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EC number: 202-009-7 | CAS number: 90-66-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
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- Boiling point
- Density
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- Additional physico-chemical information
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- Endpoint summary
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- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
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- Additional ecotoxological information
- Toxicological Summary
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- Acute Toxicity
- Irritation / corrosion
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- Genetic toxicity
- Carcinogenicity
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- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Acute Toxicity: Oral
LD50 value > 2000 mg/kg bw in female Crl:WI rats.
Acute Toxicity: Dermal
LD50 value >2000 mg/kg bw in male/female Crl:WI rats.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 28 March 2017 to 12 April 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- OECD Guidelines for Testing of Chemicals No. 423. Acute Oral Toxicity – Acute Toxic Class Method. Adopted: 17 December 2001
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Version / remarks:
- Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.tris
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Version / remarks:
- EPA Health Effects Test Guidelines (OPPTS 870.1100), United States, EPA 712-C-98-190 (1998)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- yes
- Specific details on test material used for the study:
- No further details specified in the study report.
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Crl:WI
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Species and strain: Crl:WI Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Number of animals: 6 animals, 3 animals/group
Sex: Female, nulliparous and non-pregnant
Age of animals at dosing: Young healthy adult rats, 8 weeks old
Body weight at treatment: 185 – 202 g
Acclimatization period: 5-6 days
Husbandry
Animal health: Only healthy animals were used for the test. The health status was certified by the staff Veterinarian.
Number of animal room: 522/4
Housing: 3 animals / cage
Cage type: Type II. polypropylene/polycarbonate
Bedding and nesting: “Lignocel” 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nesting material produced by J. Rettenmaier & Söhne GmbH + Co.KG (D-73494 Rosenberg, Germany) were available to animals during the study.
Copies of the Certificates of Analysis are retained in the archive at CiToxLAB Hungary Ltd.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20.4 – 24.4 °C
Relative humidity: 30 – 64 %
Ventilation: 15-20 air exchanges/hour
Enrichment: Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
The temperature and relative humidity were recorded twice daily during the acclimatisation period and throughout the study.
Food and Water Supply
Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany (batch number: 484 14771, expiry date: 30 June 2017), ad libitum, and tap water from the municipal supply, as for human consumption from a 500 ml bottle, ad libitum. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A. u. 36., Hungary). The quality control results are retained in the archives at CiToxLAB Hungary Ltd.
.Animal Identification
Animals were individually identified using numbers written on the tail with an indelible marker pen. The numbers were given on the basis of CiToxLAB Hungary Ltd.' S Master File, for each animal allocated to the treatment groups. The cages were identified by cards, with information about study code, sex, dose group, cage number and individual animal numbers. - Route of administration:
- oral: gavage
- Vehicle:
- methylcellulose
- Details on oral exposure:
- Vehicle: 1% methyl cellulose
Components of the vehicle:
Name: Distilled water
Manufacturer: Hungaro-Gal Kft.
Batch number: 802 0117
Expiry date: 23 July 2017
Name: Methyl cellulose
Manufacturer: Shin-Etsu Chemical Co., Ltd.
Batch number: 5115851
Expiry date: 27 November 2018
Formulation
The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle, in the Pharmacy of CiToxLAB Hungary Ltd. on the day of administration. The formulation container was stirred continuously up to finishing the treatment.
Justification of the dose:
The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Initially, three female animals were treated with 2000 mg/kg bw of the test item. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines (OECD 423, Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.tris). - Doses:
- The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
- No. of animals per sex per dose:
- Initially, three female animals were treated with 2000 mg/kg bw of the test item. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required.
- Control animals:
- no
- Details on study design:
- Procedure
A single oral gavage administration was followed by a 14-day observation period. On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.
OBSERVATIONS
Clinical Observations
Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body Weight Measurement
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
NECROPSY
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Release, 300 mg / kg pentobarbital sodium; Lot number: 106075, Expiry date: 31 July 2018, Produced by: Wirtschaftsgenossenschaft deutscher Tierärzte eG, Germany). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded. - Statistics:
- Not required
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol did not cause mortality at a dose level of 2000 mg/kg bw.
- Clinical signs:
- There were no systemic clinical signs noted in any animal throughout the study.
- Body weight:
- There were no treatment related body weight changes. Body weight gains of 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol treated animals during the study showed no indication of a test item-related effect.
- Gross pathology:
- There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.
- Other findings:
- No further findings detailed in the study report.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of this study, the acute oral LD50 value of the test item 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol was found to be above 2000 mg/kg bw in female Crl:WI rats.
According the GHS criteria, 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol can be ranked as "Category 5 or Unclassified" for acute oral exposure. - Executive summary:
The single-dose oral toxicity of 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.tris) in Crl:WI rats.
Two groups of three female Crl:WI rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 1 and Group 2).
A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in 1% methyl cellulose at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw.
Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.tris.
Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and 14 (before necropsy). All animals were subjected to a necropsy and a macroscopic examination.
RESULTS
Mortality
6,6’-di-tert-butyl-2,2’-thiodi-p-cresol did not cause mortality at a dose level of 2000 mg/kg bw.
Clinical Observations
There were no systemic clinical signs noted in any animal throughout the study.
Body Weight and Body Weight Gain
There were no treatment related body weight changes. Body weight gains of 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol treated animals during the study showed no indication of a test item-related effect.
Macroscopic Findings
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.
CONCLUSION
Under the conditions of this study, the acute oral LD50 value of the test item 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol was found to be above 2000 mg/kg bw in female Crl:WI rats.
According the GHS criteria, 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol can be ranked as "Category 5 or Unclassified" for acute oral exposure.
Reference
CLINICAL OBSERVATIONS
DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0 SEX: FEMALE
Cage No. |
Animal Number |
Observations |
Observation days |
Frequency |
||||||||||||
0 |
1 |
2 |
3 |
4 |
5 |
6 |
7-14 |
|||||||||
30’ |
1h |
2h |
3h |
4h |
6h |
|||||||||||
1 |
7879 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
20/20 |
7880 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
20/20 |
|
7881 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
20/20 |
|
2 |
7882 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
20/20 |
7883 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
20/20 |
|
7884 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
20/20 |
Remarks: + = present
h = hour (s) ‘ = minute
Frequency of observation = number of occurrence of observation / total number of observations
BODY WEIGHT DATA
DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0 SEX: FEMALE
Cage No. |
Animal Number |
Body weight (g) Days |
Body Weight Gain (g) |
||||||
-1 |
0 |
7 |
14 |
-1 – 0 |
0 – 7 |
7 – 14 |
-1 – 14 |
||
1 |
7879 |
219 |
197 |
226 |
239 |
-22 |
29 |
13 |
20 |
7880 |
212 |
200 |
241 |
257 |
-12 |
41 |
16 |
45 |
|
7881 |
212 |
202 |
221 |
229 |
-10 |
19 |
8 |
17 |
|
2 |
7882 |
196 |
185 |
204 |
218 |
-11 |
19 |
14 |
22 |
7883 |
196 |
190 |
209 |
229 |
-6 |
19 |
20 |
33 |
|
7884 |
206 |
200 |
224 |
237 |
-6 |
24 |
13 |
31 |
|
Mean: |
206.8 |
195.7 |
220.8 |
234.8 |
-11.5 |
25.25 |
14.0 |
28.0 |
|
Standard deviation: |
9.3 |
6.7 |
13.2 |
13.2 |
5.9 |
8.7 |
3.9 |
10.4 |
NECROPSY FINDINGS
DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0 SEX: FEMALE
Cage No. |
Animal Number |
Necropsy Date/ Necropsy Day |
External Observations |
Internal Observations |
Organ/Tissue |
1 |
7879 |
11 April 2017 Day 14 |
No external observation recorded |
No internal observations recorded |
Not applicable |
|
7880 |
11 April 2017 Day 14 |
No external observation recorded |
No internal observations recorded |
Not applicable |
|
7881 |
11 April 2017 Day 14 |
No external observation recorded |
No internal observations recorded |
Not applicable |
2 |
7882 |
12 April 2017 Day 14 |
No external observation recorded |
No internal observations recorded |
Not applicable |
|
7883 |
12 April 2017 Day 14 |
No external observation recorded |
No internal observations recorded |
Not applicable |
|
7884 |
12 April 2017 Day 14 |
No external observation recorded |
No internal observations recorded |
Not applicable |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- K1 - GLP accredited laboratory study to OECD Guideline 423 and EU Method B.1 tris
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 August 2017 to 22 August 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- See "Any other information" for details
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Version / remarks:
- Commission Regulation (EC) No 440/2008 of 30 May 2008, B.3.Tris
- Deviations:
- yes
- Remarks:
- See "Any other information" for details
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1200 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- See "Any other information" for details
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- No further details specified in the study report.
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Crl:WI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Species and strain: Crl:WI Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany.
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Number of animals: 5 animals/sex
Sex: Male and female, female rats were nulliparous and non-pregnant
Age of animals at dosing: Young adult rats
Body weight at treatment: Between 221 g and 255 g
Acclimatisation period: 5 days
Husbandry
Animal health: Only healthy animals were used for the test. The health status was certified by the staff Veterinarian.
Number of animal room: 242/6
Housing: Individual caging
Cage type: Type II. polypropylene/polycarbonate
Bedding and nesting: “Lignocel 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nest building material produced by J. Rettenmaier & Söhne GmbH + Co.KG (D-73494 Rosenberg, Germany) was available to animals during the study.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 21.1 – 28.2 °C
Relative humidity: 32 – 74 %
Ventilation: 15-20 air exchanges/hour
Enrichment: Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
The temperature and relative humidity were recorded twice daily during the acclimatisation period and throughout the study.
Food and Water Supply
Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany (batch number: 262 21592, expiry date: 31 January 2018), ad libitum, and tap water from the municipal supply, as for human consumption from a 500 mL bottle, ad libitum. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A. u. 36., Hungary).
Animal Identification
Animals were individually identified using numbers written on the tail with an indelible marker pen. The numbers were given on the basis of CiToxLAB Hungary Ltd.' s Master File, for each animal allocated to the treatment groups. The cages were identified by cards, with information about study code, sex, dose group, cage number and individual animal numbers. - Type of coverage:
- semiocclusive
- Vehicle:
- water
- Details on dermal exposure:
- Formulation
The test item was administered as a single dose. Sufficient water was used to dampen the test material to ensure good contact with the skin.
Procedure
The back of each animal was shaved (approximately 10% area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose to the shaved skin and remained in contact with the skin for the 24-hour exposure period. The test material was dampened with sufficient water before application to ensure good contact with the skin. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.
At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature. - Duration of exposure:
- 24 hours.
- Doses:
- A single dermal application was made.
- No. of animals per sex per dose:
- 10 (5 males/5 females)
- Control animals:
- no
- Details on study design:
- Clinical Observations
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Skin Irritation:
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.
Body Weight Measurement
The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.
NECROPSY
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Release, 300 mg/mL pentobarbital sodium; Lot number: 106075, Expiry date: 31 July 2018, Produced by: Wirtschaftsgenossenschaft deutscher Tierärzte eG, Germany). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded. - Statistics:
- Not specified.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol did not cause mortality at the dose level of 2000 mg/kg bw.
- Clinical signs:
- There were no systemic clinical signs noted in any animal throughout the study.
- Body weight:
- Body weight gains of 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol treated animals during the study showed no indication of a test item-related effect.
- Gross pathology:
- There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.
- Other findings:
- No local dermal signs were observed after treatment with the test item during the 14 days observation period.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol was found to be above 2000 mg/kg bw in male and female Crl:WI rats.
According to the GHS criteria, 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol can be ranked as "Category 5 or Unclassified" for acute dermal exposure. - Executive summary:
An acute dermal toxicity study was performed with test item 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol in Crl:WI rats, in compliance with OECD Guideline No. 402.
A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period.
Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).
RESULTS
Mortality
6,6’-di-tert-butyl-2,2’-thiodi-p-cresol did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical Observations
There were no systemic clinical signs noted in any animal throughout the study.
Local dermal signs
No local dermal signs were observed after treatment with the test item during the 14 days observation period.
Body weight and body weight gain
Body weight gains of 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol treated animals during the study showed no indication of a test item-related effect.
Macroscopic Findings
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.
CONCLUSIONS
Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol was found to be above 2000 mg/kg bw in male and female Crl:WI rats.
According to the GHS criteria, 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol can be ranked as "Category 5 or Unclassified" for acute dermal exposure.
Reference
CLINICAL OBSERVATIONS
DOSE LEVEL: 2000 mg/kg bw |
|
SEX: MALE |
|||||||||||||||||
Cage No. |
Animal No. |
Observations |
Observation days |
Frequency |
|||||||||||||||
0 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|||||
1h |
5h |
||||||||||||||||||
1 |
357 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
2 |
358 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
3 |
359 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
4 |
360 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
5 |
361 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
|
|||||||||||||||||||
DOSE LEVEL: 2000 mg/kg bw |
|
SEX: FEMALE |
|||||||||||||||||
Cage No. |
Animal No. |
Observations |
Observations days |
Frequency |
|||||||||||||||
0 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|||||
1h |
5h |
||||||||||||||||||
6 |
362 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
7 |
363 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
8 |
364 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
9 |
365 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
10 |
366 |
Symptom Free |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
+ |
16/16 |
Remarks: + = present
h = hour (s) Treatment day = Day 0
Frequency of observation = number of occurrence of observations / total number of observations
BODY WEIGHT DATA
DOSE LEVEL: 2000 mg/kg bw |
|
|
|
SEX: MALE |
|||
Cage No. |
Animal No. |
Body weight (g) |
Body Weight Gain (g) |
||||
Days |
|||||||
0 |
7 |
14 |
0-7 |
7-14 |
0-14 |
||
1 |
357 |
233 |
297 |
349 |
64 |
52 |
116 |
2 |
358 |
243 |
285 |
319 |
42 |
34 |
76 |
3 |
359 |
247 |
309 |
366 |
62 |
57 |
119 |
4 |
360 |
229 |
288 |
358 |
59 |
70 |
129 |
5 |
361 |
222 |
289 |
247 |
67 |
58 |
125 |
Mean: |
234.8 |
293.6 |
347.8 |
58.8 |
54.25 |
113.0 |
|
Standard deviation: |
10.2 |
9.7 |
17.8 |
9.8 |
13.1 |
21.3 |
|
|
|||||||
DOSE LEVEL: 2000 mg/kg bw |
|
|
|
SEX: FEMALE |
|||
Cage No. |
Animal No. |
Body weight (g) |
Body Weight Gain (g) |
||||
Days |
|||||||
0 |
7 |
14 |
0-7 |
7-14 |
0-14 |
||
6 |
362 |
225 |
264 |
279 |
39 |
15 |
54 |
7 |
363 |
242 |
261 |
276 |
19 |
15 |
34 |
8 |
364 |
255 |
317 |
338 |
62 |
21 |
83 |
9 |
365 |
221 |
240 |
251 |
19 |
11 |
30 |
10 |
366 |
232 |
252 |
257 |
20 |
5 |
25 |
Mean: |
235.0 |
266.8 |
280.2 |
31.8 |
143.4 |
45.2 |
|
Standard deviation: |
13.7 |
29.6 |
34.5 |
18.9 |
5.9 |
23.8 |
NECROPSY FINDINGS
DOSE LEVEL: 2000 mg/kg bw |
|
|
SEX: MALE |
||
Cage No. |
Animal No. |
Necropsy Date/ Necropsy Day |
External Observations |
Internal Observations |
Organ/ Tissue |
1 |
357 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
2 |
358 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
3 |
359 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
4 |
360 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
5 |
361 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
|
|||||
DOSE LEVEL: 2000 mg/kg bw |
|
|
SEX: FEMALE |
||
Cage No. |
Animal No. |
Necropsy Date/ Necropsy Day |
External Observations |
Internal Observations |
Organ/ Tissue |
6 |
362 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
7 |
363 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
8 |
364 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
9 |
365 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
10 |
366 |
22 August 2017 Day 14 |
No external observations |
No internal observations |
Not applicable |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- K1 - GLP accredited laboratory study to OECD Guideline 402 and EU Method B.3 tris
Additional information
Acute Toxicity: Oral
Two groups of three female Crl:WI rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 1 and Group 2).
A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in 1% methyl cellulose at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw.
Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required.
Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and 14 (before necropsy). All animals were subjected to a necropsy and a macroscopic examination.
RESULTS
Mortality
6,6’-di-tert-butyl-2,2’-thiodi-p-cresol did not cause mortality at a dose level of 2000 mg/kg bw.
Clinical Observations
There were no systemic clinical signs noted in any animal throughout the study.
Body Weight and Body Weight Gain
There were no treatment related body weight changes. Body weight gains of 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol treated animals during the study showed no indication of a test item-related effect.
Macroscopic Findings
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.
Acute Toxicity: Dermal
An acute dermal toxicity study was performed with test item 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol in Crl:WI rats, in compliance with OECD Guideline No. 402.
A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period.
Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).
RESULTS
Mortality
6,6’-di-tert-butyl-2,2’-thiodi-p-cresol did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical Observations
There were no systemic clinical signs noted in any animal throughout the study.
Local dermal signs
No local dermal signs were observed after treatment with the test item during the 14 days observation period.
Body weight and body weight gain
Body weight gains of 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol treated animals during the study showed no indication of a test item-related effect.
Macroscopic Findings
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.
Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol was found to be above 2000 mg/kg bw in male and female Crl:WI rats.
Justification for classification or non-classification
Acute Toxicty: Oral
According the GHS criteria, 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol can be ranked as "Category 5 or Unclassified" for acute oral exposure.
Acute Toxicity: Dermal
According to the GHS criteria, 6,6’-di-tert-butyl-2,2’-thiodi-p-cresol can be ranked as "Category 5 or Unclassified" for acute dermal exposure.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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