3-phenylpropionic acid

Endpoint summary

Description of key information

Short-term toxicity to fish

Fish Acute Toxicity test according to OECD Guideline 203 was conducted for (test item name) 3-phenylpropionic acid The nominal concentration selected for the experiment were 100mg/Land test fish were exposed to these concentration for 96 hours. The lethal concentrations LC50 was found to be >100 mg/L

LC0 (96 hours) (highest loading at which no mortality was observed) = No mortality was observed

LC50 (96 hours) Experimental = >100 mg/L

Short term toxicity to aquatic invertebrates

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for3-phenylpropanoic acid(CAS: 501-52-0). EC50 value was estimated to be 769.06 mg/l for Daphnia magna for 48 hrs duration.

Toxicity to aquatic algae and cyanobacteria

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 3-phenylpropanoic acid (CAS no. 501 -52 -0) (2017). EC50 value was estimated to be 122.96 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 3-phenylpropanoic acid is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Toxicity to microorganisms

In batch conversions experiment the test chemical 3-phenylpropionic acid was reduced with the highest yield (69%) with Substrate concentrations 1 mM which is equivalent to 150.1 mg/l.

Additional information

Short-term toxicity to fish

Three studies including those from experimental study and validated prediction for short term fish toxicity endpoint of target chemical 3-phenylpropanoic acid (Cas no. 501-52-0) were summarized as followed: 

 

First experimental key study by UERL laboratory; 2017 suggest the Fish Acute Toxicity test according to OECD Guideline 203 was conducted for 3-phenylpropanoic acid , The nominal concentration selected for the experiment were 100mg/Land test fish were exposed to these concentration for 96 hours. The lethal concentrations LC50 was found to be >100 mg/L. No mortality was observed at 100 mg/l in 96 hrs exposure period thus LC0 was consider to be 100 mg/l.

Above aquatic classification supported by peer review journal (Spec.Sci.Rep.Fish.No.207, Fish Wildl.Serv., U.S.D.I., Washington, DC:157 p., 1957)which indicate the short term toxicity study to Petromyzon marinus was carried out for 24 hrs. Test was performed under static conditions. After exposure to test animal at dose conc.5 mg/l of test chemical 3-phenylpropanoic acid, no mortality effects were observed on fish. Thus, the NOEC value was consider to be 5 mg/l respectively.

Last study is prediction for target from EPI Suite ECOSAR version 1.10 predicted model, indicate the 96 hours LC50 was estimated to be 683.315 mg/l on Fish for substance 3-phenylpropanoic acid (CAS no. 501-52-0) on the basis of mortality effects using neutral organics class for prediction. Based on this value, it can be concluded that the test chemical 3-phenylpropanoic acid can be considered as non toxic to fish at mentioned predicted lethal concentration thus it can be considered not classified as per the CLP classification criteria.

 

Thus based on all available studies for target gives the lethal concentration is in the range of 100-683.315 mg/l and NOEC was 5 mg/l concluded that the test chemical 3-phenylpropanoic acid (Cas no. 501-52-0) considered as non-toxic to fish and thus cannot be classified as hazardous as per the CLP criteria.

Short term toxicity to aquatic invertebrates

Short term toxicity to aquatic invertebrates for3-phenylpropanoic acid(CAS: 501-52-0)was summaries with two predicted data and two experimental studies with two read across substances are as follows:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for3-phenylpropanoic acid(CAS: 501-52-0). EC50 value was estimated to be 769.06 mg/l for Daphnia magna for 48 hrs duration.

Another study for 3-phenylpropanoic acid(CAS: 501-52-0)was predicted using EPI suite, ECOSAR version 1.1, based on the effects observed in a static freshwater system during a 48 hr exposure. The lethal concentration (LC50) for the substance is estimated to be 398.36mg/L.

Study was performed in Daphnia magna in read across benzyl butyrate (103-37-7) from Abitec laboratory (Report no: 490/16), 2016 following the OECD guideline 202. The test was performed for 48 hrs at different concentrations as control, 0, 2.5, 5.0, 10.0, 20.0; 40.0 mg/l at 95 % confidence limit of 14.7 -18.7mg/l. Reference substance used was K2Cr207. 5 daphnids after breeding were used in 4 numbers of replicates of chemical. The test was performed in temperature 20°C±1°C with taking 25ml per replicate in 50ml glass vessel for 48 hrs. Calculations of EC50 was calculated using nonlinear regression by the software Prism4.0 (GraphPadSoftware,Inc.,SanDiegoCA). After experiment the EC50 value for short term toxicity to aquatic invertebrates using OECD guideline 202 was determined to be 16.6 mg/l. Based on the value the benzyl butyrate was toxic to aquatic invertebrates but as the chemical was readily biodegradable, so it can be considered that benzyl butyrate was not hazardous to aquatic invertebrates and can be considered not classified as per the CLP regulations.

Another study was performed in read across Benzoic acid (65-85-0) which was 60-70 % structurally similar by Yasushi Kamayaet.al ,Chemosphere 59 (2005) 255–261 using Daphnia magna for 48 hrs. The young daphnids were obtained from continuous cultures in 1 liter glass beakers at 21 ± 0.3 degree C, in dechlorinated and conditioned tap water, the medium was renewed in three weeks and daphnids were fed daily with the green alga Selenastrum capricornutum. The pH of test solution was adjusted to 7.45 ± 0.05 with HCL and NaOH. The concentrations of the resultant solutions were checked before and after (48 h) exposure using a UV–visible spectrophotometer. As the experiment starts neonate were placed in 50 ml of beaker with 40 ml of test solution. All experiment was made in four replicates and performed at 21 ± 0.3 degree C under 16 h light: 8 h dark photoperiod. Immobility was observed after 24 and 48 hrs and EC 50 value was calculated. After the experiment the EC 50 value of Benzoic acid (65-85-0) for Daphnia magna was determined to be 860 mg/l in 48 hrs.

Based on the above predicted data and studies of read across chemicals it can be considered that all the above studies supported the target classification, so based on the results it was considered that all weight of evidences supported the classifications and3-phenylpropanoic acid(CAS: 501-52-0)was not hazardous to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

Toxicity to aquatic algae and cyanobacteria

2 predicted data for the target chemical 3 -phenylpropanoic acid (CAS No. 501 -52 -0) and total 3 weight of evidence studies for its read across substance were reviewed to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical 3-phenylpropanoic acid (CAS No. 501-52-0) is predicted using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances (2017).EC50 value was estimated to be 122.96 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 3-phenylpropanoic acid is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In another prediction done using the EPI Suite ECOSAR version 1.10, the short term toxicity on green algae was predicted for test substance 3 -phenylpropanoic acid (CAS No. 501 -52 -0).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 330.938 mg/l for green algae for 96 h duration. Based on this value, it can be concluded that the test chemical 3 -phenylpropanoic acid can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

In a weight of evidence study of the read across chemical Benzyl butyrate(CAS no. 103-37-7), the effect of Benzyl butyrate, CAS No. 103-37-7 was studied on the growth of fresh water green algaChlorella vulgaris[UERL study report, Sustainability Support Services (Europe) AB, Report no. 103-37-7/01/2015/AT, 2015].The study was conducted following OECD guideline 201- Alga growth inhibition test. The test concentration chosen for the study were 6.25mg/L, 12.5mg/L, 25mg/L, 50 mg/L, 100mg/L and 200mg/L. The test concentrations were prepared using stock solution of the test item using mineral media. The green alga was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of the test item. EC50 calculated graphically through probit analysis was observed to be >200mg/L.Based on this value it can be concluded that the substanceBenzyl butyrateis considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

For another read across chemical Benzoic acid (CAS no. 65-85-0), short term toxicity study was carried out using cyanobacteria (blue-green algae) Anabaena inaequalis, A. cylindrica, and A.variabilis, and the green algae Chlorella pyrenoidosa and Scenedesmus quadricauda as a test organism (GLENN W. STRATTON & CHARLES T. CORKE, 1982). The study was based on the effects of the read across compound Benzoic acid (CAS no. 65-85-0) on algae in a static fresh water system. Read across chemical was obtained from Aldrich Chemical Co., Milwaukee, Wisconsin, USA. Stock solutions of test chemical were prepared in pesticide grade acetone. The proper level of acetone (0.1 %v/v) to use in each bioassay system was determined using the solvent-pesticide interaction analysis technique. Chemical was tested at a minimum of five concentrations ranging from 0 to 100 mg/l (nominal concentration). Test organisms used for the study include (blue-green algae) Anabaena inaequalis, A. cylindrica, and A.variabilis, and the green algae Chlorella pyrenoidosa and Scenedesmus quadricauda, respectively.

A. cylindrica, and A.variabilis were obtained from the American Type Culture Collection, Reockville, Maryland, USA (ATCC 27899 and 27892, respectively) while the other culture were provided by the Department of Botany and Genetics, University of Guelph, Guelph, Ontario, Canada. Cultures of Anabaena inaequalis and A. cylindrica were maintained in a liquid nitrogen-free medium at a temperature of 20°C and a light intensity of 7000 lux on a 12 h light-dark cycle whereas the other cultures such as A.variabilis, Chlorella pyrenoidosa and Scenedesmus quadricauda were maintained under the same conditions except the growth medium was supplemented with 1.5 g NaNO3/l. Photosynthesis was assayed by following the uptake of 14CO2 from NaH14CO3 (Amersham/Searle, Oakville, Ontario, Canada). Plastic tissue culture flasks with a total internal volume of 74 ml were employed as assay chambers. Each contained 9.9ml of cell suspension (containing 6-5 × 104cyanobacterial or 1.0 × 105green algal cells/ml), 0.1 ml of radioisotope (to give a final activity of 0.1µCi/ml) and 0.01 ml of read across chemical. The flasks were incubated for 3 h and photosynthetic activity was assayed. Per cent inhibition values were calculated relative to photosynthetic activity in control systems (solvent only) and EC50 values determined by probit or regression analysis, where applicable. Analyses for significant differences (p = 0.05) were performed using Dunnett's test and Duncan's multiple range test.

Based on the effect of Benzoic acid on the photosynthesis of the test organisms, the EC50 value was determined to be 5, 60, 55, 60 and 75 mg/l for Anabaena inaequalis, A. cylindrical, A.variabilis, Chlorella pyrenoidosa and Scenedesmus quadricauda respectively. Thus, based on this value, it can be concluded that the read across chemical Benzoic acid can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, Benzoic acid can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

 

Another short term toxicity to algae study from authoritative database (J-CHECK, 2016) for the read across chemical Salicylic acid (CAS no. 69-72-7) was carried out for 72 hrs. The study was based on the effects of the read across compound Salicylic acid on algae in a static fresh water system. Based on effect on growth rate of algae, the 72 hr EC50 and NOEC value was determined to be 65 and 31 mg/l and on the basis of area under the growth curves, the 72 hr EC50 and NOEC value was determined to be 41 and 17 mg/l, respectively. Thus, based on EC50 value, it can be concluded that the substance Salicylic acid can be considered as toxic to aquatic organisms and thus can be classified as aquatic chronic category 3. Since the chemical is readily biodegradable in nature, Salicylic acid can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

 

Thus, based on the overall reported results for target chemical 3-phenylpropanoic acid (OECD QSAR toolbox version 3.4 and EPI suite, 2017) and for its read across substance (from UERL study report, peer reviewed journal and authoritative database), it can be concluded that the test substance 3 -phenylpropanoic acid can be considered as non-toxic to aquatic environment and thus can be considered to be not classified as per the CLP classification criteria.

Toxicity to microorganisms

The reduction of aromatic acid i.e 3-phenylpropionic acid by the hyperthermophilic organism Pyrococcus furiosus was investigated.

P. furiosus (DSM 3638) was grown anaerobically at 90°C in a basic medium.Yeast extract, cysteine, vitamins, and trace elements were added a Potato starch (5 g/1) was used as a carbon and energy source. Cells were grown in 100 ml bottles containing 50 ml medium,which was flushed with N2/CO2 (80/20) before inoculation. During growth, the bottles were shaken continuously at 200 rev./min. The medium was inoculated with a 2% preculture.

Analytical method used as HPLC on a Nucleosil 100 C18 5U(Alltech, Laarne, Belgium) column. A Waters 600 controller and pump and a Waters 996 photodiode array detector were used (all Millipore, Milford, USA).Methanol/1% acetic acid was used as eluent and the analysis was isocratic.

1mM substrate concentration was used in experiment which is equivalent to 150.1 mg/l.

In batch conversions 3-phenylpropionic acid was reduced with the highest yield (69%) with Substrate concentrations 1 mM which is equivalent to 150.1 mg/l.