N4,N4'-hexane-1,6-diylbis[N-butyl-6-chloro-N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,5-triazine-2,4-diamine]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11.03.2020 - 25.06.2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N4,N4'-hexane-1,6-diylbis[N-butyl-6-chloro-N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,5-triazine-2,4-diamine]

EC Number:

835-183-3

Cas Number:

83420-16-0

Molecular formula:

C56 H102 Cl2 N14

IUPAC Name:

N4,N4'-hexane-1,6-diylbis[N-butyl-6-chloro-N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,5-triazine-2,4-diamine]

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and batch number of test material:SUQIAN UNITECH CORP., LTD 190701
-Expiry Date: 24-07-2021
- Purity:91%
- Purity test date: 24-10-2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature

OTHER SPECIFICS
Due to the purity of 91% of the test item, all weighing steps were done in consideration of a correction factor of 1.0989.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant:[ye
- Age at study initiation: 9 – 11 weeks
- Weight at study initiation: Step 1: 180 – 188 g; Step 2: 158 – 166 g Step 3: 150 – 170 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Justification for choice of vehicle:The substance is insoluble in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

300, 2000 mg/kg bw.
The starting dose was selected to be 300 mg/kg bw.
A second step was performed at a dose of 2000 mg/kg bw.
A third step was performed at a dose of 2000 mg/kg bw.

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.

- Necropsy of survivors performed: yes

- Clinical signst: Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Mortality:

One animal of the third step treated with the test item at a dose of 2000 mg/kg bw was found dead
on day 8 post-application. The remaining animals survived until the end of the study at 300 or 2000 mg/kg bw.

Clinical signs:

other: No clinical signs were detected at 300 mg/kg bw during the whole observation period. The only clinical finding observed was piloerection in animals of the second step, 3 hours post-dose.All animals recovered within the fourth hour post-dosing. The clin

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study(acute toxic class) in the rat, the LD50(female) for N4,N4`-hexane- 1,6-diylbis[N-butyl-6-chloro-N,N`-bis(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,5-triazine-2,4-diamine] was
2500 mg/kg bw.

Executive summary:

In an acute oral toxicity study (OECD 423/GLP), groups of Wistar female rats (3/per step) were given a single oral dose of N4,N4`-hexane-1,6-diylbis[N-butyl-6-chloro-N,N`-bis(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,5-triazine-2,4-diamine] (91 %) in corn oil by oral gavage at doses of 300 or 2000 mg/kg bw. Animals were then observed for 14 days.

 

Oral LD50 cut off (females) = 2500 mg/kg bw

 

All animals of the first and second steps treated with the test item at a dose of 300 mg/kg bw and 2000 mg/kg bw, respectively, survived until the end of the study. The animals of the first step did not show any signs of toxicity. The only clinical finding observed was piloerection in animals of the second step, 3 hours post-dose. All animals recovered within the fourth hour post-dosing. One animal of the third step treated with the test item at a dose of 2000 mg/kg bw was found dead on day 8 post-application. The remaining animals survived until the end of the study, showing slight signs of toxicity, which were fully reversible by the end of the observation period. The most relevant clinical findings in the animals of the third step were diarrhoea and piloerection. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.