Registration Dossier

Administrative data

Hazard for aquatic organisms

Freshwater

Hazard assessment conclusion:
PNEC aqua (freshwater)
PNEC value:
4 µg/L
Assessment factor:
50
Extrapolation method:
assessment factor
PNEC freshwater (intermittent releases):
11 µg/L

Marine water

Hazard assessment conclusion:
PNEC aqua (marine water)
PNEC value:
0.4 µg/L
Assessment factor:
500
Extrapolation method:
assessment factor
PNEC marine water (intermittent releases):
1.1 µg/L

STP

Hazard assessment conclusion:
PNEC STP
PNEC value:
10 mg/L
Assessment factor:
10
Extrapolation method:
assessment factor

Sediment (freshwater)

Hazard assessment conclusion:
PNEC sediment (freshwater)
PNEC value:
8.41 mg/kg sediment dw
Extrapolation method:
equilibrium partitioning method

Sediment (marine water)

Hazard assessment conclusion:
PNEC sediment (marine water)
PNEC value:
0.84 mg/kg sediment dw
Extrapolation method:
equilibrium partitioning method

Hazard for air

Air

Hazard assessment conclusion:
no hazard identified

Hazard for terrestrial organisms

Soil

Hazard assessment conclusion:
PNEC soil
PNEC value:
1.236 mg/kg soil dw
Assessment factor:
50
Extrapolation method:
assessment factor

Hazard for predators

Secondary poisoning

Hazard assessment conclusion:
PNEC oral
PNEC value:
222.2 mg/kg food
Assessment factor:
90

Additional information

The registered substance is a reaction mass of three constituents. Two diastereomers with a cyclohexyl group (here called C6 diastereomers) and one structural isomer with a cycloheptyl group (here called C7 isomer). The C6 constituents represent ca. 78% of the substance, and the C7 constituent ca. 10%.

Environmental fate and pathways:

The registered substance was found to undergo hydrolysis at pH 9 only, with a half-life (at 25°C) of 224 hours (similar to OECD Guideline 111).

The registered substance is not readily biodegradable. However, the key biodegradation study(similar to OECD Guideline 301 C) performed on the C6 isomers of the registered substance, demonstrates that this substance disappears in a ready test and therefore is not considered persistent (P). Indeed, total primary biodegradation of the C6 isomers of the registered substance is demonstrated, to form a transformation product (C6 isomers) at 79% and Propionic acid at ca. 20%, but mineralised. The primary biodegradation is also observed for the C7 isomer of the registered substance, based on QSAR prediction (Catalogic 301C v.08.12).

To conclude on the persistence of the transformation product, ascreening non-GLP readily biodegradation study (OECD 301F) was performed on the transformation product (C6 and C7 isomers) and only 0% to 4% biodegradation was observed after 28 and 60 days. Therefore, the transformation product can be considered as potentially persistent (P) or very persistent (vP), in the absence of simulation testing.

The bioconcentration factor (BCF) of the registered substance was estimated with a QSAR model (BCFBAF model v3.01 from EPI Suite v4.1, using experimental log Kow value at 4.68) at 382 L/kg wet-wt and 435 L/kg wet-wt, for C6 and C7 isomers, respectively. Therefore, the registered substance (parent compound) should not be considered Bioaccumulable for aquatic organisms. For the transformation product, an experimental study was performed in water at two sub-lethal concentrations of the C6 isomers of the transformation product for a period of 28 days.In both concentrations extremely low BCFs were determined with a mean of 15 at the highest water concentration and <35 [LOD] at the lowest water concentration of approximately 0.007 mg/L. In addition, the BCF values of the C6 and C7 isomers of the transformation product were determined with the same QSAR model as above, at 374 L/kg wet-wt and 490 L/kg wet-wt, for C6 and C7 isomers, respectively. These data conclusively demonstrated that the breakdown product of the registered substance will not bioaccumulate to any significant degree in aquatic organisms. The second breakdown product, propionic acid is not considered to be of regulatory concern (mineralisation).

A summary of the environmental fate of the registered substance is provided in the attached document.

Finally, the adsorption coefficient (log Koc) of the registered substance was determined to be 4.3 (OECD Guideline 121 and EU Method C.19). This result indicates that the substance is immobile in soils (according to McCall et al., 1980).

Aquatic toxicity:

Aquatic datasets are presented for both the registered substance and the relevant transformation product.

For the registered substance, aquatic toxicity data are based on measured results and were used to derive the PNECs, while for the relevant transformation product, aquatic toxicity is based on QSAR predictions, and were used to conclude on the PBT Assessment.

Acute data based on international guidelines, are available to assess the short-term toxicity of the registered substance on three trophic levels: Algae, Invertebrates and Fish. Among all the species tested, an acute toxic effect was found for aquatic invertebrates and fish, with a similar sensitivity, with E(L)C50 values at 3.3 and 3.6 mg/L, respectively. No toxicity (acute and chronic) was observed on the algae up to the highest attainable concentration, measured at 1.1 mg/L in this test. In addition, one chronic study is available to assess the long-term toxicity of the registered substance on aquatic invertebrates Daphnia magna. The 21d-NOEC was determined at 0.20 mg/L.

To demonstrate that the transformation product (C6 and C7 isomers) of the registered substance is not Toxic (T) in the context of PBT assessment, the acute and chronic toxicity values on three aquatic trophic levels: Algae, Invertebrates and Fish, were estimated using two QSAR models: ECOSAR v1.11 and iSafeRat QSAR. Both QSAR results were considered reliable as the substances (C6 and C7 isomers) fall within the applicability domain of the models. The estimated lowest L(E)C50 values were 1.73 mg/L for algae, 0.93 mg/L for daphnids and 1.31 mg/L for fish. The estimated lowest chronic values were 0.73 mg/L for algae and 0.17 mg/L for daphnids and fish. In addition, one experimental study performed to assess the acute fish toxicity of the major transformation product (C6 isomers) of the registered substance to Danio rerio is available. Even if this endpoint is considered not assignable due to lacking information, the experimental 96h-LC50 at 10.7 mg/L (nominal) supports the QSAR results purporting that the transformation product (C6 and C7 isomers) of the registered substance is not Toxic in the context of PBT assessment.

To assess the toxicity to microorganisms, one study was performed on the registered substance showing no reduction in biochemical oxidation of microorganisms up to 100 mg/L, the highest concentration tested. In addition, the toxicity of the transformation product (C6 and C7 isomers) of the registered substance, to microorganisms was evaluated. No toxicity of the transformation product (mixture of C6 and C7 isomers; tested at 104.5 mg/L) was observed in the available screening non-GLP biodegradation study (OECD 301F; Firmenich, 2013). The 30 -180min EC50 value of the transformation product (C6 and C7 isomers) to activated sludge was predicted (by iSafeRat® High Accuracy QSAR v1.1) as greater than the water solubility value within the exposure period of the test. Therefore, no toxicity is predicted to sludge dwelling microorganisms.

Terrestrial toxicity:

Two terrestrial long term toxicity studies, covering two trophic levels, soil microorganisms and earthworms, were conducted on the registered substance under the request of the European authorities.

The long-term toxicity study of the registered substance on nitrogen transformation activity of soil microorganisms was performed according to the OECD Guideline 216 and EU Test Method C.21 with GLP statement (Fraunhofer, 2018). The inhibitory effect of the registered substance on nitrogen transformation was assessed by the determination of nitrate concentration in the soil samples and compared to data obtained from control soil samples. The registered substance was incubated, in a single application, in loamy sand soil over a period of 28 days in nominal concentrations of 62.5, 125, 250, 500 and 1000 mg/kg dry mass soil. Based on the results of this study, there was a concentration-effect relationship due to the test substance for the relative content of nitrate compared to the control after 28 days of incubation. The EC10 value for nitrogen transformation was determined at 161 (95% CL = 122 - 190) mg/kg dry soil, based on nominal concentrations.

The long-term toxicity study of the registered substance on survival rate, biomass, and reproduction of adult earthworms of the species Eisenia andrei was performed according to the OECD Guideline 222 with GLP statement (Fraunhofer, 2019). The worms were placed in a defined artificial soil substrate containing the registered substance, in a single application, in different nominal concentrations: 15.6, 31.3, 62.5, 125 and 250 mg/kg dry mass soil. The effects on survival rate and biomass were determined after 28 days, and the effects on reproduction were determined after 56 days.As the registered substance degrades into a transformation product at a rate of 78-80% (and Propionic acid at ca. 20%, but this latter finally mineralizing) in a ready biodegradation test (OECD 301C, Yokohama Lab, 2009), it was decided to include supplementary analytical measurements of the relevant transformation product (non-GLP), along with the measurements of the parent substance (GLP) in the soil samples at the same sampling points.According to the analytical results, the registered substance, as expected, degraded very rapidly. This rapid loss of parent substance is completely in line with the expected degradation profile of an ester. Esters are rapidly metabolised to an alcohol and an acid, but the acid moiety is extremely small and not expected to contribute to the observed toxicity (here, a complete mineralization of the Propionic acid moiety was observed). The concentrations of the relevant transformation product (the residual alcohol) increased at a rate inversely proportional to the loss of the parent substance and then itself diminished until both substances were no longer analytically measurable. The peak of concentrations of the transformation product was measured at day 3 -7. The reproductive toxicity of the registered substance to earthworms was based on initial concentrations of the test substance (measured at 17.5, 26.4, 58.5, 85.3 and 234.9 mg test item/kg dry mass soil) as this was the parent substance under review, and as the parent substance represented an acute dose at the beginning of the experiment which could account for the effects found. Use of a time weighted average for either the parent and transformation product was considered inappropriate as a means to measure chronic toxicity due to the prolonged absence of the parent and transformation product over a large portion of the study period and as the relevant transformation product, which is the residual alcohol of the registered substance, is a non-polar narcotic (MechoA 1.1) and is expected to be less toxic than the ester (the registered substance).

No decreased survival rate when compared to the control worms and no significant effect on weight change were found up to and including the highest tested concentration. However, due to maximum effects of 9 -13% reduction of weight change in the two highest treatment levels, a slight concentration-effect relationship was observed and an EC10 value was determined at 170.1 mg/kg soil (initial concentration). Regarding reproduction effects, a significant decrease in reproduction was found starting at an initial concentration of 58.5 mg test item/kg dry mass soil. The EC10 value was determined at 61.8 (CL 95%: 42.5 – 78.3) mg/kg dry mass soil (initial concentration).

In conclusion, chronic effects on terrestrial organisms were observed for the registered substance. The lowest EC10 value, determined at 61.8 mg/kg dry mass soil for reproduction of Eisenia andrei, was chosen as key value for the chemical safety assessment.

Based on a conservative estimation from Chesar, further testing on terrestrial effects does not need to be conducted as the chemical safety assessment does not indicate a need for further investigation.

Conclusion on classification

Based on data available, the registered substance is not readily biodegradable, has a log Kow value greater than 4.0 but estimated BCF values lower than 500. The acute E(L)C50 values on aquatic organisms are comprised between 1 and 10 mg/L and the lowest chronic NOEC value (on Daphnia magna) is comprised between 0.1 and 1 mg/L. Based on these conclusions and according to Regulation (EC) No 1272/2008 (CLP) criteria, the Aquatic Chronic 2 classification is relevant for this substance.