3,3',3'',5,5',5''-hexa-tert-butyl-α,α',α''-(mesitylene-2,4,6-triyl)tri-p-cresol

Endpoint summary

Description of key information

Effect level for the dermal route determined using OECD method 402. LD50 > 2000 mg/kg bw
Effect level for the oral route not determined to a specified method, however study written with clear and consice study plan. LD50 >10000 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:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to no specified methods

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: not specified

GLP compliance:

not specified

Test type:

other: Not specified

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and 5 female rats of the Sprague-Dawley strain (obtained from Harlan Industries, Inc., Indianapolis, Indiana), weighing from 200 to 208 grams, were used for this study. The rats were housed by sex, in groups of 5 rats per cage, in hanging wire-mesh cages in temperature and humidity controlled quarters. They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and Use of Laboratory Animals". The rats were conditioned for a minimum of 5 days prior to study initiation. Water and Purina Laboratory Chow were available ad libitum, except for an overnight period of approximately 18 hours Immediately preceding oral administration during which food, but not water, was withheld.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test material was administered orally by gavage as a suspension in corn oil at the following dosage level to male and female rats: 10,000 mg/kg.
The dosage level was administered at a volume of 40 ml/kg.

Doses:

10,000 mg/kg

No. of animals per sex per dose:

5 male
5 female

Control animals:

not specified

Details on study design:

Observations for pharmacotoxic signs were recorded during the first 4 hours following dosing, at 24 hours and daily thereafter for a total of 14 days. The rats were observed for mortality during the first four hours following dosing and twice daily thereafter for a total of 14 days. Body weights were recorded immediately prior to dosing (control weight) and at 7 and 14 days. All rats which died on study were subjected to gross necropsy examination as were all survivors at the end of the 14 day observation period

Statistics:

Not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

One female rat died on the first day of the 14 day study period. None of the other rats died.

Clinical signs:

other: Presented in table form, please see any otherinformation on results incl. tables.

Gross pathology:

Necropsy Findings: The following necropsy observations were obtained during the 14 day study period:
The rat (#82570) which died during the study period: Partital cannibalization, yellow stained anogenital region, stomach contains yellow creamy fluid, small intestines contain yellow creamy fluid.
Rats which were sacrificed following 14 day of observation:
No gross lesions 3/5 males, 1/4 females
Kidneys, mottled colouration 2/5 males, 3/4 females
Uterus, hydrometra 1/4 females

Other findings:

Not specified

NUMBER OF RATS SHOWING PHARMACOTOXIC SIGNS AND TIME [HOUR] (DAY) OBSERVED

	MALES	FEMALES
OBSERVATION	10,000 mg/kg	10,000 mg/kg
Normal	2 [1], 5 (2 – 14)	3 [1], 4 (2 – 14)
Hypoactivity	3 [1], 5 [2 ½, 4], 5 (1)	2 [1], 5 [2 ½, 4], 4 (1)
Death		1 (1)

 

The following body weights were obtained during the 14 day observation period

Dosage Level (mg/kg)	Individual Rat Number	Sex	Control Weight (grams)	7 Day Weight (grams)	14 Day Weight (grams)
10,000	82571	Male	202	274	328
	82572	Male	201	259	340
	82573	Male	202	225	285
	82574	Male	200	242	302
	82575	Male	204	250	280
	82566	Female	205	226	232
	82567	Female	206	258	290
	82568	Female	208	246	264
	82569	Female	202	231	235
	82570	Female	201	Died	Died

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 value was found to be greater than 10,000 mg/kg

Executive summary:

The acute oral LD50 value was found to be greater than 10,000 mg/kg

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 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:

1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Due to the physical-chemical properties, the test substance had to be applied by weight.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation: young adult rats were used
- Weight at study initiation: 217 to 268 g
- Housing: individually housed in Macrolon cages type 3, with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin, France).
- Diet: NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

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
- % coverage: 10%
- Type of wrap if used: gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage

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

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 g/kg bw (corresponding approximately to 4 ml).

Duration of exposure:

24 h

Doses:

2000 mg/kg

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:
Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
Signs and symptoms: daily for 14 days
Body weight: immediately before application and on days 7 and 14
Necropsies: The animals were submitted to a gross necropsy at the end of the observation period.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occurred in this study.

Clinical signs:

other: Piloerection and hunched posture were seen, being common symptoms in acute dermal tests. The animals recovered within 2 days.

Gross pathology:

At necropsy, no deviations from normal morphology were found.

Interpretation of results:

not classified

Remarks:

Migrated information

Conclusions:

LD50 > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
Study written with clear and concise study plan.

Justification for selection of acute toxicity – dermal endpoint
Study performed using OECD method 402