(E)-2-methylpent-2-en-1-oic acid

Endpoint summary

Description of key information

For Fragarone the following results were derived:

Species	Guideline / Method	Result	Remarks
Daphnia magna	Read across from Methacrylic acid	48-h EC50: >130 mg/L, not corrected for MW and log Kow because it is a > value and not critical	Key study, Rel. 2. Value derived from read-across to Methacrylic acid (CAS# 79 -41 -4), tested in a study equivalent to OECDTG 202
Green algae (P. subcapitata)	Read across from Methacrylic acid	72-h ErC50: 29 mg/L 72 -h NOErC: 5.3 mg/L	Key study, Rel. 2.   The effect values have been corrected for difference in log Kow and molecular weight. Values derived from read-across to Methacrylic acid (CAS# 79 -41 -4), which was tested in an OECDTG 201.

* not corrected for differences in log Kow and molecular weight between the source and target chemical as the data is qualitative (i.e. 'higher than').

Aquatic toxicity ofFragarone (CAS# 16957-70-3) based on read across from data available for Methacrylic acid (CAS# 79-41-4).

 

Introduction and hypothesis for the analogue approach

Fragarone is a 2-pentenoic acid which is methylated at the 2 position.No experimental aquatic toxicity data are available for Fragarone. For the assessment of the aquatic toxicity of Fragarone, read-across is performed to the close structural analogue Methacrylic acid. In accordance with Article 13 of REACH, lacking information may be generated by other means, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the aquatic toxicity of Fragarone the analogue approach is selected because for a closely related analogue, Methacrylic acid, reliableaquatic toxicitydata are available which can be used for read across.

Hypothesis: Fragarone has similar aquatic toxicity potential as the read-across sourceMethacrylic acid

Available information:For the source chemicalMethacrylic acid the 48-h EC50 for daphnids is >130 mg/L. The 72-h ErC50 and 72-h NOErC values are 45 mg/L and 8.2 mg/L, respectively.

In more detail:

Theshort-term toxicity to daphnidswas examined in a study according to EAP OTS 797-1300 (equivalent to OECD TG 202), and in compliance with GLP criteria (MPA, 1990). Groups of 40 Daphnia magna (4 replicates of 10 animals) were exposed to nominal test substance concentrations 0 (control), 7.2, 14, 30, 60 and 120 mg/L for 48 hours under flow-through conditions. Test substance was analysed and mean measured concentrations were determined as 6.7, 13, 32, 62 and 130 mg/L. Daphnia mobility was recorded. The 48-h EC50 was determined at >130 mg/L based on mean measured concentrations.

The algae toxicitywas investigated in a study according to OECD TG 201 and in compliance with GLP criteria (MTX, 1999). Cultures of freshwater algae (P. subcapitata) were exposed to nominal test substance concentrations of 0 (control), 0.86, 1.9, 4.1, 9.1, 20, 45 and 100 mg/L in closed vessels for 72 hours under static conditions. Test substance analysis was performed and geometric mean measured values determined as 0.85, 2.0, 3.7, 8.2, 19, 45 and 100 mg/L (88 -105% of nominal). Cell counts were made at 24, 48 and 72 hours after start of exposure and algal growth rate determined. The 72 -h ErC50 and 72 -h NOErC values were determined as 45 mg/L and 8.2 mg/L, respectively, based on geometric mean measured concentrations.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix, including physico-chemical properties and available ecotoxicological information.

Purity / Impurities

Both Fragarone and Methacrylic acid are mono-constituent substances with purities close to 100%. Neither Fragarone nor Methacrylic acid contain any impurities that are considered to impact the assessment of aquatic toxicity from read across.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation. The latter is presented in the current document.

Analogue selection: For Fragarone the analogueMethacrylic acid was found for assessing the aquatic toxicity because these two shares a common structural backbone, identical functional group (carboxylic acid) and for Methacrylic acid aquatic toxicity information is available.

Structural similarities and differences: Fragarone andMethacrylic acid have the same methyl-alkene backbone and have the same carboxylic acid as a functional group. The difference is that Fragarone has a two C longer hydrocarbon backbone (2-pentene vs. 2-propene).

 

Bioavailability:Fragarone and Methacrylic acid are similarbioavailable based on the similarity in chemical structures and physico-chemical properties: Both substances have water solubilities of >>1000 mg/L, log Kow values of <<3 and pKas around 4.5.

Reactivity: Fragarone and Methacrylic acid are both conjugated acids and are therefore categorised in the OECD Toolbox (4.2) as unspecific reactive by Verhaar and OASIS.

Conversion of the effect values from Methacrylic acid to Fragarone: As the aquatic toxicity potential of substances generally increases with increasing log Kow, Fragarone may be expected to be the more toxic substance of the two. Considering that the difference in log Kow is >0.5, the log Kow values of Fragarone and Methacrylic acid will be used for conversion of the toxicity values after an adjustment for molecular weight (as has been done during a Caracal meeting for nonanoic acid, Caracal, 2013).

Effect value Fragarone in mg/L = (45 mg/l / 86 MW, effect value of Methacrylic acid in mmol/L x (0.93, log Kow Methacrylic acid/ 1.9 Log Kow Fragarone) x 114 MW of Fragarone).

The Daphnia result will not be converted because this is a > value.

Uncertainty of the prediction:There are no uncertainties other than those already discussed above.

Conclusions for hazard assessment and risk assessment

For Fragarone no experimental aquatic toxicity information is available. Methacrylic acid information is used for read across. The algae ErC50 and NOEC of Methacrylic acid are 45 an 8.2 mg/l, respectively. For Daphnia the result is > 130 mg/l. Only the algae data will need to be corrected for difference in molecular weight and log Kow for the risk assessment, resulting in 29 and 5.3 mg/L, respectively.

Final conclusion on hazard: Fragarone has an EC50 Daphnia > 130 mg/l and an ErC50 and NOEC algae of 29 and 5.3 mg/l.

 

Data matrix presenting the information relevant for read across of Fragarone from Methacrylic acid

Common name	Fragarone	Methacrylic acid
	Target	Source
Chemical name	(E)-2-methylpent-2-en-1-oic acid	2-methylprop-2-enoic acid
Chemical structures
CAS #	16957-70-3	79-41-4
EC #	241-026-4	201-204-4
Empirical formula	C6H10O2	C4H6O2
SMILES	O=C(C(=CCC)C)O	CC(=C)C(O)=O
Physico-chemical data
Molecular weight	114	86
Physical state	Liquid	Liquid
Vp (Pa)	1.63	97
Ws (mg/L)	7858	98000
Log Kow	1.9	0.93
pKa	4.34 (SPARC calculation)	4.66 (SIDS)#
Fate and behaviour
Biodegradation	Read across	Readily biodegradable (OECD TG 301D)
Aquatic toxicity
Daphnia 48-h EC50:	>130 mg/L, not corrected because it is a > value	Used for read-across: >130 mg/L
Algae 72-h ErC50:   72-h NOErC:	Read-across from Methacrylic acid: 29 mg/L (= 0.52 mmol/L * 0.93/1.9 (log Kow) * 114 (MW)) 5.3 mg/L (= 0.095 mmol/L * 0.93/1.9 (log Kow) * 114 (MW))	45 mg/L (= 0.52 mmol/L)   8.2 mg/L (= 0.095 mmol/L)

# SIDS document on Methacrylic acid:http://www.inchem.org/documents/sids/sids/79414.pdf

Additional information

The executive summaries of the Daphnia and the algae studies are presented in the respective Enpoint summaries of these species. The read across rationale is presented below.

Aquatic toxicity of Fragarone (CAS# 16957-70-3) based on read across from data available for Methacrylic acid (CAS# 79-41-4).

 

Introduction and hypothesis for the analogue approach

Fragarone is a 2-pentenoic acid which is methylated at the 2 position.No experimental aquatic toxicity data are available for Fragarone. For the assessment of the aquatic toxicity of Fragarone, read-across is performed to the close structural analogue Methacrylic acid. In accordance with Article 13 of REACH, lacking information may be generated by other means, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the aquatic toxicity of Fragarone the analogue approach is selected because for a closely related analogue, Methacrylic acid, reliableaquatic toxicitydata are available which can be used for read across.

Hypothesis: Fragarone has similar aquatic toxicity potential as the read-across sourceMethacrylic acid

Available information:For the source chemicalMethacrylic acid the 48-h EC50 for daphnids is >130 mg/L. The 72-h ErC50 and 72-h NOErC values are 45 mg/L and 8.2 mg/L, respectively.

In more detail:

Theshort-term toxicity to daphnidswas examined in a study according to EAP OTS 797-1300 (equivalent to OECD TG 202), and in compliance with GLP criteria (MPA, 1990). Groups of 40 Daphnia magna (4 replicates of 10 animals) were exposed to nominal test substance concentrations 0 (control), 7.2, 14, 30, 60 and 120 mg/L for 48 hours under flow-through conditions. Test substance was analysed and mean measured concentrations were determined as 6.7, 13, 32, 62 and 130 mg/L. Daphnia mobility was recorded. The 48-h EC50 was determined at >130 mg/L based on mean measured concentrations.

The algae toxicitywas investigated in a study according to OECD TG 201 and in compliance with GLP criteria (MTX, 1999). Cultures of freshwater algae (P. subcapitata) were exposed to nominal test substance concentrations of 0 (control), 0.86, 1.9, 4.1, 9.1, 20, 45 and 100 mg/L in closed vessels for 72 hours under static conditions. Test substance analysis was performed and geometric mean measured values determined as 0.85, 2.0, 3.7, 8.2, 19, 45 and 100 mg/L (88 -105% of nominal). Cell counts were made at 24, 48 and 72 hours after start of exposure and algal growth rate determined. The 72 -h ErC50 and 72 -h NOErC values were determined as 45 mg/L and 8.2 mg/L, respectively, based on geometric mean measured concentrations.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix, including physico-chemical properties and available ecotoxicological information.

Purity / Impurities

Both Fragarone and Methacrylic acid are mono-constituent substances with purities close to 100%. Neither Fragarone nor Methacrylic acid contain any impurities that are considered to impact the assessment of aquatic toxicity from read across.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation. The latter is presented in the current document.

Analogue selection: For Fragarone the analogueMethacrylic acid was found for assessing the aquatic toxicity because these two shares a common structural backbone, identical functional group (carboxylic acid) and for Methacrylic acid aquatic toxicity information is available.

Structural similarities and differences: Fragarone andMethacrylic acid have the same methyl-alkene backbone and have the same carboxylic acid as a functional group. The difference is that Fragarone has a two C longer hydrocarbon backbone (2-pentene vs. 2-propene).

Bioavailability:Fragarone and Methacrylic acid are similarbioavailable based on the similarity in chemical structures and physico-chemical properties: Both substances have water solubilities of >>1000 mg/L, log Kow values of <<3 and pKas around 4.5.

Reactivity: Fragarone and Methacrylic acid are both conjugated acids and are therefore categorised in the OECD Toolbox (4.2) as unspecific reactive by Verhaar and OASIS.

Conversion of the effect values from Methacrylic acid to Fragarone: As the aquatic toxicity potential of substances generally increases with increasing log Kow, Fragarone may be expected to be the more toxic substance of the two. Considering that the difference in log Kow is >0.5, the log Kow values of Fragarone and Methacrylic acid will be used for conversion of the toxicity values after an adjustment for molecular weight (as has been done during a Caracal meeting for nonanoic acid, Caracal, 2013).

Effect value Fragarone in mg/L = (45 mg/l / 86 MW, effect value of Methacrylic acid in mmol/L x (0.93, log Kow Methacrylic acid/ 1.9 Log Kow Fragarone) x 114 MW of Fragarone). The Daphnia result will not be converted because this is a > value.

Uncertainty of the prediction:There are no uncertainties other than those already discussed above.

Conclusions for hazard assessment and risk assessment

For Fragarone no experimental aquatic toxicity information is available. Methacrylic acid information is used for read across. The algae ErC50 and NOEC of Methacrylic acid are 45 an 8.2 mg/l, respectively. For Daphnia the result is > 130 mg/l. Only the algae data will need to be corrected for difference in molecular weight and log Kow for the risk assessment, resulting in 29 and 5.3 mg/L, respectively.

Final conclusion on hazard: Fragarone has an EC50 Daphnia > 130 mg/l and an ErC50 and NOEC algae of 29 and 5.3 mg/l.

 

Data matrix presenting the information relevant for read across of Fragarone from Methacrylic acid

Common name	Fragarone	Methacrylic acid
	Target	Source
Chemical name	(E)-2-methylpent-2-en-1-oic acid	2-methylprop-2-enoic acid
Chemical structures
CAS #	16957-70-3	79-41-4
EC #	241-026-4	201-204-4
Empirical formula	C6H10O2	C4H6O2
SMILES	O=C(C(=CCC)C)O	CC(=C)C(O)=O
Physico-chemical data
Molecular weight	114	86
Physical state	Liquid	Liquid
Vp (Pa)	1.63	97
Ws (mg/L)	7858	98000
Log Kow	1.9	0.93
pKa	4.34 (SPARC calculation)	4.66 (SIDS)#
Fate and behaviour
Biodegradation	Read across	Readily biodegradable (OECD TG 301D)
Aquatic toxicity
Daphnia 48-h EC50:	>130 mg/L, not corrected because it is a > value	Used for read-across: >130 mg/L
Algae 72-h ErC50:   72-h NOErC:	Read-across from Methacrylic acid: 29 mg/L (= 0.52 mmol/L * 0.93/1.9 (log Kow) * 114 (MW)) 5.3 mg/L (= 0.095 mmol/L * 0.93/1.9 (log Kow) * 114 (MW))	45 mg/L (= 0.52 mmol/L)   8.2 mg/L (= 0.095 mmol/L)

# SIDS document on Methacrylic acid:http://www.inchem.org/documents/sids/sids/79414.pdf