2,6-di-tert-butyl-4-(4,6-bis(octylthio)-1,3,5-triazin-2-ylamino)phenol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 19, 1992 - June 16, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987-02-24)

Deviations:

yes

Remarks:

(test conducted with 1600 mg/kg bw, the max. technically achievable concentration)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,6-di-tert-butyl-4-(4,6-bis(octylthio)-1,3,5-triazin-2-ylamino)phenol

EC Number:

213-590-1

EC Name:

2,6-di-tert-butyl-4-(4,6-bis(octylthio)-1,3,5-triazin-2-ylamino)phenol

Cas Number:

991-84-4

Molecular formula:

C33H56N4OS2

IUPAC Name:

2,6-di-tert-butyl-4-(4,6-bis(octylthio)-1,3,5-triazin-2-ylamino)phenol

Details on test material:

- Physical state: Solid, white
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

other: Tif: RAI f1 (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-Geigy Ltd., Animal Production, 4332 Stein, Switzerland
- Age at study initiation: Young adult rats
- Weight at study initiation: 225 - 289 g
- Housing: Individual housing in Macrolon cages type 3 with standardised soft wood bedding (Societe Parisienne des Sciures, Pantin, France)
- Diet: ad libitum NAFAG 890 Tox, NAFAG, Gossau/ SG, Switzerland
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: 0.5 % (w/v) Carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80

Details on dermal exposure:

TEST SITE
- Area of exposure: Back of the rat
- % coverage: ≥ 10
- Type of wrap: Gauze-lined semi-occlusive dressing fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing the skin with lukewarm water
- Time after start of exposure: 24 h

VEHICLE
- Amount(s) applied: 4 ml/kg bw
- Concentration: 40 %

OTHER
24 h before study begin an area of the back of the rat was shaved with an electric clipper (at least 10 % of the body surface)

Duration of exposure:

24 h

Doses:

1600 mg/kg bw
Due to the physical-chemical properties, the test substance had to be suspended in a higher vehicle volume (40 instead of 50%). Adhering to guidelines and SOP, and respecting the maximal application volume (4 ml/kg) a limit dose of 1600 mg/kg has been appplied by direct weighing.

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 weighing: Immediately before study begin and on days 7 and 14
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs and symptoms (daily for 14 days), mortality (daily: a.m and p.m on working days, a.m. on weekend days)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 600 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred in this study.

Clinical signs:

other: In males and females on application day and the following day slight piloerection was seen. The animals recovered within 2 days.

Gross pathology:

No deviations from normal pathology were found.

Any other information on results incl. tables

Table 1: Body weight in male and female animals after day 0, 7 and 14

Body weight [g]
Males (dose = 1600 mg/kg bw)
animal ID	day 0	day 7	day 14
1	270	306	355
2	259	280	296
3	289	303	345
4	271	292	316
5	276	304	329
mean	273	297	328.2
SD	10.9	11	23.4
Females (dose = 1600 mg/kg bw)
animal ID	day 0	day 7	day 14
1	226	231	236
2	225	232	237
3	238	237	263
4	260	265	277
5	235	257	267
mean	236.8	244.4	256
SD	14.1	15.6	18.5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Upon an acute dermal administration and a 14 day post-treatment observation period, the LD50 was determined to be > 1600 mg/kg body weight.

Executive summary:

The acute dermal toxicity of the test substance was assessed in a toxicity study following OECD guideline 402 and in compliance with GLP. The test article was administered to five rats of each sex by dermal application at 1600 mg/kg body weight for 24 hours. Higher doses were technically not possible. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. Piloerection was seen, being a common symptom in acute dermal tests. The animals recovered within 2 days. At autopsy, no deviations from normal morphology were found. The dermal LD50 value of the test substance in rats was established to exceed 1600 mg/kg body weight.