1,3,5-tris[[4-tert-butyl-3-hydroxy-2,6-xylyl]methyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April - June 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3,5-tris[[4-tert-butyl-3-hydroxy-2,6-xylyl]methyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

EC Number:

254-996-9

EC Name:

1,3,5-tris[[4-tert-butyl-3-hydroxy-2,6-xylyl]methyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Cas Number:

40601-76-1

Molecular formula:

C42H57N3O6

IUPAC Name:

tris[(4-tert-butyl-3-hydroxy-2,6-dimethylphenyl)methyl]-1,3,5-triazinane-2,4,6-trione

Constituent 2

Reference substance name:

Cyanox (TM) 1790 Antioxidant

IUPAC Name:

Cyanox (TM) 1790 Antioxidant

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approx. 8-9 weeks old)
- Weight at study initiation: +/- 20% of the sex mean
- Fasting period before study: yes, overnight
- Housing: individually housed in Makrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 6 - 26 April

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1% in water

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females (2 groups of 3 females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy performed: yes, all animals

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture was noted in all animals on days 1 and/or 11.

Gross pathology:

No toxicologically relevant abnormalities were found at macroscopic post mortem examination of the animals.
One animal showed pelvic dilation in both kidneys. This finding is occasionally seen among rats of this age and strain and was therefore considered not related to treatment.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of CYANOX® 1790 Antioxidant in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results, CYANOX® 1790 Antioxidant does not have to be classified and has no obligatory labelling requirement for acute oral toxicity.

Executive summary:

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 423, the test item was administered to two groups of 3 female Sprague Dawley rats ata single dose level of 2000 mg/kg bw.

No mortalities or clinical signs were noted.

In conclusion, the LD50 ofthe test itemisdeterminedto be> 2000 mg/kg body weight by oral route in the rat.