PubMed · 2898801
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Y Jaccard, A Pécoud. 1988. [Springtime rhinoconjunctivitis: current findings].. https://pubmed.ncbi.nlm.nih.gov/2898801/
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Fifty-nine simple analogues of the antipsoriatic agent, anthralin, have been prepared by modifying the positions of the 1,8-hydroxyl groups, replacement of the hydroxyl groups, substitution at the oxygen functions, introduction of additional functional groups into various positions of the anthracenone nucleus, or removal of particular structural elements. The compounds were evaluated for their antiproliferative action against human keratinocytes and inhibition of the generation of leukotriene B4 in polymorphonuclear leukocytes, which may be useful to resolve the proliferative and inflammatory aspects of psoriasis, respectively. Even though many anthracenones were more potent inhibitors of leukotriene biosynthesis than anthralin, none of the compounds was substantially more effective as this drug in suppressing keratinocyte cell growth. There is an absolute requirement for two hydroxyl groups peri to a hydrogen bond acceptor such as a keto or an imino group for high potency. In addition to further delineating the nature of the pharmacophore for this class of compounds, also naphthalenedione with a peri hydroxyl group was identified as a pharmacophore with antiproliferative activity against keratinocyte growth.
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Hydrodesulfurized kerosine (HDS kerosine), applied dermally, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, using a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. A preliminary acute dermal irritancy test demonstrated that dilution of HDS kerosine in either a light (100 Saybolt universal seconds, SUS) or moderate viscosity (340 SUS) USP mineral oil reduced irritation of the neat material comparably. Similar dermal absorption was observed in vitro for neat HDS kerosine or diluted in either of the mineral oils. HDS kerosine diluted to 494 (60%), 330 (40%), or 165 (20%) mg/kg/day in Squibb mineral oil (340 SUS) was applied daily at 1 ml/kg to the shaved backs of rats for 7 wk (premating, mating to d 19 of gestation) to females and 8 wk to males. Dams and litters were sacrificed on postpartum d 4 and males were sacrificed within the following week. HDS kerosine produced slight to moderate skin irritation at the highest dose in both sexes but no apparent maternal, reproductive, or developmental toxicity. No clinical signs of toxicity and no effects on body weight, food consumption, or absolute organ weights were observed. Relative kidney weights were heavier in male rats at the high dose. Skin changes were observed microscopically in male rats in all groups and in females at the high dose. No microscopic changes were observed in reproductive organs of parental animals. There were no differences in mean number of corpora lutea, implantation sites, and live pups per litter, and no gross anomalies were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or = 93%. In conclusion, the no observable adverse effect level (NOAEL) for HDS kerosine for reproductive and developmental toxicity in rats is 494 mg/kg/d.