Registration Dossier

Administrative data

Description of key information

Acute oral toxicity:  no deaths seen in rats exposed at 2000 mg/kg
Acute inhaled toxicity: no data available.
Acute dermal toxicity: no deaths seen in rats exposed at 2000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01November 2013 to 29 November 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study carried out to guideline requiremnets and in compliance with GLP
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF 12 Nousan No 8147, 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
certificate of Compliance with GLP issued by UK GLP Monitoring Authority included in report
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Sprague Dawley Crl:CD (SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 226 - 240g
- Fasting period before study: overnight
- Housing: Group housing 3 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 -23 deg C
- Humidity (%): 40 - 70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 07 November To: 29 November
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10mL/kg bodyweight
- Justification for choice of vehicle: none stated
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
2000 mg/animal
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequent observations on day of dosing and twice per day thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,other: macroscopic pathology of vranial, thoracic and abdominal cavities
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no deaths during study
Clinical signs:
Loose faeces in two females dosed at 2000 mg/kg. first noted 30 min after dosing and then not observed from end of Day 2 onwards
Body weight:
Bodyweight loss noted in one rat, all other rats achieved satisfactory bodyweight gain
Gross pathology:
NO abnormalities noted
Other findings:
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute median lethal dose (LD50) to rats of 3-Phenylpropyl benzoate was >2000 mg/kg bodyweight
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
One well conducted study performed under GLP in accordance with a recognised guideline.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 November 2013 to 11 December 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD guidelines and in compliance with GLP
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF 12 Nousan No 8147 (2000)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
certificate of compliance from UK GLP Monitoring Authority included in report
Test type:
standard acute method
Species:
rat
Strain:
other: Crl:CD (SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: Males = 342 - 380g; Females = 234 - 255g
- Fasting period before study: none
- Housing: group housed in groups of 5 rats of same sex
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 deg C
- Humidity (%): 40-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12h dark: 12 h light

IN-LIFE DATES: From: 21 November 2013 To: 11 December 2013
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 mm x 50 mm
- % coverage:
- Type of wrap if used: porous gauze covered with non-irritating dressing and then a waterproof dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water with dilute detergent
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.86 mL/kg
- Concentration (if solution):
- Constant volume or concentration used: yes
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24 hours
Doses:
1.86 ml/kg body weight, specific gravity 1.077 g/ml
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: daily for any signs of reaction and mortalities, after dosing and frequently in Day 1, subsequently twice per day. Bodyweights on Days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: body weights, macroscopic pathology of cranial, thoracic and abdominal cavities
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deathes
Clinical signs:
Very slight erythema was seen in all females from Day 3, resolving in all instances by Day 6. In addition, bandage reactions (off the treatment site) were seen in all females and two males from Day 2, generally resolving by Day 9, but persisting in one animal (No. E9) until termination on Day 15
Body weight:
All animals were considered to have achieved satisfactory body weight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The acute median lethal dermal dose (LD50) to rats of 3-Phenylpropyl benzoate was demonstrated to be greater than 2000 mg/kg body weight.
Executive summary:

The acute median lethal dermal dose (LD50) to rats of 3-Phenylpropyl benzoate was demonstrated to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
One well conducted study performed under GLP in accordance with a recognised guideline.

Additional information

Acute oral toxicity

An acute toxicity test was performed to determine the acute toxicity by oral exposure to 3-PPB. The study was conducted in accordance with a relevant test guideline and in compliance with GLP.

A group of three fasted female rats received a single oral gavage dose of the test substance, formulated in corn oil, at a dose level of 2000 mg/kg body weight. As results at this dose level indicated the acute lethal oral dose of the test substance to be greater than 2000 mg/kg body weight, in compliance with the study guidelines, a further group of three fasted females was similarly dosed at 2000 mg/kg body weight to complete the study. There were no deaths during the study. The clinical signs observed during this study were loose faeces in two females dosed at 2000 mg/kg. This sign was first noted approximately 30 minutes after dosing and was not observed from the end of Day 2 onwards. A loss in bodyweight was noted for one rat during the second week of the observation period. All other animals were considered to have achieved satisfactory body weight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15. Based on these results, the acute median lethal dose (LD50) to rats of 3-Phenylpropyl benzoate was >2000 mg/kg bodyweight

Acute inhalation toxicity

No data available

Acute dermal toxicity

An acute toxicity test was performed to determine the acute toxicity by dermal exposure to 3-PPB. The study was conducted in accordance with a relevant test guideline and in compliance with GLP.

A group of ten rats (five males and five females) received a single topical application of the test substance, as supplied, at a dose level of 2000 mg/kg body weight, for a duration of 24 hours. The animals were retained for a 14 day observation period during which clinical signs, dermal reaction and body weight investigations were performed. There were no deaths and no systemic response to treatment in any animal. Very slight erythema was seen in all females, these reactions had resolved by Day 6. In addition, bandage reactions were seen in all females and two males from Day 2, generally resolving by Day 9 but persisting until termination for one animal. All animals were considered to have achieved satisfactory body weight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15. Based on these results, the acute median lethal dermal dose (LD50) to rats of 3-Phenylpropyl benzoate was demonstrated to be greater than 2000 mg/kg body weight.


Justification for selection of acute toxicity – oral endpoint
One valid study available.

Justification for selection of acute toxicity – dermal endpoint
One valid study available.

Justification for classification or non-classification

The acute toxicity results for 3 -PPB were reviewed with reference to the EU interpretation of CLP, EU Regulation 1272/2008. On the basis that the available tests confirmed the oral LD50 value to be greater than 2000 mg/kg, and the dermal LD50 value to be greater than 2000 mg/kg bodyweight, 3 -PPB does not require classification as toxic by the oral or dermal exposure.