2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug-Sep 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 Feb 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

31 Jul 1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

EC Number:

419-740-4

EC Name:

2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Cas Number:

137658-79-8

Molecular formula:

C36 H45 N3 O4

IUPAC Name:

2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-{3-[(2-ethylhexyl)oxy]-2-hydroxypropoxy}phenol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: Z-2759
- Expiration date of the lot/batch: Sep 1997
- Purity: 99.3%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container, at room temperature (approx. 20°C)
- Stability under test conditions: Stable under storage conditions
- Solubility and stability of the test substance in the solvent/vehicle: Stable in corn oil for at least 48 hours

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was placed into a glass beaker on a tared Mettler PM 460 balance and the vehicle (corn oil) was added. A weight by volume dilution was prepared using a glass rod.
- Homogeneity of the test article in the vehicle was maintained during treatment using the same glass rod.
- The preparation was made shortly before dosing.

OTHER SPECIFICS:
- Description: Yellowish solid

Test animals

Species:

rat

Strain:

other: Hanlbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4 4414 Fullinsdorf / Switzerland
- Age at study initiation: males: 8 weeks, females: 11 weeks
- Weight at study initiation: males: 226.5 - 247.7 g, females: 197.4 - 217.7 g
- Housing: Groups of five in Makrolon type-4 cages with autoclaved standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch no. 85/94 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period [16h] prior to application). Results of analyses for contaminants are included in the report.
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, available ad libitum. Results of bacteriological, chemical and contaminant analyses are included in the report.
- Acclimation period: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
- Identification: By unique cage number and corresponding color-coded spots on the tail.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): humidity between 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark (light period between 6.00 a.m. to 6.00 p.m.), music during the light period.

IN-LIFE DATES:
Treatment 19-AUG-1996
Observation 19-AUG-1996 to 02-SEP-1996
Termination 02-SEP-1996

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was washed with lukewarm tap water and dried with disposable paper towels
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw, 4 ml/kg bw

Dermal administration was used because this is one possible route of human exposure during manufacture, handling and use of the test article.

Duration of exposure:

24h

Doses:

2000 mg/kg bw, 4 ml/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

Mortality / Viability: Four times during test day 1 and once daily for surviving animals during days 2-15.
Body Weights: On test days 1 (pre-administration), 8 and 15 for surviving animals.
Clinical Signs: Each animal was examined for changes in behaviour and appearance (with special emphasis on the application area, except for the time when the semi-occlusive dressing was in place) four times during day 1, and once daily during days 2-15. All abnormalities were recorded.

PATHOLOGY
Necropsy
Necropsies were performed by experienced prosectors. 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. Thereafter, they were discarded.

Statistics:

The LOGIT-Model could not be used as no deaths occurred

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths occurred during the study as a result of treatment with the test article.

Clinical signs:

other: Neither clinical signs of systemic toxicity nor local effects of the test article on the skin at the application site were observed during the observation period.

Gross pathology:

No macroscopical organ findings were noted at necropsy.

Any other information on results incl. tables

Table 1: Body weights (gram)

Group / Sex	Animal	Day 1	Day 8	Day 15
Group 1 / Males (2000 mg/kg)	1	242.0	275.9	299.2
	2	234.9	260.0	298.6
	3	247.7	268.9	294.0
	4	239.0	252.3	258.9
	5	226.5	249.9	273.1
	Mean	238.0	261.4	284.8
	St.dev.	8.0	11.0	17.9
	n	5	5	5
Group 1 / Females (2000 mg/kg)	6	198.8	207.4	220.7
	7	197.4	199.7	210.8
	8	216.0	249.4	247.8
	9	217.7	222.7	235.8
	10	216.6	223.6	237.2
	Mean	209.3	221.0	230.4
	St.dev.	10.2	19.2	14.6
	n	5	5	5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The mean lethal dose of the test substance after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated, because LD50 : greater than 2000 mg/kg

Executive summary:

A group of five male and 5 female HanIbm:WIST (SPF) rats was treated with the test substance at 2000 mg/kg by dermal application. The test article was suspended in vehicle (corn oil) at a concentration of 0.5 g/ml and administered at a volume of 4 ml/kg. Four times during day 1 and once daily during days 2-15 the animals were examined for clinical signs. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 before administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study period. Neither clinical signs of systemic toxicity nor local effects of the test article on the skin at the application site were observed during the observation period. A slight loss of body weight in one female animal (no. 8) was observed during the second observation week. No macroscopic organ findings were observed at necropsy.