Reaction mass of 2-(1,1-dimethylethyl)-4-{[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio}-5-methylphenyl 3-(dodecylthio)propionate and thiobis[2-(1,1-dimethylethyl)-5-methyl-4,1-phenylene] bis[3-(dodecylthio)propionate]

Endpoint summary

Description of key information

The acute median lethal oral dose (LD50) to rats of AO-26 was demonstrated to be greater than 2000 mg/kg bodyweight.

The acute lethal dermal dose (LD50) to rats of AO-26 was demonstrated to be greater than 2000 mg/kg bodyweight.

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:

21 January 2013-15 February 2013

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Species:

rat

Strain:

other: Crl:CD (SD) albino rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 208 to 224 g
- Fasting period before study:
- Housing:They were housed in groups of three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet (e.g. ad libitum): The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet), except for overnight prior to and approximately four hours after dosing. This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
- Water (e.g. ad libitum):Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: 6 Days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr): The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light):12 hours continuous light and 12 hours continuous dark per 24 hours.

IN-LIFE DATES: From: Day 1 To: Day 15

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
The test substance was formulated at a concentration of 200 mg/mL in the vehicle
MAXIMUM DOSE VOLUME APPLIED: Administered at a volume of 10 mL/kg bodyweight.

Doses:

The test substance was formulated at a concentration of 200 mg/mL in the vehicle and administered at a volume of 10 mL/kg bodyweight.

No. of animals per sex per dose:

A group of three fasted female rats received a single oral gavage dose of the test substance,formulated in corn oil at a dose level of 2000 mg/kg bodyweight.

Control animals:

not specified

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Cages of rats were checked at least twice daily for any mortalities.

Clinical signs:

other: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nat

Gross pathology:

All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose (LD50) to rats of AO-26 was demonstrated to be greater than 2000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute oral toxicity of AO-26 an Antioxidant for plastics, to the rat. A group of three fasted female rats received a single oral gavage dose of the test substance,

formulated in corn oil at a dose level of 2000 mg/kg bodyweight. As results at this dose level indicated the acute lethal oral dose of the test substance to be greater than 2000 mg/kg bodyweight, in compliance with the study guidelines, a further group of three fasted females was similarly dosed at 2000mg/kg bodyweight to complete the study.

Results

There were no deaths during the study. Clinical signs of reaction to treatment comprised loose faeces seen in three females dosed at 2000 mg/kg. These signs were first noted approximately four hours after dosing. Recovery, as judged by external appearance and behaviour, was complete by Day 2. A low bodyweight gain was noted for one female on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Conclusion

The acute median lethal oral dose (LD50) to rats of AO-26 was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK).
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately eight to nine weeks of age
- Weight at study initiation: bodyweights were in the range 246 to 374 g
- Housing:The cages were solid bottomed polycarbonate cages
with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake
bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate
intervals.
- Diet (e.g. ad libitum): The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet). This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
- Water (e.g. ad libitum):Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr): The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light): Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

IN-LIFE DATES: From: Day 1 To: Day 15

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure:Dorso-lumbar region of each rat.
- % coverage: 10% of the total body surface area.
- Type of wrap if used: The treatment area (approximately 50 mm x 50 mm) was covered with porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
At the end of the 24 hours exposure period the dressing was carefully removed and the
treated area of skin was washed with a weak solution of detergent, to remove any residual test substance. The treated area was blotted dry with absorbent paper.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):2 mL/kg bodyweight.
- Constant volume or concentration used: yes

Duration of exposure:

24 Hours

Doses:

1 dose

No. of animals per sex per dose:

A group of ten rats (five males and five females) was treated at 2000 mg/kg bodyweight.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

There were no deaths and no clinical signs were observed.

Clinical signs:

other: No dermal reactions were observed for any animal.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal dermal dose (LD50) to rats of AO-26 was demonstrated to be greater than 2000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute dermal toxicity of AO-26 an antioxidant for plastics, to the rat.

A group of ten rats (five males and five females) received a single topical application of the test substance, at a dose level of 2000 mg/kg bodyweight, for 24 hours.

Results

There were no deaths and no clinical signs were observed.

No dermal reactions were observed for any animal.

A bodyweight loss was noted for one female on Day 8 and low bodyweight gains were noted for one female on Day 8 and two females on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Conclusion

The acute lethal dermal dose (LD50) to rats of AO-26 was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

The LD50 by oral and dermal administration to rats was determined to be greater than 2000 mg/kg; on this basis no classification is required for oral and dermal toxicity according to the CLP regulation.