Phosphinylidynetrimethanol

Endpoint summary

Description of key information

- Acute oral toxicity [OECD 423, acute toxic class method; GLP]: LD50 in female rats >2000 mg/kg bw.

- Acute inhalation toxicity: Taking into account the very low vapour pressure of the registration substance, exposure via the inhalation route is unlikely; it is therefore considered justified to omit this endpoint information.

- Acute dermal toxicity: The physicochemical and toxicological properties of the registration substance suggest no potential for a significant rate of absorption through the skin; it is therefore considered justified to omit this endpoint information.

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:

Experimental phase: 2018-03-13 - 2018-04-12

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)

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at +10 to +25°C, in the tightly closed original container and stored in a cool, dry and well-ventilated place, protected from heat and sunlight.

Species:

rat

Strain:

other: Rat (Rattus norvegicus) / CD / Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories,
Research Models and Services,
Germany GmbH
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: 180 - 216 g
- Housing: Granulated textured wood, cages were changed and cleaned twice a week, Periodic analysis of the bedding material for contaminants based on EPA/USA is conducted by LUFA-ITL
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534, feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 10%
- Photoperiod (hrs dark / hrs light): dark/light periods: 12 hours each.

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

0.8% aqueous hydroxypropylmethylcellulose

Details on oral exposure:

Tris(hydroxymethyl)phosphine oxide (THPO) was suspended in 0.8% aqueous hydroxypropylmethylcellulose to the appropriate concentrations. 0.8% aqueous hydroxypropylmethylcellulose was chosen as vehicle as it is known not to produce toxic effects.
VEHICLE: - Concentration in vehicle: 300 and 2000 mg/kg b.w.
- Amount of vehicle (if gavage): 10 mL/kg b.w.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Started with 300 mg/kg b.w., according to the OECD/EC guidelines:

Doses:

300 and 2000 mg/kg b.w.
Started with 300 mg/kg b.w.

No. of animals per sex per dose:

2 dose level groups of 6 female animals each

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration
- Necropsy of survivors performed: yes, at the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded.
- Other examinations performed: changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on prematurely deceased animals were made at least once daily to minimize loss of animals during the study. The time of death would have been recorded as precisely as possible. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Preliminary study:

Due to the small number of animals used with this method, there is no need to perform a range finding test.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died prematurely

Clinical signs:

other: Under the present test conditions, single oral administrations of 300 or 2000 mg Tris(hydroxymethyl)phosphine oxide (THPO)/kg b.w. did not reveal any signs of toxicity.

Gross pathology:

No pathological changes were observed at necropsy.

Other findings:

no details given

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (14d): > 2000 mg Tris(hydroxymethyl)phosphine oxide (THPO)/kg b.w.

Executive summary:

In this GLP study the acute toxicity after a single oral administration to rats of the test item Tris(hydroxymethyl)phosphine oxide (THPO) was carried out according to OECD Guideline for the Testing of Chemicals No. 423 - Acute oral toxicity - Acute Toxic Class Method (17 December 2001) and EC No. 440/2008 method B.1 tris (Acute oral toxicity - Acute toxic class method, 30 May 2008). Under the present test conditions, the single oral administrations of 300 or 2000 mg THPO/kg b.w. did not reveal any signs of toxicity. All animals gained the expected body weight. No animal died prematurely. The LD50 value (14 days) was determined to be > 2000 mg THPO / kg b.w.  According to the EC Regulation 1272/2008 and subsequent regulations, the test material does not require classification for acute oral toxicity. Also according to the Globally Harmonized Classification System (GHS) the test item requires no labelling (as LD50 > 2000 mg/kg b.w.).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

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

Acute toxicity: via oral route

The acute oral toxicity of the test material THPO was investigated in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Under the present test conditions, the single oral administrations of 300 or 2000 mg THPO/kg b.w. did not reveal any signs of toxicity. All animals gained the expected body weight. No animal died prematurely. The LD50 value (14 days) was determined to be > 2000 mg THPO / kg b.w. 

Acute toxicity: via inhalation route

Testing via the inhalation route is not appropriate taking into account the very low vapour pressure of the registration substance THPO.

Acute toxicity: via dermal route

Testing via the dermal route is not appropriate since the physicochemical and toxicological properties of the registration substance THPO suggest no potential for a significant rate of absorption through the skin.

Justification for classification or non-classification

On the basis of the available acute toxicity data via the oral route, the registration substance THPO does not require classification for lethal effects following a single exposure according to Regulation 1272/2008/EC.