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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Read-across from data on benzoic acid as evaluated by ECHA/RAC (2012)

see read-across justification attached in section 13.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
No data is available for sucrose benzoate. Therefore data on benzoic acid is used for read-across. For inducing reproductive toxicity the substance has to be absorbed in order to reach the sex organs and the embryo/ foetus. Therefore, read-across to data on benzoic acid is considered especially relevant as exposure to sucrose benzoate would not lead to systemic exposure to sucrose benzoate but benzoic acid and sucrose (see toxicokinetic section and read-across justification attached in section 13).
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
organ weights and organ / body weight ratios
histopathology: non-neoplastic
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
organ weights and organ / body weight ratios
histopathology: non-neoplastic
Key result
Reproductive effects observed:
no
Conclusions:
No data is available for sucrose benzoate. Therefore data on benzoic acid is used for read-across purposes.
For benzoic acid reproductive toxicity was assessed in a non-guideline 3-generation study performed in rats with 0, 0.5 and 1% benzoic acid added to the diet, corresponding to approximate doses of 0, 250 and 500 mg/kg bw/d. These doses failed to produce detectable toxic effects on parental and offspring generations or reproductive capacity (ECHA/RAC 2012). For inducing reproductive toxicity the substance has to be absorbed in order to reach the sex organs and the embryo/ foetus. Therefore, read-across from data on benzoic acid is considered especially relevant as exposure to sucrose benzoate would not lead to systemic exposure to sucrose benzoate but benzoic acid and sucrose (see toxicokinetic section). Based on lack of effects on fertility of benzoic acid, no concern can be concluded for sucrose benzoate as well.
Executive summary:

No data is available for sucrose benzoate. Therefore data on benzoic acid is used for read across purposes.

For benzoic acid reproductive toxicity was assessed in a non-guideline 3-generation study performed in rats with 0, 0.5 and 1% benzoic acid added to the diet, corresponding to approximate doses of 0, 250 and 500 mg/kg bw/d. These doses failed to produce detectable toxic effects on parental and offspring generations or reproductive capacity (ECHA/RAC 2012). For inducing reproductive toxicity the substance has to be absorbed in order to reach the sex organs and the embryo/ foetus. Therefore, read-across from data on benzoic acid is considered especially relevant as exposure to sucrose benzoate would not lead to systemic exposure to sucrose benzoate but benzoic acid and sucrose (see toxicokinetic section). Based on lack of effects on fertility of benzoic acid, no concern can be concluded for sucrose benzoate as well.

Additional information

No data is available for sucrose benzoate. Therefore data on benzoic acid is used for read across purposes.

For benzoic acid reproductive toxicity was assessed in a non-guideline 3-generation study performed in rats with 0, 0.5 and 1% benzoic acid added to the diet, corresponding to approximate doses of 0, 250 and 500 mg/kg bw/d. These doses failed to produce detectable toxic effects on parental and offspring generations or reproductive capacity (ECHA/RAC 2012).

 Based on lack of effects on fertility of benzoic acid, no concern can be concluded for sucrose benzoate as well.

Effects on developmental toxicity

Description of key information

Read-across from data on benzoic acid as evaluated by ECHA/RAC (2012)

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
No data is available for sucrose benzoate. The evaluation is therefore based on read across from data on benzoic acid, For inducing reproductive toxicity the substance has to be absorbed in order to reach the sex organs and the embryo/ foetus. Therefore, read-across to data on benzoic acid is considered especially relevant as exposure to sucrose benzoate would not lead to systemic exposure to sucrose benzoate but benzoic acid and sucrose. See also toxicokinetic section and read-across justification attached in section 13.
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
1 130 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
food consumption and compound intake
mortality
Key result
Abnormalities:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
600 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
changes in postnatal survival
Key result
Abnormalities:
effects observed, treatment-related
Localisation:
other: soft tissue and skeletal
Description (incidence and severity):
Effects observed at 1610 mg/kg/day (maternal dose)
Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
1 610 mg/kg bw/day
Treatment related:
yes
Relation to maternal toxicity:
developmental effects as a secondary non-specific consequence of maternal toxicity effects
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
No data is available for sucrose benzoate. Therefore the conclusion is based on read across from benzoic acid.
Based on three developmental toxicity studies on benzoic acid/ benzoate using dose levels in the range of 50 – 1610 mg/kg/d RAC concluded benzoic acid not to be classified for developmental toxicity as no developmental effects occurred even at highly maternal toxic levels (ECHA/RAC 2012).
For inducing reproductive toxicity the substance has to be absorbed in order to reach the sex organs and the embryo/ foetus. Therefore, read-across to data on benzoic acid is considered relevant as exposure to sucrose benzoate would not lead to systemic exposure to sucrose benzoate but benzoic acid and sucrose (see toxicokinetic section).
Based on lack of effects on fertility and development of benzoic acid, no concern can be concluded for sucrose benzoate as well.
Executive summary:

No data is available for sucrose benzoate. Therefore the concludion is based on read across to benzoic acid.

Based on three developmental toxicity studies on benzoic acid/ benzoate using dose levels in the range of 50 – 1610 mg/kg/d RAC concluded benzoic acid not to be classified for developmental toxicity as no developmental effects occurred even at highly maternal toxic levels (ECHA/RAC 2012).

For inducing reproductive toxicity the substance has to be absorbed in order to reach the sex organs and the embryo/ foetus. Therefore, read-across to data on benzoic acid is considered especially relevant as exposure to sucrose benzoate would not lead to systemic exposure to sucrose benzoate but benzoic acid and sucrose (see toxicokinetic section). 

Based on lack of effects on fertility and development of benzoic acid, no concern can be concluded for sucrose benzoate as well.

Additional information

Read-across data on benozic acid:

Doses up to 500 mg/kg bw/d did not produce detectable adverse effects on

development of the offspring or on sexual function or fertility in parental animals. No

increase in offspring variations and malformations was observed up to doses that

produced maternal toxicity (> 1000 mg/kg bw/d benzoic acid). In a single study, a 4.5

% offspring mortality (1/22) was observed at the highest dose level (~1130 mg/kg

bw/d benzoic acid) administered with the food during the whole gestational period (ECHA/RAC 2012).

Justification for classification or non-classification

Based on the availble information benzoic acid is according to RAC (2012) not to be classified for reproductive toxicity.

Based on read-across from the data on benzoic acid the substance sucrose benzoate is not to be classified for reproductive toxicity.

Additional information