3-phenylpropyl acetate

Endpoint summary

Description of key information

3-Phenylpropyl acetate is not likely to be toxic upon repeated exposure by oral route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose 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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.4

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material: 3-Phenylpropyl acetate- Molecular formula: C11H14O2- Molecular weight: 178.23 g/mol- Smiles notation:c1(CCCOC(C)=O)ccccc1- Substance type: Organic- Physical state: No data

Species:

rat

Strain:

CF-1

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Details on route of administration:

not specified

Vehicle:

not specified

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

not specified

Frequency of treatment:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

not specified

Sacrifice and pathology:

not specified

Other examinations:

not specified

Statistics:

not specified

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

not specified

Dose descriptor:

NOAEL

Effect level:

699.5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant changes were noted at the mentioned dose level

Critical effects observed:

not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Ester, aliphatic attach [-C(=O)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 Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "i"

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: "j"

Referential boundary:The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "k"

Similarity boundary:Target: CC(=O)OCCCc1ccccc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Allyl esters (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR AN2 OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "p"

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: "q"

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: "r"

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

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.66

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.84

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for 3-phenylpropyl acetate is predicted 699.5 mg/Kg bw/day.

Executive summary:

Repeated oral toxicity was estimated for 3-phenylpropyl acetate using SSS QSAR prediction database (2016). The study assumed the use of male and female CFE strain rats in subchronic study. Since no significant alteration were noted at the mentioned dose level, hence, the No Observed Adverse Effect Level (NOAEL) for 3-phenylpropyl acetate is predicted to be 699.5 mg/Kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

699.5 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from K2 prediction database

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Prediction model based estimation and data from read across chemicals have been reviewed to determine the toxic nature of 3- Phenylpropyl acetate. The summary is as mentioned below:

Repeated oral toxicity was estimated for 3-phenylpropyl acetate using SSS QSAR prediction database (2016). The study assumed the use of male and female CFE strain rats. Since no significant alteration were noted at the mentioned dose level, hence, the No Observed Adverse Effect Level (NOAEL) for 3-phenylpropyl acetate is predicted to be 699.5 mg/Kg bw/day.

A subacute study was conducted (Sustainability Support Services, 2014) to evaluate the toxic effects of repeated administration of Benzyl Propionate (RA CAS no 122 -63 -4) in male and female Sprague-Dawley rats by gavage. Benzyl Propionate was administered to 6 animals/sex/species with vehicle as corn oil at doses of 0, 250, 500 and 1000 mg/kg/bw/day for 28 days. All rats of 250, 500 and 1000 mg/kg/bw/day dose group survive though-out the study, Benzyl Propionate have no effect on mortality. Blood samples for Clinical Biochemistry and Haematology were collected. No abnormalities occurred that could be directly attributed to benzyl propionate treatment. Although significant change in relative weights of liver, ovaries and lungs of female were observed in 1000 mg/kg/bw/day dose groups. No treatment related gross pathological or histological changes were seen and findings were not considered to be benzyl propionate dependent and hence considered to be of no toxicological importance. Therefore the No Observed Adverse Effect Level (NOAEL) for repeated dose toxicity study was considered to be 1000 mg/kg/bw/day in male and female Sprague-Dawley rats when exposed to Benzyl Propionate by oral route for 28 days.

In a subacute study (Sustainability Support Services, 2014), the toxic effects of repeated oral administration of Rose Crystals Ex-Benzaldehyde (2,2,2-trichloro-1-phenylethyl acetate) (RA CAS no 90 -17 -5) was evaluated in male and female Sprague-Dawley rats. Rose Crystals Ex-Benzaldehyde was administered at doses of 0, 250, 500 or 1000 mg/kg/body weight/day for 28 concurrent days. All rats of 250, 500 or 1000 mg/kg/body weight/day groups survived throughout the study. Thus, Rose Crystals Ex-Benzaldehyde seemed to have no effect on mortality. Blood samples for clinical biochemistry and haematology were collected, and no abnormalities that could be directly attributed to chemical treatment were observed. Although significant change in organ weights were observed in animals treated with 250 or 500 mg/kg/body weight/day, no chemical-related gross pathological or histological changes were seen. The findings were regarded not to be Rose Crystals Ex-Benzaldehyde-dependent and hence considered to be of no toxicological importance. Therefore, the No Observed Adverse Effect Level (NOEAL) for the current repeated dose toxicity study was considered to be 1000 mg/kg/body weight/day in male and female Sprague-Dawley rats when exposed to Rose Crystals Ex-Benzaldehyde by oral route for 28 days.

14 days toxicity study was performed by Abdo et al (1986) for Benzyl acetate (RA CAS no 140 -11 -4). Benzyl acetate was administered to group of 5 male and female B6C3F1 mice for 14 consecutive days by gavage route in corn oil at dose concentration of 0,125, 250, 500, 1,000, or 2,000mg/kg body weight. Animals were observed daily for mortalities and clinical signs. Necropsies were performed on all animals. Mortalities were observed in the 2000 mg/Kg dose mice within 3 days of treatment. Compound-related clinical signs were observed including ruffled fur, ataxia in males and labored breathing, hyperactivity in females at 2000 mg/Kg. No statiscally significant difference was observed in body weight in treated and control. Hence the No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg bw/day.

The above mentioned study was also performed using rats. Benzyl acetate (RA CAS no 140 -11 -4) was administered to group of 5 male and female F344/N rats for 14 consecutive days by gavage route in corn oil at dose concentration of 0, 250, 500, 1,000, 2,000 or 4,000 mg/kg body weight. Animals were observed daily for mortalities and clinical signs.Necropsies were performed on all animals.All animals of the 2000 or 4000 mg/Kg test group died and was considered to be dose related. Gross necropsy findings revealed reddening of the cecum in 4000 mg/Kg dosed animals. Hence, the No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg bw/day.

Based on the weight of evidence data summarized, 3- Phenylpropyl acetate is not likely to be toxic upon repeated exposure by oral route.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

Data is from prediction database; The No Observed Adverse Effect Level (NOAEL) for 3-phenylpropyl acetate is predicted to be 699.5 mg/Kg bw/day.

Justification for classification or non-classification

Based on the weight of evidence data summarized, 3- Phenylpropyl acetate is not likely to be toxic upon repeated exposure by oral route.