Hydrogen trifluoromethoxyborate(1-), compound with methanol (1:1)

Endpoint summary

Description of key information

Acute oral toxicity:

In a GLP-compliant acute oral toxicity study performed according to EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method) (BASF, 1995), the substance was administered to rats via gavage in olive oil at doses of 200 and 2000 mg/kg. No mortality was observed at 200 mg/kg, whereas all animals in the 2000 mg/kg group died within 3 hours after administration. Clinical signs included impaired general state and dyspnea at 200 mg/kg and poor general state, dyspnea, apathy, staggering ataxia, paresis and cyanosis at 2000 mg/kg. The animals in the 2000 mg/kg group showed hemorrhages in the mucosa of the glandular stomach and substance discoloration of contents in the small intestines.

No experimental data on acute inhalation or acute dermal toxicity with the complex of  boron trifluoride with methanol are available.  Boron trifluoride is classified as skin and eye corrosive and consequently the complex can also be regarded as corrosive, which was confirmed in a Skin corrosion study in rabbits according to OECD Guideline 404 (see IUCLID section 7.3.1).

The following studies (read-across) conducted with boron trifluoride, boron trifluoride dihydrate and methanol further underline the acute toxicity /  corrosiveness of the complex.

Acute inhalation toxicity:

-Key / Read across to  boron trifluoride dihydrate:

In a publication of Rusch et al. from 1986, groups (5/sex) of Fischer 344 rats (approx. 7 weeks old) were treated whole body via inhalation route with the read across substance boron trifluoride dihydrate (CAS No. 13319-75-0). Animals were exposed for 4 hours at concentrations of 1.01, 1.22, 1.32 and 1.54 mg/L. Animals were then observed for 14 days. All animals were examined at the end of the chamber equilibration period, at 0.25, 0.5, 0.75 and 1h during exposure, at 0, 1, 2 and 24 h post exposure and daily during the 14-day post-exposure observation period. Body weights were recorded on days 1, 2, 4, 7 and 14. Necropsy was performed on all animals.
Mortality was observed in all dosing groups: 3/10 (1.01 mg/L), 2/10 (1.22 mg/L), 8/10 (1.32 mg/L) and 9/10 (1.54 mg/L). Observed clinical signs included dry and moist rales, gasping, excessive oral and nasal discharge, and lacrimation, indicative of respiratory distress and irritation. Recovery was apparent for the rats surviving beyond study day 6 post exposure.
The LC50 (4 h) was calculated to be around 1210 mg/m3 when rats were whole body exposed by inhalation to aerosols of BF3 dihydrate.

-Supporting / Read across to boron trifluoride and boron trifluoride dihydrate:
The acute inhalation toxicity of the read across substance boron trifluoride dihydrate (CAS No. 13319-75-0) was evaluated in a 4-hour, single-exposure study in rats according to a protocol comparable to the OECD Guideline 403 (Rusch et al., 2008). The test substance was initially administered to a single group of ten male and ten female Sprague Dawley rats via whole-body exposure at concentrations of 0, 10, 30, 100 mg/m3 (nominal) (8.53±2.83, 24.6±10.3 and 74.4±11.9 mg/m3 (analytical)). All animals were examined at the end of the chamber equilibration period, at 0.25, 0.5, and 1h during exposure, at 0, 1, 2 and 24 h post exposure and twice daily during the 14-day post-exposure observation period for those animals not sacrificed 24 h post exposure. Body weights were recorded daily from pretreatment until sacrifice.
There were no unscheduled deaths. There were no effects on body weight or body weight gain. The larynx showed treatment-related histopathological findings in rats in the 74.4-mg/m3 exposure level group. Based on the results of this study, the LC50 of BF3 was higher than 74.4+/-11.9 mg/m3 when male and female rats were exposed for a single, 4-hour period.

Quite similar LC50 ranges were reported in other publications: LC50 (4 h) of 1180 mg/m3 (Kasparov et al. 1972) and LC50 (1 h) of 899.34 -1439.56 mg/m3 (Vernot et al. 1977), indicating that the substance has a high potential of acute toxicity by inhalation.

The NOAEL for respiratory irritation following a single exposure of 4 hours to low dose levels was estimated around 24.6 mg/m3 (Rusch et al., 2008).

- Supporting / Read across to methanol:

The 4-hour LC50 of the read across substance methanol (CAS no. 67 -56 -1) in rats (via nose/head exposure) was calculated to be 128.2 mg/L (BASF, 1980b). For a 6 -hour exposure under the otherwise same conditions was calculated to be 87.5 mg/L. Clinical signs of toxicity were aqueous secretion of eyes and nose, labored breathing, staggering, apathy, and narcosis.

A similar range of toxicity values is reported for the mouse: LC50 (2.25 h) = approx. 79 mg/L (Von Burg, 1994).

In cats, a LC50 value of approx. 43.7 mg/L was obtained after a 6-hour exposure (Von Burg, 1994). A shorter duration of 4.5 hours led to a LC50 value of 85.4 mg/L (Von Burg, 1994).

Studies in Rhesus monkeys indicate lethal concentrations (% mortality not reported) of 1.3 mg/L (after 41 hours), 13 mg/L (after 18 hours) and 52 mg/L methanol (after 1–4 hours). Blindness associated with optic nerve atrophy was reported. Eventual recovery from this lesion was observed (McCord, 1931; only limited documentation).

Justification for classification or non-classification

Legal classification regarding acute toxicity is available for the read across substances boron trifluoride and methanol:

Classification, Labelling, and Packing Regulation (EC) No. 1272/2008, Table 3.1 List of harmonised classification and labelling of hazardous substances:
- boron trifluoride:  Acute Tox. 2 (H330: Fatal if inhaled)
- methanol: Acute Tox. 3 (H301 + H311 + H331: Toxic if swallowed, in contact with skin or if inhaled)

[ Separate legal classification of boron trifluoride dihydrate (CAS 13319-75-0) is not available.]

Considering legal classification and study results, the complex of boron trifluoride with methanol should be classified with respect to acute toxicity as follows:

Based on the legal classification under Regulation (EC) No. 1272/2008 of the read across substances  boron trifluoride and methanol and the experimental data available for boron trifluoride methanol, methanol, and boron trifluoride dihydrate, the following classification and labelling is proposed for the test substance:
Acute Tox. 3 (H311 + H331): Toxic in contact with skin and if inhaled

Acute Tox. 4 (H302): Harmful if swallowed
under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation EC No 605/2014.

In addition, the legal classification as STOT SE cat. 1 for methanol is adopted.