Discussion of HF PEL for CAL OSHA HEAC

Discussion of HF PEL for CAL OSHA HEAC

Cooper / Cohen

10/10/07

Revised September 5, 2008 with addendum at end

Reference Limits

Hydrogen fluoride

CAS 7664-39-3

/ TWA
(8 hour) / Ceiling / STEL
(15 min) / IDLH
(30 minute)
Odor threshold range 0.042-3 ppm / - / - / - / -
Cal OSHA PEL (as F) / 3ppm / - / 6 ppm
Fed OSHA PEL (1978) / 3 ppm / - / 6 ppm / -
NIOSH REL (2000 review) / 3 ppm / 6 ppm / - / 30 ppm
ACGIH (2005) / 0.5 ppm / 2 ppm / - / -
OEHHA acute REL
(1999) / 0.3 ppm (1 hour exposure) / - / - / -
OEHHA chronic REL
24 hour, 7 day (2002) / 0.04 ppm / - / - / -
Prop 65 NSRL - none / - / - / - / -
Norway (1999) / 0.8 ppm
Germany (1990) / 3 ppm / -
MAK / 2 ppm / - / - / -
Sweden (1989) / 2 ppm / - / - / -
UK (1991) / - / - / 3 ppm- 10 minute STEL / -
Australia (1990) / 3 ppm / - / - / -

Critical Effects

Acute / Chronic
irritation to the eyes, nose, throat, fluoride in plasma, decreased FVC / skeletal fluorosis, increases in pelvic bone density

Discussion of Significant Literature

PEL Value

1. This Cal OSHA PEL review is prompted by changes in the 2005 ACGIH TLV TWA. The TLV value was set lower than Cal OSHA PEL and Fed OSHA PEL.

1. The basis for the ACGIH lowering of the TLV was Lund 1999 citing CD3 cell presence in bronchoaveolar lavage (BAL) fluid from human subjects after inhalation of HF at concentrations of 0.7-2.4 mg/m3. An increase in CD3 cells indicates an inflammatory response. The LOAEL was established by the study at ~0.7 ppm (0.6 mg/m3) and the ACGIH TLV of 0.5 ppm was set accordingly.

1. Lund 1997 studied 20 healthy male non-smoking volunteers exposed to constant HF concentrations between 0.2 mg/m3 to 5.2 mg/m3 for 60 minutes. The conclusion recommends that concentrations of HF should be kept well below 2.5 mg/m3 (3ppm HF) to avoid the primary irritation symptoms involving the upper airway and eyes.

Note that symptoms were not reported at 15-minute intervals but following the 60 minutes of exposure. All of the symptoms were reversible after exposure – some lasted up to four hours. The main subjective symptoms involved the upper airway and eye – similar to other highly water soluble gases.

1. An OEHHA acute REL was established in 1999 at 0.3 ppm value for HF based on a one-hour exposure. This determination used Lund 1997 above but did not reference the Lund 1999 study. The OEHHA value was determined by extrapolating a one-hour concentration of 2.4 mg/m3 and adding an intraspecies uncertainty factor of 10 yielding 0.24 mg/m3 or a one-hour REL of 0.3ppm HF.

1. An OEHHA chronic REL was established in 2002 at 0.04 ppm value for HF. based on 24-hour/7 day exposure. This study based the REL on Derryberry 1963, a human exposure study from a fertilizer plant. Collings 1951 reported that fluorides are absorbed from the respiratory tract equally well either as the inhaled gas or the phosphate rock dusts. The LOAEL from Derryberry 1963 was considered to be 1.98 mg/m3 HFand the NOAEL 1.13 mg/m3 HF.

These values were then converted to a 24-hour / 7-day OEHHA REL of 0.04 ppm HF using the BMC05 benchmark concentration, day/time conversions, an uncertainty factor for intraspecies variation = 10 and a cumulative uncertainty factor =10.

It can be argued, however, that the total uncertainty factor of 10 applied by OEHHA is too high in this case. OEHHA values are designed to protect the public which includes sensitive populations not typically found in the workforce – children, patients under treatment, etc..

The LOAEL is based on borderline fluorosis effects. Early signs of fluorosis are reportedly most apparent in radiographs of the lumbar spine and pelvis per Brailsford 1948. The 14-year study findings in Derryberry 1963 were subclinical and the radiological findings of chest and pelvic exams were all grade 1 or below.

The Derryberry 1963 paper cites:

“Seventeen individuals (23%) were tabulated as showing bone density changes of minimal or questionable degree. In none of the films was there sufficient change in the osseous tissue to justify an interpretation exceeding this degree. Furthermore, the radiologist has stated that none of the radiographs showed sufficient increase in bone density to be recognized as such in routine radiological practice. In this study, therefore, “increased bone density” refers to questionable or minimal changes recognized with prior knowledge that the individuals had a potential fluoride exposure.”

OEHHA cited the critical effect as increased bone density (skeletal fluorosis). This endpoint is derived from results which are questionable to minimal, subclinical, not expressing any disability, and the effects might have gone undetected in routine medical practice without a prior knowledge of the potential HF exposure. Hence, it is reasonable to assume that a 10-fold intraspecies uncertainty factor is too high. If the factor is reduced to 3, the OEL could be calculated as:

Derryberry 1963 NOAEL (1.22 conversion to ppm) /3 intraspecies factor = 0.46 ppm

This value being in agreement with the ACGIH TLV of 0.5 ppm. If the BMC05 benchmark concentration is used instead of the NOAEL, the PEL value calculates to 0.31ppm which is within statistical range of the ACGIH TLV of 0.5 ppm.

1. Kaltreider 1972 established the LOAEL between 2.4 ppm and 6ppm HF.

1. The Russian study, Sadilowa 1964, was the only study reviewed which established a significantly lower occupational exposure limit of 0.01 mg/m3 HF = 0.01 ppm HF. This study was found as a reference in a WHO document on HF. The study was considered and rejected based on the following:

-Significant issue- the endpoint was light sensitivity (reflex to light) and odor threshold rather than eye, nose, or throat irritation or skeletal fluorosis, & these endpoints are not replicated in the literature

-Significant issue – the study is non-replicable in the literature, no other study supported this low of an OEL

-This study was not referenced in the OEHHA chronic or acute reviews

-This study was not referenced in the 2005 ACGIH TLV documentation

STEL Value

1. The Cal OSHA STEL should be lower than 6 ppm HF since various references reviewed describe reversible irritation effects between the 2 ppm (ACGIH Ceiling) and the 6 ppm (Cal OSHA STEL).

1. Largent 1961 describes human volunteer exposure to low-level HF (2.6 – 4.7 ppm HF) as causing slight irritation to the face, nose, and eyes in addition to facial erythema during the exposures.

1. Lund 1997 concluded that concentrations of HF should be kept well below 3 ppm to avoid irritation symptoms involving the upper airway and eyes.

1. The OEHHA 1 hour acute REL was established at 0.3 ppm based on Lund 1997.

1. Based on the data reviewed, a value of 2 ppm HF value isnear or below most of the observed LOAELs for irritation (Largent 1961, Dalbey 1998, Lund 1997, Largent 1960, Kaltreider 1972).

Hence, it is assumed that a short-term exposure limit of 2 ppm should be sufficient to preventshort termas well asresidual irritation.

Conclusion SEE FINAL RECOMMENDATION IN ADDENDUM AT THE END OF THIS DOCUMENT(PEL 0.4 ppm 8-hour TWA and STEL 1 ppm)

Based on this discussion, the recommendation is to lower the Cal OSHA PEL for HF as follows:

From / To
PEL = 3.0 ppm; STEL = 6.0 ppm / PEL = 0.5 ppm; STEL = 2.0 ppm

Reference list – HF

Journal Articles and Documents

1. Saric M et.al. Am J Industrial Med 9:239-42 1986

2. Machle W, Thamann F, Kitzmiller K, et al. 1934. The effects of the inhalation of hydrogen

ride: I. The response following exposure to high concentrations. J Ind Hyg 16:129-145.

3. Dalbey W, Dunn B, Bannister R, et al. 1998a. Acute effects of 10-minute exposure to hydrogen

fluoride in rats and derivation of a short-term exposure limit for humans. Regul Toxicol Pharmacol 27:207-216.

4. Dalbey W, Dunn B, Bannister R, et al. 1998b. Short-term exposures of rats to airborne

hydrogen fluoride. J Toxicol Environ Health 55(4):241-275.

5. Derryberry OM, Bartholomew MD, Fleming RBL. 1963. Fluoride exposure and worker

health. Arch Environ Health 6:503-514.

6. Haskell Laboratory. 1988. Test results of acute inhalation studies with anhydrous hydrogen

fluoridewith cover letter dated 03/16/88. Newark, DE. EPA/OTS. FYI-OTS-0388-0607.

7. Kaltreider NL, Elder MJ, Cralley LV et al. 1972 Health survey of aluminum workers

with special reference to fluoride exposure. J Occup Med 14(7): 531-541

8. Kleinfeld M. 1965. Acute pulmonary edema of chemical origin. Arch Environ Health 10:942-

946.

9. Largent EJ. 1952. Rates of elimination of fluoride stored in the tissue of man. AMA Arch Ind

Hyg Occup Med 6:37-42.

10. Largent EJ. 1954. Metabolism of inorganic fluorides. In: Fluoridation as a public health

measure. Washington, DC: American Association for the Advancement of Science, 49-78.

11. Largent EJ. 1960. The metabolism of fluorides in man. AMA Archives of Industrial Health

21:318-323.

12. Lund K, Ekstrand J, Boe J, et al. 1997. Exposure to hydrogen fluoride: an experimental

study in humans of concentrations of fluoride in plasma, symptoms, and lung function. Occup Environ Med 54(1):32-37.

13. Lund K, Refsnes M, Ramis I, et al. 2002. Human exposure to hydrogen fluoride induces

acute neutrophilic eicosanoid, and antioxidant changes in nasal lavage fluid. Inhal Toxicol 14:119-132.

14. Lund K, Refsnes M, Sandstrom T, et al. 1999. Increased CD3 positive cells in

bronchoalveolar lavage fluid after hydrogen fluoride inhalation. Scand J Work Environ Health 25(4):326-334.

15. Machle W, Kitzmiller K. 1935. The effects of the inhalation of hydrogen fluoride: II. The

response following exposure to low concentration. J Ind Hyg Toxicol 17:223-229.

16. Rosenholtz MJ, Carson TR, Weeks MH, et al. 1963. A toxicopathologic study in animals after

brief single exposures to hydrogen fluoride. Am Ind Hyg Assoc J 24:253-261.

17. RyeWA. 1961. Fluorides and phosphates -- clinical observations of employees in phosphate

operation. International Congress on Occupational Health, July 25-29, 1960, 361-364.

18. Sadilova MS, Selyankina KP, Shturkina OK. 1965. Experimental studies on the effect of

hydrogen fluoride on the central nervous system. Hyg Sanit 30:155-160.

19. Wohlslagel LC, Dipasquale LC, Vernot EH. 1976. Toxicity of solid rocket motor exhaust:

Effects of HCl, HF, and aluminum on rodents. Journal of Combustion Toxicology 3:61.

Books Excerpts

1. Prager J.C. Environmental Contaminant Reference Databook Vol 1

NY,NY, Van Nostrand Reinhold 1995 p 751

2. Largent E.J.Fluorosis. The Health Aspects of fluorine compounds

Ohio State University Press, Columbus, Ohio, 1961 pp34-48

3. Stokinger HE. 1949. Toxicity following inhalation of fluorine and hydrogen fluoride. In:

Voegtlin C, Hodge HC, eds. Pharmacology and toxicology of uranium compounds. New York, NY: McGraw Hill Book Company, 1021-1057.

Data available on HF

Cooper

8/28/07

ATSDR

Toxicological profile for fluorides, HF (2003, 400 pages)

Medical management guidelines

Public Health Statement

Tox FAQs

Cal EPA

OEHHA – Acute (1999) (see end of document for Internet link)

OEHHA – Chronic (2002) (see end of document for Internet link)

ARB – Toxic Air contaminant Fact Sheet

CDC

Facts about HF

Case definition for HF poisoning

CHRIS

CHRIS Manual HF

European Chemical Bureau

Draft RAR on HF

IUCLID Dataset – HF

OJ L 144/72 of the EU Communities Commission Recommendation 4/29/2004

EU risk assessment report – HF

EU summary Risk Assessment report

Gene-Tox

HF

HSDB

Hazardous Substances Data Bank – HF

NIOSH

NIOSH pocket guide

NIOSH IDLH

Manual of analytical methods

NIOSH Specific medical tests published in the literature

NIOSH – occupational health guidelines (1978)

NIOSH Criteria Document (1976)

OSHA

OSHA comments on vacated PELs (1989)

OSHA Method ID110

RTECS

HF

TSCA Test Submissions

Initial Submission – Dow Chemical

WHO

Environmental Health Criteria

Poison Information Monographs PIM 268

Below are websites for acute and chronic reference exposure level (REL) documents from OEHHA on HF, which are referred to in the template document:

Chronic REL for fluorides including hydrogen fluoride

( Chronic RELs website)

Acute REL for hydrogen fluoride

( Acute RELS website)

Additional comments on HF for HEAC

Mike Cooper in response to HEAC meeting discussion Sept. 5, 2008

Prepared Sept. 5, 2008

1. Proposed PEL and STEL in October 2007

PEL 0.5 ppm

STEL 2.0 ppm

Basis

ACGIH TLV basis was Lund 1999 citing CD3 cells in bronchoavelolar lavage (BAL). LOAEL 0.7ppm. OEHHA acute REL (1999) at 0.3 ppm for 24/7 study which calculates to 0.4ppm. OEHHA chronic REL (2002) at 0.04 ppm based on Derryberry (1963). OEHHA used uncertainty factor of 10. Argument that if uncertainty factor was 3 not 10, the PEL would be 0.31ppm which is statistically near the ACGIH TLV value. STEL considered these data and Kalteider LOAEL between 2.4 –6ppm.

1. Questions during presentation

Julia – PEL of 0.5ppm is close to LOAEL in Lund 0.7ppm

Asked how STEL was determined

Asked to focus PEL on Lund (1999)

Document should clarify the clinical significance of CD3 cells in BAL

Agreed that Derryberry should not be used for PEL

Mark – HEAC should focus on LOAEL not LOEL, meaning focus on (clinical)

effect levels rather than focus on any measureable changes even if not potentially harmful; suggested that all studies cited should be listed

Sara- Was a complete literature study done

1. Revisions and Basis
2. Literature documents provided to Cal OSHA
3. Lund and Derryberry are what they are, both have outcomes to consider.
4. It is not clear the dose response for CD3 cells in BAL are related to clinical or dose response. It is not known how often or how long these cells have to be present to imitate or e a marker for a clinical effect.
5. Authors can support a PEL of 0.4 ppm and STEL of 1.0 ppm. STEL here is simply approximately 3x the PEL.

1. Revised PEL and STEL

PEL 0.4 ppm

STEL 1.0 ppm