[No public or meaningful name is available]

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.
The substance is a liquid at 20°C and 1013 hPa, the melting point is <-20°C, the boiling point could not be determined because at 130.3 °C the sample starts to decompose slowly and at 225.0 °C the decomposition becomes more rapidly, and hence, it is liquid at all relevant handling temperatures, no potentially inhalable particles need to be regarded.
The vapour pressure of the substance was determined to be 1.5x10-5 Pa at 25°C (298K) (vapor pressure balance 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 vapour pressure of 1.5 x 10E-5 Pa at 25°C, the registered substance has a very low vapour pressure and does not need to be regarded as 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 2.43 for the amine part and 4.80 for the anionic part. Hence, a certain potential for absorption is given.
Nevertheless, 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 is no relevant 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, so 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, 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 ordinary limit dose of 2000 mg/kg was tested as lowest dose and led to only one death in 10 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

Study period:

2017-09-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable company statement

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:

amber

Odour:

other: not available, not determined out of health and safety reasons

Conclusions:

The determination of the test item's appearance / physical state / colour was determined scientifically reasonably by visual and sensorical inspection. There is no indication given that the results are not reliable. According to the observations made, we certify that this substance can be described as follows:
- Physical state (at 20 °C and 1013 hPa): liquid
- Colour: amber

Executive summary:

The visual description of the colour and the physical state (at 20°C and 1013 hPa) resulted in the following: test substance is an amber liquid.

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

Study period:

2017-12-11 (experimental phase)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 102 (Melting point / Melting Range)

Deviations:

not applicable

Qualifier:

according to guideline

Guideline:

other: P4411, Glasübergangs-/ Erweichungstemperatur

Deviations:

not specified

GLP compliance:

no

Type of method:

differential scanning calorimetry

Key result

Melting / freezing pt.:

< -20 °C

Atm. press.:

1.013 Bar

Decomposition:

no

Remarks on result:

other: No melting point observed above -20 °C

Conclusions:

The study was performed equivalent to OECD 102 with DSC measurement 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 observed above -20 °C, Glass transition was seen at -77.0 °C (onset).

Executive summary:

The study was performed equivalent to OECD 102 with DSC measurement. No melting point observed above -20 °C, Glass transition was seen at -77.0 °C (onset).

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:

2017-12-11 (experimental phase)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 103 (Boiling Point/Boiling Range)

Deviations:

not applicable

Qualifier:

according to guideline

Guideline:

other: A0217 TGA

Deviations:

not specified

GLP compliance:

no

Type of method:

other: Thermogravimetric analysis (TGA)

Key result

Atm. press.:

1.013 Bar

Decomposition:

yes

Decomp. temp.:

>= 130.3 °C

Remarks on result:

other: At 130.3 °C the sample starts to decompose slowly and at 225.0 °C the decomposition becomes more rapidly.

Conclusions:

The study was performed similar to OECD 103 using TGA on the substance to be registered itself, the test procedure is well documented and therefore reliability of Klimisch 2 has been assigned. At 130.3 °C the sample starts to decompose slowly and at 225.0 °C the decomposition becomes more rapidly.

Executive summary:

The study was performed similar to OECD 103 using TGA. At 130.3 °C the sample starts to decompose slowly and at 225.0 °C the decomposition becomes more rapidly.

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:

2017-12-08 - 2017-12-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 104 (Vapour Pressure Curve)

Version / remarks:

Method 104 of the OECD Guidelines for Testing of Chemicals, 23 March 2006

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.4 (Vapour Pressure)

Version / remarks:

Method A.4 Vapour Pressure of Commission Regulation (EC) No 440/2008 of 30 May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

effusion method: vapour pressure balance

Key result

Temp.:

25 °C

Vapour pressure:

0 Pa

Remarks on result:

other: mean

Conclusions:

The vapour pressure was determined in a GLP guideline study according to OECD 104 and EU method A.4 without deviations on the registered substance itself. Hence, there is no indication given that the results are not reliable.
The vapor pressure of the test item has been determined to be 1.5 x 10-5 Pa at 25°C.

Executive summary:

The vapor pressure of the test item has been determined to be 1.5 x 10-5 Pa at 25 °C, using a vapor pressure balance method designed to be compatible with Method A.4 Vapour Pressure of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 104 of the OECD Guidelines for Testing of Chemicals, 23 March 2006.