5-butoxy-2-[4-(4-butoxy-2-hydroxyphenyl)-6-(2,4-dibutoxyphenyl)-1,3,5-triazin-2-yl]phenol

Endpoint summary

Description of key information

The acute oral and dermal toxicity of the test item was determined in two tests accroding GLP and OECD guideline 401 and 402, respectively. All animals survived until the scheduled day of necrospy. Clinical signs, changes in behaviour or marcoscopic signs were not observed. LD50 for oral and dermal acute toxicity is considered to be  > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd
- Age at study initiation: females: 10 weeks, males: 8 weeks
- Weight at study initiation: females: 169.8 - 181.5g, males: 199.6 - 208.3g
- Fasting period before study: approximately 16.5 hours
- Housing: Groups of three
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433, batch no. 40/99, rat maintenance diet (Provimi Kliba AG, Kaiseraugst) available ad libitum (except for the ovemight fasting period prior to intubation).
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hour/12 hour

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml / kg body weight

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each animal was examined for changes in appearance and behavior four times during day 1, and once daily during days 2-15. A description of all abnormalities was recorded. Bodies were weighted on test day 1 (pre-administration), 8 and 15. Mortality was monitored four times during test day 1 and once daily during days 2-15.
- Necropsy of survivors performed: yes, at the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhone Merieux GmbH) at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg body weight). The animals were examined macroscopically and all abnormalities recorded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No signs of toxicity

Mortality:

No death occurred during the study.

Clinical signs:

other: No clinical signs were noted during the observation period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

No signs of toxicity were observed up to a dose of 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Fuellinsdorf/ Switzerland
- Age at study initiation: 9 weeks for the males, 12 weeks for the females
- Weight at study initiation: male = 236.5 - 259.6, female = 199.2 - 226.8
- Housing: goups of 5 animals
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433, batch no. 40/99, rat maintenance diet (Kliba Miihlen AG, Kaiseraugst) available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on dermal exposure:

TEST SITE
- % coverage: approximately 10 % of the total body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tap water and dried with disposable paper towels

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.0 ml /kg body weight

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were examined for changes in appearance and behavior four times during day 1, and once daily during days 2-15. Body were weighted on test day 1 (pre-administration), 8 and 15. Mortality/Viability was observed four times during test day 1 and once daily during days 2-15.
- Necropsy of survivors performed: yes, at the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhone Merieux GmbH, D-88471 Laupheim) at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg body weight). The animals were examined macroscopically and all abnormalities recorded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No signs of toxicity observed

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

No signs of toxicity were observed up to a dose of 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

There are two reliable studies available to assess the acute oral and dermal toxicity of the test substance.

In a GLP conform study, two groups, each using three female or three male Hanlbm: WIST (SPF) rats, were treated with the test substance at 2000 mg/kg by oral gavage according to OECD guideline 423 (RCC Ltd, 2000). The test article was suspended in vehicle (polyethylene glycol PEG 300) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No death occurred during the study. Clinical signs were not observed during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The LD50 in rat is considered to be greater than 2000 mg/kg body weight.

In a GLP conform study, a group of five male and five female Hanlbm: WIST (SPF) rats was treated with the test substance at 2000 mg/kg by dermal application (RCC Ltd, 1999). The test article was suspended in vehicle (polyethylene glycol PEG 300) at a concentration of 0.5 g/ml and administered at a volume of 4 ml/kg. The animals were examined for clinical signs four times during day 1 and once daily during days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No death occurred during the study. Clinical signs were not observed during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The LD50 in rat is considered to be greater than 2000 mg/kg body weight.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008, as amended for the thirteenth time in Regulation (EU) No 2018/1480. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008.