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Description of key information

BONA free acid was tested for repeated dose toxicity  (OECD SISDS SIAM 19). The substance caused an increase in bilirubin in both sexes, a slight increase in liver weight in females of the high dose group and adrenal necroses in two females of the mid and high dose group, repectively. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
12 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Reasons for read across

The test item is the sodium salt of a naphthoic acid. In an acidic enviroment (e.g. stomach), the salt complex becomes dissociated into the sodium cation and the organic acid. Therefore, it is acceptable to derive repeated dose toxicity data from the free acid.

Statement of repeated dose toxicity (OECD SIDS SIAM 19)

In a 28 day gavage study in Wistar rats ( 0, 12, 60, 300 mg/kg bw/day), performed in accordance with the old OECD TG 407 (1981), 3-hydroxy-2-naphthoic acid had no influence on body weights, food consumption and behaviour of the animals. In the high-dose group, an increased water consumption was observed during the first two study weeks; at the end of the study, the serum phosphate levels were significantly decreased and bilirubin levels were increased in serum and urine in both sexes. Females showed a slight, but statistically significant increase in liver weights at 300 mg/kg bw/day (without histopathological correlate)(no further details available). At histopathology, one female of the high-dose and one female of the mid-dose group showed adrenal necroses. NOEL: 60 mg/kg bw/day (males), 12 mg/kg bw/day (females).

Poorly documented studies in rats involving repeated administration by the inhalation route gave indications of an effect on the kidneys (kidney necroses were reported after 10-days inhalation of 100 mg/m3)(Prosolenko NV and Vasilenko NM, 1979).

Conclusion

After repeated administration to rats by the oral route for 28 days, there were indications of a possible effect on the adrenals in females at dose levels of 60 mg/kg bw/day and above. The only effects observed in males were a significantly reduced serum phosphate level and increased levels of bilirubin in serum and urine at a dose level of 300 mg/kg bw/day. The same findings, and, in

addition, increased liver weights were reported for females at 300 mg/kg bw/day. NOEL (male): 60 mg/kg bw/day; NOEL (female): 12 mg/kg bw/day.

Poorly documented studies in rats involving repeated administration by the inhalation route gave indications of an effect on the kidneys (kidney necroses were reported after 10-days inhalation of 100 mg/m3)

Justification for classification or non-classification

The data given above are from secondary sources and not suitable for a statement of classification.