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Long-term toxicity to fish

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Description of key information

Parent compound (CAS 107-31-3):

Data waiving according to Annex XI of Regulation (EC) No.1907/2006.

Moreover, the rapid hydrolysis will be the major fate process of the methyl formate under environmentally relevant conditions (pH 7-9). Therefore, this estimate may be of low relevance. Thus, the assessment of the long-term toxicity of the substance is based on the available experimental data for the hydrolytic products: formic acid and methanol.

Hydrolysis product methanol (CAS 67-56-1):

Key:

Based on the available 96-h LC50 of = 15400 mg/L (Lepomis macrochirus, EPA-660/3-75-009; published at Bulletin of Environmental Contamination and Toxicology 37: 615-621, 1986) a NOEC for the long-term toxicity to fish of 154 mg/L was derived (ACR approach, 2021).

Supporting:

In early-life-stage bioassay conducted with Oryzias latipes (Gonzales-Doncel et al., 2008), NOECs range between 7900 - 15800 mg/L. Although this in-vitro study was not conducted according to current standard guidelines, the results give a clear indication of the low hazard potential (acute and long-term) of methanol to aquatic organisms

Hydrolysis product formic acid (CAS 64-18-6):

Data waiving according to Annex XI of Regulation (EC) No.1907/2006 and  Annex IX, Section 9.1.6, Column 2 of Regulation (EC) No 1907/2006

Key value for chemical safety assessment

Fresh water fish

Fresh water fish
Dose descriptor:
NOEC
Remarks:
Hydrolysis product methanol (CAS 67-56-1)
Effect concentration:
154 mg/L

Additional information

Parent compound (CAS 107-31-3):

In Annex XI of Regulation (EC) No 1907/2006, it is laid down that there may be sufficient weight of evidence from several independent sources of information leading to the assumption/conclusion that a substance has or has not a particular dangerous property, while the information from each single source alone is regarded insufficient to support this notion. In the mentioned case further testing on vertebrate animals for that property shall be omitted. In this case the present substance was tested in short-term aquatic tests (algae, daphnia and fish). With regard to daphnids, fish and algae, the experimental data on short-term toxicity to aquatic organisms do not indicate toxicity up to the test item concentration of 100 mg/L. Experimental long-term toxicity data are available for algae. The 72-h EC10 was determined to be 140.7 mg/L (nominal, BASF AG, 1988). Overall, none of the test showed acute or chronic toxic effects (algae). In Annex IX, Section 9.1.6, Column 2 of Regulation (EC) No 1907/2006, it is laid down that long-term toxicity testing on fish shall be proposed by the registrant if the chemical safety assessment indicates the need to investigate further the effects on fish. According to Annex I of this regulation, the chemical safety assessment triggers further action when the substance or the preparation meets the criteria for classification as dangerous according to CLP-Regulation (EC) No 1272/2008 and its second adaptation 286/2011 or is assessed to be a PBT or vPvB. The hazard assessment of the substance reveals neither a need to classify the substance as dangerous to the environment, nor is it a PBT or vPvB substance, nor are there any further indications that the substance may be hazardous to the environment. In addition, the substance is readily biodegradable (93% CO2 evolution, after 28 days, OECD 310, BASF SE, 1997).

Moreover, according to the available hydrolysis study for the substance, Methyl formates' susceptibility to hydrolysis increases with pH as well as with temperature. The hydrolysis half-life ranges from 410 h at pH 4 and 20 °C to less than 1 hour at pH 9 and 25 °C (OECD 111, BASF SE, 2010). Therefore, it can be concluded, that under environmentally relevant conditions (pH 7-9) the rapid hydrolysis will be the major fate process of the methylformate due to the short half-life in aqueous solution. Therefore, this estimate may be of low relevance. Thus, the assessment of the long-term toxicity of the substance is based on the available experimental data for the hydrolytic products: formic acid and methanol. Therefore, and for reasons of animal welfare a long-term toxicity test with fish is not provided.

Hydrolysis product methanol (CAS 67-56-1):

Key:

The information requirements will be fulfilled using a weight-of-evidence approach based on the scheme provided in REACH Guidance Document R.7b (v4.0, ECHA, 2017: Figure R.7.8-2) and in accordance with Annex XI Section 1.2. 

Step 1: The structure as well as the physico-chemical properties of the Substance are clearly identified. The Substance is readily biodegradable; therefore, relevant metabolites do not need to be considered. 

Step 2: The substance does not produce an alert for protein binding in the schemes by OECD and OASIS (OECD QSAR Toolbox v4.4; see document under ‘Attached background material’ in IUCLID Ch. 6.1.2 - ACR approach), which is an indication of the absence of elevated toxicity. The mode of action of the Substance is basesurface narcotic based on the acute aquatic toxicity MOA by OSAIS. According to the toxicity classification by ECOSAR the substance is neutral organic. It was not possible to classify the Substance according to Verhaar. Therefore, it can be concluded that the Substance has a mode of action similar to narcotic substances and critical long-term effects are not to be expected.

Step 3 and 4: No relevant for the assessment experimental data are available on the long-term toxicity to fish for the Substance itself. 

Step 4a/b: Reliable QSAR predictions or in-vitro results for long-term toxicity to fish are not available. 

Step 5: Acute and long-term toxicity for the aquatic environment, as well as supporting information have been taken from studies with the Substance itself. Information on the long-term toxicity to fish are not available. Fish are not the most sensitive aquatic trophic level (96-h LC50 =15400 mg/L). The Substance is neither acutely nor chronically hazardous to the aquatic environment according to the CLP-Regulation (EC) No 1272/2008. The long-term toxicity to fish is derived using the Acute-to-Chronic (ACR) approach. The detailed description as well as the result of the ACR approach will be provided in the update of the IUCLID as part of IUCLID Chapter 6.1.2. The ACR approach is an important method to predict acceptable no-effect values (NOEC) from acute toxicity data (LC50, EC50). The method is valuable for the risk assessment of chemical substances, which has been successfully assessed for several chemicals, including organic substances (including alkylamines) with a narcotic mode of action (modified acute aquatic toxicity classification of Verhaar) to which the Substance belongs (May et al., 2016; Kienzler et al., 2016; ECETOC, 2003). Based on these three publications, a conservative ACR of 100 was selected which covers at least 90% of all organic chemicals; therefore, the derived NOEC can be regarded as reliable and sufficiently protective. Based on the available 96-h LC50 of = 15400 mg/L (Lepomis macrochirus, EPA-660/3-75-009; published at Bulletin of Environmental Contamination and Toxicology 37: 615-621, 1986) a NOEC for the long-term toxicity to fish of 154 mg/L was derived. The available short-term as well as the long-term toxicity data do not lead to a classification of the Substance as chronically hazardous to the aquatic environment following the CLP-Regulation (EC) No 1272/2008. With regard to the PBT assessment, further testing is also not required as the Substance is readily biodegradable and the substance is therefore neither persistent (P) nor very persistent (vP). The Substance is also neither bioaccumulative (B) nor very bioaccumulative (vB) based on the available low experimentally determined Log Kow of -0.77 (measured Smith & Hansch, 2000). The available short-term toxicity data for the three trophic levels (fish, aquatic invertebrates and algae) do not indicate a concern for a high sensitivity of aquatic organisms. In addition, the Substance holds no relevant classification. Therefore, further testing does not seem justified and long-term toxicity testing on fish should therefore not be carried out to avoid unnecessary testing on vertebrate animals. Avoiding unnecessary testing of vertebrate animals is also in line with the REACH regulation, which states in §25 that testing on vertebrate animal shall be undertaken as a last resort. This is further supported by the EU Directive on the protection of animals used for scientific purposes (EU, 2010) and the EURL ECVAM strategy to replace, reduce and refine the use of fish in aquatic toxicity and bioaccumulation testing (EURL ECVAM, 2014). 

Step 6: The intrinsic properties of the Substance indicate that significant and relevant long-term effects on fish will not occur. The Substance has no specific mode of action and does not produce structural alerts for relevant effects. The derived NOEC of 1554 mg/L indicates that long-term effects on fish are not to be expected. In addition, the Substance is readily biodegradable and will therefore be easily removed from the aquatic environment; thus, reducing the exposure of the aquatic environment. Therefore, and in accordance with REACH Regulation 1907/2006, Annex XI, Section 1.2, further testing on vertebrate animals will be omitted for reasons of animal welfare. The Registrant will not perform a long-term toxicity test on fish.

Supporting: Additionally, in an early-life-stage bioassay conducted with Oryzias latipes (Gonzales-Doncel et al., 2008), NOECs range between 7900 - 15800 mg/L. Although this in-vitro study was not conducted according to current standard guidelines, the results give a clear indication of the low hazard potential (acute and long-term) of methanol to aquatic organisms.

Hydrolysis product formic acid (CAS 64-18-6):

In Annex XI of Regulation (EC) No 1907/2006, it is laid down that there may be sufficient weight of evidence from several independent sources of information leading to the assumption/conclusion that a substance has or has not a particular dangerous property, while the information from each single source alone is regarded insufficient to support this notion. In the mentioned case further testing on vertebrate animals for that property shall be omitted. In this case the present substance was tested in short-term aquatic tests (algae, daphnia and fish) along with the chronic study on aquatic invertebrates (daphnia). With regard to daphnids, fish and algae, the experimental data on short-term toxicity to aquatic organisms do not indicate toxicity up to the test item concentration of 100 mg/L. Experimental long-term toxicity data are available for algae and daphnia. For algae the 72-h EC10 was determined to be 295 mg/L (nominal, analytically verified, Frauenhofer, 2005), for daphnia the 21-d NOEC was determined to be >= 100 mg/L (nominal, BASF AG, 2007). Overall, none of the test showed acute or chronic toxic effects (algae, daphnia).

In Annex IX, Section 9.1.6, Column 2 of Regulation (EC) No 1907/2006, it is laid down that long-term toxicity testing on fish shall be proposed by the registrant if the chemical safety assessment indicates the need to investigate further the effects on fish. According to Annex I of this regulation, the chemical safety assessment triggers further action when the substance or the preparation meets the criteria for classification as dangerous according to CLP-Regulation (EC) No 1272/2008 and its second adaptation 286/2011 or is assessed to be a PBT or vPvB. The hazard assessment of the substance reveals neither a need to classify the substance as dangerous to the environment, nor is it a PBT or vPvB substance, nor are there any further indications that the substance may be hazardous to the environment. In addition, indirect exposure to sediment is unlikely since the substance is readily biodegradable (93% CO2 evolution, after 28 days, OECD 310, BASF SE, 1997). 

Therefore, and for reasons of animal welfare a long-term toxicity test with fish is not provided.