bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide

Endpoint summary

Description of key information

Acute toxicity: oral:gavage, Sprague-Dawley rat m/f, 5/sex/dose, limit test: LD50 > 2000 mg/kg, LD0≥2000 mg/kg, no mortalities, no relevant clinical symptoms (piloerection, soft faeces) observed (OECD 401, GLP)

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:

1995-11-02 - 1995-11-16 (Experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

OECD Guideline for Testing of Chemicals No. 401 "Acute Oral Toxicity". Adopted: 24 February 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Hsd/Ola:Sprague-Dawley(CD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester, Oxon, England
- Age at study initiation: approximately four to seven weeks
- Weight at study initiation: 100 to 118 g
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 2 hours after dosing.
- Housing: The rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A standard laboratory rodent diet (SDS LAD 1) was provided ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: All the rats were acclimatised to the experimental environment for a period of seven days prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animal room temperature was set to achieve a temperature of 22 + 3°C.
- Humidity (%): Relative humidity was not controlled but was anticipated to be in the range 30 - 70% RH.
Permanent daily recordings of these parameters were made and these are archived with other Department raw data. Any slight deviation in temperature and humidity that may have occurred was not considered to have affected the integrity or validity of the study
- Air changes (per hr): Air exchange was maintained at 10 to 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a lime switch to provide 12 hours of artificial light (0700 ― 1900 hours) in each 24-hour period.

The rat was chosen as it has been shown to be a suitable model for this type of study and is the animal recommended in the test guideline.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
none used

MAXIMUM DOSE VOLUME APPLIED: 1.9 ml

DOSAGE PREPARATION (if unusual): The test item was administered, as supplied, at a volume of 1.9 ml/kg bodyweight (specific gravity 1.0484).

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 / sex / dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: Cages of rats were checked at least twice daily for any mortalities.
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of approximately three hours). 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). This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturdays and Sundays. The nature and severity of the clinical signs and time were recorded at each observation.
Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
Macroscopic pathology: All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral dose of the test item to a group of ten rats (five males and five females) at a dosage of 2.0 g/kg bodyweight.

Clinical signs:

other: Piloerection was observed in all rats within ten minutes of dosing. This sign persisted and was accompanied in all animals on Day 2 only by soft to liquid faeces. There were no other clinical signs and recovery, as judged by external appearance and behavi

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Interpretation of results:

GHS criteria not met

Remarks:

EU implementation

Conclusions:

The study was conducted under GLP according to OECD TG 401 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies. Hence, the results can be considered as sufficiently reliable to assess the acute oral toxicity in rats. The determined LD50 value is >2000 mg/kg bw, the LD0 ≥ 2000 mg/kg, as none of the animals died after gavage of 2000 mg/kg bw. The result is suitable to determine the classification of the test item. According to Regulation (EC) No. 1272/2008, the substance does not need to be classified as acute toxic cat. IV or higher.

Executive summary:

A study was performed to assess the acute oral toxicity of the test item to rats. The method followed was that described in OECD Guideline for Testing of Chemicals No. 401 "Acute Oral Toxicity", Adopted: 24 February 1987.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, as supplied, at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to treatment were confined to piloerection and soft to liquid faeces, seen in ail rats. Recovery was complete in all instances by Day 3.

All rats achieved satisfactory bodyweight gains throughout the study.

No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal oral dose to rats of Bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide was found to be greater than 2.0 g/kg bodyweight, the substance does not need to be classified as acute toxic cat. IV or higher according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available study was performed according to OECD 401 under GLP. The method is to be considered scientifically reasonable with negligible deficiencies and methodological variations due to the intrinsic properties of the test item, which are foreseen in the guideline. Hence, the results can be considered as sufficiently reliable to assess the acute oral toxicity in rats. The determined LD50 value is >2000 mg/kg bw, the LD0 ≥ 2000 mg/kg in rats, so an underestimation of the actual hazard is highly unlikely. Hence, the database is of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the available study no indication is given that the substance would need to be classified as acute toxic or poses any relevant risk for humans, as the animal model is considered sufficient to assess the inherent hazard of the substance via the oral route. Testing for toxicity via inhalation was considered not necessary as it would reveal no additional information and is also scientifically not relevant due to the intrinsic properties of the test item, e.g. low vapour pressure. Further, testing via the dermal route can be omitted as the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation). The tonnage-driven data requirements are hence fully met, no data gaps were identified, and the substance does not need to be classified as acute toxic.

Justification for classification or non-classification

The available study via the oral route revealed LD50 and even LD0 (≥) values above 2000 mg/kg in rats, which is the limit value for classification as acutely toxic Cat. 4 via the oral route. Also, the given physico-chemical and toxicological data give no indication that testing for acute inhalation toxicity would result in LC50 values below 5 mg/L or testing for acute dermal toxicity would result in LD50 values below 2000 mg/kg. Hence, classification criteria are not met and the registered substance does not need to be classified as acute toxic according to Regulation 1272/2008 and amendments.