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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
557 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
The available study report is short but concise and a NOAEL can be derived.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There is no reproductive toxicity data on methyl benzoate. Please see section 13 for justification of read across from benzoic acid and sodium benzoate.

Since in a 4-generation study with benzoic acid (Kieckebusch and Lang, 1960), a NOEL of 500 mg/kg bw/day (557 mg/kg bw/day methyl benzoate) for systemic and reproductive effects was determined, it can be concluded that benzoic acid (methyl benzoate) does not need to be classified for reproductive toxicity.

The reproductive toxicity of the substance methyl benzoate is characterised on the basis of valid and reliable studies with the read-across substances benzoic acid and sodium benzoate. It has to be considered that the enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol, which is not released from benzoic acid or sodium benzoate. The toxicity of the metabolite methanol has to be addressed, as it may contribute to the reproductive toxicity of methyl benzoate. Please refer to section 5.11 for a discussion.


Short description of key information:
Oral: NOEL (Parental/F1) = 557 mg/kg bw/day methyl benzoate (data derived from benzoic acid study, where parental/F1 NOEL = 500 mg/kg bw/day)
Inhalation: no data
Dermal: no data

Justification for selection of Effect on fertility via oral route:
A study with methyl benzoate is not available. Read across from a study on reproductive toxicity of benzoic acid can be done. This study is considered as reliable with restrictions

Effects on developmental toxicity

Description of key information
Rat, mouse: NOEL (maternal/teratogenicity) = 165 mg/kg bw/day methyl benzoate (data derived from sodium benzoate study, where maternal/teratogenicity NOEL = 175 mg/kg bw/day).
Hamster: NOEL (maternal/teratogenicity) = 283 mg/kg bw/day methyl benzoate (data derived from sodium benzoate study, where maternal/teratogenicity NOEL = 300 mg/kg bw/day).
Rabbit: NOEL (maternal/teratogenicity) = 236 mg/kg bw/day methyl benzoate (data derived from sodium benzoate study, where maternal/teratogenicity NOEL = 250 mg/kg bw/day).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
165 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The available oral (gavage) studies similar to OECD TG 414 were conducted in rats, mice, hamsters and rabbits. An additional very concise oral (feeding) study of developmental toxicity in rats is considered as supporting study.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

No developmental toxicity data on methyl benzoate is available. Read across from sodium benzoate was performed (see read across justification document in section 13).

Weight of evidence studies

The teratogenicity studies with sodium benzoate were conducted in rats, mice, hamsters and rabbits (Morgareidge 1973). The test substance was administered by oral gavage at doses of up to 175, 175, 300 and 250 mg/kg bw/day to pregnant rats, mice, hamsters and rabbits, respectively. The NOEL derived for maternal and developmental effects was determined at 175, 175, 300 and 250 mg/kg bw/day in rats, mice, hamsters and rabbits, respectively. These maternal and developmental NOEL values correspond to 165, 165, 283 and 236 mg/kg bw/day of methyl benzoate, respectively in rats, mice, hamsters and rabbits.

Supporting study

The teratogenicity study with sodium benzoate was conducted in Wistar rats (Onodera et al, 1978). Doses of 1, 2, 4 and 8 % sodium benzoate were administered in diet. The NOAEL derived for maternal and developmental effects was determined at 2 % or about 1330 mg/kg bw/day dose of sodium benzoate. This maternal and developmental NOAEL value corresponds to 1257 mg/kg bw/day methyl benzoate.

The developmental toxicity of the substance methyl benzoate is characterised on the basis of valid and reliable studies with the read-across substances benzoic acid and sodium benzoate. It has to be considered that the enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol, which is not released from benzoic acid or sodium benzoate. The toxicity of the metabolite methanol has to be addressed, as it may contribute to the developmental toxicity of methyl benzoate. Please refer to section 5.11 for a discussion.

 


Justification for selection of Effect on developmental toxicity: via oral route:
A study on developmental toxicity of methyl benzoate is not available. Read across from the well documented studies in rats, mice, hamsters and rabbits on the developmental toxicity of Sodium benzoate can be done. In all these studies no maternal and developmental toxicity was observed up to the highest applied doses.

Justification for classification or non-classification

- Reproductive toxicity:

Based on the above stated assessment of the reproduction toxicity potential of methyl benzoate (and the read across substances benzoic acid and sodium benzoate) is deemed not to be toxic to reproduction. Accordingly, the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

Developmental toxicity:

Based on the above stated assessment of the developmental toxicity potential of Methyl benzoate, the substance could not be classified for developmental toxicity/teratogenicity according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

Additional information