Supporting Documentation for MassDEP Air Guidelines
HYDRAZINECASRN: 302-01-2
Update: November 30, 2011 /
Massachusetts Air Guidelines[1]:
AAL = 0.0002 ug/m3 (0.0002 ppb)[2] (annual average concentration)
TEL = 0.04 ug/m3 (0.03 ppb) (24-hour average concentration)
Chemical Properties: (HSDB 2010)
Odor Characteristics: / Ammonia-like, fishy (Ruth 1986)
Odor Threshold: / 3000 ug/m3 (Ruth 1986)
Irritant: / Yes, to mucous membranes, nose, throat, and upper respiratory tract
Sensitizer: / Yes, from repeated dermal contact (CalEPA 2000)
Chemical Class: / Colorless fuming, oily liquid above 36oF
Boiling Point: / 113.5oC
Melting Point: / 2.0oC
Vapor Pressure: / 14.4 mm Hg at 25oC
Molecular Weight: / 32.05
Unit Conversion factor: / 1.3108 ug/m3 per ppb at 25oC
Critical Effects[3]:
· Amyloidosis and hemosiderosis of the liver (fatty liver), and thyroid amyloidosis in study animals; consistent with the liver effects reported following a human poisoning.
· Target organ systems affected include liver, thyroid, adrenal glands, kidneys, spleen and central nervous system.
Potentially Susceptible Populations:
· People with compromised liver, kidney, or thyroid function.
· Children, people with asthma or a compromised respiratory system.
TEL Basis for Criteria:
Available chronic inhalation noncancer toxicity values:
REL 0.2 ug/m3 (CalEPA 2000)
The REL of 0.2 ug/m3 derived by CalEPA (2000) was selected as the basis of the TEL.
TEL = 0.2 ug/m3 x 0.2 (RSC) = 0.04 ug/m3 (0.03 ppb)
The CalEPA REL is based on the study by Vernot et al. (1985) where 200 male Golden Syrian hamsters/group were exposed to 0, 0.25, 1, and 5 ppm (0, 0.33, 1.31, 6.55 mg/m3) hydrazine 6 hours/day, 5 days/week for 1 year, then observed for 1 year. Dose-related increases in amyloidosis were observed in a number of organs, including the liver, thyroid, adrenal glands, spleen, and kidneys. In the same study, 100 Fischer 344 rats/sex were exposed to 0, 0.05, 0.25, 1, and 5 ppm (0, 0.65, 0.33, 1.31, 6.55 mg/m3) hydrazine using the same exposure regimen (Vernot et al. 1985). Effects in rats (squamous metaplasia of the larynx, trachea and nasal epithelium, and inflammation of the larynx and trachea) were only observed at the highest exposure level, 5 ppm (6.55 mg/m3). Female mice exposed to 1 ppm (1.31 mg/m3) using the same exposure protocol had an increased incidence of hyperplastic lymph nodes, endometriosis and inflammation of the uterine tube (Vernot et al. 1985).
The REL is based on evaluation of incidence of amyloidosis and hemosiderosis in the liver and thyroid amyloidosis in male hamsters at the lowest concentration studied, 0.25 ppm (0.33 mg/m3) (Vernot et al. 1985, CalEPA 2000).
The LOAEL of 0.25 ppm (0.33 mg/m3) was adjusted to a human equivalent concentration from animal to human based on RGDR = 1 for systemically distributed gases (USEPA, 1994); and from discontinuous exposure to continuous exposure, 6 out of 24 hours and 5 out of 7 days per week, yielding a LOAELHEC of 0.045 ppm (0.0589 mg/m3) (CalEPA 2000). The LOAEL HEC was divided by a composite uncertainty factor of 300 (CalEPA 2000).
REL = 0.0589 mg/m3 = 0.0001965 mg/m3, rounded to 0.2 ug/m3
3 x 10 x 10
Uncertainty factors:
UFA (extrapolation from animals to humans) = 3
UFH (human population variability in response) = 10
UFL (LOAEL-NOAEL) = 10
Default values were applied for each of the uncertainty factors. CalEPA does not apply a UF to account for missing information on reproductive or developmental effects.
Human studies – A case report of a person occupationally exposed to unknown concentrations of hydrazine once per week for 6 months (Sotaniemi et al. 1971) was reported in CalEPA (2000). Following each exposure the worker showed symptoms of conjunctivitis, lethargy and tremors for 1-2 days. Following the last exposure, the worker developed a fever, vomiting and diarrhea that progressed to abdominal pain, incoherence and death 3 weeks later. Liver and kidney damage along with tracheitis, bronchitis and heart muscle degeneration were found at autopsy. These effects are consistent with the liver, kidney and upper respiratory tract effects observed in the animal studies.
The epidemiology studies reported by CalEPA (2000) were limited to evaluating mortality of workers in a hydrazine manufacturing facility. No increase in mortality was reported for lung cancer, other cancers, or causes other than cancer. However, these studies had very limited statistical power to detect effects.
Developmental and reproductive effects – No studies were reported that evaluated these effects.
Neurotoxicity - No studies were reported that evaluated these effects.
Immunotoxicity - No studies were reported that evaluated these effects.
A relative source contribution factor of 0.2 is incorporated into the final value.
Cancer Classification:
USEPA (1991): B2, probably human carcinogen
IARC (2006): Group 2B, possibly carcinogenic to humans.
NTP (2005): Reasonably anticipated to be a human carcinogen.
NTEL Basis for Cancer Assessment:
Estimates of cancer unit risks are available from USEPA and CalEPA:
4.9x10-3 (ug/m3)-1 finalized 4/91 (USEPA 1991)
4.9x10-3 (ug/m3)-1 adopted from USEPA’s UR (CalEPA 2009).
The UR of 4.9x10-3 per ug/m3 derived by USEPA (1991) was selected as the basis of the NTEL.
NTEL = 1 x 10-6/4.9 x 10-3 per ug/m3 = 0.0002 ug/m3 (0.00015 ppb, rounded to 0.0002 ppb)
The UR derived by USEPA is the only estimate of hydrazine cancer toxicity associated with inhalation exposure that was located. The USEPA UR is based on the incidence of nasal cavity adenoma or adenocarcinoma observed in male rats exposed to 0, 1.0 and 5.0 ppm (1.31 and 6.55 mg/m3) hydrazine vapor (MacEwen et al. 1981). The UR was derived using a linearized multistage procedure, extra risk calculated using Global 82 (USEPA 1991). The animal exposure was adjusted to human equivalent doses based on 365 days of exposure and 910 experimental days (assumed to be full life span for the rat), and a rat body weight assumed to be 350 g (additional details not provided) (USEPA 1991).
As reported by USEPA (1991), F344 rats were exposed to 0, 0.25, 1, and 5 ppm (0, 0.33, 1.31, 6.55 mg/m3) hydrazine vapor (97% pure) for 6 hours/day, 5 days/week for 1 year, then observed for 1 year. Statistically significant increases in nasal cavity adenoma and adenocarcinoma were observed in rats exposed to 1 and 5 ppm (McEwen et al 1981). Mice and hamsters exposed using the same exposure conditions had an increased incidence of lung adenomas at 1 ppm and nasal cavity polyps at 5 ppm hydrazine.
Hydrazine exposure increased the incidence of tumors in several strains of mice, rats and hamsters when animals are exposed in water by gavage, in drinking water, inhalation and injection (USEPA 1991).
Hydrazine is considered a mutagenic chemical after testing positive in both in vitro and in vivo test systems (USEPA 1991). Human carcinogenicity data are inadequate, limited to mortality data from two hydrazine manufacturing plants (USEPA 1991).
USEPA conducted a screening-level literature review in 2002 indicating that new studies have been identified that have the potential to change the cancer toxicity value. (USEPA 2002)
References:
CalEPA (California Environmental Protection Agency). 2000. Hot Spots Risk Assessment Guidance. Office of Environmental Health Hazard Assessment. Available: http://www.oehha.ca.gov/air/allrels.html (accessed March 29, 2010).
CalEPA (California Environmental Protection Agency). 2009. Air Toxics Hot Spots Program Technical Support Document for Cancer Potencies. Office of Environmental Health Hazard Assessment. Available: http://www.oehha.ca.gov/air/hot_spots/tsd052909.html (accessed March 29, 2010).
HSDB (Hazardous Substances Data Base). 2010. Available: http://toxnet.nlm.nih.gov (accessed March 29, 2010).
IARC (International Agency for Research on Cancer). 2006. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Available: http://monographs.iarc.fr/ENG/Preamble/index.php (accessed March 29, 2010).
MacEwen, JD, Vernot, EH, Haun, CC, Kinkead, ER, Hall (III), A. 1981. Chronic inhalation toxicity of hydrazine: Oncogenic effects. Air Force Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, Ohio. NTIS, Springfield, VA (as cited in USEPA 1991).
MassDEP (Massachusetts Department of Environmental Protection). 2011. Methodology for Updating Air Guidelines: Allowable Ambient Limits (AALs) and Threshold Effects Exposure Limits (TELs). Office of Research and Standards. Available: http://www.mass.gov/dep/toxics/stypes/aboutaal.htm
NTP (National Toxicology Program). 2005. Report on Carcinogens, Eleventh Edition; U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program.
Ruth, JH. 1986. Odor thresholds and irritation levels of several chemical substances: a review. Am. Ind. Hyg. Assoc. 47A:142-151.
Sotaniemi, E, Hivonen, J, Isomaki, H, Takkunen, J, and Kaila, J. 1971. Hydrazine toxicity in the human. Report of a fatal case. Ann. Clin. Res. 3:30-33 (as cited in CalEPA 2000).
USEPA (U.S. Environmental Protection Agency). 1991. Integrated Risk Information System (IRIS). Available: http://www.epa.gov/iris/ (accessed February 1, 2010).
USEPA (U.S. Environmental Protection Agency). 1994. Methods for Derivation of Inhalation Reference Concentrations (RfCs) and Application of Inhalation Dosimetry. U.S. Environmental Protection Agency, Office of Research and Development, Office of Health and Environmental Assessment, Washington, DC, EPA/600/8-90/066F.
USEPA (U.S. Environmental Protection Agency). 2002. Integrated Risk Information System (IRIS). Available: http://www.epa.gov/iris/ (accessed February 7, 2011).
Vernot, EH, MacEwan, JD, Bruner, RH, Haun, CC, Kinkead, ER, Prentice, DE, Hall, A, Schmidt, RE, Eason, RL, Hubbard, GB, and Young, JT. 1985. Long-term inhalation toxicity of hydrazine. Fundam. Appl. Toxicol. 5:1050-1064 (as cited in CalEPA 2000).
Update History:
TEL/AAL first listed – 1990.
TEL/AAL updated and summary added – 2011
Massachusetts Department of Environmental Protection
Office of Research and Standards
Hydrazine 4
[1] The process used for selecting and deriving Threshold Effects Exposure Limits (TELs), Non-Threshold Effects Exposure Limits (NTELs) and Allowable Ambient Limits (AALs) is described in MassDEP (2011).
[2] Guidance values are presented with 1 significant figure in units of ug/m3; for convenience, values in units of ppb are calculated based on the rounded guidance value in units of ug/m3 then rounded to 1 significant figure in units of ppb for presentation.
[3] This summary document provides information about the toxicity data supporting the available toxicity values for this chemical and the rationale for selecting among values. It is not intended to be a comprehensive summary of all toxicity information for this chemical.