Hydrogen fluoride

Endpoint summary

Description of key information

Waivers are appropriate for acute oral, dermal and inhalation toxicity as HF is a corrosive substance.  No acute oral toxicity data are available.  However, several non-standard acute inhalation toxicity studies are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

the study does not need to be conducted because a study on acute toxicity by the inhalation route is available

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

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

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

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.

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.

Preliminary study:

Not applicable

Sex:

female

Dose descriptor:

other: NOEL

Effect level:

271 ppm

Exp. duration:

10 min

Remarks on result:

other: mouth breathing

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.

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.

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.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1963

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Older published study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity of HF in guinea-pigs; 15 minute exposure

GLP compliance:

no

Remarks:

: older published study, pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals or test system and environmental conditions:

Young white male guinea pigs of a derived Hartley strain, bred in-house. The guinea pigs weighed 225-285g.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The exposure chamber was a 400l dynamic gassing chamber, operated at an air flow of 200l/min. An expansion tank and kerosene manometer were used, housed in a constant temperature box at 68oC.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Chamber air samples were collected in either gas bottles or in two absorbers in series each containing 20ml of 0.2N NaOH. The sampling rate was from 0.1-4 l/min. Samples collected in gas bottles were cooled before adding the 20ml of 0.2N NaOH. Samples wer

Duration of exposure:

15 min

Concentrations:

Lethal exposures: various concentrations (not stated).

No. of animals per sex per dose:

10 male guinea pigs per group

Control animals:

yes

Details on study design:

Groups of guinea pigs were exposed to various lethal concentrations of hydrogen fluoride vapours for 15 minutes. Surviving guinea pigs were weighed daily and observed for 14 days after exposure. Clinical observations were made following exposure, body weights were recorded daily and mortalities recorded.

Statistics:

The LC50 value was calculated using the method of Bliss (1952).

Preliminary study:

Not applicable

Sex:

male

Dose descriptor:

LC50

Effect level:

4 327 ppm

95% CL:

4 006 - 4 672

Exp. duration:

15 min

Remarks on result:

other: The slope is 15.5 and standard error of slope is plus or minus 4.8

Mortality:

Mortality occurred, but numbers of animals that died are not provided. Some deaths were reported to occur during the post-exposure observation period.

Clinical signs:

other: Conjunctival and nasal irritation as shown by reddened conjunctivae, pawing at the nose, marked lacrimation, nasal secretion and sneezing. These signs were not seen 1 week following exposure (in surviving animals). Respiratory distress and general weaknes

Body weight:

Body weight loss was observed in surviving animals. Guinea pigs displayed a 25% reduction in body weight during the first week, compared to controls, after which their weight gain paralleled the controls but did not reach it.

Gross pathology:

Not examined.

Other findings:

No further information.

The LC50 value for HF was 4327 ppm for guinea pigs exposed to hydrogen fluoride vapour for 15 minutes.

Interpretation of results:

other: not derived - non-standard species and expousre time

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 value was 4327 ppm for guinea pigs exposed to hydrogen fluoride vapour for 15 minutes.

Executive summary:

Male Hartley guinea pigs were exposed to concentrations of hydrogen fluoride vapour, at various concentrations for 15 minutes. The LC50 value was calculated to be 4327 ppm. Exposure resulted in mortalities, although numbers and times of death are not reported. Exposure resulted in conjunctival and nasal irritation, respiratory distress and general weakness, and body weight loss.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

other: literature review

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: UK Health and Safety Executive (HSE) review article, summarising available acute inhalation toxicity data.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Review article detailing several LC50 values obtained in published acute inhalation toxicity studies

GLP compliance:

not specified

Test type:

other: literature review

Species:

other: rat, mouse and monkey

Details on test animals or test system and environmental conditions:

The article reports LC50 values for rats, mice and monkeys.

Route of administration:

inhalation

Details on inhalation exposure:

Various studies reported. The Haskell 1988 study used nose only exposure.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

5 - 60 min

Concentrations:

Rat: 966 to 18200 ppm.
Mouse: 342 to 6247 ppm.
Monkey: 1774 ppm.

No. of animals per sex per dose:

No information available

Control animals:

not specified

Details on study design:

No information available in review.

Statistics:

No information available in review.

Preliminary study:

Not applicable.

Dose descriptor:

LC50

Effect level:

18 200 ppm

Exp. duration:

5 min

Remarks on result:

other: Rat (Higgins et al, 1972)

Dose descriptor:

LC50

Effect level:

14 600 ppm

Exp. duration:

5 min

Remarks on result:

other: Rat (Haskell Laboratory, 1988)

Dose descriptor:

LC50

Effect level:

6 620 ppm

Exp. duration:

15 min

Remarks on result:

other: Rat (Haskell Laboratory, 1988)

Dose descriptor:

LC50

Effect level:

2 890 ppm

Exp. duration:

30 min

Remarks on result:

other: Rat (Haskell Laboratory, 1988)

Dose descriptor:

LC50

Effect level:

2 300 ppm

Exp. duration:

30 min

Remarks on result:

other: Rat (Haskell Laboratory, 1988)

Dose descriptor:

LC50

Effect level:

6 247 ppm

Exp. duration:

5 h

Remarks on result:

other: Mouse (Higgins et al, 1978)

Dose descriptor:

LC50

Effect level:

1 774 ppm

Exp. duration:

60 min

Remarks on result:

other: Monkey (Darmer et al, 1972)

Mortality:

No information available

Clinical signs:

other: No information available

Body weight:

No information available

Gross pathology:

No information available

Other findings:

No information available

LC₅₀ values for Hydrogen Fluoride

Species	Duration of Exposure (min)	LC50(ppm)	Reference
Rat	5	18200	Higginset al, 1972
		14600	Haskell Laboratory, 1988
	15	6620	Haskell Laboratory, 1988
	30	2890	Haskell Laboratory, 1988
		2300	Haskell Laboratory, 1988
	60	2300	Haskell Laboratory, 1990
		1610	Haskell Laboratory, 1988
		1395	Wohlslagelet al, 1976
		1276	Darmeret al, 1972
		966	Vernotet al, 1977
Mouse	5	6247	Higginset al, 1972
	60	501	Darmeret al, 1972
		456	Vernotet al, 1977
		342	Wohlslagelet al, 1976
Monkey	60	1774	Darmeret al, 1972

Conclusions:

Various acute inhalation LC50 values are reported for rats, mice and monkeys. The Haskell Laboratory data was considered to be the most reliable and accurate by Meldrum (1999).

Executive summary:

Various acute inhalation LC50 values are reported for rats, mice and monkeys. The Haskell Laboratory data was considered to be the most reliable and accurate by Meldrum (1999).

Reference 4

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

27 October 1989 to 12 December 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary GLP study, similar to current guidelines.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Crl:CDBR

Sex:

male

Details on test animals or test system and environmental conditions:

Young adult male Crl:CDBR rats were received from Charles River Breeding Laboratories, New York. Rats were 8 weeks old at the start of the study ad weighed between 240 and 307 g. Rats were quarantined for 1 week prior to testing. They were housed in pairs in suspended stainless steel wire mesh cages. Individuals were identified by ear marks and tail colour markings (water-insoluble markers). Purina Certified Rodent Chow #5002 and water were available ad libitum (except during exposure).
Animal rooms were maintained on a 12 hour light/dark cycle. Temperature was maintained at 23±2°C, and relative humidity was 50±10%.

Route of administration:

inhalation: gas

Type of inhalation exposure:

head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The rats were placed in Teflon-coated perforated stainless steel cylinders fitted with conical nose pieces, there were four restrainers per chamber. Test atmospheres of HF were generated by metering anhydrous HF in a polymethyl-methacrylate exposure chamber with an internal volume of approximately 23.3 L. HF cylinders were placed water baths heated to 30-40°C. Houseline air, previously conditioned by filtration and drying, was mixed with HF prior to entering the chamber. Atmospheres were generated at either low or high relative humidity. Houseline air had a relative humidity of approximately 10%. To increase humidity, houseline air was passed through a flask containing water at ambient temperature which raised the relative humidity to ~60%.
Each group was exposed head-only for 1 hour.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Samples were collected from the rats breathing zone at 10-20 min intervals. Samples were analysed using a fluoride specific ion electrode

Duration of exposure:

1 h

Concentrations:

Measured concentrations dry air: 950, 1550, 1690, 1730, 1800, 2030, 2040, 2260, 2420, 2730.
Measured concentrations humid air: 1290, 1940, 2060, 2200, 2210, 2490, 2620.

No. of animals per sex per dose:

4 males per group

Control animals:

no

Details on study design:

All rats were weighed prior to exposure and surviving rats were weighed and observed daily (weekends and bank holidays were generally excluded) for 14 days post exposure. In addition, two groups of 4 male rats were exposed to a sublethal concentration (~1800 ppm) at high and low relative humidity. Two rats from each groups were killed after 1 day and after 14 days recovery; representative samples of respiratory tract tissues (i.e. nose, larynx, pharynx, trachea and lungs) were obtained and examined by light microscopy.

Statistics:

The LC50 was calculated by probit analysis as described by Finney.

Preliminary study:

See Valetine (1988)

Sex:

male

Dose descriptor:

LC50

Effect level:

2 240 ppm

95% CL:

2 060 - 2 580

Exp. duration:

1 h

Remarks on result:

other: dry air

Sex:

male

Dose descriptor:

LC50

Effect level:

2 340 ppm

95% CL:

2 180 - 2 630

Exp. duration:

1 h

Remarks on result:

other: humid air

Mortality:

Deaths generally occurred 1-7 days post-exposure; deaths during exposure were rare.

Clinical signs:

other: During the 14 day observation period the clinical signs observed were indicative of the corrosive nature of HF. Respiratory distress, oral, nasal and ocular discharges, corneal opacity, shut or partially closed eyes, facial hair loss, nasal, facial and ea

Body weight:

Exposed animals generally incurred severe weight losses within 1 day exposure which persisted for several days. In surviving rats, weight recovery usually began within 3-5 days.

Gross pathology:

Representative sections of the nose, larynx/pharynx, trachea and lungs were examined from rats exposed to HF at either 1630 ppm in dry air or 1910 ppm in humid air. One day after exposure, pathologic injury was limited exclusively to the anterior section of the nose although minimal olfactory epithelial necrosis was noted in 1 rat from the dry air group. The nasal injury was characterised by extensive acute necrosis of respiratory epithelium with inflammation and vascular thrombosis in adjacent submucosal tissues. No compound-related injury was observed in either the more posterior portions of the nose, nor in the trachea or lung. By 14 days after treatment, some squamous metaplasia of respiratory epithelium and slight inflammation in the 1630 ppm group was observed.

Other findings:

None reported.

Changing the type of impinger from glass to Teflon-coated resulted in more accurate measurements of chamber concentration, and explained the results of the previous study (Valentine, 1988) where lower LC50 values were obtained for humid air. With Teflon-coated impingers a higher recovery was obtained from humid atmospheres; it was calculated that the glass impinger used in the previous study was underestimating the HF concentration by 26%.

The relative humidity was measured in the chambers during the exposure with rats present, and it was found that the low humidity air increased from 10% to 43% whilst the high humidity air increased fom 60% to 76%.

Conclusions:

In comparison with the dry air LC50 value, no significant increase in HF toxicity was associated with higher relative humidity. LC50 values for dry and humid air were 2240 ppm and 2340 ppm, respectively.

Executive summary:

In the preliminary studies (Valentine, 1988), the inhalation toxicity of HF increased with the relative humidity of the dilution air. To determine whether the apparent increase in toxicity was real or due to a sampling artefact, additional analytical trials and animal experiments were conducted. In the animal studies, groups of 4 male Crl:CDBR rats underwent head-only 1 hour exposures to HF. Anhydrous HF was diluted in either dry (~10% relative humidity) or humid (~60% relative humidity) air. Two additional groups were exposed to a sublethal concentration and killed 1 or 14 days after exposure for microscopic examination of respiratory tissues. In contrast to the previous studies, no difference in toxicity was found between the dry and humid atmospheres when Teflon-coated sampling tubes were used instead of glass tubes. LC50 values for dry and humid air were 2240 ppm and 2340 ppm, respectively.

Most deaths occurred 1 -7 days post exposure following prolonged weight losses. Clinical signs indicative of respiratory tract irritation, ocular irritation, and dermal corrosion were commonly seen. Pathological examination of rats killed 1 day after exposure to a sublethal concentration showed that compound-related microscopic lesions occurred exclusively in the nose.

Reference 5

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity in the rat (5 minute exposure)

GLP compliance:

no

Remarks:

: older published study, pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

Wistar rats weighing between 250 and 275g. Quality control checks were carried out on each shipment of rats to ensure only healthy rats were used in the toxicity studies.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The rats were exposed in a dynamic flow system using a standard Rochester chamber, modified to present the rats with a precisely timed 5 mminute inhalation challenge.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Continuous monitoring using specific ion electrodes.

Duration of exposure:

5 min

Concentrations:

11550, 12440, 12890, 15990, 17615, 17750, 18580, 20730, 21125, 22355, 22740, 23540 and 25690 ppm.

No. of animals per sex per dose:

10 rats per concentration, sex not recorded.

Control animals:

not specified

Details on study design:

Rats were exposed for 5 minutes to various concentrations of hydrogen fluoride vapour. Mortalities were recorded. The rats were observed closely for 7 days following exposure.

Statistics:

LC50 values calculated according to the method of Litchfield and Wilcoxon.

Preliminary study:

Not applicable.

Sex:

not specified

Dose descriptor:

LC50

Effect level:

18 200 ppm

95% CL:

15 965 - 20 748

Exp. duration:

5 min

Mortality:

100% mortality occurred at 25690 ppm and 10% mortality occurred at 12440 ppm. Delayed deaths were routinely observed, with peak mortality occurring approximately 24 hours after exposure. Some occasional deaths occurred 3-4 days later.

Clinical signs:

other: Pulmonary oedema was seen in the majority of exposed animals at varying degrees of severity. In rats that died during or shortly after exposure to concentrations above the LC50 value, pulmonary haemorrhage was a common finding.

Body weight:

Not examined.

Gross pathology:

Not examined.

Other findings:

No further information.

The 5 minute LC50 value for rats was 18200 ppm.

Interpretation of results:

not classified

Remarks:

Migrated information : non-standard exposure period - extrapolation not possible Criteria used for interpretation of results: not specified

Conclusions:

The 5 minute LC50 value was 18200 ppm.

Executive summary:

The acute toxicity of hydrogen fluoride vapour was determined in Wistar rats in a single 5 minute exposure. 100% mortality occurred at 25690 ppm and 10% mortality occurred at 12440 ppm. Delayed deaths were routinely observed (24 hours following exposure). Pulmonary oedema was seen in the majority of exposed animal, with varying degrees of severity.

Reference 6

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1963

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Older published study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity in the rat (up to 1 hour exposure)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Young white male rats of a derived Wistar strain, bred in-house. The rats weighed 100-120g.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The exposure chamber was a 400l dynamic gassing chamber, operated at an air flow of 200l/min. An expansion tank and kerosene manometer were used, housed in a constant temperature box at 68oC.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Chamber air samples were collected in either gas bottles or in two absorbers in series each containing 20ml of 0.2N NaOH. The sampling rate was from 0.1-4 l/min. Samples collected in gas bottles were cooled before adding the 20ml of 0.2N NaOH. Samples wer

Duration of exposure:

5 - 60 min

Remarks on duration:

5, 15, 30 and 60 minute exposures

Concentrations:

Lethal exposures: various concentrations (not stated).

No. of animals per sex per dose:

20 male rats per group

Control animals:

yes

Details on study design:

Groups of rats were exposed to various concentrations of hydrogen fluoride vapour for either 5, 15, 30 or 60 minutes. Surviving rats were weighed daily and observed for 14 days after exposure. Clinical observations were made following exposure, body weights were recorded daily and mortalities recorded.

Statistics:

The LC50 values for each exposure time were calculated using the method of Bliss (1952).

Preliminary study:

Not applicable

Sex:

male

Dose descriptor:

LC50

Effect level:

4 970 ppm

95% CL:

4 584 - 5 388

Exp. duration:

5 min

Remarks on result:

other: The slope is 11.8 and the standard error of the slope is plus or minus 4.2

Sex:

male

Dose descriptor:

LC50

Effect level:

2 689 ppm

95% CL:

2 397 - 3 016

Exp. duration:

15 min

Remarks on result:

other: The slope is 9.4 and the standard error of the slope is plus or minus 2.1

Sex:

male

Dose descriptor:

LC50

Effect level:

2 042 ppm

95% CL:

1 901 - 2 192

Exp. duration:

30 min

Remarks on result:

other: The slope is 14.0 and the standard error of the slope is plus or minus 3.3

Sex:

male

Dose descriptor:

LC50

Effect level:

1 307 ppm

95% CL:

1 212 - 1 410

Exp. duration:

60 min

Remarks on result:

other: The slope is 10.7 and the standard error of the slope is plus or minus 3.8

Mortality:

Mortality occurred, but numbers of rats that died are not provided. Some deaths were reported to occur during the post-exposure observation period.

Clinical signs:

other: Conjunctival and nasal irritation as shown by reddened conjunctivae, pawing at the nose, marked lacrimation, nasal secretion and sneezing. These signs were not seen 1 week following exposure (in surviving animals). Respiratory distress and general weaknes

Body weight:

Body weight loss was observed in surviving animals. Compared to controls, surviving rats exhibited a 10-15% reduction in body weight during the first 3-7 days after exposure, after which weights returned to normal.

Gross pathology:

Lesions were found (differing quantitatively from that of controls) in the kidneys, liver, nasal passage, bone marrow and skin of exposed rats.

Other findings:

No further information.

The LC50 values were 4970, 2690, 2040 and 1310 ppm for rats exposed to hydrogen fluoride vapour for 5, 15, 30 and 60 minutes, respectively.

Interpretation of results:

very toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LC50 values were 4970, 2690, 2040 and 1310 ppm for rats exposed to hydrogen fluoride vapour for 5, 15, 30 and 60 minutes, respectively.

Executive summary:

Male Wistar rats were exposed to lethal concentrations of hydrogen fluoride vapour, at various concentrations for either 5, 15, 30 or 60 minutes. The LC50 values were 4970, 2690, 2040 and 1310 ppm for rats exposed to hydrogen fluoride vapour for 5, 15, 30 and 60 minutes, respectively. Exposure resulted in mortalities, although numbers and times of death are not reported. Lesions were observed in the kidneys, liver, nasal passages, bone marrow and skin. Exposure resulted in conjunctival and nasal irritation, respiratory distress and general weakness and body weight loss.

Reference 7

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

22 April 1986 to 30 November 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Proprietary GLP study, data regarding high humidity exposures are not reliable

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

other: British Naval Engineering Standard 713

Principles of method if other than guideline:

Acute inhalation toxicity; expoure times of up to 60 minutes

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Crl:CDBR

Sex:

male

Details on test animals or test system and environmental conditions:

Young adult male Crl:CDBR rats were received from Charles River Breeding Laboratories, New York. Rats were quarantined for 1 week prior to testing. Rats were housed in pairs in suspended stainless steel wire mesh cages. Individuals were identified by ear markings and tail colour marking (water-insoluble markers). Purina Certified Rodent Chow #5002 and water were available ad libitum (except during exposure). At the start of the study the rats were 8 weeks old and weighed approximately 200 to 300 g.
The animal rooms were maintained on a 12 hour light/dark cycle. The temperature was maintained at 23±2°C and the relative humidity at 50±10%.

Route of administration:

inhalation: gas

Type of inhalation exposure:

head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The rats were restrained in perforated, Teflon-coated stainless steel cylinders fitted with conical nose pieces. Rats were exposed head-only.
Initially, atmospheres of HF were generated by metering the gaseous test material, 2% HF in nitrogen into a Lucite exposure chamber with an internal volume of ~23.2 L. 4 rats in the restraint tubes were fitted to the chamber. Houseline air was conditioned though Drierite, activated charcoal and HEPA filters and mixed with oxygen and gaseous HF prior to entering the chamber. Total airflow was ~12 L/min.

In further studies liquified HF was used (2% HF in nitrogen became unavailable). Cylinders of anhydrous HF were placed in a water bath maintained at ~38°C. HF was mixed with houseline air prior to entering the chamber. Total airflow through the exposure chamber was ~12 L/min. The exposures were conducted at either of two relative humidity conditions: low relative humidity exposures were conducted with houseline air with a relative humidity of 0.1-8.7%; high relative humidity exposures were conducted by passing houseline aiir through a flask containing water at ambient temperature to raise the relative humidity to 40-60%.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

All samples were collected from the breathing zone of the rats, and analysed using a fluoride ion specific electrode (Orion). Typically 1 sample was taken during the 5 min exposure; 3 during the 15 min exposure; 3 during the 30 min exposure and 5 during t

Duration of exposure:

5 - 60 min

Remarks on duration:

5, 15, 30 or 60 minutes

Concentrations:

Gaseous HF 30 min exposure: 902, 974, 1180, 1400, 1880, 1930, 2450, 2520, 2790, 2880, 3900 and 4190 ppm.
Anhydrous HF: 576 to 20500 ppm (depending on exposure time)

No. of animals per sex per dose:

4 males per group

Control animals:

no

Details on study design:

Male rats were exposed in head-only inhalation chambers in groups of 4 for 5, 10, 15, 30 or 60 minutes at varying concentrations and either high or low relative humidity. Rats were weighed prior to exposure, and were observed for clinical signs of toxicity during exposure. Surviving rats were weighed and observed daily for at least 14 days post exposure.
Mortality data were obtained from 6-15 exposures per time point.

Statistics:

The LC50 was calculated for each time point and relative humidity condition by probit analysis (Finney).

Preliminary study:

Not applicable

Sex:

male

Dose descriptor:

LC50

Effect level:

2 300 ppm

95% CL:

1 970 - 2 580

Exp. duration:

30 min

Sex:

male

Dose descriptor:

LC50

Effect level:

1 610 ppm

Exp. duration:

60 min

Remarks on result:

other: low relative humidity

Mortality:

Most deaths occurred within 1-2 days of exposure, however some rats died up to 10 days post exposure. In general, time to death increase as the exposure concentration increased. LC50 values are listed in Table 1.

Clinical signs:

other: Immediately after exposure, most rats from all groups exhibited corneal opacities and laboured breathing. These signs were observed in both the dry and humid exposure groups and were generally noted at lower concentrations for humid air. During the 14 day

Body weight:

Most rats had severe (20-60 g) weight losses within 1 day of exposure. Although some rats began to regain weight 2 days after exposure, persistent weight loss occurred in most surviving rats for up to 10 days post exposure.

Gross pathology:

Not performed.

Other findings:

None reported.

Table 1. LC50 values and 95% confidence limits.

Exposure time (min)	Calculated LC50 (ppm)	95% Confidence Limits		No. Rats
		Lower	Upper
Pressurised HF/nitrogen
30	2300	1970	2580	12
Anhydrous HF – Dry Air
5	14600	13300	16200	9
15	6620	5450	10600	12
30	2890	2540	3310	15
60	1610	1250	1860	9
Anhydrous HF – Humid Air
5	10700	6990	18000	12
15	2470	1530	4800	9
30	1110	450	1960	14
60	541	431	657	6

Conclusions:

The acute 60 minute inhalation toxicity of HF was 1610 ppm in male rats at low relative humidity. Only data regarding low humidity exposures can be considered reliable.

Executive summary:

The acute toxicity of hydrogen fluoride was determined in a series of experiments investigating the effects of exposure time, HF concentration and humidity. Groups of 4 rats were exposed to HF in head only chambers for 5, 15, 30 or 60 minutes. Exposure atmospheres were either low relative humidity (< 10%) or humid (40 -60% relative humidity). Lower LC50 values were associated with humid air compared to dry air; the LC50 for dry air was comparable to values quoted in the literature (1610 ppm), whilst the LC50 for humid air was lower (541 ppm). Clinical signs indicative of the corrosive nature of HF were observed among all groups. These signs included respiratory distress, ocular and nasal discharges, corneal opacity, necrotic lesions of the eyes, face and ears, and severe weight losses during the recovery period. Most deaths occurred within 1 -2 days exposure, although some delayed deaths were noted. The authors concluded that the data regarding humid atmospheres should be treated with caution, because additional work was required to determine whether the observed toxicity was a real effect of humidity of attributable to procedural/analytical problems associated with the method of HF analysis. Only data regarding low humidity exposures can be considered reliable.

Reference 8

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published [paper

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Assessment of acute inhalation toxicity in rats and mice (1-hour exposure)

GLP compliance:

no

Test type:

other: non-guideline

Limit test:

no

Species:

other: rats and mice

Strain:

other: Sprague Dawley and ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals consisted of groups of ten male CFE (Sprague Dawley derived) rats weighing between 250 and 325 grams and groups of 10 female CF-1 (ICR derived) mice with weights ranging from 25 to 32 grams.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Hydrogen fluroide vapour was supplied to the exposure chamber from steel steel tanks of the pure liquid material or from gas cylinders of a 1% concentration HF in dried nitrogen. Metering of the contaminant was accomplished with a Teflon flowmeter or a Hastings Raydist Mass Flowmeter (Model LF-20K).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

60 min

Concentrations:

The HF vapour concentration was between 1087 and 1765 ppm.

No. of animals per sex per dose:

10 male CFE (Sprague-Dawley derived) rats per concentration.
10 female CF-1 (ICR derived) mice per concentration.

Control animals:

not specified

Details on study design:

Animals were observed for toxic signs and mortality during the exposure and for a period of 14 days post exposure. A representative number of test animals that died following treatment or were sacrified after the 14 day observation period were submitted for gross and histopathlogical examination.

Hydrogen fluoride vapour was supplied to the exposure chamber from steel tanks of the pure liquid material or from gas cylinders of a 1% concentration HF in dried nitrogen.

The exposure chamber was a modified Longley type utilizing a sliding cage drawer to permit rapid insertion and withdrawal of test animals from the contaminant chamber. Partially dreid air with a relative humidity of approximately 23% was metered at a rate of 11 cfm to one quadrat of the Longley chamber having a volume of 22.1 cubic feet.

Continuous analysis of HF concentrations in the exposure chamber were possible by taking known volumes of chamber atmosphere and mixing in a gas scrubber column with known amounts of aqueous reagent absorber. The soultion was then passed through a flow cell containing specific ion and reference electrodes. Calibration of the electrodes was done prior to every exposure.

Statistics:

None reported.

Preliminary study:

No preliminary study

Sex:

male

Dose descriptor:

LC50

Effect level:

1 395 ppm

95% CL:

1 302 - 1 495

Exp. duration:

60 min

Remarks on result:

other: Rats

Sex:

female

Dose descriptor:

LC50

Effect level:

342 ppm

95% CL:

315 - 372

Exp. duration:

60 min

Remarks on result:

other: Mice

Mortality:

Mortality was observed in rats at and above a concentration of 1108 ppm. For mice, mortality was noted at a concentration of 278 ppm and above.

Clinical signs:

other: Symptoms of rats and mice during exposure included eye and mucous membrane irritation, respiratory distress, corneal opacity and erythema of exposed skin.

Body weight:

Not stated.

Gross pathology:

Pathlogical examination of rats dying during or after exposure showed pulmonary congestion, intraalveolar edema and some cases of thymic hemorrhage. Mice exhibited pulmonary congestion and hemorrhage.

Other findings:

No further findings.

RATS		MICE
HF Concentration (ppm)	Mortality	HF Concentration (ppm)	Mortality
1087	0/10	263	0/10
1108	2/10	278	1/10
1405	3/10	324	7/10
1565	8/10	381	6/10
1765	10/10	458	9/10

Interpretation of results:

other: : non-standard exposure period - extrapolation not possible

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

The 60 minute LC50 values for rats and mice exposed to HF vapours are 1395 ppm and 342 ppm respectively.

Executive summary:

The acute inhalation toxicity of HF was investigated in male rats and female mice exposed for 60 minutes. LC50 values for rats and mice exposed to HF vapours are 1395 ppm and 342 ppm respectively. Symptoms in rats and mice during exposure included eye and mucous membrane irritation, respiratory distresss, corneal opacity and erythema of exposed skin. Pathlogical examination of rats dying during or after exposure showed pulmonary congestion, intraalveolar edema and some cases of thymic hemorrhage. Mice exhibited pulmonary congestion and hemorrhage.

Reference 9

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-standard published study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Investigation of the acute effects of 10-minute inhalation exposure to hydrogen fluoride in rats

GLP compliance:

no

Remarks:

: older, published study

Test type:

other: non-standard

Limit test:

no

Type of inhalation exposure:

other: mouth-breathing model

Duration of exposure:

>= 2 - <= 60 min

Concentrations:

Concentrations of HF ranged from 593 to 8621 ppm for 2-min exposures and from 135 to 1764 ppm for 10-min exposures. Additional exposures were performed for 60 min at 20 and 48 ppm HF

No. of animals per sex per dose:

20 female

Control animals:

yes

Sex:

female

Dose descriptor:

LC50

Effect level:

3 847 ppm

Exp. duration:

10 min

Greater toxicity is noted in mouth-breathing rats compared to nose-breathing rats. Effects of exposure to HF in nose-breathing rats were limited to the nose, whereas trachea, bronchial and deep lung effects were seen in mouth-breathing rats.

Interpretation of results:

other: not relevant

Conclusions:

Greater toxicity is noted in mouth-breathing rats compared to nose-breathing rats. Effects of exposure to HF in nose-breathing rats were limited to the nose, whereas trachea, bronchial and deep lung effects were seen in mouth-breathing rats.

Executive summary:

Concentrations of HF ranged from 593 to 8621 ppm for 2-min exposures and from 135 to 1764 ppm for 10-min exposures. Additional exposures were performed for 60 min at 20 and 48 ppm HF. Greater toxicity is noted in mouth-breathing rats compared to nose-breathing rats. Effects of exposure to HF in nose-breathing rats were limited to the nose, whereas trachea, bronchial and deep lung effects were seen in mouth-breathing rats.

Reference 10

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published peer reviewed study, non-guideline but appears to be a robust well conducted study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute toxicity determined by nose breathing and pseudo-mouth breathing methods in rats

GLP compliance:

not specified

Test type:

fixed concentration procedure

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Male Fischer-344 rats, SPF weighing 245-270 g.

Route of administration:

inhalation: gas

Type of inhalation exposure:

other: nose only and pseudo-mouth-breathing

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Rats were fitted with mouthpieces with attached silastic endotracheal tubes (mouth breathers) under anaesthesia. Nose breathers were anaesthetised but allowed to wake up without further treatment. After recovery from anaesthesia the rats were placed in partial body flow plethysmographs and attached to an exposure chamber.The rats were provided clean filtered air for 5 minutes. HF was mixed with filtered air and delivered to the rats for 30 minutes. Following exposure, clean air was delivered to the rats for a further 15 minutes.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Samples were quantitatively drawn through midget impingers at a rate of 400 ml/min into buffers, and samples were analysed with calibrated ion-specific electrodes. A minimum of 3 samples were collected per exposure

Duration of exposure:

30 min

Concentrations:

Nominal: 1300 ppm. Actual: 1295±25 ppm and 1294±67 ppm (~823 mg/m3)

No. of animals per sex per dose:

6 rats per group

Control animals:

yes

Details on study design:

The rats were habituated to the plethysmographs for 3 days prior to the test. Rats were exposed in to HF in two groups - the pseudo-mouth breathing group fitted with endotracheal tubes and the nose breathing group. Controls were exposed to air only. Rats were euthanised 24 hours post exposure for histological examination.

Statistics:

Two-tailed t-test for unpaired data and the Mann-Whitney nonparametric test.

Preliminary study:

Not applicable.

Sex:

male

Dose descriptor:

other: concentration level

Effect level:

1 300 ppm

Exp. duration:

30 h

Remarks on result:

other: mouth breathing exposure 25% mortality within 24 hours

Mortality:

No mortality occurred in the nose breathing rats. 25% mouth breathing rats died within 24 hours of exposure to HF.

Clinical signs:

other: Not reported

Body weight:

All rats in the nose breathing groups, including controls, lost weight after exposure. HF exposed rats lost more weight than the air only controls, beginning 24 hours post exposure. Rats in the mouth breathing groups generally showed a smaller reduction in body weight than the nose breathing groups. HF rats lots an average of ~ 25 g.

Gross pathology:

Lung wet weights of mouth breathing rats were significantly higher than those of the air exposed controls.

Other findings:

Histopathology: no abnormalities were found in the nasal passages of the nose breathing rats exposed to air only. The nose breathing rats exposed to HF had a fibrinonecrotic rhinitis that varied from moderate to very severe, which was accompanied by large fibrin thrombi in the submucosa and haemorrhage. Polymorphonuclear leukocytes (PMN) were found enmeshed in fibrin in the nasal passages, relatively few PMN were in the submucosa.
Nasal sections were generally normal after inhalation by the mouth breathing rats. However, exudated and/or blood were occasionally found in the turbinates, especially in the regions furthest away from the nostrils.
In a small number of nose breathing rats exposed to HF, the trachea showed a mild suppurative inflammatory reaction in the proximal mucosa, but was not significantly different from the appearance of the trachae of air exposed rats. Mouth breathing rats had a diffuse, very severe fibrinonecrotic tracheitis with moderate influx of PMN in and around the trachea.
No abnormalities were detected in the lower respiratory tracts of nose breathing rats. The lungs of mouth breathing rats exposed to HF had focal areas of necrotising bronchitis of the major bronchi, which was significantly greater than that found in air exposed mouth breathing rats. In the alveolar region, scattered foci of PMN in some alveolar ducts and nearby alveoli were observed.

Mouth breathing exposure to HF caused higher mortality rates and major tissue disruption in the trachea. The effects of exposure differ depending on the inhalation route.

Conclusions:

Mouth breathing exposure to HF caused higher mortality rates compared to nose breathing exposure, and major tissue disruption in the trachea.

Executive summary:

Rats were exposed to 1300 ppm HF for 30 minutes, via either nose only breathing or pseudo-mouth breathing. No mortality occurred in the nose breathing rats. 25% mouth breathing rats died within 24 hours of exposure to HF. Major tissue disruption was seen in the trachea of mouth breathing rats, whilst tissue injury was confined to the nasal region in nose breathing rats. Lung wet weights of mouth breathing rats were significantly higher than those of the air exposed controls. The effects of HF exposure differ depending on the route of inhalation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2 240 ppm air

Physical form:

inhalation: gas

Quality of whole database:

Klimisch 1, GLP study to OECD 403 (Valentine, 1990).
The majority of remaining studies are Klimisch 2, non-GLP studies or pre-date GLP to no guideline or non-OECD guideline (Stavert et al, 1991, Dalbey et al, 1998, Wohlspagel et al, 1976, Valentine, 1988, Higgins et al, 1972, Meldrum, 1999, Dalbey et al, 1998).
Rosenholtz et al, 1963, is a Klimisch 4 study which pre-dates GLP.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute oral toxicity

No data are available. A waiver is appropriate for this endpoint as the substance is corrosive and oral exposure will result in rapid tissue destruction. It is noted that HF is classified in the EU as 'Very toxic if swallowed'.

Acute inhalation toxicity

A waiver is appropriate for this endpoint as the substance is corrosive and exposure will result in rapid tissue destruction.

However, several published literature studies of non-standard design are available in a number of species and have been summarised. Rosenholtz et al (1963), reported LC50 values of 4970, 2690, 2040 and 1310 ppm in the rat for exposure durations of 5, 15, 30 and 60 minutes, respectively. Signs of toxicity included ocular and nasal irritation and respiratory distress. Higgins et al (1972) report a 5 -minute LC50 value of 18200 ppm for the rat; deaths are reported to be delayed (24 hours) and were associated with pulmonary oedema. Rosenholtz et al (1963) also report a 5 -minute LC50 value of 4327 ppm for HF in the guinea pig. The results of these studies indicate that HF should be classified as 'Very toxic by inhalation', which is consistent with the current classification of HF. The EU RAR for HF reviews similar data and reports 1 -hour inhalation LC50 values of 280 mg/m3 in the mouse and 817 -1900 mg/m3 in rats. The RAR also notes that inhalation exposure of humans may damage the respiratory tract. A study by Dalbey et al (1998) notes more severe effects of HF inhalation in rats exposed mouth-only compared to those exposed nose-only.

Acute dermal toxicity

A waiver is appropriate for this endpoint as the substance is corrosive and dermal exposure will result in rapid tissue destruction at the site of contact. However, some published studies are available and are summarised.

Derelanko et al (1985) investigated the dermal toxicity of diluted hydrofluoric acid in the rabbit and demonstrated local corrosive effects but no systemic toxicity. Cox & Osgood (1994) similarly showed corrosive effects following dermal application of hydrofluoric acid. The results of these studies are not of relevance for classification of the substance for acute dermal toxicity, however it is noted that HF is classified in the EU as 'Very toxic by skin contact'. The EU RAR for HF also notes that dermal contact with liquid or gaseous HF can cause severe dermal lesions and may also result in systemic (cardiac) effects which may be fatal.

Justification for classification or non-classification

Hydrogen fluoride is classified according to the CLP Regulation (EC) 1272/2008 in Acute Toxicity Category 2 (H300, H330) and Acute Toxicity Category 1 (H310). This classification is consistent with the data reviewed and no change is proposed.