Boron trifluoride

Endpoint summary

Description of key information

All the studies pointed out that BF3 (gas) or BF3 dihydrate cause signs of respiratory distress and two well conducted studies showed that BF3 dihydrate is responsible for kidney toxicity (necrosis of proximal tubular epithelium).

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

6 mg/m³

Study duration:

subchronic

Species:

rat

Additional information

Several studies are available for that endpoint but only one subacute toxicity study and one subchronic toxicity study are of good quality. All the studies pointed out that BF3 (gas) or BF3 dihydrate causes signs of respiratory distress, and two of them showed that BF3 dihydrate may be responsible for kidney toxicity (necrosis of proximal tubular epithelium). This effect was observed in the two Rusch studies (subacute toxicity study and 90 -day toxicity study) and is correlated with increase of Fluorine amounts in urine and in serum that were not considered as adverse but that are related to kidney effects. The significance of kidney effects in the subchronic toxicity study remains not very clear since it was observed in only 2 rats at the highest dose group, but has to be taken into account since it was observed in two studies (subacute, subchronic).

In the key study (Rusch study, 1986), rats were exposed to aerosols of BF3 dihydrate for 13 weeks, the NOAEL was 6 mg/m3 and the LOAEL was 17 mg/m3 for effects on kidney. Increase of fluorine amounts in serum and in urine were observed but were not considered as adverse since no signs of toxicity was associated and since it was reversible or partially reversible (as the recovery period was only 2 week, a full reversibility was not observed for urinary fluorine); nevertheless they were related to treatment.

Clinical signs of respiratory irritation were seen at all dose levels, but without abnormal histological findings. The only abnormal histological findings were observed at the highest dose group, in kidney, were there was a necrosis of the renal tubular epithelium in 2 rats and which was the apparent cause of a death in one of the animals.

In a subacute toxicity study (Rush, 1986), rats exposed for 2 weeks at highest concentration of BF3 dihydrate (0, 24, 66 and 180 mg/m3) and all presented signs of respiratory distress but the only histopathological findings revealed only a necrosis and pyknosis of the proximal tubular epithelium in the kidneys of the high exposure group rats, whom mortality was 100%.

The Torkelson study is 6 months toxicity study where rats were exposed to about 2.8 mg/m3, 8.2 g/m3 or 11.9mg/m3 of BF3 (gaz). The major observed effect was respiratory irritation. Toxicity also involved pneumotitis and dental fluorosis. This study was questionable because of methodological deficiencies: for example BF3 was directly instilled into the exposure chambers in order to avoid a formation of aerosols of BF3-hydrates. Air humidity was kept down to 30 % which is unusually low. Even the glass was corroded by this rather artificial procedure. The Rusch study appears to be more appropriate and relevant, regarding both experimental generation of BF3 or BF3 dihydrate (BF3 dihydrate aerosols and were formed and administered in the Rusch study into an atmosphere with 60 % humidity) and general experimental study design. Nevertheless, the interest of the Torkelson study to have a duration period of 6-month, and respiratory irritation observations are coherent with those of Rusch.

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

Justification for classification or non-classification

Boron trifluoride may be responsible for kidney toxicity (necrosis of proximal tubular epithelium). For this effect, the NOAEL is low (6 mg/m3 in the 90 -day toxicity study), but as it this study is based on observations in only two animals in the Rusch and as the significance and the relevance of kidney effects remain unclear, a STOT RE 1 according to CLP doesn't seem justified. A STOT RE 2 is proposed.

According to the directive 67/548/EEC, the substance should be classified R48/20.