Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 2 (2007) / Chapter Skim
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Appendix 6 Caprolactam
Appendix 6 Caprolactam
Pages 264-299
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From page 264... ...
Caprolactam has been TABLE 6-1 Physical and Chemical Propertiesa Formula C6H11 NO Chemical name Caprolactam Synonyms Hexahydro-2-H-azepin-2-one, 6-Aminocaproiclactam, epsilon caprolactam, 2-Oxohexamethyleneimine, 6 Hexanelactam CAS registry no. 105-60-2 Molecular weight 113.2 Vapor pressure 6.0 mm Hg @ 120 ºC (800 Pa at 120 ºC [ACGIH 1991]
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From page 265... ...
. Thus, NASA was prompted to evaluate caprolactam for potential health hazards at this concentration and to recommend a spacecraft water exposure guideline (SWEG)
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From page 266... ...
Twenty-four hours after a single oral bolus dose of 14C-caprolactam at 0.18 mg/kg, about 77% of radioactivity was excreted in the urine, 3.5% in the feces, and 1.5% in the expired air. Elimination of radioactivity was most rapid in the urine during the initial 6 h following the dose.
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From page 267... ...
(1987) reported that rats fed a diet containing 3% caprolactam for 2 or 3 wk excreted approximately 16% of the caprolactam ingested as the 4-hydroxy metabolite and a small amount as the nonhydroxylated acid, 6-aminohexanoic acid.
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From page 268... ...
drinking water and Ozarka commercial bottled water served as controls for this blinded study. Based on the results, it was concluded that at the maximum concentration of 13 mg/L of caprolactam, the water was declared acceptable for drinking.
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In the survival determination studies, rats and mice were given single gavage doses of caprolactam at 681, 1,000, 1,470, 2,150, and 3,160 mg/kg for male and female rats and 1,000, 1,470, 2,150, 3,160 and 4,640 mg/kg for male and female mice. The doses were delivered in corn oil.
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. oral doses of 300, 600, 900, 1,200 and 1,500 mg/kg was conducted.
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were fed diets containing caprolactam at 0, 50, 250, or 500 mg/kg/d for 10 wk. Body weights of the parental generations and their offspring (in the 250 and 500 mg/kg/d groups)
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From page 272... ...
A LOAEL and a NOAEL for the increased BUN are identified as 250 mg and 50 mg/kg/d, respectively. Although there was an increase of about 15% in the ratio of kidney weight to body weight in 0.1%- and 0.5%-dose groups of male rats, this effect was not seen in female rats.
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From page 273... ...
NTP also conducted a 13-wk subchronic feeding study (NTP 1982) in which groups of male and female F244 rats were fed diets containing caprolactam at 0, 625, 1,250, 2,500, 5,000, or 7,500 ppm (estimated dose range of 0-1,125 mg/kg for male and female rats)
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From page 274... ...
Only periodic data on body weight and food consumption were collected, and no serum or urine clinical chemistry measurements were done. From the dose-related decrement in mean body weight gain and feed consumption, it appears that the LOAEL is 1,120 mg/kg/d for the rat, and 3,000 mg/kg/d for mice (NTP 1982)
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No gene mutations were seen in mammalian cells exposed in vitro to caprolactam. In human lymphocyte cultures in vitro, caprolactam failed to induce sister chromatid exchanges, but it increased chromosomal aberrations.
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From page 276... ...
. Only the mean body weights of dosed rats and mice decreased compared to those of control groups in a dose-related fashion.
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From page 277... ...
TABLE 6-3 Summary of Genotoxicity Studies on Caprolactam Without Metabolic With Metabolic Concentrations (μg/mL unless Test System End Point Activation Activation otherwise noted) LED or HIDa Salmonella typhimurium Forward mutation Negative Negative 500 TM677 S
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melanogaster Sex-linked recessive lethal Negative NA 15,000 ppm injection mutation CHO cells, rat hepatocytes DNA single- stranded Negative Negative 113-11,300 breaks, unscheduled DNA synthesis Chinese hamster V79 lung Gene mutations (hprt Negative Negative 1,000-3,000 cells (in vitro) locus)
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viral enhancement Human lymphocytes in vitro Gene mutation Negative Negative 8,000 Human lymphocytes in vitro Sister chromatid exchange Negative Negative 1,000 Human lymphocytes in vitro Chromosomal aberrations Positive, negative, Various 270 (+ ve)
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Rats received ip injections of Nnitrosodiethylamine followed by four ip injections of N-methyl-Nnitrosourea followed by 0.1% N-bis (2-hydroxy-propyl) nitrosamine in their drinking water for 2 wk.
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1988) , the body weights (on days 1, 7, and 21 of lactation)
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In the 1,000 mg/kg group, the maternal mortality was greater than 50%. On days 6-11, the mean body weight changes (and food consumption)
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In 1977, the Safe Drinking Water Committee of the National Research Council (NAS
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From page 284... ...
. The values listed were based on ACs for each duration according to Methods for Developing Spacecraft Water Exposure Guidelines (NRC 2000)
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From page 285... ...
or 4,640 mg/kg and female Gavage 1.6 g/kg, once Rat Hohenesee 1951 Death; LD50 of 1.6 g/kg Gavage 1,000 mg/kg, once Rat, mouse, Lethality 30% in rats, 70% in mice, 30% in See Gross 1984 guinea pig, guinea pigs, and 60% in rabbits rabbits Oral bolus 1.5 g/kg, once Rat, male Induction of TAT and TPO, max at 6 h Friedman and Salerno 1980 Oral bolus 0, 300, 600, 900, 1,200, or Rat, male Induction of TAT and TPO, only above Friedman and 1,500 mg/kg 300 mg/kg Salerno 1980 Gavage 425 mg/kg, two doses in 1 d Rat, female Increased SGPT Kitchin and Brown 1989 Diet 1% and 5% (1.0 g/kg and 1.8 Rat, male Inhibition of protein synthesis; significant Friedman and g/kg measured) , pair fed for 7 decrease in food consumption; body weight Salerno 1980 d reductions; induction of TAT and TPO Diet 0, 250, 500, 750, 1,000, or Rat, male and No deaths; pale, mottled kidneys in all NTP 1982 1,500 mg/kg, 14 d female dosed groups of male rats; incidences of 60 100% Diet 0, 250, 500, 750, 1,000, or Mouse, male No deaths; no compound-related effects NTP 1982 1,500 mg/kg, 14 d and female (Continued)
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, 90 d consumption Diet 0, 5,000, 10,000, 15,000, or Mouse, male Deaths in the two high-dose groups; very NTP 1982 20,000, 30,000 ppm (for dose and female severe reductions in body weight (25-63%) ; rates see text)
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From page 287... ...
of male interstitial testicular tumors, also in pituitary carcinomas; NTP declared this not significant Diet 0, 7,500, or 15,000 ppm Mouse, male No increase in severity or frequency of NTP 1982 (estimated doses included in and female degenerative changes in the lesions noted in the document) , 2 y dosed versus controls; alveolar/bronchiolar adenomas or lymphomas or leukemia of hematopoietic systems showed a negative trend with respect to dose Abbreviations: LD50, the dose lethal to 50% of test subjects; LD100, the dose lethal to 100% of test subjects; NTP, National Toxicology Program; SGPT, serum glutamic-pyruvic transaminase, also known as serum alanine aminotransferase; TAT, tyrosine aminotransferase; TPO, tryptophan oxygenase.
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From page 288... ...
TABLE 6-6 Spacecraft Water Exposure Guidelines for Caprolactama Duration SWEG (mg/L) Toxicity End Point Reference 1d 200 Hepatotoxicity Kitchin and Brown 1989 10 d 100 Renal effects (adopted 100-d Powers et al.
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From page 289... ...
Therefore, an odor threshold value is not calculated. NASA taste tests indicated that at least up to a concentration of 13 mg/L, water containing caprolactam will not be objectionable to drink.
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From page 290... ...
, where 1,100 mg /kg = LOAEL; 70 kg = nominal body weight; 10 = LOAEL to NOAEL; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; and 10 d/7 d = time extrapolation factor.
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From page 291... ...
, where 50 mg/kg/d = NOAEL for BUN; 70 kg = nominal body weight; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; and 100 d/90 d = time extrapolation factor. Another study that was considered for calculating a 100-d AC was Serota et al.
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From page 292... ...
, where 250 mg/kg = NOAEL; 70 kg = nominal body weight; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; and 100 d/70 d = time extrapolation factor. NASA's Position and Rationale for 10-d and 100-d ACs The SWEG for the 100-d duration will be accepted as the SWEG for 10-d duration, instead of the calculated value of 200 mg/L as 10-d AC.
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From page 293... ...
The feed consumption in the highest-dose groups was only 70-80% of that of controls, and thus, body weights were lower. The NRC committee had recommended in the past that body weight changes should not be used to set ACs when it is known that changes occurred because of reduced food consumption.
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From page 294... ...
used in the NTP 2-y carcinogenicity study for rats, which did not produce any compoundrelated long-term adverse tissue pathology, and calculate an AC using only the species extrapolation factor, a concentration of 1,400 mg/L would be obtained as the AC. Thus, the use of 100 mg/L as the 1,000-d AC is justified and conservative.
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From page 295... ...
Note: The rationale for adopting the 100-d SWEG as 10-d SWEG has been discussed at the end of the 100-d AC derivation section in this document. Also, these values will not be protective of individuals who may be allergic to nylon who may show hypersensitivity to caprolactam ingestion.
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IX. Results of 50 coded compounds tested for the National Toxicology Program.
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1987. Developmental toxicity studies of caprolactam in the rat and rabbit.
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2000. Methods for Developing Spacecraft Water Exposure Guidelines.
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From page 299... ...
1989. Allergic contact dermatitis from epsilon-amino-caproic acid.
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