Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 1 (2004) / Chapter Skim
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Appendix 5: 2-Mercaptobenzothiazole
Appendix 5: 2-Mercaptobenzothiazole
Pages 169-202
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From page 169... ...
NASA-Johnson Space Center Toxicology Group Habitability ancI Environmental Factors Branch Houston, Texas PHYSICAL AND CHEMICAL PROPERTIES 2-Mercaptobenzothiazole (MBT) forms pale yellow monoclinic needles or leaflets and has a disagreeable odor (see Table 5-1)
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Drinking water on the International Space Station (ISS) will be generated from recycled hygiene water, urine, and humidity condensate, and supplemented by water from the shuttle or the Russian spacecraft Progress.
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The data described below are predominantly for ~4C-labeled MBT ingested in corn oil and, as such, do not distinguish between the parent compound, metabolites, and ~4C that has entered the cellular carbon pool. Absorption In rats dosed by gavage with ~4C-labeled MBT in corn oil, nearly all the radioactivity administered was rapidly excreted in the urine, indicating nearly complete absorption of MBT from the gut (el Dareer et al.
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At ~ h after a dose of ~4C-labeled MBT at 0.50 mg per kilogram (kg) in corn oil following daily doses at 0.51 mg/kg for 14 days Air, the tissues with the highest concentrations of radioactivity were the kidneys, thyroid, liver, plasma, and whole blood (el Dareer et al.
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(1979) reported finding similar metabolites in the urine of guinea pigs; however, they reported a sulfate derivative of MBT, for which el Dareer et al.
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1989~. An LD50 of 1,558 mg/kg was reported in male mice gavage dosed with MBT in a 5°/O gum arable aqueous suspension; 1,490 mg/kg was reported in similarly treated female mice; and 3,148 mg/kg was reported in male mice gavage dosed with MBT in corn oil (Ogawa et al.
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From page 175... ...
1989~. Convulsions were seen, however, in mice given single oral doses of MBT at approximately 1,500 mg/kg in 5% gum arable solution or 3,148 mg/kg in corn oil (Ogawa et al.
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, including MBT, have been used by members of the North American Contact Dermatitis Group for diagnostic patch testing of large numbers of patients presenting with suspected allergic contact dermatitis. The frequency of positive reactions to MBT for 3,440 patients tested between 1996 and 1998 is shown in Table 5-3 along with the results from previous years (Marks et al.
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Although the concentrations required to induce irritation in sensitized guinea pigs were greater than those reported in MBT-sensitive humans, the challenge exposure duration in guinea pigs was only one-fourth (1 d) that in the humans volunteers (4 d)
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From page 178... ...
Treatment of male and female F-344/N rats by gavage with MBT suspended in corn oil at doses up to 2,500 mg/kg/d for 16 ~ produced no compound-related gross pathologic effects other than slightly reduced weight gain (Dieter 1988~. Similarly treated B6C3F~ mice that received up to 1,500 mg/kg/d also displayed no compound-related gross pathologic effects other than post-gavage lethargy after day 1, but four of five females that received 1,500 mg/kg/d died before the end ofthe study, as did four off~ve males and five of five females that received 3,000 mg/kg/d (Dieter 1988~.
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(1989) reported an increased incidence of cell infiltration ofthe interstitium ofthe kidneys in male SIc:~dY mice after 20 mo of a diet containing MBT at 480 ppm or 1,920 ppm, as shown in Table 5-5.
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(cell infiltration ofthe interstitium ofthe kidney) in male mice.
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For MBT workers without concomitant exposures to PAB, there were no associations between exposure to MBT and increased rates of most malignant neoplasms. Exceptions include~prostate cancer, which was high in all cumulative exposure categories and an unexposed internal comparison group, suggesting that the findings for prostate cancer were related to some extraneous personal or occupational factor that was affecting all groups equally.
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From page 182... ...
Rats developed dose related tumours of the adrenal gland but there is no carcinogenic activity in mice." Those authors did not comment on the interpretation of the NTP results. Cancer in Animals MBT administered at the maximum tolerated doses did not cause increased tumor incidences in two hybrid mouse strains (C57Bl/6 x C3H/Anf and C57BL/6 x AKR)
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were observed for mononuclear cell leukemia and pancreatic acinar cell adenomas. Increased tumor incidences with dose related trends 07 < 0.05)
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184 an 5 o ·_I .~ Cal .= as o ·_I Cal V EN ·_I ad V]
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Survival of the high-dose group of female mice was significantly lower than that of vehicle controls after week 27. The conclusions reported by NIP for their 2-y studies were as follows: · There was some evidence of carcinogenic activity of MBT for male F-344/N rats, indicated by increased incidences of mononuclear cell leukemia tNDR]
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From page 186... ...
186 C ~ D O Fin Z HER Z C~ =o D Z ~ O I, O ,~ O ~ ~ y o ~ _ S D :: O E ~ ~ e ~ lrl ¢ ~ D ~ ~ ~ z · ~ Ct A to to · C)
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187 .> A ·> A ~ A Z ~ Z o = oo ~ ~ ~ oo .
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Reproductive Toxicity No evidence was found that MBT causes adverse effects on reproduction. In rats fed a diet containing MBT at 0, 12, 37.9, and 120 ppm and dimethyIdithiocarbamate at 0, 13S, 486, and 1,380 ppm, no cumulative effects on reproduction or lactation performance through the F2 generation were noted (Lehman 1965~.
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189 an C)
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190 5 V X an C)
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191 To Cal Cal 'd ~ A an as U
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The available data from human epidemiological studies show no increased risk of mortality from cancer due to exposure to MBT, but the confounding effect of concomitant exposures to known carcinogen 4-aminobiphenyl does not permit one to rule out a weak contribution by MBT to the observed rate of carcinogenesis. An NTP study of MBT administered by gavage yielded some evidence of carcinogenicity in male and female rats and equivocal evidence of carcinogenicity in female mice.
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From page 193... ...
Ofthe five, the data for mononuclear cell leukemia in male rats and for pancreatic acinar cell adenomas in male rats could not be used because, although the low-dose response was more than double the zero-dose response, the high-dose response was less than the zero-dose response. Of the remaining tumor types (adrenal gland pheochromocytomas in male rats, adrenal gland pheochromocytomas in female rats, and pituitary gland adenomas in female rats)
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From page 194... ...
. Thus, the following equation, based on Crump and Howe's 1984 multistage model, with only the first stage dose-related, was used to calculate the exposure concentrations, D, that would yield a tumor risk of 10-4 for exposure durations of 10, 100, and 1,000 d: d (25,600)
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Allergic Dermatitis MBT is a known sensitizer for allergic contact dermatitis. However, no data were found in the scientific literature on the effects of exposure to MBT by ingestion in sensitized individuals.
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From page 196... ...
(3 x 10 x 10 x 2.~= 30mg/L. Although a standard lifetime is 70 y, and the longest exposure duration for which we currently set SWEG values is 1,000 d, the calculated ACs were not increased by a time factor, because the policy ofthe subcommittee has been to avoid increasing the AC for exposure durations shorter than the duration for which we have data.
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From page 198... ...
. Since recovery from MBT-induced CNS depression has been shown to occur within 4 h in mice, the same AC value is used for all exposure durations.
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.1986. Disposition of 2-mercaptobenzothiazole-ring-UL 14C 2-mercaptobenzothiazole disulfide-ring-UL 14C in Fischer 344 male and female rats dosed orally.
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Guin.1988. Isolation, via activity-directed fractionation, of mercaptobenzothiazole and dibenzothiazyl disulfide as 2 allergens responsible for tennis shoe dermatitis.
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2000. Methods for Developing Spacecraft Water Exposure Guidelines.Washington,DC: NationalAcademy Press.
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1988. Comparative studies of the sensitization potential of morpholine,2-mercaptobenzothiazole and 2 oftheir derivatives in guinea pigs.
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