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Description of key information

Read-across from data on benzoic acid from acute toxicity studies by the the oral, dermal and inhalational route.

Read-across of these data to sucrose benzoate is considered a very precautious approach, as sucrose benzoate because of low water solubility (3 mg/L) and high molacular weight (1175 g/mol) can be considered as far less bioaccessible and bioavailable than benzoic acid by the oral, dermal and inhalational route.

See read-across justification attached to section 13.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
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 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 < LD502000 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.

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.

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
Body weight:
All surviving rats, males and females, exhibited normal body weight gains during the 14 day observation period.
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)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data on benzoic acid used for conclusion by RAC

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
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 aross justification document in section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 12.2 mg/L air
Interpretation of results:
GHS criteria not met
Conclusions:
No data available for sucrose benzoate. Therefore data on benzoic acid is used for read across. The inhalational LC50 is above 12,2 mg/L for benzoic acid (ECHA/RAC 2012)
As a precautious approach read-across to data from benzoic acid is made for assessing the potential for systemic toxicity of sucrose benzoate. Thus, based on a LC50 above 12.2 mg/L for inhalational exposure to benzoic acid a low acute toxic potential by the inhalational route is to be expected for sucrose benzoate as well. No classification should apply for this end-point.

The read-across to sucrose benzoate for acute inhalation exposure from benzoic acid is considered conservative dueto very low water solubility (3 mg/L) which makes sucreose benzoate very litte bioaccessible and bioavailble to exert any form for acute toxic response. As only a low degree of hydrolysis can be expected to occur in the lungs this makes read-across to benzoic acid very conservative.
Executive summary:

No data available for sucrose benzoate. Therefore data on benzoic acid is used for read across. The inhalational LC50 is above 12,2 mg/L for benzoic acid (ECHA/RAC 2012)

As a precautious approach read-across to data from benzoic acid is made for assessing the potential for systemic toxicity of sucrose benzoate. Thus, based on a LC50 above 12.2 mg/L for inhalational exposure to benzoic acid a low acute toxic potential by the inhalational route is to be expected for sucrose benzoate as well. No classification should apply for this end-point.

The read-across to sucrose benzoate for acute inhalation exposure from benzoic acid is considered conservative due to  very low water solubility (3 mg/L) which makes sucreose benzoate very litte bioaccessible and bioavailble to exert any form for acute toxic response. As only  a low degree of hydrolysis can be expected to occur in the lungs this makes read-across to benzoic acid very conservative.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
xxxx
See attached document in section 13
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1150 (Acute inhalation toxicity)
GLP compliance:
not specified
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
Ten rats (4 units of 2 or 3 rats/unit to prevent piling) were placed in a sealed 59.1 liter glass chamber and exposed to a dynamic atmosphere containing the dust of the test material. A Wright Dust Feeder controlled addition of the test substance; airflow regulated by a flowmeter. The rats were observed continuously during the 4-hour exposure, and for a period of 14 days following exposure.
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The rats were placed in a sealed 59.1 liter glass chamber and exposed to a dynamic atmosphere containing the dust of the test material. A Wright Dust Feeder controlled addition of The test substance; airflow regulated by a flowmeter.
Duration of exposure:
4 h
No. of animals per sex per dose:
10 rats (2-3 rats per unit)
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
12.2 mg/L air
Exp. duration:
4 h
Mortality:
All rats survived the 4-hour exposure and the 14-day observation period.
Clinical signs:
other: Signs during the exposure period included occasional increased motor activity and slight erythema. At the conclusion of exposure, 1 rat exhibited salivation.
Body weight:
At 24 hours and through the 14-day observation period, all rats appeared normal and exhibited normal body weight gains.
Interpretation of results:
GHS criteria not met
Executive summary:

Ten rats (4 units of 2 or 3 rats/unit to prevent piling) were placed in a sealed 59.1 liter glass chamber and exposed to a dynamic atmosphere containing the dust of the benzoic acid by Wright Dust Feeder controlled system and airflow regulated by a flowmeter. The rats were observed continuously during the 4-hour exposure, and for a period of 14 days following exposure. All of the rats survived the 4-hour exposure and the 14-day observation period. Signs during the exposure period included occasional increased motor activity and slight erythema. At the conclusion of exposure, 1 rat exhibited salivation. At 24 hours and through the 14-day observation period, all rats appeared normal and exhibited normal body weight gains.

Endpoint:
acute toxicity: inhalation
Type of information:
other: summary from ECHA/RAC opinion
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: RAC opinion
Justification for type of information:
Three studies on acute inhalational toxicity were evaluated by ECHA/RAC (2012).
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 12.2 mg/L air
Interpretation of results:
GHS criteria not met
Conclusions:
The RAC opinion concludes that no acute toxicity classification and labelling is proposed for benzoic acid for inhalation.
Executive summary:

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

Results from 2 of the 3 inhalation test were above the cut-off value for classification while one test result may meet the range of Acute Tox. 4 (Category 4 criterion: 1 < LD50 (4h, dust) 5 ppm. This was from a rat study where the LD50 (1h, form not specified) was > 0.026 mg/l. The results from this study are however highly uncertain, as no rat strain and sex is specified and there is no information on applied doses and applied form of the chemical substance.

RAC concludes that benzoic acid shows very low acute toxicity and therefore, no acute toxicity classification and labelling is proposed for benzoic acid.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
0.012 mg/m³
Quality of whole database:
Data on benzoic acid used for conclusion by RAC

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
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 was used as 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. This is considered a conservative approach since sucrose benzoate having a low water solubility (3 mg/L) and as a rather large molecule (MW: 1174 g/mol) can be considered as less bioaccessible and boiavailable by dremal contact compared to benzoic acid. See read-across justification attached to section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal acute toxicity of Sucrose benzoate was based on read across to studies performed with benzoic acid.

Thus, based on a dermal LD50 above 2000 mg/kg for benzoic acid a low acute toxic potential by the dermal route is to be expected for sucrose benzoate as well. No classification should apply for this end-point for Sucrose benzoate.
Executive summary:

The dermal acute toxicity of Sucrose benzoate was based on read across to studies performed with benzoic acid.  

In three dermal acute toxicity studies performed with dermal exposure to rabbits the LD50 of benzoic acid was found to be above 2000 mg/kg; 5000 mg/kg and 10000 mg/kg, respectively.

As a precautious approach read-across to data from benzoic acid can be made for assessing the potential for dermal toxicity of sucrose benzoate.

This is considered a conservative approach since sucrose benzoate having a low water solubility (3 mg/L) and as a rather large molecule (MW: 1174 g/mol) can be considered as far less bioaccessible and boiavailable by dermal contact compared to benzoic acid. See read-across justification attached to section 13.

Thus, based on a dermal LD50 above 2000 mg/kg for benzoic acid a low acute toxic potential by the dermal route is to be expected for sucrose benzoate as well. No classification should apply for this end-point.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
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:
EPA OTS 798.1100 (Acute Dermal Toxicity)
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on dermal exposure:
The test compound was applied once only to a shaved area of the back of each rabbit at a dose of 2000 mg/kg bw.
Duration of exposure:
24 h
Doses:
2000 mg/kg/day
No. of animals per sex per dose:
4
Control animals:
not specified
Details on study design:
The test compound was applied once only to a shaved area of the back of each rabbit at a dose of 2000 mg/kg bw.
The skin of 1 male and 1 female was abraded with a scalpel blade prior to test application.
The area was wrapped with a gauze bandage and occluded with plastic wrap. The bandages were removed and the backs washed
24 hours after application. The rabbits were observed for a period of 14 days.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal toxicity of benzoic acid was determined according to the method EPA OTS 798.1100. LD50 of benzoic acid was found to be > 2000 mg/kg/day for acute dermal toxicity
Executive summary:

The acute dermal toxicity of benzoic acid was determined according to the method EPA OTS 798.1100.

The test compound was applied once only to a  shaved area of the back of each rabbit at a dose of 2000 mg/kg bw. The skin of 1 male and 1 female was abraded with a scalpel blade prior to test application. The area was wrapped with a gauze bandage and occluded with plastic wrap. The bandages were removed and the backs washed

24 hours after application. The rabbits were observed for a period of 14 days.

LD50 was found to be > 2000 mg/kg/day for acute dermal toxicity

Endpoint:
acute toxicity: dermal
Type of information:
other: Data summary/Expert opinion (RAC)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline followed
Principles of method if other than guideline:
The methods was considered suitable for evaluation of the present endpoint by ECHA/RAC
Species:
rabbit
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Interpretation of results:
GHS criteria not met
Conclusions:
In 3 dermal studies using rabbits LD50 of benzoic acid above 2000 mg/kg; 5000 mg/kg and 10 000mg/kg were found.
RAC considers that these values do not warrant classification and labelling for acute dermal toxicity. LD50 is > 2000 mg/kg/day
Executive summary:

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

"All results from the three studies are above the Category 4 criterion: 1000 < LD50 < 2000 mg/kg). The lowest LD50 was for rabbit (2000 mg/kg bw). RAC considers that these values do not warrant classification and labelling for acute dermal toxicity".

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data on benzoic acid used for conclusion by RAC

Additional information

Justification for classification or non-classification

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.

The acute toxicity by inhalation of Sucrose benzoate was estimated based on read across to benzoic acid. Based on a LC50 above 12.2 mg/L for acute inhalational exposure to benzoic acid in rats a low acute toxic potential by the inhalational route is to be expected for sucrose benzoate as well. No classification should apply for this end-point.

The dermal acute toxicity of Sucrose benzoate was based on read across to studies performed with benzoic acid.  In three dermal acute toxicity studies performed with dermal exposure to rabbits the LD50 of benzoic acid was found to be above 2000 mg/kg; 5000 mg/kg and 10000 mg/kg, respectively.

Thus, no classification should apply for this end-point.