Reaction mass of Phenol, dodecyl-, sulfurized, calcium salts and benzene and butene and calcium carbonate and calcium dihydroxide and sulphur trioxide

Endpoint summary

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:

2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Modern GLP study conducted in accordance with OECD test guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HsdBrlHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 8 to 9 weeks of age
- Weight at study initiation: 174- 190 g ; The weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: overnight fasting prior to dosing
- Housing: The animals were housed in groups of up to five during the acclimatisation period in cages that conform to the 'Code of Practice for th e Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), th e rats were housed in groups of three in similar cages.

- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham was freely available to the animals at a ll times except for a period of overnight fasting prior to dosing which continued until approximately three hours after dos ing. Each batch of diet had been analysed for specific constituents and contaminants by the manufacturer.

- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles. The water had been periodically analysed for specific contaminants.

- Acclimation period: Rats were arbitrarily selected from the delivery boxes and allocated to the appropriate number of cages using a sequence that reduced selective bias. The condition of the animals was assessed daily throughout the acclimatisation period of seven to nine days. A second inspection was performed prior to study commencement to ensure the animals were suitable for the study. Ove rtly healthy animals were arbitrarily allocated to the study groups at least one day prior to dosing.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 40 to 70% RH
- Air changes (per hr): at least 15 air changes per hour
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test article was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. Individual doses (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the specific gravity for the neat material (SG = 1.216 g/mL).

Doses:

2000 mg/kg

No. of animals per sex per dose:

six animals

Control animals:

no

Details on study design:

A group of three female fasted rats was given the test article as a single dose on Day 1 at a dose level of 2000 mg/kg. Doses were administered orally, by gavage, using plastic syringes and rubber catheters. Each rat was dosed once on Day 1, by passing the tip of a catheter along the oesophagus and instilling the test article into the gastric lumen. This was followed by a further group of three fasted females at the same dose level. The test article was administered undiluted. All animals were killed on Day 15 by intraperitoneal injection of sodium pentobarbitone. After exsanguination a full macroscopic necropsy was performed and all lesions recorded. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.

Statistics:

no data

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral dose of the test article among rats dosed at 2000 mg/kg.

Clinical signs:

other: No clinical signs were seen.

Gross pathology:

Necropsy on Day 15 revealed a soft, dark irregular mass on the liver of one animal with the left and right median lobes adhering to the diaphragm. An additional lobe between the left and right median lobes of the liver was noted in another animal.

Other findings:

no other findings

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The lethal oral dose was established to exceed 2000 mg/kg, therefore the test material was considered to have no significant acute toxic risk if swallowed and did not meet the criteria for classification according to Commission Directive 2001/59/EC.

Executive summary:

The study was conducted to assess the acute toxicity of the test article following a single oral administration to small groups of rats. The study was conducted according to the OECD guidelines 423 and followed the OECD Good Laboratory Practice. A group of three female fasted rats was given the test article as a single dose on Day 1 by oral gavage at a dose level of 2000 mg/kg. This was followed by a further group of three fasted females at the same dose level. The test article was administered undiluted. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths following a single oral dose of test article among rats dosed at 2000 mg/kg. No signs of systemic toxicity were noted during the study. Necropsy on Day 15 revealed a soft, dark irregular mass on the liver of one animal with the left and right median lobes adhering to the diaphragm. An additional lobe between the left and right median lobes of the liver was noted in another animal.

The acute median lethal oral dose was found to exceed 2000 mg/kg, therefore the test material was considered to have no significant acute toxic risk if swallowed and did not meet the criteria for classification according to Commission Directive 2001/59/EC.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Modern GLP study conducted in accordance with OECD test guideline, has Klimisch score 1

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 370 mg/kg bw

Quality of whole database:

Modern GLP study conducted in accordance with OECD test guideline, has Klimisch score 1

Additional information

Acute toxicity oral

A limit test study conducted in accordance with the OECD 423 guideline reported that there were no deaths following a single oral dose of test article among rats dosed at 2000 mg/kg. No signs of systemic toxicity were noted during the study. Necropsy on Day 15 revealed a soft, dark irregular mass on the liver of one animal with the left and right median lobes adhering to the diaphragm. An additional lobe between the left and right median lobes of the liver was noted in another animal. The acute median lethal oral dose was found to exceed 2000 mg/kg.

 

Acute toxicity dermal

A limit test study conducted in accordance with the OECD 402 guideline reported that there were no unscheduled deaths during the observation period following a single dermal administration of test article onto the dorsal trunk under a gauze patch among rats dosed at 2370 mg/kg. There were no systemic signs of toxicity noted in any animal at any observation time point and local findings at the dosing site were restricted to test item residues at the test site, which was seen in all animals on Day 2 only. The acute median lethal dermal dose was found to exceed 2370 mg/kg.

Acute toxicity inhalation

In accordance with Rule 8.5 of Annex VIII of the REACH Regulation, a study of the acute inhalation toxicity is not required, since studies of acute toxicity via oral exposure and via dermal exposure have been provided. Furthermore, the potential for inhalation exposure to occur is considered negligible.

Justification for selection of acute toxicity – oral endpoint
Key study conducted to OECD guideline and GLP standards.

Justification for selection of acute toxicity – dermal endpoint
Key study conducted in accordance with OECD guideline and GLP standards.

Justification for classification or non-classification

Acute toxicity oral

Results from a study conducted in accordance with OECD 423 guideline reported no signs of systemic toxicity or did not produce test-material-related mortality. The acute median lethal oral dose was found to exceed 2000 mg/kg, therefore the test material was considered to have no significant acute toxic risk if swallowed and did not meet the criteria for classification according to CLP Regulation (EC) 1272/2008.

Acute toxicity dermal

Results from a study conducted in accordance with OECD 402 guideline reported no signs of systemic toxicity did not produce test-material-related mortality or did not produce dermal irritation. The acute median lethal dermal dose was found to exceed 2370 mg/kg, therefore the test material was considered to have no significant acute toxic risk if in contact with skin and did not meet the criteria for classification according to CLP Regulation (EC) 1272/2008.

Acute toxicity inhalation

No acute inhalation toxicity data are available. Based on the low acute toxicity via both the oral and dermal routes of exposure, no classification for acute inhalation toxicity is proposed.