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Administrative data

Description of key information

Oral: 
The studies available on the analogue sodium benzoate are feeding studies in rat and mice (one drinking water study in mice). Mice seem to be less susceptible to the effects of the analogue than rats. Effects are severe decrease of body weight with effects in the liver. The no effect level is 2% in the diet of rats. In the reports available different conversion methods are used to calculate the actual test substance intake. This may have been done by actual measurement of food intake, but is not clearly described in the publications. Therefore a calculation was done based on the factors as described in the WHO report (EHS Environmental Health Criteria 240). This leads to a NOAEL of 1000 mg/kg bw based on the 2% dietary level in rats.
In a chronic toxicity/carcinogenicity study in rats (Sodemoto, 1979) no signs of toxicity were reported at 2% of the analogue in feed (stated to be equivalent to 1000 mg/kg bw).
Dermal: A study is available with a NOAEL of the key study of > 2500 mg/kg bw/day (Marroquin, 1981).
Inhalation: A study is available with a NOAEL of the key study of 250 mg/m3 (Benson, 1981). These findings were primarily attributed to the physico-chemical properties of these fine low-solubility particles.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
2 (reliable with restrictions)

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
250 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
1 (reliable without restriction)

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 500 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Quality of whole database:
1 (reliable without restriction)

Additional information

Oral:

No adequate studies with the test substance are available. Several studies are available on the structural analogue sodium benzoate.

A short-term dietary study (10 days)with sodium benzoate in rats and mice (Fujitani, 1993) showed a NOAEL of 905 mg/kg bw in rats and of 3571 mg/kg bw in mice. Effects included decreased body weight and increased (rel) liver weights with enlarged (glossy) hepatocytes and eosininophilic foci around the protal vein. In high dosed decreased kidney weights were reported without histopathological changes. In addition, in a 35 day study in rats with sodium benzoate (Sodemoto, 1979) animals at the highest dose groups died. Symptoms in decendents were severe decrease in body weight. Morpholical effects were limited to atrophy of the spleen and lymphnodes at 4 and 8% in diet. At the NOAEL 2% in diet no morphological changes were reported. In a limited reported 90-day study on sodium benzoate in rats (Weil, 1953) a NOAEL of 2620 mg/kg bw was established based on reduced body weight gain, increased relative liver and kidney weights and pathological changes in liver and kidneys at 6290 mg/kg bw/day. The overall NOAEL for repeated dose toxicity is based on a chronic toxicity study and is set at 1000 mg/kg bw/day (Sodemoto, 1979).

Dermal:

A 21-day dermal toxicity study with rabbit (Marroquin, 1981) which run on Benzoic acid (65-85-0) is available. No effects were found at the highest dose level, thus the NOAEL was > 2500 mg/kg bodyweight.

Inhalation:

A repeated inhalation toxicity study with rat (Benson, 1981) which was run on Benzoic acid (65-85-0) is available. All test concentrations induced local effects: nasal redness and discharge and pulmonary fibrosis and inflammatory cell infiltrates in the lungs that can be related to the irritant properties of the test substance. Hence these are not taken into account in relation to classification.

No systemic effects were noted at 25 mg/m3. At 250 mg/m3 a very slight decrease in absolute kidney weight was seen in females only (body weight was also slightly lower (not significantly) than in control females). At the highest dose level mortality, decreased body weights as well as decreased liver kidney and lung weights were reported. No histopathological findings except in the lungs were reported. The NOAEL for local effects is < 25 mg/m3; The NOAEL for systemic effects is 250 mg/m3. At 1,200 mg/m3 significant adverse toxicological effects were observed.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
This study was carried out according to a reliable method using rats.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
This study was carried out according to OECD Guideline 412 using rats.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
This study was carried out according to EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days) using rabbits.

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: other

Justification for classification or non-classification

Oral: NOAEL > 1000 mg/kg bw in a chronic toxicity study > 90 days

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.9.2 and 3.9.3 the substance is not classified for the repeated oral toxicity endpoint.

Dermal: A dermal value of 833 mg/kg bw (which is above 200 mg/kg bw) does not lead to the substance being classified.

Inhalation: Classification of STOT RE comes from the consideration of the dose/concentration which has been shown to produce significant health effects. In Bensen 1981 significant systemic toxic effects were seen to occur at 400 mg/m3 (28 day result: 1,200 mg/m3). Local effects are not taken into consideration as these are considered to be related to the irritant nature of the substance and not associated with substance toxicity itself. This then leads to the substance not being classified for inhalation (STOT RE effect >200 mg/m3).