α-d-Glucopyranoside, β-d-fructofuranosyl, benzoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

No data available for sucrose benzoate. Therefore data on benzoic acid is used for read across. As a precautious approach read-across to data from benzoic acid is made for assessing the potential for systemic toxicity of sucrose benzoate. Please see attached read across justification document in section 13

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: data summary from ECHA/RAC opinion

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: RAC opinion

Principles of method if other than guideline:

Collection of data relevant to the classification of Benzoic acid

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rats

Effect level:

> 2 000 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

The low acute toxicity of benzoic acid in most species does not warrant classification and labelling for this endpoint.

Executive summary:

The summary below is based on the conclusion from RAC-opinion (2012) on harmonised CLP-classification of Benzoic acid:

In 12 out of 14 oral tests LC50/LD50 values for acute oral toxicity higher than the upper limits for classification and labelling as Acute Tox. 4 (Category 4 criterion: 300 < LD50 ≤ 2000 mg/kg) was found. In rodents one LD50 value of 1700 mg/kg bw (under the highest limit of the classification criterion) was found in rats.

The low acute toxicity of benzoic acid in most species does not warrant classification and labelling for this endpoint. The cat represents the most sensitive mammalian species tested. This sensitivity is thought to be related to species-specific deficiencies in benzoate metabolism (no glucuronidation pathway). Therefore, RAC concluded that the moderate acute oral toxicity observed in cats was not considered relevant for human health risk assessment and/or classification and labelling.

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

Study is referenced in OECD SIDS report, ref 73: Angenelli et al 1985

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

other: Spartan

Sex:

male/female

Details on test animals or test system and environmental conditions:

25 male and 25 female Spartan rats weighing 200 to 250 grams.

Route of administration:

oral: unspecified

Vehicle:

corn oil

Doses:

500, 1250, 1984, 3150, and 5000 mg/kg.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

All rats were observed for mortality continuously during the first 4 hours after dosing, at 24 hours and once daily thereafter for a total of 14 days. Body weights were recorded initially and at 14 days.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 742 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 279 - <= 3 299

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 360 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 042 - <= 2 726

Mortality:

Dose level (mg/kg) Mortality
500 0/5
1250 0/5
1984 0/5
3150 4/5
5000 5/5

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of benzoic acid in male albino rats was calculated to be 2742 mg/kg (2279-3299 mg/kg). The acute oral LD50 of benzoic acid in female albino rats was calculated to be 2360 mg/kg (2042-2726 mg/kg).
A combined acute oral LD50 for benzoic acid in male and female albino rats was calculated to be 2565 mg/kg (2292-2870 mg/kg)

Executive summary:

Acute oral toxicity of Benzoic acid was tested in rats according to Directive 84/449/EEC, B.1 "Acute toxicity (oral)"

25 male and 25 female Spartan rats weighing 200 to 250 grams were used for this study. The test compound was suspended in corn oil and administered orally at the following dosage levels: 500, 1250, 1984, 3150, and 5000 mg/kg. Five rats of each sex were used at each dosage level. Volumes of 10 ml/kg bw were administered at all dosage levels.

All rats were observed for mortality continuously during the first 4 hours after dosing, at 24 hours and once daily thereafter for a total of 14 days. Body weights were recorded initially and at 14 days.

All surviving rats, males and females, exhibited normal body weight gains during the 14 day observation period.The acute oral LD50 of benzoic acid in male albino rats was calculated to be 2742 mg/kg (2279-3299 mg/kg). The acute oral LD50 of benzoic acid in female albino rats was calculated to be 2360 mg/kg (2042-2726 mg/kg). A combined acute oral LD50 for benzoic acid in male and female albino rats was calculated to be 2565 mg/kg (2292-2870 mg/kg)

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

α-d-Glucopyranoside, β-d-fructofuranosyl, benzoate

EC Number:

235-795-5

EC Name:

α-d-Glucopyranoside, β-d-fructofuranosyl, benzoate

Cas Number:

12738-64-6

Molecular formula:

C12-H22-O11.x-C7-H6-O2; x=5-8

IUPAC Name:

α-d-Glucopyranoside, β-d-fructofuranosyl, benzoate

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rats

Effect level:

> 2 000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral acute toxicity of Sucrose benzoate was estimated based on read across to benzoic acid. 12 out of 14 oral tests showed an LC50/LD50 value for acute oral toxicity higher than the upper limits for classification and labelling as Acute Tox. 4 (Category 4 criterion: 300 < LD50≤2000 mg/kg). The low acute toxicity of benzoic acid in most species does not warrant classification and labelling for this endpoint.

Read-across to sucrose benzoate from benzoic acid is considered a worst case approach since very low degree (if any) oral absroption of non-hydrolysed sucrose benzoate is expected (see toxicokinetic section). When hydrolysed benzoic acid and sucrose are generated. Only the acute toxic potential of benzoic is relevant to be considered as sucrose (included on Annex IV) generated by the hydrolysis is considered without acute toxic potential.

Executive summary:

The oral acute toxicity of Sucrose benzoate was based on read across to studies performed with benzoic acid, which is a major component of the substance.

In a study performed with spartan rats, the acute oral LD50 of benzoic acid in female albino rats was calculated to be 2360 mg/kg (2042-2726 mg/kg). The combined acute oral LD50 for benzoic acid in male and female albino rats was calculated to be 2565 mg/kg (2292-2870 mg/kg).

RAC has colleced data on acute toxicity of benzoix acid and found that 12 out of 14 oral tests showed an LC50/LD50 value for acute oral toxicity higher than the upper limits for classification and labelling as Acute Tox. 4 (Category 4 criterion: 300 < LD50≤2000 mg/kg). Results under the highest limit of the criterion: Oral: Rat, LD50=1700 mg/kg bw.

The low acute toxicity of benzoic acid in most species does not warrant classification and labelling for this endpoint. The cat represents the most sensitive mammalian species tested. This sensitivity is thought to be related to species-specific deficiencies in benzoate metabolism (no glucuronidation pathway). Therefore, the moderate acute oral toxicity observed in cats was not considered relevant for human health risk assessment and/or classification and labelling.

Read-across to sucrose benzoate from benzoic acid is considered a worst case approach since very low degree (if any) oral absroption of non-hydrolysed sucrose benzoate is expected (see toxicokinetic section). When hydrolysed benzoic acid and sucrose are generated. Only the acute toxic potential of benzoic is relevant to be considered.