Table 1.
Characteristics of Select FARs Pertaining to Tissue Cross-Linking In Vivo
|
Chemical |
Structure |
Predicted Octanol/Water Partition Coefficient, LogP |
% Max Allowed Concentration (mM Conversion) |
Mutagenicity |
Toxicity: Method, Species, Dose, Exposure Time |
| Diazolidinyl urea [DAU; CAS No.: 78491-02-8; MWt: 278.22 g/mol; formula: C8H14N4O7] | −5.398 ± 0.86656 | 0.521 (17.97 mM) | Nonmutagenic*48 | LD50 oral, rat, 2600 mg/kg; LD50 dermal, rabbit, >2000 mg/kg63 | |
| Imidazolidinyl urea [IMU; CAS No.: 39236-46-9; MWt: 388.29 g/mol; formula: C11H16N8O8] | −4.930 ± 0.95957 | 0.621 (15.45 mM) | - | LD50 oral, rat, 11,300 mg/kg64 | |
| Sodium hydroxymethylglycinate [SMG; CAS No.: 70161-44-3; MWt: 127.07 g/mol; formula: C3H6NO3.Na] | −1.19758 | 0.521 (39.06 mM) | Nonmutagenic†54 | LD50 oral, rat, 2100 mg/kg, LD50 dermal, rabbit, >2000 mg/kg54 | |
| DMDM hydantoin [DMDM; CAS No.: 6440-58-0; MWt: 188.18 g/mol; formula: C7H12N2O4] | −1.078 ± 0.65459 | 0.621 (31.88 mM) | Nonmutagenic‡50 | LD50 oral, rat, 3720 mg/kg; LD50 oral, rat, >2000 mg/kg50 | |
| 5-Ethyl-1-aza-3,7 dioxabicyclo[3.3.0]octane [OCT; CAS No.: 7747-35-5; MWt: 143.18 g/mol; formula: C7H13NO2] | 0.274 ± 0.49660 | 0.321 (20.95 mM) | - | LD50 oral, rat, >3600 mg/kg; LD50 dermal, rabbit, 1948 mg/kg53 | |
| Bronopol [BP; CAS No.: 52-51-7; MWt: 199.99 g/mol; formula: C3H6BrNO4] | 1.150 ± 0.63161 | 0.121 (5 mM) | Nonmutagenic§51 | LD50 oral, rat, 180 mg/kg51 | |
| 2-hydroxymethyl-2-nitro-1,3-propanediol [HNPD; CAS No.: 126-11-4; MWt: 151.12 g/mol; formula: C4H9NO5] | −0.115 ± 0.77062 | - | Nonmutagenic||52 | LD50 oral, rat, 1917 mg/kg; LD50 oral, mouse, 10,550 mg/kg62 |
Nonmutagenic: Ames, micronucleus assay.
Nonmutagenic: Ames, 100% sodium hydroxymethylglycinate; mouse micronucleus; rat hepatocyte/DNA repair assay; in vivo, in vitro rat hepatocyte UDS assay.
Nonmutagenic: Ames, salmonella, 55% DMDM, 0.001 to 5 μL/plate; salmonella/mammalian-microsome preincubation mutagenicity assay, salmonella, 2.0 μL/plate; mutagenic, L5178 TK ± mouse lymphoma assay, 0.01 to 1.0 μg/mL; L5178 TK ± mouse lymphoma assay, 0.006 to 0.2 μL/mL; chromosome aberrations assay, Chinese hamster ovary cells, 0.3 μL/mL.
Nonmutagenic: Ames, salmonella, with and without metabolic activation, dose not specified.
Nonmutagenic: Ames, salmonella with and without metabolic activation, 1000 μg/plate; chromosomal aberration.