Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 1 (2004) / Chapter Skim
Currently Skimming:
Appendix 6: Nickel
Appendix 6: Nickel
Pages 203-247
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 203... ...
, and because nickel has been implicated as a cause of chronic dermatitis, it was necessary to assess if an appreciable health risk exists for the presence of nickel as soluble nickel salts in the spacecraft drinking water. Nickel also 203
|
From page 204... ...
Nickel dust or insoluble forms such as nickel sulfides will not be considered. Occurrence and Use Nickel salts are used extensively in electroplating and in the manufacture of alloys, catalysts, and high capacity batteries.
|
From page 205... ...
In general, it has been reported that in animals 1-10% of nickel administered as nickel salts either in the diet or by gavage is absorbed (Sun
|
From page 206... ...
These data indicate that the presence of food significantly decreased the absorption of nickel. Absorption from solutions was higher for more soluble nickel compounds (Ishimatsu et al.
|
From page 207... ...
(1994) examined nickel-iron interactions both in vivo after an oral dose and in vitro using isolated perfused jejunal and ileal segments from iron deficient and iron sufficient rats.
|
From page 208... ...
Oral administration of radioactive 63Ni2+ to mice resulted in higher accumulation of 63Ni2+ in the spinal cord than in the cerebellum or frontal cortex (Borg and Tjalve 1989~. In control rats, there appeared to be a difference in the levels of nickel in bones between males and female rats 0.53 parts per million (ppm)
|
From page 209... ...
(1994) reported that excretion of nickel following a single oral dose given to women after an overnight fast was found to decrease with increasing age, suggesting that nickel absorption may decrease with age.
|
From page 210... ...
Soluble nickel compounds are more toxic than less soluble nickel compounds. For example, although the oral LD50s (doses lethal to 50°/O of subjects)
|
From page 211... ...
Nickel as nickel acetate at 0,1,100, or 1,600 ppm administered in the diet to male and female mice for 4 wk resulted in decreases in body weight at 100 and 1,600 ppm in females, whereas that change was seen only at 1,600 ppm in males (Weber and Reid 1969~. Liver and heart cytochrome oxidase, liver isocitric dehydrogenase, and kidney and heart maleic dehydrogenase were also decreased.
|
From page 212... ...
Decreased body weights, decreased food intake, and clinical signs of toxicity, including ataxia, lethargy, altered breathing, lower body temperature, and discoloration of the extremities, were observed. Kidney, liver, and spleen weights were lower in the mid-dose and high-dose groups.
|
From page 213... ...
The 1988 American Biogenics Corporation study reported changes in heart weight in rats exposed to nickel as NiCI2 at 8.6 mg/kg/d by the oral route for 91 d. One study indicated that nickel ingestion could be neurotoxic.
|
From page 214... ...
There were dose-related decreases in bone marrow cellularity and decreases in granulocyte macrophage colony forming units (CFUs) and pluripotent stem-cell proliferative response CFUs.
|
From page 215... ...
Significant reductions in body weights were noted. In addition, histopathologic examinations showed an increased incidence of focal myocardial fibrosis.
|
From page 216... ...
The reason for that is unclear. In female rats exposed to nickel as NiCI2 at 10-100 ppm (1, 3, or 10 mg/kg/~)
|
From page 217... ...
than are nickel compounds (Sunderman 1984~. The primary target molecules for nickel attack appear to be proteins, especially those proteins closely associated with the chromosome and with DNA repair (Lynn et al.1997~.
|
From page 218... ...
completed three 2-y inhalation carcinogenicity studies with three nickel compounds two insoluble nickel compounds, Ni3S2 and NiO (high temperature) , and one soluble nickel compound, NiSO4 in F-344 rats and B6C3F~ mice.
|
From page 219... ...
There were less pronounced noncarcinogenic effects, less than seen with other insoluble nickel compounds, in both species in both genders. There has been a lack of agreement among several organizations in the classification of nickel as a potential human carcinogen.
|
From page 220... ...
reported that a single oral dose of nickel at 5.6 mg produced exacerbation in nine of 12 subjects with hand eczema. The same individuals did not react to placebos, as confirmed in several later studies.
|
From page 221... ...
An aggravation of hand eczema was found in six of 12 by day 4 after the start ofthe challenge, and although excess nickel was excreted by 2 ~ after the last treatment, further exacerbation of hand eczema was observed in 10 of 12 through day 11. In a double-blind randomized study in which nickel-sensitive subjects were given an oral dose of nickel at 0.5 mg (as NiSO4)
|
From page 222... ...
222 at sin U
|
From page 223... ...
223 O an ~ .t on o Jo .m ~ as an ~ no g' ~ m~ ~ o Ct o no ~ o as $O =O ~ o as no ~ as .= as To Do .
|
From page 225... ...
225 ct cat an of ~ al °° A c)
|
From page 226... ...
were set based on acceptable concentrations (ACs) for each duration following the methods for developing spacecraft water exposure guidelines (SWEGs)
|
From page 227... ...
ACGIH's air standard for soluble nickel compounds is 0.1 mg/m3 (under revision) ; OSHA's air standard is 1 mg/m3 for soluble nickel compounds; and NIOSH's recommended exposure limit (REL)
|
From page 228... ...
bThe values incorporate a safety factor of 3 to partially protect astronauts against the risk of an allergic response to nickel ingestion. These levels do not protect people who are already hypersensitive to nickel.
|
From page 229... ...
For modeling they considered the data from two subchronic studies: one by American Biogenics Corporation (1988) in which nickel chloride administered by gavage for 92 ~ resulted in decreased body weights in males, and another by Dieter et al.
|
From page 230... ...
(1990) on the worsening of hand eczema and erythema in 12 nickel-sensitive women who were challenged with a diet that included low doses of nickel could not be used because they were conducted in only nickel-sensitive subjects.
|
From page 231... ...
fed weanling rats (OSU brown rats, gender not known, 35 ~ old, body weights 90 g, six rats per group) a diet containing various levels of nickel acetate (10, 50, or 100 mg/kg/~)
|
From page 232... ...
100-d AC Based on American Biogenics Corporation (19XX) In the American Biogenics 90-d gavage study, male and female rats (30 per gender)
|
From page 233... ...
in the 1 08-mg/kg/d and 1 50-mg/kg/d dose groups. Significant decreases in spleen andbone marrow cellularity, decreasedbone marrow proliferative response, dose-related decreases in the spleen lymphoproliferative response to a B-cell mitogen, and treatment-related increases in nephrosis in the 108-mg/kg/d and 150-mg/kg/d dose groups were the other significant effects.
|
From page 234... ...
(mg/kg) BMDLo~ Method Spleen cellulant~ 63.8 108 150 24.8 42 Lymphoproliferative 7.9 NA 44 3.0 1.7 response to LPSa Bone marrow 9.8 cellularity Granulocyte 12 macrophage CFUs b Stem cell proliferative response CFUsb aImmune function responses were evaluated by spleen cellularity and lymphoproliferative response to T-cell and B-cell mitogens; in this case only B-cell mitogen LPS data is included.
|
From page 235... ...
Parameter NOAELa BMDL PCV 8.0 1.8 Hemoglobin 8.0 2.5 ALP 5.0 8.0 aBecause the BMDLo~ values are much lower than the experimentally observed NOAELs, ACs calculated based on the NOAEL are the values of choice. Abbreviations: AC, acceptable concentration; ALP, plasma alkaline phosphatase; BMDLo~, lower 95°/O confidence limit on the benchmark dose corresponding to a 1% risk; PCV, packed cell volume.
|
From page 236... ...
were calculated using factors of 10 for species extrapolation and 3 for nickel sensitivity. A time extrapolation factor for 90 d to 100 d also was applied.
|
From page 237... ...
100-d AC for Behavioral Effects Adult male rats were fed NiCI2 at 0, 10, or 20 mg/kg/d via a 10 g daily food ration. Following 14 ~ of exposure, animals were trained over a period of 61 ~ to lever-press for food on a VI-2 operant training schedule while continuing to ingest the indicated daily doses of nickel (Nation et al.
|
From page 238... ...
In that study, female B6C3F~ mice were given NiSO4 at 0, 44, 108, and 150 mg/kg/d in drinking water for 180 d. Significant changes in the immune system, decreases in water consumption, decreases in bone marrow cellularity, mild renal tubular damage, and thymic atrophy were significant toxic effects noted at the two highest doses.
|
From page 239... ...
239 hi ¢ J O Cat O O V ¢ A_ o Cat o V Al Cat ¢ to to to 8 ~ oo oo ~ o Do ~ 2= Z VO C)
|
From page 240... ...
240 5 A V V ¢ Cal Cal o Cat to to to to o to ~ 2= O == Cal o .
|
From page 241... ...
(mg/kg) BMDLo~ NOAEL Spleen cellularity 63.8 108 150 4.5 7.5 Lymphoproliferative 7.9 NA 44 0.55 0.3 response to LPS Bone marrow 9.8 44 108 0.7 3.08 cellularity Granulocyte 12 NA 44 0.8 0.3 macrophage CFUs Stem cell proliferation 7.6 44 108 0.5 3 CFUs Abbreviations: AC, acceptable concentration; BMDLo~, the lower 95°/O confidence limit on the benchmark dose corresponding to a 1% risk; CFU, colony forming unit; LPS, lipopolysaccharide.
|
From page 242... ...
Nickel allergy and hand eczema. Contact Dermatitis 1~3~:129-35.
|
From page 243... ...
1998. Non-cancer risk assessment for nickel compounds: Issues associated with dose-response modeling of inhalation and oral exposures.
|
From page 244... ...
1993. Mutagenicity of soluble and insoluble nickel compounds at the apt locus in G12 Chinese hamster cells.
|
From page 245... ...
2000. Methods for Developing Spacecraft Water Exposure Guidelines.
|
From page 246... ...
.1988b. Two-generation reproduction and fertility study of nickel chloride administered to CD rats in the drinking water: Fertility and reproductive performance of the Fit generation.
|
From page 247... ...
1999. Predictions and correlations of carcinogenic potentials of nickel compounds by short-term in vitro assays using C3H IOT1/2 mouse embryo cells.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.