Registration Dossier

Administrative data

Description of key information

Target substance is unlikely to be toxic as a result of the read-across from a subacute oral study of a source substance. NOEL (28 days repeated dose, Wistar): ≥ 1000 mg/kg bw.

Key value for chemical safety assessment

Additional information

Annex XI of Regulation 1907/2006 and the REACH Guidance (R 6.2) permits the grouping of chemicals (chemicals categorisation).Barratt and Illing (2007, revised 2009a; 2009b, see attachmentsin section 13 of IUCLID data set) set out justification for an initial grouping of the polyols (oligomers and polymers) using a named core substance, with varying numbers of attached propoxy groups (or propoxy and ethoxy groups). The properties of the core substance and the repeating unit should be reflected in the polyols. The repeating unit is essentially non-toxic. If there are toxic properties associated with a core substance, these properties should reduce with increasing numbers of repeating units (i.e. increasing molecular weight).If both the core substance and the repeating unit are non-toxic, it can be anticipated that there will be no toxicity in the polyol.

 

A second round of grouping was based on allocation of the NLP polyols formed from different named core substances to one of two categories. The first group was those NLP polyols linked to the core substance by an ether linkage (category 1) and the second group (category 2) was those linked by a secondary/tertiary amine linkage.

Category 1 consists of:

·        Sucrose, propoxylated, >1-16.5 moles propoxylated

·        propylidyne trimethanol, propoxylated, >1-6.5 moles propoxylated

·        Glycerin, propoxylated, >1-6.5 moles propoxylated

·        Propan-1,2-diol, propoxylated, >1-4.5 moles propoxylated

·        Pentaerythritol, propoxylated, >1-8.5 mol propoxylated.

·        Nitrilotriethanol, propoxylated, 1-6.5 moles propoxylated.

The registered substance is a complex substance (UVCB) which can be regarded as a mixture of Sucrose, PO and Glycerin, PO, two members of the grouping "NLP polyols linked to the core substance by an ether linkage" (= category 1). As, in all cases, the ether linked NLP polyols are non-toxic, it is anticipated that any mixture of them or any co-initiated polyol formed using a mixture of initiators will have a similar lack of toxicity. Thus the hazard profile for the multicomponent substance can be sufficiently described by the information of the individual constituents and it is unnecessary to test this co-initiated polyol.

The physico-chemical properties of these source substances and the target substance are very similar as displayed in Table 1.

Table 1: Comparison of physico-chemical properties of source substances with target substance

 

 

Source Substances

Target Substance

 

Glycerin + PO

Sucrose + PO

Glycerin + Sucrose + PO

Appearance

liquid

liquid

liquid

Melting point

no MP

no MP

no MP

Boiling point

Decomposition >= 290°C

no BP

Decomposition >= 210°C

Relative density

1.08 (20°C)

1.122 (20°C)

1.132 (20°C)

Partition coefficient

> -1.82 < -0.73

> -3.60 < -3.25

> -0.7 < 1.1

Water solubility

completely miscible

240 g/L (25°C)

completely miscible

Surface tension

53 nM/m (20°C; at 1 mg/L)

54.54 nM/m (20°C; at 1 mg/L)

61.3 nM/m (20°C; at 1 mg/L)
(Glycerol + PO)

Flashpoint

163°C (no information on pressure available)

149.5°C (1003 hPa)

198°C (1013 hPa)

Auto flammability

305°C (1014 ha)

355°C (1000 hPa)

350°C (1008 hPa)

Flammability

no pyrophoric properties
does not emit flammable gases in contact with water

no pyrophoric properties
does not emit flammable gases in contact with water

no pyrophoric properties
does not emit flammable gases in contact with water

Explosiveness

no explosive properties

no explosive properties

no explosive properties

Oxidising properties

no oxidising properties

no oxidising properties

no oxidising properties

Viscosity

560.6 mPa (20°C)

26.63 Pa s (20°C)

21.47 mPa s (20°C)

 

Therefore, in line with Annex XI, 1.2 of Regulation (EC) No 1907/2006, read-across (many-to-one) was chosen for the registered substance (Polyether Sucrose + Glycerin+ PO) and thus no toxicological study has been performed with registered substance itself.

The model being used to justify read-across (many-to-one) is that the toxicity of the polyether polyol is derived from the core substance (initiator) and the repeating unit. While for propoxylated polyols the repeating unit is probably not classifiable, any toxicological property requiring classification is derived from the core substance. The fact, that the target chemical is formed from core substances (Sucrose and Glycerin) which are the same for two source substances (Sucrose, PO and Glycerin, PO), suggests that there are no major differences between these source substances and the target substance which may affect the toxicological properties. Due to the closeness of the compounds, polyols grouping data (= source substances data) is lead for Polyether Sucrose + Glycerin + PO (= target substance) according to Table 2 (see section 13 of IUCLID data set).

Results 'read across' from study on 2, 2', 2''-nitrilotriethanol, propoxylated, as permitted by Annex XI paragraph 1.5, based on the justification in the report by Barratt and Illing (2007, revised 2009a; 2009b. The report identifies that 2, 2', 2''-nitrilotriethanol, propoxylated is the most bioavailable of the NLP polyols linked by an ether group, and the lack of toxicity, seen for it and for the components (sucrose, glycerin and -propane-1,2-diol) of Sucrose, PO and Glycerin, PO, should be considered representative of of the lack of toxicity of the ether linked polyol. Thus, on animal welfare grounds this test should not be undertaken on Sucrose, PO and Glycerin PO. For further details concerning the grouping, consult the report of Barrat and Illing in section 13 of IUCLID data set.

The need for further testing for individual NLP polyols under the REACH Regulation can be significantly modified if arrangements for grouping into categories and ‘read across’, based on the principles in Annex XI can be used. The justifications and the proposed categories are set out in Part 1 of Barratt and Illing (2007, revised 2009a). 'Read across' based on (a) the same bond linking the core moiety and the repeating unit moiety (b) molecular weight distributions. Sucrose is listed in Annex 4 of the regulation. Experimental data on core substances, repeating units, selected polyols within the category and 'read across' based on bioavailabilities indicates that the propoxylated substances in this category are not classifiable in respect of their repeated dose toxicity.This categorisation for read across has also been used to justify read across for tests required by Annex VII and VIII. There is sufficient available information for an adequate hazard characterisation and a chemical safety assessment. In view of this ‘weight of evidence’ approach and the need to consider animal welfare, no further testing is proposed (Illing and Barratt, 2009b)

Oral exposure route - read-across with other polyol linked to the core substance by an ether linkage:

In a repeated dose oral toxicity study in rats (Wistar, OECD TG 407), 2,2',2" -Nitrilotriethanol, propoxylated was adimistered via gavage to 5 rats/sex/dose at 0, 100, 300, 1000 mg/kg bw for 4 weeks.. No death was observed in either sex. No clinical effects were observed in both sex of all dose groups.There was no effect observed upon haematological, clinical biochemistry or macroscopic examination at any dose. Based on these results the NOAEL was considered to be1000 mg/kg bw/day. If at all the slight changes in thyroids of females at 1000 mg/kg were related to the treatment, they are regarded as an indirect and adaptive effect.

Justification for classification or non-classification

Based on the results of the available repeated dose toxicity study with a member of the grouping "Polyols linked to the core substance by an ether linkage", classification of repeated dose toxicity for the oral route is not warranted for the target substance according to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP)Regulation (EC) No.1272/2008.