Toxicity of Rocket Fuels: Comparison of Hydrogen Peroxide with Current Propellants.


David R.Mattie, PhD, AFRL/HEST, Wright-Patterson AFB, OH

ABSTRACT

The toxicity of hydrogen peroxide and current exposure limits will be presented in this paper. Toxicity data and exposure limits will also be presented for unleaded gasoline, kerosene and hydrazine. The toxicity of hydrogen peroxide will be compared to gasoline, which is universally known and used by everyone as a fuel. The toxicity of hydrogen peroxide will also be compared to kerosene, one of the first propellants, and to hydrazine, which is very toxic and a candidate for replacement by a less toxic compound.

INTRODUCTION


The propellant community is currently examining the potential applications for hydrogen peroxide as a propellant. In order to safely handle a propellant the potential hazards must be known. This paper will summarize the toxicity of hydrogen peroxide and include the current exposure standards. Hydrogen peroxide will also be compared to unleaded gasoline, kerosene and hydrazine. Unleaded gasoline was included because everyone is familiar with gasoline since it is used to fuel personal vehicles. Kerosene is representative of higher carbon hydrocarbon fuels and is also RP-1, one of the first propellants. Because hydrazine is so toxic, everyone who uses hydrazine would prefer a less toxic replacement. The exposure standards for these three compounds will also be included.

DISCUSSION

The toxicity of hydrogen peroxide (HP) will be presented as acute (single dose), repeated dose, chronic (greater than 90 days/13 weeks), carcinogenic, genotoxic and reproductive. Metabolism of HP will also be described. The toxicity of HP varies based on the percentage of the solution, with the higher % concentrations being more toxic.

Acute

A solution of 70% HP has an oral LD50 of 75 mg/kg in the male rat (FMC, 1979a). The dermal LD50 is 690 mg/kg for 90% HP in the rabbit (Hrubetz et al. 1951). Inhalation data is difficult to interpret due to a lack of a clear understanding between vapor and aerosol and the exact % concentration tested. Vapors are not very toxic because of the low vapor pressure of HP. High aerosol concentrations can be lethal (Punte et al. 1953), but the low effect concentration for effects on respiratory lining is 60 mg/m3 (Kondrashov, 1977). Low concentration % of HP are not skin irritants (3,6,8,10,35) but 50 and 70% HP are corrosive to skin or severe irritants; low concentration % of HP are eye irritants (8,10,35) while 70% is a severe irritant (ECETOC, 1993). HP (6% or lower) was negative in a standard sensitization test but higher concentrations were not tested (Du Pont, 1953).

Repeated Dose

Repeated dosing involves more than one intermittent exposure or continuous exposure greater than one day. The route of exposure is usually oral or inhalation. Oral exposure is either via drinking water or by injection directly into the stomach (gavage). Inhalation exposure is for 2 to 8 hours per day for x number of days or is a continuous exposure for a given length of time. Inhalation exposure can be to the vapor only or to an aerosol, which also involves vapor as well. Repeated oral exposure in drinking water caused a decrease in body weight gain in most studies and resulted in deaths of rats and mice at concentration % of HP greater than 1% (ECETOC, 1993). Two repeated dosing studies involving oral gavage showed progressively more changes in blood parameters at lower concentrations (30-168 mg/kg), decrease in body weight starting at 60 mg/kg and organ weight changes without histopathology, except for erosion and scars of mucosa of stomach, only at the highest dose of 506 mg/kg (Kawasaki et al. 1969 and Ito et al. 1976). Repeated exposure to vapors of HP are irritating to the respiratory system, bleach fur of animals and cause effects on the lung at doses 10 mg/m3 or higher. A no effect level for inhalation exposure to HP is difficult to establish from the literature (ECETOC, 1993). There is no repeated dermal dosing data from exposure to liquid HP on the skin. The no effect level for vapor exposure was reported to be 0.1 mg/m3 by Kondrashov (1977).

Chronic

Chronic exposure in a toxicology test is a repeated dose that is received for longer than 90 days, preferably one year minimum. Longer exposure to HP by either gavage or in drinking water resulted in lower % concentrations producing the effects described under repeated dosing. In chronic studies it appears that the stomach and intestines will eventually be affected by HP.

Carcinogenicity

Pathology of stomach and intestines in mice exposed long-term may progress to cancer. In rats only non-malignant papillomas of forestomach are found, not malignant tumors. HP is not an initiator of skin cancer but may be weak promoter of skin and intestinal tumors. The mechanism for HP carcinogenicity appears to be non-genotoxic (not a direct effect on genetic material). The tumors are at the site of direct contact with HP after continuous inflammation and hyperplasia (pathology) for a period of time (ECETOC, 1993).

Genotoxicity

HP is genotoxic to bacteria as tested in the standard Ames test. HP is also genotoxic to mammalian cells in culture, inducing sister chromatid exchange, DNA single-strand breaks (gene mutations), chromosomal aberrations, micronuclei, unscheduled DNA synthesis and transformation. However, the genotoxic potential of HP is dependent upon direct contact with genetic material. Direct contact of cells with HP is usually only at the site of initial contact during whole body exposure while cells in culture are all uniformly exposed without the benefit of the bodies ability to metabolize HP (ECETOC, 1993).

Reproductive

Limited reproductive parameters have been reported in the literature. Male fertility was assessed in mice. A 1% dose of HP for 21 days had no effect on fertility (Wales et al. 1959). This study is usually performed with rats. Rats exposed to 0.005-50mg/kg HP by gavage for 6 months showed effects at the high dose. The female cycle was effected, sperm motility decreased, only 3 out of 9 female rats produced litters of pups and there was a decrease in the body weights of pups (Antonova, 1974). A teratology study is designed to assess the potential of a chemical to cause birth defects. There was insufficient data to determine if HP is a teratogen (ECETOC, 1993).

Metabolism

HP decomposes to oxygen and water after contacting mammalian tissues. HP is a normal product of cell metabolism. Cells contain the enzymes catalase and peroxidase, which catalize the breakdown reaction to oxygen and water. HP can also be reduced by cells to a highly reactive hydroxyl radical.

Occupational Exposure Limits

The accepted occupational exposure limit for HP as an 8 hour time weighted average (TWA) is 0.14 mg/m3 or 0.1 ppm (ACGIH, 1997). Short-term exposure limits (STEL in mg/m3) range from 2.8 - 4.2 (5-15 min). In the United Kingdom (UK) the STEL is 3 (for 10 min) while the United States (US) does not have an accepted value. A ceiling is accepted by some countries with a range of 1-2 mg/m3. Both the UK and US do not have a ceiling value. The National Institute for Occupational Safety and Health (NIOSH) set an immediately dangerous to life and health standard (IDLH) of 80 ppm.

Comparison to Other Fuels and Propellants

Table 1 shows the comparative toxicity data for unleaded gasoline, kerosene and hydrazine.

Gasoline is relatively non-toxic after a single or acute exposure by all routes. The major hazard is a slight potential for skin irritation. Kerosene has a low potential for hazard from the oral and inhalation route of exposure but is irritating to the skin and has the potential to be a skin sensitizer (cause allergic response). Hydrazine is considered very toxic according to the classification based on acute LD50 data. Exposure to the vapor of hydrazine is very toxic as well. Hydrazine is so irritating to the skin that it is considered corrosive. Hydrazine is irritating to the eyes and is a very strong sensitizer (allergen).

Gasoline and kerosene are not mutagenic based on 11 and 4 assays, respectively, for each fuel. This indicates a low potential to cause cancer in humans. However, gasoline is an animal carcinogen but through mechanisms that are not relevant to worker exposure (ACGIH, 1997). The National Institute for Occupational Safety and Health (NIOSH) considers gasoline to be a potential occupational carcinogen. Since gasoline is only pumped once or twice a week and is not a daily 8 hour exposure, the occupational level of concern does not affect the average individual. Kerosene is not mutagenic and is not listed as a potential carcinogen. Genotoxicity data for hydrazine indicates it is mutagenic. Hydrazine is a known animal carcinogen. Although the data is insufficient to classify hydrazine as a human carcinogen, it is classified as a suspected human carcinogen.

The no effect level (NOEL) for repeated dose exposure to gasoline was 3866 ppm for a rat study and probably 0.1 mg/L for rats exposed to kerosene. The average NOEL for hydrazine studies was 0.2 ppm (0.26 mg/m3) which is orders of magnitude lower than gasoline and the same order of magnitude as HP, if 0.1 mg/m3 is accepted as the NOEL. Based on slightly higher incidence of nasal tumors observed in rats at 0.05 ppm, the TLV for hydrazine was lowered to 0.01 ppm (ACGIH, 1997).

SUMMARY AND CONCLUSIONS


Both HP at high concentration per cent and hydrazine are acutely toxic, except HP is not a sensitizer. HP and hydrazine are toxic after repeated exposure with very low no effect levels. Both HP and hydrazine are genotoxic and are considered animal carcinogens. Hydrazine is considered a suspected human carcinogen. HP still needs to be assessed for teratogenic effects but adverse reproductive effects have been reported. Hydrazine is not teratogenic and but is toxic and lethal to fetuses. Hydrazine has not been adequately assessed for other reproductive endpoints. Both HP and hydrazine have low exposure limits with the ACGIH standard for hydrazine being recently lowered to two orders of magnitude lower than HP. The OSHA standard was lowered one order of magnitude for hydrazine.

REFERENCES


Hrubetz, M. C., Conn, L. W., Gittes, H. R., MacNamee, J. K. and Williams, J. H. 1951. The cause of the increasing intravenous toxicity of 90% hydrogen peroxide with progressive dilutions. Chemical Corps Medical Laboratories Res. Rep. 75. Army Chemical Center, Edgewood, MA, 1-13.

FMC. 1979a. Acute oral toxicity of 70% hydrogen peroxide in rats, study ICG/T79027-01. FMC, Princeton, NJ, 1.

Punte, C. L., Saunders, L. E. and Krakow, E. H. 1953. The inhalation toxicity of aerosols of 90% hydrogen peroxide. Chemical Corps Medical Laboratories Res. Rep. 189. Army Chemical Center, Edgewood, MA, 1-11.

Kondrashov, V. A. 1977. On comparative toxicity of hydrogen peroxide vapours with their inhalation and dermal modes of action. Gig. Tr. Prof. Zabol 10, 22-25.

ECETOC. 1993. Joint Assessment of Commodity Chemical No. 22: Hydrogen Peroxide, CAS No. 7722-84-1, Brussels.

Du Pont. 1953. Primary irritancy and skin sensitization tests, Memphis hydrogen peroxide 3%, Medical research project. Du Pont, Wilmington, DE, 1-5 +1-2.

Kawasaki, C., Kondo, M., Nagayama, T., Fakeuchi, Y. and Nagano, H. 1969. Effect of hydrogen peroxide on the growth of rats. Shokuhim Eisegaku Zasshi (J. Jap. Food Hygiene Soc.) 10, 68-72.

Ito, R., Kawamura, H., Chang, H. S., Toida, S., Matsuura, S., Hidano, T., Nakai, S., Inayoshi, Y., Matsuura, M. and Akuzawa, K. 1976. Oral safety of hydrogen peroxide acute and subacute toxicities. Toho Igakki Zasshi (J. Medical Soc. Toho) 23, 531-537.

Wales, R. G., White, I. G. and Lamond, D. R. 1959. The spermicidal activity of hydrogen peroxide in vitro and in vivo. J. Endocrin. 18, 236-244.

Antonova, A.1974. Argumentation hygienique de la concentration limite admissible en peroxyde d'hydrogene dans les reservoirs d'eau. O. Gigiena I sanit. 10, 20-22.

American Conference of Governmental Industrial Hygienists (ACGIH), 1997. Documentation of TLVs and BEIs. ACGIH, Cincinnati, OH.

Table 1. Summary of Toxicity Data for Unleaded Automotive Gasoline, Kerosene and Hydrazine.

TOXICITY DATA

UNLEADED GASOLINE

KEROSENE

HYDRAZINE

ACUTE:

ORAL LD50

14.1 g/kg

>4.3 g/kg (RP-1)

>5.0 g/kg

59 mg/kg, mouse

60 mg/kg, rat

INHALATION LC50

Not Determined

>5.2 mg/L (aerosol)

>saturated vapor

252 ppm, mouse

750 ppm, rat

DERMAL LD50

>5 ml/kg

>2 g/kg

91 mg/kg

SKIN IRRITATION

slight

moderate to severe

Severe (corrosive)

EYE IRRITATION

None

practically nonirritating

Delayed irritant

SENSITIZATION

None

Skin sensitizer, None

Strong Allergen

MUTAGENICITY

Negative (in 11 assays)

Negative (in 4 assays)

Positive (in 9 assays)

ANIMAL CARCINOGEN

ANIMAL CARCINOGEN

REPEATED DOSE:

TERATOLOGY

Negative

Negative

Negative

REPRODUCTIVE

Data base inadequate

Data base inadequate

Data base inadequate

INHALATION

1) 5 days/wk; 6 hr/day

1552 ppm for 90 days - squirrel monkey

No effects

2) 5 days/wk; 6 hr/day

3866 ppm for 90 days - male and female rats

No effects except for male male specific renal lesion

1) 5 days/wk; 6 hr/day

0.02, 0.048, 0.10 mg/L for

67 days - male rats

- 2 deaths:

- 0.048 at 16 days

- 0.10 at 30 days

- increased alk phos in one HD rat

2) 5 days/wk; 6 hr/day

0.02, 0.048, 0.10 mg/L for

68 days - male dogs

No effects

Effects liver, kidneys and lungs:

1 ppm, rat, 24h/d for 90days/TCLo

5 ppm, rat, 6h/d for 26 WK/TCLo

1 ppm, mouse, 24h/d, 90d/TCLo

14 ppm, dog, 6h/d for 90d/TCLo

1 ppm, monkey, 24h/d, 90d/TCLo

14 ppm, G. pig, 6h/d, 14WK/TCLo

14 ppm, hamster, 6h/d for 52 WK/TCLo

EXPOSURE LIMITS:

TWA STEL

TWA STEL

TWA STEL

OSHA

300 ppm 550 ppm

900 mg/m3 1500 mg/m3

None

0.1 ppm none

0.13 mg/m3 (skin)

ACGIH

300 ppm 500 ppm

890 mg/m3 1480 mg/m3

None

0.01 ppm none

0.013mg/m3 (skin)

NIOSH

None

100 mg/m3

0.03 ppm (2H) none

0.04 mg/ m3

IDLH = 80 ppm

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