Hydrogen fluoride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published peer reviewed study

Data source

Reference

Reference Type:

publication

Title:

Short-term exposures of rats to airborne hydrogen fluoride

Author:

Dalbey W, Dunn B, Bannister R, Daughtrey W, Kirwin C, Reitman F, Wells M & Bruce J

Year:

1998

Bibliographic source:

Journal of Toxicology and Environmental Health, Part A 55: 241-275

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity following nose only and mouth breathing exposure

GLP compliance:

not specified

Test type:

other: non-standard method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen fluoride

EC Number:

231-634-8

EC Name:

Hydrogen fluoride

Cas Number:

7664-39-3

Molecular formula:

FH

IUPAC Name:

hydrogen fluoride

Details on test material:

HF (99.99% purity) was obtained from Matheson Gas Products.

Test animals

Species:

rat

Strain:

other: Sprague-Dawley derived VAF/Plus Crl:CD(SD)BR

Sex:

female

Details on test animals or test system and environmental conditions:

The rats were female Sprague-Dawley derived VAF/Plus Crl:CD(SD)BR, obtained from Charles River. All rats were at least 8 weeks old at the start of exposure.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

other: nose only and mouth only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

HF was diluted with air (dried, filtered and rehumidified to ~50% relative humidity) before reaching the rats. Nearly all of the surfaces of the exposure system that came into contact with HF were covered with Teflon or high density polyethylene.
During exposures the animals were in holding tubes designed for head-only exposures. Mouth breathing rats were anaesthetised for insertion of canulae into the trachea. The cannulas were removed immediately following exposure. Nose breathing rats were anaesthetised but allowed to wake up without insertion of a cannula.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Once during each exposure using an ion specific electrode

Duration of exposure:

2 - 60 min

Remarks on duration:

2, 10 or 60 min

Concentrations:

34 to 8621 ppm. Ct products (ppm x min) were ~1200, ~2800, ~9500, 14540, ~17000, 38470, ~70000 and 122340.

No. of animals per sex per dose:

20 females per group

Control animals:

yes

Details on study design:

Sham exposed controls were included. The majority of groups were sacrificed approximately 1 day following exposure. A recovery group was included; mouth breathing rats exposed to 1454 ppm for 10 minutes were allowed a 3 or 14 week recovery period. A nose breathing group was included at each exposure time period for comparison.
Rats were received in several shipments, an exposed group and a sham-exposesd group was chosen from each shipment.
Body weights were recorded on the day of exposure and at sacrifice. All surviving animals were observed immediately after exposure and on the following day for clinical, pharmacological or toxicological signs. Ten rats per group were used for bronchoalveolar lavage (BAL), haematology and serum chemistry, the remaining 10 were used for pulmonary function tests, histopathology and organ weights.

Statistics:

ANOVA, and Duncan's multiple range test.

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

other: NOEL

Effect level:

271 ppm

Exp. duration:

10 min

Remarks on result:

other: mouth breathing

Effect levels 2

Sex:

female

Dose descriptor:

other: NOEL

Effect level:

593 ppm

Exp. duration:

2 min

Remarks on result:

other: mouth breathing

Mortality:

One rat died overnight in the 8621 ppm x 2 min group; 2 died overnight in the 4887 ppm x 2 min group, and 1 died in the 1764 x 10 min group.

Clinical signs:

other: Immediately after exposure wet rales were observed in both mouth breathing and nose breathing groups. Rales were observed in sham exposed and HF exposed rats, however there was a higher incidence of rales in HF rats. Cloudy appearance of the eyes was note

Body weight:

Exposure to HF generally did not appear to significantly affect body weight by day after exposure. Most control and exposed groups lost 0-11 g in mean body weight between the day of exposure and the following day.
In the recovery groups, mean body weight tended to be lower in exposed animals than the controls.

Gross pathology:

Mouthing breathing rats:
There was a lack of collapse of the lungs in 6/10 rats in the 8621 ppm for 2 min group and 3/10 in the 1764 ppm for 10 min group. Lungs from rats in these groups had visibly reddened areas. Changes in organ weights were limited to the mouth breathing groups that received the highest exposures to HF. Spleen weight was significantly decreased in the 8621 ppm for 2 min group, and thymus weight was significantly decreased in the 8621 ppm for 2 min group and the 1764 ppm for 10 min group. Wet weight of the right middle lung lobe was increased with the two highest HF concentrations with 2 min exposures and the highest 10 min exposure. Dry weight also increased with the 2 min exposures.
There were no major changes observed in the recovery groups at sacrifice.

Other findings:

Statistically significant increases in AST, ALT and SDH occurred at 8621 ppm for 2 min. RBC count, haemaglobin and haematocrit all tended to increase at 1764 ppm for 10 min and 8621 ppm for 2 min.
Biochemical markers in the BAL increased in a dose-related manner with both 2 and 10 min exposures (Table 1).
Lung volumes were decreased in the 8621 ppm for 2 min group, and a similar but non-significant decrease was seen in the 4887 ppm for 2 min group.
Tracheal lesions consisted primarily of mucosal necrosis, acute inflammation, oedema, and fibrinopurulent exudate in the lumen of the trachea. Necrosis of the mucosal epithelium of the primary bronchi was seen in the lungs of rats from the highests two dose rates at 2 min exposure times, and the highest concentration at the 10 min exposure time.
Effects of HF exposure in the nose breathing animals were confined to the nose. Haemorrhage, necrosis and acute inflammation were observed in the ventral meatus of the nose, the site most affected in these animals. The nasoturbinates were similarly affected.

Any other information on results incl. tables

Breathing rate was reduced in nose breathing animals exposed to 1669 or 6392 ppm. It was thought that the presence of rales in sham exposed mouth breathing rats was due to insertion of the cannula. The primary lesions appeared to be the most severe at the point of entry; the trachea in mouth breathing animals and the nose in nose breathing groups.

Summary of significant effects resulting from mouth breathing HF exposures.

Ct^a	Endpoint	2-min exposure	10-min exposure	60-min exposure
~ 17000	Mortality	5%	5%
	Blood	¿AST, ALT, SDH, RBC, Hb, Hct	¿SDH, Hb, Hct
	BAL	¿TP, MPO, LDH, G-6-PDH, ß-gluc., PMN, sialic acid	¿TP, MPO, LDH, ß-gluc., PMN, sialic acid
	Weights	¿spleen and thymus weight,¿wet and dry lung weight	¿wet lung weight
	Histology	Tracheal inflammation, exudate and necrosis. Bronchial exudate and necrosis, alveolitis	Tracheal inflammation, exudate and necrosis. Bronchial exudate
~9500	Mortality	10%	None^b
	Blood	¿SDH	¿AST
	BAL	¿TP, MPO, LDH, ß-gluc., PMN, sialic acid	¿PMN, MPO
	Weights	¿wet and dry lung weight	None
	Histology	Tracheal inflammation, exudate and necrosis. Bronchial exudate and necrosis, alveolitis	Tracheal necrosis ˜ controls
~2800	Mortality	None	None	None
	Blood	¿AST	None	None
	BAL	¿TP, MPO, LDH, ß-gluc.	None	None
	Weights	None	None	None
	Histology	Tracheal necrosis ˜ controls	None	None
~1200		None	None	None

Abbreviations: aspartate aminotransferase (AST), alanine aminotransferase (ALT),ß-Glucuronidase (ß-gluc.), glucose-6-phosphate dehydrogenase (G-6-PDH), haemoglobin (Hb), haematocrit (Hct), lactate dehydrogenase (LDH), myeloperoxidase (MPO), polymorphonuclear leukocytes (PMN), red blood cells (RBC), sorbitol dehydrogenase (SDH), total protein (TP).

^aCt = (concentration of HF in ppm)(minutes of exposure)

^bNone = no observed treatment related effect.

Applicant's summary and conclusion

Conclusions:

The 2 minute NOEL in female rats was 573 ppm HF, the 10 minute NOEL was 271 ppm.

Executive summary:

Rats were exposed to HF at varying concentrations up to 8621 ppm for 2, 10 or 60 minutes. Inhalation exposures were limited to mouth breathing or nose breathing only. Effects of exposure were generally limited to the respiratory tract and included alveolitis, bronchial lesions, altered parameters of bronchoalveolar lavage, mucosal necrosis, inflammation and fibrinopurulent exudate in airways. Observed changes were concentration related and appeared more pronounced near the point of entry (i.e. nose or trachea). A group of rats exposed to 1454 ppm for 10 minutes had fully recovered from the acute effects at 3 and 14 weeks post-exposure. The 2 minute NOEL in female rats was 573 ppm HF, the 10 minute NOEL was 271 ppm.