Benzyl benzoate

Endpoint summary

Description of key information

Acute oral toxicity studies are available in the rat and mouse; an early acute dermal toxicity study is also available in the rat.

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:

31 January 1985 to 26 February 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The test material was probably administered, at various concentrations in peanut oil, as the technical grade material but no information was available to confirm purity.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

Standard limit test according to OECD 401

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A Tuck & Sons Ltd, Essex, UK
- Age at study initiation: 4-6 weeks old
- Weight at study initiation: 119-148g males and 118-148g females
- Fasting period before study: yes, overnight unti 2 hours aftre dosing
- Housing: groups of five by se in polypropylene cages
- Diet (e.g. ad libitum):Rat & Mouse Expanded No.1, supplied by SDS Witham, Essex; ad libitum
- Water (e.g. ad libitum): ad libitum access to tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 40-55%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 31 January 1985 To: 26 February 1985

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: For range finding test - 20, 100, 200, 300 and 400 mg/ml and for the main study 400 mg/ml
- Amount of vehicle (if gavage): dose volume was 5 mL/kg bw
- Justification for choice of vehicle: arachis oil used basd on suitability during range-finding investigations

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

DOSAGE PREPARATION (if unusual): prepared freshly for each dose administration

Doses:

range-finder: 100, 500, 1000, 1500 and 2000 mg/kg bw

main study: 2000 mg/kg bw

No. of animals per sex per dose:

2 in range finder; 5 in main study

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequent hourly observations on day of dosing; daily checks thereafter; bodyweights recorded on days 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

Not required

Preliminary study:

The range finding investigation revealed no mortalities in the dose range 100 to 2000 mg/kg bw. Hunched posture, lethargy, decreased respiratory rate and piloerection were frequently observed in the range-finder groups but the signs and severity of clinical response showed no treatment relationship. Recovery from systemic effects was complete within three days for all groups.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at the limit dose

Mortality:

There were no deaths in the main study, following dosing at 2000 mg/kg bw.

Clinical signs:

other: Hunched posture, lethargy, piloerection, ptosis and a decreased respiratory rate were commonly observed shortly after dosing with infrequent cases of body tremors also noted. Recovery from all signs was complete by Day 4.

Gross pathology:

Macroscopic examination at necropsy revealed congested lungs for one rat (normally an agonal response) and pale areas on the gastric glandular region for one rat. No other macroscopic abnormalities were apparent.

Other findings:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 for benzylbenzoate was greater than 2000 mg/kg bw in rats.

Executive summary:

In a standard acute oral study in rats, in accordance with test guideline OECD 401, groups of five male and female rats were dosed at 2000 mg/kg bw. Clinical signs including hunched posture, decreased respiratory rate, lethargy, ptosis and pilo-erection were apparent shortly after dosing but recovered within 4 days. The acute oral median lethal dose for benzylbenzoate was greater than 2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Reliable rat study supported by data in the mouse

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:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Published study with limited details relating to methods. Study pre-dates adoption of regulatory test guidelines.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Screening test

GLP compliance:

no

Test type:

other: Draize primary skin irritation screening test

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No details provided

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No details provided for method of application

Duration of exposure:

Not specified in publication, normal exposure period in Draize method is 4 hours.

Doses:

2.0 mL/kg bw

No. of animals per sex per dose:

No data

Control animals:

not specified

Statistics:

No data

Preliminary study:

No information

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 mL/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths occurred

Mortality:

No mortality in skin irritation tests.
Benzyl benzoate displays a toxic threshold with a sharp demarcation at circa 2.0 mL/kg bw. Delayed deaths occurred following a single high dose topical application. Animals that died exhibited no clinical signs prior to death.

Clinical signs:

other: No signs of systemic toxicity observed

Gross pathology:

no data

Other findings:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of benzyl benzoate was found to be >2 mL/kg bw (~2000 mg/kg bw) under the conditions of this assay.

Executive summary:

The acute dermal LD50 of benzyl benzoate was investigated in a screening assay in the rabbit and was found to be >2 mL/kg bw (~2000 mg/kg bw).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Non-standard screening study in the rabbit

Additional information

Benzyl benzoate is shown to be of low acute toxicity by the oral and dermal routes. The acute oral LD50 of benzyl benzoate was reported to be >2000 mg/kg bw in the rat (Collier & Hewitt, 1985); an acute oral LD50 of 3253 mg/kg bw is reported in the mouse (Hoffman, 1972). Draize et al (1947) report an acute dermal LD50 value of >2 mL mg/kg bw (~2000 mg/kg bw) in a screening study performed in the rabbit.

 

Justification for selection of acute toxicity – oral endpoint
Regulatory limit test according to OECD 401, in the preferred species

Justification for selection of acute toxicity – dermal endpoint
Only one study available for this endpoint

Justification for classification or non-classification

No classification is required for acute oral and dermal toxicity according to the CLP Regulation.

Benzyl benzoate harmonised classification according to CLP Regulation 1272/2008 is Acute Tox 4, H302. The interpretation reflects the agreed classification rather than the observed experimental results.