Acid Catalysed Reaction Products of 3,7-dimethyl-2,6-octadienal in the presence of ethanol

Endpoint summary

Description of key information

The registered substance is a UVCB substance with poorly soluble components of different solubility. 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 Citrathal Concentrate S TW gave an acute fish 96h LL50 of > 4mg/L (limit test), daphnia 48h EL50 of 10.7 mg/L and a green algae 72h ErL50 of 3.58 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 has been assessed based on both:

a)   The chronic aquatic toxicity data for algae (ErL10 = 2.68 mg/L) which results in no classification and

b)   The acute aquatic toxicity data of the substance (daphnia EL50 = 10.7 mg/L), environmental fate data for the constituents (log Kow range of 2 to 7.6, Study 16-E116) and the fact that the substance as a whole did not meet the strict criterion for readily biodegradable. It was not possible to include the acute fish data in this chronic hazard assessment because, for animal welfare reasons, only a limit test was performed. No effects were seen at the concentration of 4mg/L.

Since the majority of the substance (approx. 80%) is composed of constituents with a log Kow ≥ 4 and the substance did not meet the strict criterion for readily biodegradable, the substance is classified Aquatic Chronic 3 (H412) according to the CLP Regulation 1272/2008/EC & adaptation 286/2011/EC based on the daphnia EL50 of 10.7 mg/L. 

 

The components present in the UVCB registered substance can be divided into C7-C10 hydrocarbons (MW 94 to 136), C10-C12 monooxygenated compounds (MW 150 to 180) and higher molecular weight unknowns. The higher molecular weight unknowns are not expected to exhibit any effects to the aquatic environment based on their low water solubility (0.14 to 0.325 mg/L, Lange 2017), high log Kow values (5.5 to 7.6, Pacella, 2016) and the fact that the presence of these components in the WAFs of the acute aquatic toxicity tests was negligible. Therefore, two assessment entities have been used to assess the environmental exposure and environmental risk of the UVCB substance. One assessment entity is the group of C7-C10 hydrocarbons and the other assessment entity is the group of C10-C12 mono-oxygenated compounds. In order to derive appropriate PNECS for the risk assessment, the aquatic toxicity of the individual constituents have been considered.

 

Assessment Entity: C7-C10 Hydrocarbons

 

The identified C7-C10 hydrocarbons present in the UVBC are listed in the table below. In the absence of any experimental data owned by the lead registrant, the acute EC50 or LC50 values for three trophic levels were estimated using ECOSAR v2. All substances are assigned to the neutral organic ECOSAR class confirming that they are expected to act via the same mode of action, baseline narcosis.

 

Constituent Name	Molecular Formula	CAS	Fish 96h LC50 mg/L	Daphnia 48h LC50 mg/L	Green Algae 96h EC50 mg/L
alpha-terpinene	C10H16	99-86-5	0.380	0.278	0.592
para-cymene	C10H14	99-87-6	1.78	1.21	1.94
terpinolene	C10H16	586-62-9	0.291	0.215	0.482
para-alpha-dimethyl styrene	C10H12	1195-32-0	1.77	1.21	1.93
1-methyl-1,3-cyclohexadiene	C7H10	1489-56-1	5.34	3.41	4.17

 

The EC50 or LC50 QSAR estimates across all species and all components are within a narrow range with the lowest value being 0.215 mg/L and the highest value 5.34 mg/L. The estimates are considered reliable given that the QSAR models are valid and the components fall within their applicability domain. Experimental data available for terpinolene supports the reliability of the predictions: 96h fish LC50 = 0.805 mg/L, 48h daphnia EC50 = 0.634 mg/L, 72h algae ErC50 = 0.692 mg/L (key studies in REACH registration for CAS 586-62-9). Given that the estimated and experimental data shows that daphnia is the most sensitive species for this group of chemicals, only the daphnia LC50 predictions for the unsaturated monoterpene hydrocarbon components are included in the dossier as a robust study summary. Applying a conservative approach, the lowest estimated value of 0.215 mg/L has been chosen for derivation of PNEC aquatic for the assessment entity “C7-C10 hydrocarbons”.

 

Assessment Entity: C10-C12 Oxygenated compounds.

 

The identified C10-C12 oxygenated compounds present in the UVCB are listed in the table below. In the absence of any experimental data owned by the lead registrant, the acute EC50 or LC50 values for the three trophic levels were estimated using ECOSAR v2.0. 

 

Constituent Name	Molecular Formula	CAS / SMILES input to model	Fish 96h LC50 mg/L	Daphnia 48h LC50 mg/L	Green Algae 96h EC50 mg/L	ECOSAR class
p-menth-1-en-8-ol	C10H18O	98-55-5	8.07	5.18	6.42	Neutral organics
(Z)-3,7-dimethylocta-2,6-dienal	C10H16O	106-26-3	0.162 Unreliable QSAR invalid	5.79	5.14	Vinyl /Allyl /Propargyl Aldehydes
2-(4-methylphenyl)propan-2-ol	C10H14O	1197-01-9	16.7	13.8	7.29	Benzyl Alcohols
(E)-3,7-dimethylocta-2,6-dienal	C10H16O	141-27-5	0.162 Unreliable QSAR invalid	5.79	5.14	Vinyl /Allyl /Propargyl Aldehydes
2-(4-methylcyclohexa-2,4-dienyl)propan-2-ol	C10H16O	1686-20-0 OC(C)(C)C1C=CC(C)=CC1	12.4	7.82	8.92	Neutral Organics
1-​(1-​ethoxy-​1-​methylethyl)​-​4-​methyl-benzene	C12H18O	68279-51-6 CC(OCC)(C)C(C=C1)=CC=C1C	4.5	2.98	4.23	Neutral Organics
2-(4-methylenecyclohex-2en-1-yl)-propan-2-ol	C10H16O	65293-09-6 CC(O)(C1C=CC(CC1)=C)C	10.6	6.69	7.87	Neutral Organics

  

The EC50 or LC50 estimates for the neutral organic constituents and the benzyl alcohol range from 2.98 to 13.8 mg/L. The estimates are considered reliable given that the QSAR models are valid and the components fall within their applicability domain. Experimental data available for p-menth-1-en-8-ol suggests that the estimates are conservative: 96h fish LC50 = 70 mg/L based on nominal concentrations, 48h daphnia EC50 = 73 mg/L based on nominal concentrations and 72h algae ErC50 = 68 mg/L based on time-weighted measured concentrations (key studies in REACH registration for CAS 98-55-5). The actual measured concentrations were 63 to71% nominal in the fish study (corrected LC50 ≈ 44mg/L) and 70% in the daphnia study (corrected EC50 = 51 mg/L).

 

ECOSAR v2 assigns (Z)-3,7-dimethylocta-2,6-dienal and (E)-3,7-dimethylocta-2,6-dienal to the “vinyl/allyl/propargyl aldehyde” SAR class and predicts a low fish LC50 of 0.162mg/L compared to the daphnia and algae EC50 values of 5.79 and 5.14 mg/L. The fish prediction, however, is considered unreliable. On subsequently checking the QSAR equations in ECOSAR (both v2 and v1.11), it appears that the predicted fish LC50 of 0.162mg/L originates from the ECOSAR v1.11 vinyl/allyl aldehyde equation and not either of the Vinyl/Allyl/Propargyl Aldehydes equations listed in ECOSAR v2 (see table below, log Kow = 3.4453 as estimated by ECOSAR, MW = 152.24). This indicates an error in the ECOSAR v2 programme. Furthermore, the equation automatically used by ECOSAR is considered invalid given its low coefficient of determination (R2). More relevant is the predicted value of 2.774 mg/L, which has been manually calculated from the “Vinyl/Allyl/Propargyl Aldehydes hindered” equation.

 

SAR class	Equation Log 96h LC50 (mmol) =	R2	N	Log Fish 96-h LC50 (mmol/L)	Fish 96h LC50 (mmol/L)	Fish 96-h LC50 mg/L
Vinyl/Allyl, ECOSAR v1.11	-0.0966 (log Kow) – 2.6414	0.0446	4	-2.9742	0.001062	0.162
Vinyl/Allyl/Propargyl Aldehydes-hindered ECOSAR v2	-0.532 (log Kow) + 0.0934	0.8966	4	-1.7395	0.018218	2.774
Vinyl/Allyl/Propargyl Aldehydes-unhindered ECOSAR v2	0.0315 (log Kow) – 2.415	0.0064	4	-2.3065	0.004937	0.752

 

There is available measured data for 3,7-dimethylocta-2,6-dienal (CAS 5392-40-5, Citral, mixture of Z and E isomers) from the ECOSAR training set and REACH registration dossier.

 

ECOSAR training set: 96h fish LC50 = 4.1 mg/L, 48h daphnia LC50 = 6.3 mg/L, 96h algae EC50 = 5.5 mg/L (reference: SIDS, 2004).

REACH dossier: 96h fish LC50 = 6.78 mg/L, 48h daphnia LC50 = 6.8 mg/L, 72h algae EbC50 = 16.1 mg/L. ErC50 = 103.8 mg/L.

 

The experimental fish LC50 values of 4.1 and 6.78 mg/L are in fairly close agreement to the predicted value of 2.774 mg/L from theVinyl/Allyl/Propargyl Aldehydes-hindered equation, thus supporting the reliability of this prediction and confirming that the values of 0.162 and 0.752 mg/L from the invalid SAR equations are not reliable.

 

Given that the lowest measured LC50 value for Citral is 4.1 mg/L and that this is within the predicted range of 2.98 – 13.8 mg/L for the other known C10-C12 oxygenated constituents, it was considered appropriate to use this experimental value to derive PNEC aquatic for this assessment entity. The published fish 96h LC50 value has been included in the dossier as a robust study summary.

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 substance because any effect results obtained would be unsuitable for derivation of PNEC STP. Different partitioning in the environment of the components present in the UVBC substance would make comparison with PEC meaningless. 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.

 

- For the "C7-C10 hydrocarbon" group, the representative component Terpinolene was found to be readily biodegradable in a test performed at 10 mg/L. Thus this concentration has been used to represent the NOEC for this group.

 

- For the "C10-C12 oxygenated" group, the representative substance Terpineol was found to be readily biodegradable in tests performed at 100 and 10 mg/L. In the former an inhibition control was also included. It showed that Terpineol has no inhibitory effect on the micro-organisms at the test concentration of 100mg/L. Thus this concentration has been used to represent the NOEC for this group.