (females) and 236 g (males)
- Fasting period before study: none
- Housing: single
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): approx 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 2016-02-29 To: 2016-03-16

- Fur clipping about 24 hours before administration

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: About 40 cm²
- % coverage: 10%
- Type of wrap if used: semi- occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied: 5.71 ml/kg bw
- Concentration (if solution): 35g/100ml
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 3 g/kg bw

Duration of exposure:

24h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Statistics:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Clinical signs:

other: other: none

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Other findings:

Local effects: In all male animals well-defined erythema (grade 2) was observed on study day 1 and persisted in two of these animals until study day 3.
In three animals very slight erythema (grade 1) was noticed from study day 2 until study day 3.
From study day 6 until study day 7, severe erythema (grade 4) was notediced in all male animals and decreased to moderate erythema (grade 3) from study day 8 until study day 10.

Slight edema (grade 2) was seen in all male animals on study day 1. Thereafter, very slight edema (grade 1) was noticed in these animals from study day 2 until study day 10.
From study day 1 until study day 7, erythema and edema were observed beyond the application area. Test item residues were noted in all male animals from study day 1 until study day 3, while incrustations were seen in these animals from study day 6 until study day 10.
In three male animals scaling was observed on study day 13 and 14.

In all female animals well-defined erythema (grade 2) was observed on study day 1 and persisted in one animal until study day 3. In four females very slight erythema (grade 1) was seen from study day 2 until study day 3 and persisted in one of these animals until study day 7.
In one animal severe erythema (grade 4) was seen from study day 6 until study day 7 which, regressed to moderate erythema (grade 3) from study day 8 until study day 10.
In another animal moderate erythema (grade 3) was observed on study day 6 and decreased stepwise to well-defined erythema (grade 2) on study day 7 and 8 and to very slight erythema (grade 1) on study day 9 and 10.

Slight edema (grade 2) was observed in all female animals on study day 1 and persisted in one of these females up to study day 3. In four females very slight edema (grade 1) was seen from study day 2 until study day 3 and persisted in one of these animals until study day 10.
From study day 1 until study day 3, 6 or 7, erythema and edema were observed beyond the application area.
Test item residues were noted in all female animals from study day 1 until study day 3, while incrustations were seen in two of these animals from study day 6 until study day 10.
In one female animal scaling was observed from study day 13 until study day 14.

Nature and duration of local clinical signs(males)
Dose (mg/kg bw):		5000
Sex:		male
Application:		1
No. of animals:		5
Animal No.:		R 818	R 819	R 820	R 821	R 822
Abnormalities:
Erythema grade 1:		d2 - d3	d2 - d3	d2 - d3	-	-
Erythema grade 2:		d1	d1	d1	d1 - d3	d1 - d3
Erythema grade 3:		d8 - d10	d8 - d10	d8 - d10	d8 - d10	d8 - d10
Erythema grade 4:		d6 - d7	d6 - d7	d6 - d7	d6 - d7	d6 - d7
Edema grade 1:		d2 - d10	d2 - d10	d2 - d10	d2 - d10	d2 - d10
Edema grade 2:		d1	d1	d1	d1	d1
Test item residues:		d1 - d3	d1 - d3	d1 - d3	d1 - d3	d1 - d3
Incrustations:		d6 - d10	d6 - d10	d6 - d10	d6 - d10	d6 - d10
Scaling:		d13 - d14	d13 - d14	d13 - d14	-	-
Erythema and edema beyond the application area:		d1 - d7	d1 - d7	d1 - d7	d1 - d7	d1 - d7

Nature and duration of local clinical signs(females)
Dose (mg/kg bw):		5000
Sex:		female
Application:		1
No. of animals:		5
Animal No.:		R 823	R 824	R 825	R 826	R 827
Abnormalities:
Erythema grade 1:		d2 - d3	d2 - d3	d2 - d3; d9 - d10	-	d2 - d7
Erythema grade 2:		d1	d1	d1; d7 - d8	d1 - d3	d1
Erythema grade 3:		-	d8 - d10	d6	-	-
Erythema grade 4:		-	d6 - d7	-	-	-
Edema grade 1:		d2 - d3	d2 – d10	d2 - d3	-	d2 - d3
Edema grade 2:		d1	d1	d1	d1 - d3	d1
Test item residues:		d1 - d3	d1 - d3	d1 - d3	d1 - d3	d1 - d3
Incrustations:		-	d6 - d10	d6 - d10	-	-
Scaling:		-	d13 - d14	-	-	-
Erythema and edema beyond the application area:		d1 - d3	d1 - d7	d1 - d6	d1 - d3	d1 - d3

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Additional information

The local effects recorded during the observation period are related to the use of corn oil as vehicle. The substance itself is poorly soluble in water and has therefore little possibility to interact with the skin. However, for the acute dermal toxicity study, the design requires optimization of skin contact and corn oil was used. The substance is soluble in corn oil and cn therefore be applied with much better coverage and contact efficiency.

The irritating effects are important when assessing solutions in organic solvents. They are not relevant when working with the dry substance or aqueous suspensions.

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. No mortality occurred at the limit dose of 5000 mg/kg bw in the acute dermal toxicity study. No adverse effects were observed upon subacute oral dosing with 1000 mg/kg bw. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.

 

Data on acute inhalation is not available as the particle size of the substance is in the non-inhalable size range.