2-Propenoic acid, 2-methyl-, monoester with 1,2-propanediol, reaction products with dipropylene glycol and 1,1'-methylenebis[isocyanatobenzene]

Endpoint summary

Additional information

Justification for grouping of substances and read-across

There are no data available for the aquatic toxicity of UMA 121 (EC No. 923-201-3). In order to fulfil the standard information requirements set out in Annex VII-IX, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

ID	CAS	EC No.	Chemical Name	Molecular formula	MW
Target	--	923-201-3	Propanol, oxybis-, oligomeric reaction products with 1,1'-methylenebis[isocyanatobenzene], propylene glycol monomethacrylate-blocked	C 35,8 H 41,8 N 2,6 O 9,6	> 500 g/mol
Source 1	27813-02-1	248-666-3	2-hydroxypropylmethacrylate	C7H12O3	144 g/mol

 

The above mentioned substances are considered to have similar properties and/or activities with regard to aquatic toxicity. The available endpoint information is used to predict the same endpoints for UMA 121 (EC No. 923 -201 -3)

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Aquatic toxicity

No experimental data is available on the aquatic toxicity of UMA 121. However, based on the molecular structure and intrinsic properties of the substance, the aquatic environment is of minor relevance as target compartment for UMA 121 and no significant toxicity to aquatic organisms is expected.

UMA 121 is the reaction product of the following substances:

- Methylendiphenyldiisocyanate, isomer mixture of 4,4’- and 4,2’-MDI (MDI) CAS No. 26447-40-5

- Dipropylene glycol (DPG) CAS No. 25265-71-8

- 2 -hydroxypropylmethacrylate (HPMA) CAS No. 27813-02-1

The reaction product is a solid resin containing the polymer HPMA-MDI-(DPG-MDI)n-HPMA as homologues of n = 0, 1, 2, 3, etc. (no upper limit defined) as well as free HPMA.

The water solubility of UMA 121 was determined to be 0.4 mg/L in an OECD 105 study. However, taking into account that the water solubility is 130 g/L for HPMA (ECHA website, Registered substances) and 0.0002 - 0.002 mg/L for the shortest UMA homologue (n=0) (WSKOW v1.42 and WATERNT v1.01), it can be assumed that the 0.4 mg/L solubility is mainly due to HPMA and that the dissolution of UMA homologues is negligible. Additionally, it should be noted that the test substance was pestled to a powder for the purpose of the water solubility study. The resulting solubility value thus represents an absolute worst case compared to the water solubility of the substance in its normal resin form.

Release of UMA 121 to surface waters is unlikely, as it will be removed in sewage treatment plants to a high extent. As stated in the “Guidance on information requirements and chemical safety assessment Chapter R.7b: Endpoint specific guidance”, insoluble chemicals will be removed in the primary settling tank or fat trap of sewage treatment plants (ECHA, 2012). Possible remaining amounts would be adsorbed to the activated sludge. However, as discussed above HPMA is far more soluble than the rest of the constituents and might thus dissolve into the water phase. But due to its ready biodegradability it would most likely be removed through biodegradation by activated sludge (ECHA website, Registered substances).

If UMA 121 were to be released into the aquatic environment, HPMA might dissolve into the aqueous phase. The UMA homologues (n = 0, 1, 2, 3, etc.) are poorly soluble in water and have high log Kow (> 5; KOWWIN v1.68) and log Koc values (> 5; KOCWIN v2.00). Apart from a possible release of HPMA, UMA 121 is thus expected to remain stable and inert in the aqueous environment. The toxic potential of HPMA and the UMA homologues is thus discussed separately below.

HPMA:

Due to its high solubility, HPMA may be released from UMA 121 into water. However, experimental data available on the toxicity of HPMA to aquatic organisms indicate low toxicity. No effects were observed at concentrations below 100 mg/L in acute studies with fish and Daphnia. For algae, both NOEC and ErC50 were > 97 mg/L (measured; nominal 100 mg/L). In a chronic study with Daphnia a NOEC of 42.2 mg/L was obtained.

UMA homologues (n = 0, 1, 2, 3, etc.):

Due to their low solubility in water (< 0.002 mg/L, WSKOW v1.42 and WATERNT v1.01) and high adsorption potential, UMA homologues are not expected to be released from UMA 121 under environmental conditions. Even if minor amounts were to be released into natural waters, their uptake by organisms is considered unlikely. The smallest homologue HPMA-MDI-HPMA (n=0) has a molecular weight of 538.60 g/mol. For the larger homologues (n≥1) molecular weights are above 900 g/mol. All homologues have log Kow values above 5 (KOWWIN v1.68). These constituents are therefore unlikely to cross biological membranes. According to Lipinski’s “rule of 5”, developed to identify drug candidates with poor oral absorption, a molecular weight > 500 g/mol and a log Kow > 5 indicate a low potential of absorption after oral uptake (Lipinski, 1997). Toxicity to aquatic organisms is thus unlikely due to minimal exposure via water and improbable uptake by organisms.

Furthermore, a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test (OECD 422) conducted with UMA 121 did not reveal any test substance-related effect (Takawale, 2013). As stated in the “Guidance on information requirements and chemical safety assessment Chapter R.11: PBT Assessment”, the complete absence of effects in mammalian long-term studies is an indication that the compound is either chronically non-toxic and/or that it is not taken up to a significant extent.

In conclusion, UMA 121 is not expected to be of concern to aquatic organisms, as it will remain inert in the aquatic environment, except for possible release of HPMA, the toxicity of which has been shown to be low.

References:

Lipinski CA, Lombardo F, Dominy BW, and Feeney PJ. 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv.Drug Deliv.Rev. 23: 3-25