3-phenylpropionic acid

Endpoint summary

Description of key information

LD50 was estimated to be 2726 mg/kg bw when Spartan male and female rats were orally exposed with 3-phenylpropanoic acid.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 3-Phenylpropionic acid
- Molecular formula (if other than submission substance): C9H10O2
- Molecular weight (if other than submission substance): 150.176 g/mole
- Substance type: Organic

Species:

rat

Strain:

other: Spartan

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

No data available

Doses:

2726 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 726 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> Organic disulfides OR Low reactive OR Low reactive >> N-substituted aromatic amides by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) by Protein binding potency

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "o"

Similarity boundary:Target: OC(=O)CCc1ccccc1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.76

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.79

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2726 mg/kg bw when Spartan male and female rats were orally exposed with 3-phenylpropanoic acid.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3-phenylpropanoic acid. The LD50 was estimated to be 2726 mg/kg bw when Spartan male and female rats were orally exposed with 3-phenylpropanoic acid.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 726 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from peer-reviewed journal

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, 3-phenylpropanoic acid has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in mice and rats for 3-phenylpropanoic acid along with the study available on structurally similar read across substance benzyl propionate (CAS no 122-63-4), benzyl formate (CAS no 104-57-4) and benzyl butyrate (CAS no 103-37-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3-phenylpropanoic acid. The LD50 was estimated to be 2726 mg/kg bw when Spartan male and female rats were orally exposed with 3-phenylpropanoic acid.

In another experimental study conducted by Schafer et al (Arch. Environ. Contain. Toxicol. 14, 111-129, 1985), Deer mice were treated with 3-phenylpropanoic acid in a graduated dosage scale by gavage using water, corn oil, or 1.0% carbopol as carriers and observed for mortality for 3 days. No 50 % mortality was observed in treated mice at 1600 mg/kg bw. Therefore, Approximate LD50 was considered to be > 1600 mg/kg bw when Deer mice were treated with 3-phenylpropanoic acid orally by gavage.

It is further supported by experimental conducted bySustainability Support Services (Europe) AB(2014)on structurally similar read across substance benzyl propionate (CAS no 122-63-4),Six female Wistar rats were selected for acute oral toxicity study and perform as perOECD Guideline for Testing of Chemicals No. 423, “Acute Oral Toxicity (Acute Toxic Class Method). Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were re­corded on day 0 (prior to dosing) 7 and 14.Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chromodacryorrhea from day 2 to 6 and with moderate to mild lethargy from day 3 to 9 post dosing followed by normal observation till day 14. In addition, No external and internal gross pathological changes were observed in all the six female rat treated with 2000 mg/kg body weight during terminal sacrifice. Under the conditions of test; The acute oral LD50(cut-off value) of Benzyl propionate was 5000 mg/kg body weight.

Also it is further supported by experimental study given by McGinty et al (Food and Chemical Toxicology 50 (2012) S486–S490) on structurally similar read across substance benzyl propionate (CAS no 122-63-4), rats were treated with benzyl propionate in the concentration of 205, 256, 3200, 4000 and 5000 mg/kg orally by gavage and observed for 14 days for mortality and clinical sign. The incidence of mortality was 0/10, 4/10, 5/10, 9/10 and 9/10 from low to high dose. All deaths occurred by day two. Piloerection, lethargy, tremors and chromodacryorrhea were observed in 2560 mg/kg and above. Therefore, LD50 was considered to be 3300 mg/kg bw (3030-3570) when rats were treated with benzyl propionate orally by gavage.

This is again supported by experimental study given by McGinty et al (Food and Chemical Toxicology 50 (2012) S402–S406) on structurally similar read across substance benzyl formate (CAS no 104-57-4), Sherman–Wister male and female rats were treated with benzyl formate in the concentration of 5000 mg/kg bw orally by gavage and observed for 14 days. Mortality was seen in all animals on day one of treatment at 5000 mg/kg bw. Ataxia, diuresis and prostration were observed in treated male and female rats at 5000 mg/kg bw. Therefore, LD5 was considered to be < 5000 mg/kg bw when Sherman–Wister male and female rats were treated with benzyl formate orally by gavage.

Finally it supported by experimental study given by Jenner et al (Food and Cosmetics Toxicology Vol. 2, pp. 327-343. 1964.) on structurally similar read across substance benzyl butyrate (CAS no 103-37-7), Groups of 10 young adult Osborne-Mendel male and female rat were treated with benzyl butyrate orally by gavage. Deaths were observed from 4 hrs -4 days in treated rat. Depression, scrawny appearance, tremors were observed in higher doses. Therefore, LD50 was considered to be 2330 mg /kg bw (1940-2800) when Osborne-Mendel male and female rat were treated with benzyl butyrate orally by gavage.

Thus, based on the above Prediction and studies on 3-phenylpropanoic acid and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3-phenylpropanoic acid can be “Not classified” for acute oral toxicity.

Justification for classification or non-classification

Based on the above Prediction and studies on 3-phenylpropanoic acid and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3-phenylpropanoic acid can be “Not classified” for acute oral toxicity.