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Abstract-It is shown that in contrast to the use of coupling constants, chemical shift criteria may lead to unambiguous structural elucidations in pseudorotational frameworks (pentacycles, heptacycles, etc.).

Paraffin waxes and white mineral oils are distinct petroleum products separated from a common feedstock by crystallization, where only n-alkanes, iso-and cyclo-alkanes with a linear backbone of $ 20 carbon atoms long, selectively crystalize out from the oil to form the wax, which is solid at room temperature, whereas oils remain liquid. Up until the 90's, these differences were reflected in separated regulatory assessments. A paradigm shift occurred when Fischer 344 rats (F-344) developed liver epithelioid granuloma following exposure to low and medium viscosity oils or waxes. This lesion was used as common denominator between these products to be jointly assessed under the common term "mineral hydrocarbons -MHC", obviating compositional differences. This regulatory paradigm dominated for the next 30 years, exacerbated by the EFSA 2012 evaluation using the analytical term "MOSH" (mineral oil saturated hydrocarbons) which encompassed these products under single chromatography fraction. The reconstruction of historical developments, together with recent EFSA-sponsored studies of toxicity and accumulation and supporting literature, has allowed us to understand the etiology of the F-344 rat hepatic epithelioid granuloma, which is presented in an adverse outcome pathway (AOP). Considering chemical composition, it clearly demonstrates that the hepatic effects in F-344 rats caused by linear alkanes of waxes are irrelevant for humans. Waxes are thus not MOSH and should thus be evaluated on their own merit. The term MOSH should not include n-alkanes and be exclusively used to mineral oil fractions when considering their chemical makeup for a relevant human hazard assessment.

Abstract-From a 300 MHz spectral study of mono-to trisubstituted cyclohexanes, allowing a re-examination of some of their 'H NMR spectral parameters, it is shown that it is possible to predict with reasonable accuracy the shifts (in CCI,) of the ring protons. A substantial feature in this is the validity of the (questioned) additivity of multiple effects. It is also shown that with respect to shift alterations, equatorial ring protons behave anomalously, which cannot be explained by any existing theoretical model. STARTING with the pioneering paper by Booth,' there has been an ever increasing interest in the chemical shift alterations caused by substituting one or more hydrogen atoms by alkyl (e.g. methyl) groups in cyclohexane.2-6 The influence of methyl groups is also well documented' in saturated 1,3-diheterocycIic compounds, In parallel with the availability of more experimental data, several attempts to correlate the observed phenomena have been published and theoretical chemical shift models have also been proposed.s*9 One of the major points of discussion is the reported lack in additivity by sandwiching an axial proton between two equatorial methyl group^.^,^ Unfortunately, apart from an early publication by Muller and Tosch,lo the 'H N M R spectrum of one of the key compounds (cis-1,3-dimethylcyclohexane) has never been discussed thoroughly. By using a superconducting NMR spectrometer it is now possible for us to fill this gap. For comparative purposes we have also investigated the other mono-to trimethyl substituted cyclohexanes, together with i-propyl and t-butyl substituted analogues. EXPERIMENTALThe mono-, di-and trimethylcyclohexanes were prepared by catalytic reduction in ethanol of the parent aromatic hydrocarbon with hydrogen (90 kg/cm2, 100 " C ) and rhodium on alumina as the catalyst. The separation of the isomers was carried out by gas chromatography on a 20 m, 2.5 cm 0.d. column, stationary phase SE-30 on Chromosorb and hydrogen as the eluting gas. The identity of the compounds was checked by comparison of the fingerprint region of the I R spectra with those published in the literature." The ' H N M R spectra were run in carbon tetrachloride, bromobenzene and a-bromonaphthalene (aBN) on a Varian HR-300 spectrometer. The product concentration was approximately 5 v/v and TMS was used as the internal reference. Brominated aromatic solvents were chosen, because they were found to induce relatively important ASIS effects, which helped considerably in assignments and measurements of the splittings due to spin coupling interactions. A correlation of this ASIS effect and chemical structure of the present compounds is currently under investigation. RESULTSThe measured chemical shifts for the different protons in the pertinent compounds are presented in Table I . With the exception of cis-l,3-dimethylcyclohexane (Spec. Nos. 0703 and 0704), cis-cis-l,3,5-trimethylcyclohexane (Spec. No. 0705) and the corresponding trans-cis isomer (Spec. No. 0706), we have not yet been able to analyse the NMR spectra com...