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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - October 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
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:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
CYANOX® 1790 Antioxidant
IUPAC nomenclature - Tris(4-tert-butyl-3-hydroxy-2,6-dimethylbenzyl) isocyanurate
Synonym - [tris(4-t-butyl-3-hydroxy-2,6-dimethyl-benzyl)-s-triazine-2,4,6-(1H,3H,5H) trione]
Lot WP1031901
Appearance - White powder, odorless
CAS No. 40601-76-1
Molecular Formula - C42H57N3O6
Molecular Weight - 699.92 g/mole
Purity > 99%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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. 11 weeks old)
- Weight at study initiation: +/- 20% of the sex mean
- 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: 12 - 26 April

Administration / exposure

Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% in water
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on Day 1.
Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
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.

Dose level (volume): 2000 mg/kg bw (10 ml/kg bw)

DOSAGE PREPARATION:
The formulation (w/w) was 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.

- 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 time of onset, degree and duration were recorded and the symptoms graded according to fixed scales.
- Necropsy performed: yes, all animals
Statistics:
No statistics needed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea was noted in four males and two females on Days 1 and/or 2. One male showed flat posture on Day 1. White staining of the treated skin was seen in all animals on Day 2. One female showed scales on the treated skin between Days 4 and 11.
Body weight:
No effect on body weight gain was noted.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal 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 dermal toxicity.
Executive summary:

An acute dermal toxicity test with male and female rats was performed under GLP principles. The rats were exposed occlusively for 24 hours to 2000 mg/kg bw and observed for 14 days after removal of the test substance. No mortality, clinical signs or particular findings at necropsy were observed.

Based on these results, the LD50 of the test substance was found to be > 2000 mg/ kg bw and therefore the test substance is not classified.