@article{freeman_jeong_claxton_2013, title={Characterization of metabolites of genotoxic 4,4 '-aminoalkoxyazobenzene dyes}, volume={99}, ISSN={["0143-7208"]}, DOI={10.1016/j.dyepig.2013.06.001}, abstractNote={Abstract Invariably these days the molecular design of non-genotoxic azo dyes takes into consideration the potential genotoxicity of aromatic amines arising from reductive cleavage of the azo bonds (–N N–), with those dyes producing carcinogenic amines no longer suitable for commerce. Much less is known about structural factors leading to genotoxic azo dyes having their –N N– bonds intact. This point came to the forefront when it was determined that hydrophobic 4,4′-aminoalkoxyazobenzene dyes such as 4-(3-(2-hydroxyethoxy-4-amino)phenylazo)- N , N -bis(2-hydroxyethyl)aniline are mutagenic but their reductive-cleavage products are not. Consequently, a study that was undertaken to unveil the basis for the mutagenic activity of such dyes. The initial study involved the synthesis and evaluation of the mutagenicity of a group of substituted 4,4′-diaminoalkoxyazobenzene dyes, to test our hypothesis which stated that the mutagenicity of 4-(3-(2-hydroxyethoxy-4-amino)phenylazo)- N , N -bis(2-hydroxyethyl)aniline arises from the metabolic cleavage of N -hydroxyethyl groups in the parent dye, leading ultimately to 4-(3-(2-hydroxyethoxy-4-amino)phenylazo)aniline. The key goal of the present work was to provide underpinning for results from mutagenicity testing, by isolating and identifying metabolites from S9 treatments. In this regard, title dyes such as 4-(3-(2-hydroxyethoxy-4-amino)phenylazo)- N , N -bis(2-hydroxyethyl)aniline were treated with rat or hamster liver S9 in the absence of Salmonella typhimurium and results from TLC and HPLC analysis of product mixtures from S9 treatments indicated that metabolism involved N -dehydroxyethylation to give 4-(3-(2-hydroxyethoxy-4-amino)phenylazo)- N -(2-hydroxyethyl)-aniline and 4-(3-(2-hydroxyethoxy-4-amino)phenylazo)aniline when rat liver S9 was used and reductive cleavage of the azo bonds to give the corresponding aromatic amines was also observed when hamster liver S9 was used. The analysis of product mixtures further indicated that rat liver S9 metabolism involved deacetylation of O -acetyl groups in the case of 4-(3-(2-hydroxyethoxy-4-amino)phenylazo)- N , N -bis(2-acetoxyethyl)aniline.}, number={2}, journal={DYES AND PIGMENTS}, author={Freeman, Harold S. and Jeong, Euigyung and Claxton, Larry D.}, year={2013}, month={Nov}, pages={496–501} }
 @article{wang_freeman_d claxton_2007, title={Synthesis and mutagenic properties of 4,4'-diamino-p-terphenyl and 4,4'-diamino-p-quaterphenyl}, volume={123}, ISSN={["1472-3581"]}, DOI={10.1111/j.1478-4408.2006.00058.x}, abstractNote={4,4′‐Diamino‐p‐terphenyl and 4,4′‐diamino‐p‐quaterphenyl were synthesised from readily available chemical intermediates. These compounds, along with 1,4‐diaminophenylene and benzidine were examined in the Salmonella microsome assay with strains TA98 and TA100. The results of this study indicate that the mutagenicity of these diamines was the greatest for 4,4′‐diamino‐p‐terphenyl, followed by diaminophenylene and benzidine, with 4,4′‐diamino‐p‐quaterphenyl showing no mutagenicity.}, number={1}, journal={COLORATION TECHNOLOGY}, author={Wang, Jinlong and Freeman, Harold S. and D Claxton, Larry}, year={2007}, pages={34–38} }
 @article{wang_freeman_d claxton_2007, title={Synthesis and mutagenic properties of direct dyes from 4,4'-diamino-p-terphenyl and 4,4'-diamino-p-quaterphenyl}, volume={123}, ISSN={["1472-3581"]}, DOI={10.1111/j.1478-4408.2006.00059.x}, abstractNote={Disazo direct dyes were synthesised using bis‐diazotisation and coupling reactions involving 4,4′‐diamino‐p‐terphenyl and 4,4′‐diamino‐p‐quaterphenyl. The formation of the target dyes was confirmed by electrospray mass spectrometry and their mutagenicity was examined in the Salmonella microsome assay using TA98 and TA100. While most of these dyes were clearly non‐mutagenic, results from the Prival modification of the standard assay showed that Congo Red and its homologue derived from 4,4′‐diamino‐p‐terphenyl were clearly mutagenic.}, number={1}, journal={COLORATION TECHNOLOGY}, author={Wang, Jinlong and Freeman, Harold S. and D Claxton, Larry}, year={2007}, pages={39–45} }
 @article{bae_freeman_warren_claxton_2006, title={Evaluation of new 2,2 '-dimethyl-5,5 '-dipropoxybenzidine- and 3,3 '-dipropoxybenzidine-based direct dye analogs for mutagenic activity by use of the Salmonella/mammalian mutagenicity assay}, volume={603}, ISSN={["1879-3592"]}, DOI={10.1016/j.mrgentox.2005.11.007}, abstractNote={As part of a continuing study aimed at establishing structure–activity relationships and heuristic principles useful for the design of non-genotoxic azo dyes, a series of new direct dyes based on two non-mutagenic benzidine analogs, 2,2′-dimethyl-5,5′-dipropoxybenzidine and 3,3′-dipropoxybenzidine, were evaluated for mutagenic activity in Salmonella typhimurium strains TA98 and TA100. These strains are widely used for mutagenicity screening and have been shown to detect the mutagenic activity of benzidine analogs. While some toxicity was seen with some dyes at high doses, all of the dyes examined were judged non-mutagenic with and without metabolic activation in the standard Salmonella plate-incorporation assay. The results in the standard test are consistent with the properties of the diamines themselves. However, only one of the dyes was non-mutagenic when a reductive-metabolism pre-incubation assay was used. The results of this study suggest that although benzidine analogs are potential replacements for benzidine, there is a need to understand which mutagenic products are produced when reductive metabolism is present. There is also a need to know whether or not metal complexes of these dyes are mutagenic. Such information will allow the development of new non-mutagenic azo dyes.}, number={2}, journal={MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS}, author={Bae, JS and Freeman, HS and Warren, SH and Claxton, LD}, year={2006}, month={Feb}, pages={173–185} }
 @article{freeman_esancy_claxton_esancy_1991, title={Color, yes; cancer, no}, volume={21}, number={7}, journal={Chemtech}, author={Freeman, H. S. and Esancy, J. F. and Claxton, L. D. and Esancy, M. K.}, year={1991}, pages={438} }
 @article{freeman_esancy_claxton_1990, title={AN APPROACH TO THE DESIGN OF NONMUTAGENIC AZO DYES - ANALOGS OF THE MUTAGEN CI DIRECT BLACK 17}, volume={13}, ISSN={["0143-7208"]}, DOI={10.1016/0143-7208(90)80013-F}, abstractNote={The effect on mutagenicity caused by incorporating an alkoxy substituent into the structure of a disazo hydrophilic dye has been investigated. The results of this study indicate that while bulky alkoxy groups are useful in lowering the mutagenicity of certain analogs of CI Direct Black 17, the decrease observed is less than that noted for a series of monoazo disperse dyes. The color and fastness properties of these novel disazo dyes are also described.}, number={1}, journal={DYES AND PIGMENTS}, author={FREEMAN, HS and ESANCY, JF and CLAXTON, LD}, year={1990}, pages={55–70} }
 @misc{esancy_freeman_claxton_1990, title={THE EFFECT OF ALKOXY SUBSTITUENTS ON THE MUTAGENICITY OF SOME AMINOAZOBENZENE DYES AND THEIR REDUCTIVE-CLEAVAGE PRODUCTS}, volume={238}, ISSN={["0921-8262"]}, DOI={10.1016/0165-1110(90)90036-B}, abstractNote={15 aminoazobenzene dyes and 7 of their reductive-cleavage products were examined in the Salmonella/microsome assay with strains TA98, TA100, TA1535, TA1537 and TA1538. Dyes tested included 5 derivatives of 4-aminoazobenzene with different alkoxy substituents (-OCH3, -OCH2CH3, -OCH2CH2 CH3, -OCH2CH2CH2CH3 or -OCH2CH2OH) in the 8-position as well as the corresponding derivatives of 4-[(4-aminophenyl)azo]-N,N-diethylaniline and 4-[(4-aminophenyl)azo]-N,N-bis(2-hydroxyethyl)aniline. In general, as the size of the substituent ortho to the primary amino group of the dyes was increased, the mutagenicity decreased. A similar trend was observed for the reductive-cleavage products. The results from the latter aspect of this study suggest that the mutagenicity of aminoazobenzene dyes can not be accounted for solely from the properties of their reductive-cleavage products.}, number={1}, journal={MUTATION RESEARCH}, author={ESANCY, JF and FREEMAN, HS and CLAXTON, LD}, year={1990}, month={Jan}, pages={1–22} }
 @misc{esancy_freeman_claxton_1990, title={THE EFFECT OF ALKOXY SUBSTITUENTS ON THE MUTAGENICITY OF SOME PHENYLENEDIAMINE-BASED DISAZO DYES}, volume={238}, ISSN={["0921-8262"]}, DOI={10.1016/0165-1110(90)90037-C}, abstractNote={16 phenylenediamine-based disazo dyes were examined in the Salmonella/mammalian microsome assay with strains TA98, TA100 and TA1538. All of the dyes contain an alkoxy group ortho to one of the azo linkages. Increasing the size of this alkoxy substituent from 1 to 4 carbons led to a decrease in mutagenic activity in certain instances while no change was noted in other cases. Comparison of the mutagenicity of the disazo dyes with their potential reductive-cleavage products suggests that (1) the reductive-cleavage products are not solely responsible for the mutagenicity of the disazo dyes, and (2) significant reductive-cleavage of the disazo dyes is not taking place in the standard Salmonella assay.}, number={1}, journal={MUTATION RESEARCH}, author={ESANCY, JF and FREEMAN, HS and CLAXTON, LD}, year={1990}, month={Jan}, pages={23–38} }