Reaction products of 7-hydroxy-3,7-dimethyloctanal and methyl 2-aminobenzoate

Endpoint summary

Description of key information

The registered substance is a UVCB substance. It is a mixture of reaction products, with some remaining starting materials, Methyl Anthranilate and Hydroxycitronellal. The reaction products are unstable in solution, being on purpose, precursors for Methyl anthranilate and Hydroxycitronellal. For such a mixture, the acute effect loading level (typically expressed as the EL50 or LL50) from aquatic tests using water-accommodated fractions (WAFs) may be used directly for classification. Studies performed on Aurantiol Pure gave an acute fish 96h LL50 of 75mg/L, a daphnia 48h EL50 of 67 mg/L and a green algae 72h ErL50 of > 100 mg/L. Since all EL50 values are > 1mg/L, the substance is not classified for short-term hazards to the aquatic environment according to the CLP Regulation 1272/2008/EC.

 

Chronic aquatic toxicity data is only available for one trophic level (algae). Therefore, the long-term hazard (chronic) has been assessed based on:

 

a)   The chronic aquatic toxicity data for algae for the registered substance as such (ErL10 = 59 mg/L) which results in no classification

b)   The acute aquatic toxicity data for the registered substance as such (daphnia EL50 = 67mg/L, fish LL50 = 75mg) and environmental fate data for the constituents of Aurantiol Pure (log Kow of 1.3, 1.8 and 4.8). These represent respectively the two starting materials, hydroxycitronellal and methyl anthranilate, and the condensation product(s). Since the latter are present in the neat product at > 25%, the registered substance as such might be considered as classified Aquatic Chronic 3 (H412). However, the condensation products will be rapidly hydrolysed to the two starting materials in the aquatic environment. Therefore, approach (c) is considered more relevant.

c) The classification, aquatic toxicity and environmental fate data of the transformation products, Hydroxycitronellal and Methyl Anthranilate. Neither substance has an environmental classification according to company REACH registrations and CLP notifications nor are they listed with a harmonised classification in Annex VI to the CLP regulation. This is supported by the ready biodegradability, log Kow and acute aquatic data presented in this dossier.

 

Thus it is concluded that the registered substance poses no long-term (chronic) aquatic hazard and is not classified under any chronic categories.

 

To assess the environmental exposure and environmental risk of the registered UVCB, the substance is considered to be composed of the two breakdown products: Hydroxycitronellal and Methyl Anthranilate. In order to derive appropriate PNECS for the risk assessment, aquatic toxicity information for these two substances has been gathered and, applying a conservative approach, the worst-case EC50 or LC50 value chosen for each assessment entity.

 

Both substances have been registered under REACH. The EC/LC 50 values as reported on the ECHA dissemination website are provided in the table below. The OECD Toolbox was searched for any additional experimental data. Furthermore, the acute aquatic toxicity has been estimated using ECOSAR v2. The measured log Kow values of 1.3 (Hydroxycitronellal) and 1.8 (Methyl Anthranilate) were used as input.

Endpoint	Hydroxycitronellal REACH Data	Hydroxycitronellal OECD Toolbox v3.4.0.17	Hydroxycitronellal ECOSAR v2	Methyl Anthranilate REACH Data	Methyl Anthranilate OECD Toolbox v3.4.0.17	Methyl Anthranilate ECOSAR v2
Fish, 96h LC50 mg/L	31.6^a	31.6^a 34.4^i	22.7^e	32.35^b* 22.91^b~ 16.23^b# 9.12^b^§	32.3^b* 22.9^b~ 16.2^b# 9.12^b^§	26.5^f 83.6^g
Daphnia, 48h EC50 mg/L	410^a	410^a	22.1^e	21.9^c	18.2^h	56.2^f 25.7^g
Green Algae, EC50 mg/L	123^a (72h, growth rate)	123^a	12.0^e (96h)	11.67 ^d (96h)	-	24.7^f 55.3^g (96h)

a)    Experimental, based on nominal concentrations, static design, proprietary owned studies

b)    Experimental, measured / nominal concentrations not specified, static design, publication, Clark L et al; Pesticide Science 39 (4): 313-7 (1993); * Atlantic salmon, ~ rainbow trout, # channel fish,§ blue gill

c)    WoE based on 2 QSAR values

d)    ECOSAR, Ester QSAR; version of Ecosar and the log Kow used is not specified

e)    Aldehyde (Mono) class

f)     Ester class

g)    Anilines (Hindered) class

h)    Experimental, static design, US EPA 1992, Pesticide Ecotoxicity Database

i)     Russom, C.L., Bradbury, S.P., Broderius, S.J., Drummond, R.A., Hammermeister, D.E, 1997, Emvironmental Toxicology and Chemistry, Vol 16, No 5, pp 948-967. Note: Data reported in the OECD Toolbox, Fathead Minnow 96h LC50 of 34.4 mg/L for CAS 107-75-5, could not be found in the original publication.

Assessment Entity: Hydroxycitronellal

Experimental data is available for all three trophic levels. The Fish 96h LC50 value of 34.4mg/L reported in the OECD Toolbox could not be found in the original publication of Russom et al, 1997. All remaining experimental EC50/LC50 values are based on nominal concentrations and as such may under-estimate the aquatic toxicity of the substance if it is unstable. The ECOSAR EC/LC50 predictions are lower and more conservative. These predictions are considered reliable given that the QSAR models are valid and the target substance falls within their applicability domain (Log Kow < 5 for daphnia and fish QSAR, Log Kow < 6.4 for algae QSAR and MW < 1000 for all three models). The individual aldehyde (mono) QSAR equations are available in the ECOSAR v2 HELP menu. The statistics to assess robustness and predictivity are as follows: fish, n = 64, R2 = 0.4787; daphnia, n = 14, R2 = 0.7311; green algae, n = 6, R2 = 0.8115.

The lowest estimated value of 12 mg/L (green algae 96h EC50) has been chosen for derivation of PNEC aquatic for the assessment entity “Hydroxycitronellal”. A robust study summary for this QSAR prediction has been included in this dossier.

 

Assessment Entity: Methyl Anthranilate

Experimental data is available for fish and daphnia. The reported fish 96h LC50 values range from 9.1 to 32.35 mg/L (4 species, publication Clark et al, 1993) and the determined daphnia EC50 is 18.2 mg/L (US EPA, 1999). ECOSAR assigns methyl anthranilate to both the ester and aniline (hindered) ECOSAR class. The former gives lower estimates for green algae and fish, with the latter LC50 prediction of 25.5 mg/L (ECOSAR v2) being in reasonable agreement to the reported experimental values of 9.1 to 32.35 mg/L. For the daphnia endpoint the order of prediction is reversed with the aniline (hindered) QSAR giving the more conservative lower EC50 value (25.7 mg/L versus 56.2 mg/L, ECOSAR v2). The former is in-line with the US EPA experimental value of 18.2 mg/L as reported in the OECD Toolbox and key value of 21.9 mg/L (based on two QSARS) used in the REACH dossier of Methyl anthranilate. The ECOSAR Ester Green Algae 96h EC50 prediction in the REACH dossier of 11.67 mg/L is lower than the value of 24.7 mg/L obtained here. This likely reflects the use of a different log Kow value and different version of ECOSAR, both of which are not specified on the ECHA dissemination website.

The lowest EC/LC 50 value, which is the experimental 96h LC50 of 9.1 mg/L for blue gill fish has been chosen for derivation of PNEC aquatic for the assessment entity “Methyl Anthranilate”. A robust study summary for this experimental result has been included in the dossier.

 

Toxicity to Microorganisms

Information on toxicity to STP microorganisms is required as part of the environmental risk assessment. An activated sludge respiration test (e.g. OECD 309) has not been performed on the registered UVCB substance because any results obtained would be unsuitable for derivation of PNEC STP. In order to derive appropriate PNECs, relevant information for the two assessment entities employed in the environmental exposure and risk assessment has been used.

Absence of microbial toxicity can often be inferred from biodegradation studies. If a compound degrades well in a ready biodegradability test, or does not inhibit the degradation of a positive control at a certain concentration, this concentration can be used as a NOEC value.

Hydroxycitronellal and Methyl Anthranilate were found to be readily biodegradable in tests performed at 10 mg/L and 100mg/L respectively. In the latter an inhibition control was also included. It showed that Methyl Anthranilate has no inhibitory effect on the micro-organisms at the test concentration of 100mg/L. Thus a NOEC of 10mg/L has been used to derivation PNEC STP for the assessment entity “Hydroxycitronellal” and a NOEC of 100mg/L for the assessment entity “Methyl Anthranilate”.