Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 2 (2007) / Chapter Skim
Currently Skimming:
Appendix 8 Formate
Appendix 8 Formate
Pages 342-363
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 342... ...
. In industry, formic acid is used as a food preservative, in a variety of chemical syntheses, in tanning leather, as a decalcifying agent, and in the preservation of silage (Liesivuori 1986; Dorland 1988; Thompson 1992)
|
From page 343... ...
absorption of formate is almost total, as seen in cases of accidental and intentional self poisoning with formic acid solutions (Naik et al.
|
From page 344... ...
. In monkeys, whose sensitivity to the ocular toxicity of methanol is similar to that of humans, the half-life of formic acid in the blood is about 31-51 minutes (min)
|
From page 345... ...
-old patient remained relatively constant until blood pH was normalized by bicarbonate treatment, after which formate concentrations declined, suggesting that formate elimination may be pH dependent (Jacobsen et al.
|
From page 346... ...
. No reports were found in the literature of ocular toxicity in humans who had ingested formic acid or formate, whereas ocular toxicity is commonly seen in cases of human exposure to methanol.
|
From page 347... ...
Also, the fact that formate was being constantly produced by metabolism of ingested methanol means that elevated blood concentrations of formate were maintained for a prolonged period in methanol-intoxicated humans as opposed to rapidly declining to near background levels in the formate-treated rabbits, presumably from metabolism. Clinical observations in methanolintoxicated humans have shown that in its initial stages, developing ocular toxicity can be reversed, even >24 h after methanol ingestion, by treatments such as bicarbonate, fomepizole or ethanol, iv folinic acid, or dialysis, which reduce blood formate concentrations and metabolic acidosis (Barceloux et al.
|
From page 348... ...
Significant reductions in ERG a-wave and b-wave amplitude were not observed until 60 h after methanol administration, although blood formate concentrations reached the plateau level of about 180 μg/mL by 12 h, the earliest time of measurement. Another group of rats in this experiment was treated with higher doses of methanol so that blood formate concentrations increased almost linearly from a baseline of 0.8 mM (36 μg/mL)
|
From page 349... ...
Equally importantly, because these experiments involved a single dose of formate and methanol, the resulting reversible intracellular hypoxia may not have been prolonged enough to produce lasting injury, whereas the high reactivity of formaldehyde would be expected to cause immediate local injury. From the above observations, it appears that the production of ocular toxicity by formate requires that the formate blood concentration remain elevated ( 180 μg/mL)
|
From page 350... ...
Summary The published literature on the toxic effects of formate in humans and animals is summarized in Table 8-2. Probably because it is not a common contaminant and because it is a normal product of metabolism, no organizations have set drinking water exposure limits for formate.
|
From page 351... ...
1978 infusion male; n = 3/4 0.5 M sodium formate buffer 39-50 h Maccaca Optic disc edema with normal vascular bed Martin-Amat (Na:H=10:1) 140 mg/kg/h iv mulatta monkey, and intracellular edema with intraaxonal et al.
|
From page 352... ...
Verstraete et al. 1989 1.2 mg/mL in blood at 8 h Unknown Human Coma; severe metabolic acidosis; optic disc McMartin et posthospitalization edema al.
|
From page 353... ...
Also, although the weight of evidence in both humans and animals, as presented above in the toxicity sections, strongly indicates that retinal toxicity requires 24-60 h of continuous blood formate concentrations > 315 μg/mL, SWEG values were calculated to avoid even brief, transient blood formate concentrations 180 μg/mL. A 1-h blood half-life, twice that reported for monkeys (whose sensitivity to formate is similar to humans)
|
From page 354... ...
formate concentrations, however, would be excessively conservative. To allow for interindividual differences in metabolic rates and temporal fluctuations in hepatic tetrahydrofolate concentrations, it should be sufficient to assume a maximum half-life of 1 h for individuals exposed to formate (not derived as a product of methanol metabolism)
|
From page 355... ...
× e( 0.69315 t) Figure 8-1 illustrates the predicted kinetics of formate concentrations in the blood over a >5-d period in crewmembers ingesting 2.8 L/d of U.S.provided ISS water (containing formate at 86 μg/mL)
|
From page 356... ...
rats showed reductions in the b wave as early as 24 h after methanol administration and profound attenuation or complete elimination of the b wave by 48-60 h after methanol administration. Thus, the sensitivity of rats in Eells et al.'s 1996 study to formateinduced ocular toxicity is similar to that of humans, and concentrations of formate in drinking water that do not increase blood formate concentrations above 180 μg/mL should be acceptable for humans.
|
From page 357... ...
10-d, 100-d, and 1,000-d SWEGs Experimental data on which one could base the calculation of a safe concentration of formate in drinking water for exposure durations of 10 d are unavailable, so one must extrapolate from the available data on shorter-term exposures based on reasonable assumptions. Although the kinetics of the ocular toxicity of formate is, to some extent, dependent on both the concentration of formate in the blood and the duration of exposure, the weight of evidence indicates that there is an effective threshold concentration of formate below which ocular toxicity will not occur re
|
From page 358... ...
Therefore, the ACs and SWEGs for all exposure durations longer than 1 d can be set at 2,500 μg/mL in drinking water (see Table 8-4 for a summary of ACs and SWEGs) : 10-d SWEG = 2,500 μg/mL 100-d SWEG = 2,500 μg/mL 1,000-d SWEG = 2,500 μg/mL RECOMMENDATIONS To refine the data on which the longer-term SWEGs are based, studies should be performed to determine the minimum level of inhibition of cytochrome c oxidase that leads to detectable ocular toxicity and the concentration of formate that will produce that level of inhibition.
|
From page 359... ...
Formate 359 300 For fractionated consumption of 2.8 L of water containing 2,500 μg formate/mL and assuming a 1-h metabolic half-life (ERG effects) 48-h NOAEL, dysfunction 60-h LOAEL 250 for retinal μg Formate/mL Blood 200 150 100 50 0 0 4 8 100 124 128 104 108 112 116 120 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 12 Hours FIGURE 8-3 Calculated blood formate kinetics for a 70-kg person ingesting water containing formate at 2,500 μg/mL.
|
From page 360... ...
TABLE 8-4 Acceptable Concentrations (ACs) 360 Acceptable Concentrations (mg/L)
|
From page 361... ...
Formic acid concentration in blood and urine as an indicator of methanol exposure.
|
From page 362... ...
II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey.
|
From page 363... ...
2000. Methods for Developing Spacecraft Water Exposure Guidelines.
|
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.