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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING

According to REACH Annex VIII column 2, 8.5.2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.
As the substance is a liquid at 20°C and 1013 hPa, the melting point is <-20°C, the boiling point is 215°C under atmospheric conditions, and hence, it is furthermore liquid at all relevant handling temperatures, no potentially inhalable particles need to be regarded.
The vapour pressure of the substance was determined to be 3.5x10-5 Pa and 7.1x10-5 Pa at 20°C (293K) and 25°C (298K) (isothermal TGA effusion method, OECD 104). According to the BG Bau [BG Bau 2017; Berufsgenossenschaft der Bauwirtschaft, http://www.bgbau.de/gisbau/lehrgang/a-z/dampfdru.htm, download of 2017-09-08], a vapour pressure of p < 0.01 hPa (i.e. 1 Pa) is very low, p = 1-10 hPa low and p > 10 hPa is high. The 31. BImSchV describes an organic substance as volatile if it has a vapour pressure of 0.01 kPa (i.e. 10 Pa) or more at 293.15 K. Also, according to ECHA’s guidance, substances are not available for inhalation as a gas in a relevant manner with a vapour pressure less than 0.5 kPa (i.e. 500 Pa) (or a boiling point above 150°C) [ECHA, 2008]. With a boiling point of 215°C and a vapour pressure of 7.1 x 10E-5 Pa at 25°, the registered substance has a very low vapour pressure and does not need to be regarded a volatile. Hence, the potential inhalation of the substance as a gas is not given and does not need to be regarded. Further, sufficient precautionary measures exclude the formation of droplets of inhalable size or aerosols. In consequence, exposure of humans via inhalation is not likely.

The registrant concludes further that testing is scientifically not necessary and would not reveal any additional information which cannot be derived from other available acute toxicity data, so that testing can be omitted due to animal welfare:
According to ECHA’s guidance, moderate log P values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. The experimentally determined LogPow is >7.2 at 35°C (major component), lying above that value and so hindering diffusion.
However, any lipophilic compound may be taken up by micellular solubilisation. This mechanism may be of particular importance for highly lipophilic compounds (Log Pow >4), particularly those that are poorly soluble in water (1 mg/L or less) that would otherwise be poorly absorbed. Although water solubility of the registered substance is way less than 1 mg/l, i.e. <4.5 µg/l, exposure is practically not given.
So, the design of an OECD 403 study (5 mg/l actual concentration of respirable substances) may overestimate the actual exposure, if it would be possible anyway to convert the substance into an inhalable form.
Further, there are no signs of toxicity obvious via the oral route. There is no study available fulfilling the criteria of an OECD 403 study (and required) for the acute inhalation toxicity of the test item; however, there is other information on acute toxicity in rats available:

Acute toxicity study according to OECD 401: LD50 > 2000 mg/kg, LD0 ≥ 2000 mg/kg, no mortalities, no relevant clinical symptoms (piloerection, soft faeces) observed
Due to the lack of relevant toxicity at the application of 2000 mg/kg bw test item via the oral application route, and the fact that the LD50 values could only be determined as greater than 2000 mg/kg, the LD50 > 2000 mg/kg bw will be further taken into account.

According to OECD guideline 403 (Acute inhalation toxicity), the concentration of respirable particles for limit testing is 5 mg/L over 4 h. Taking into account for rats a standard respiratory volume of 0.2 l/min and average body weight of 250 g (Guidance on information and requirements and chemical safety assessment, chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, ECHA, http://echa.europa.eu/web/guest/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment), a total respiratory volume of 48 litre over 4 h can be assumed. This would result in a total dose of 240 mg per rat, which is equivalent to 960 mg/kg bw.
Assuming in a worst-case scenario, although not relevant based on the phys.-chem. properties of the substance, that this total dose will be absorbed to 100%, and assuming furthermore that the orally applied amount is only absorbed to 50%, this dose would correspond to an oral dose of 1920 mg/kg bw. This is below the limit dose in oral and dermal tests and also below the actual LD50 via the oral application route, as only the limit dose of 2000 mg/kg was tested and led to no deaths or relevant signs of toxicity in all dosed animals.
Hence, it can be reasonably assumed that an additional acute toxicity test via the inhalation route would reveal an LC50inhalation > 5 mg/l.

So, in summary, it can be reasonably assumed that an additional testing for acute inhalation toxicity would not reveal any further relevant information and consequently, testing can be omitted due to animal welfare.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Remarks:

physical state

Reference

Endpoint:

appearance / physical state / colour

Type of information:

other: observation

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: acceptable company statement (specification data on manufactured product requires strict adherence to conform within range and so is reliable)

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Visual description of the colour (in daylight by an observer with normal colour vision) and the physical state (at 20°C and 1013 hPa)
- Determination of the odour at room temperature and comparison to other substances of characteristic odours

GLP compliance:

no

Physical state at 20°C and 1013 hPa:

liquid

Key result

Form:

liquid

Colour:

orange

Odour:

characteristic of sulfur-containing compounds

Substance type:

organic

Conclusions:

The determination of the test items appearance / physical state / colour was determined scientifically reasonably by visual inspection at 20°C. There is no indication given that the results are not reliable.
- physical state at 20°C and 1013 hPa: liquid
- colour: orange
- odour: characteristic

Executive summary:

The visual description of the colour, the physical state (at 20°C and 1013 hPa) and the determination of the odour resulted in the following: test substance is a orange liquid with a characteristic odour.

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Remarks:

melting point

Reference

Endpoint:

melting point/freezing point

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

non-GLP

Qualifier:

according to guideline

Guideline:

other: DIN 51007

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

other: ASTM D 3418-99

Deviations:

not specified

GLP compliance:

no

Type of method:

differential scanning calorimetry

Key result

Melting / freezing pt.:

< -20 °C

Decomposition:

no

Sublimation:

no

Remarks on result:

other: no information on atm. pressure available

Conclusions:

The study was performed according to DIN 51007 & ASTM D 3418-99 on the substance to be registered itself, the test procedure is well documented and therefore reliability of Klimisch 2 has been assigned. No melting point was observed below a lower limit of -20 °C.

Executive summary:

The melting point of the test substance was determined by DSC in a study according to DIN 51007 & ASTM D 3418-99. No melting point was observed below a lower limit of -20 °C, hence, the melting point is < -20°C.

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Remarks:

boiling point

Reference

Endpoint:

boiling point

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-05-04 - 2017-05-05 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 103 (Boiling Point/Boiling Range)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.2 (Boiling Temperature)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

differential scanning calorimetry

Remarks:

A measurement with the capillary method was performed to clarify the results of the DSC measurements.

Specific details on test material used for the study:

- Storage condition of test material: Ambient temperature (10 °C to 30 °C)

Key result

Boiling pt.:

>= 215 °C

Decomposition:

yes

Remarks on result:

other: The test item boiled under decomposition starting at 215 °C (atmospheric conditions). The decomposition started before boiling occurred.

Conclusions:

The boiling temperature was determined according to a scientifically valid method, i.e. EU method A.2 under GLP, in a well-documented study, hence, the following result for the test material can be considered as reliable: The test item boiled under decomposition starting at 215 °C (atmospheric conditions). The decomposition started before boiling occurred.

Executive summary:

The purpose of this study was the determination of the boiling point of bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide according to European Commission Regulation (EC) No. 440/2008, A.2. Boiling point / boiling range and OECD test guideline, OECD 103 Boiling point / boiling range.

Under consideration of the results from the thermal stability (ambiguous onset) and the capillary method it was concluded that the test item boiled under decomposition starting at 215 °C. The decomposition started before boiling occurred.

Cross-reference 4

Reason / purpose for cross-reference:

data waiving: supporting information

Remarks:

vapour pressure

Reference

Endpoint:

vapour pressure

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-06-22 - 2017-08-04 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.4 (Vapour Pressure)

Version / remarks:

EC Guideline A.4. Vapour Pressure. August 24, 2009

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 104 (Vapour Pressure Curve)

Version / remarks:

OECD Guideline104. Vapour Pressure. March 23, 2006

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7950 (Vapor Pressure)

Version / remarks:

EPA Product Properties Test Guideline OPPTS 830.7950: Vapor pressure. August 1996.

Deviations:

no

GLP compliance:

yes

Type of method:

effusion method: isothermal thermogravimetry

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: sponsor

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In refrigerator (2-8°C)

Key result

Temp.:

20 °C

Vapour pressure:

0 Pa

Remarks on result:

other: 2.6E-7 mmHg

Key result

Temp.:

25 °C

Vapour pressure:

0 Pa

Remarks on result:

other: 5.3E-7 mmHg

Conclusions:

The study was performed according to OECD TG 104 under GLP on the substance to be registered itself, the test procedure is well documented and therefore reliability of Klimisch 1 has been assigned. The isothermal TGA effusion method was applied for the determination of the vapour pressure of the test item. The vapour pressure of the test item at 20°C (293K) and 25°C (298K) was 3.5 x 10-5 Pa and 7.1 x 10-5 Pa, respectively.

Executive summary:

The isothermal TGA effusion method was applied for the determination of the vapour pressure of the test item acc. OECD TG 104 under GLP. The vapour pressure of the test item at 20°C (293K) and 25°C (298K) was 3.5x10^-5 Pa and 7.1x10^-5 Pa, respectively.