Orexins/hypocretins cause sharp wave- and theta-related synaptic plasticity in the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic signaling.

Orexins (OX), also called hypocretins, are bioactive peptides secreted from glucose-sensitive neurons in the lateral hypothalamus linking appetite, arousal and neuroendocrine-autonomic control. Here, OX-A was found to cause a slow-onset long-term potentiation of synaptic transmission (LTPOX) in the hippocampus of young adult mice. LTPOX was induced at Schaffer collateral-CA1 but not mossy fiber-CA3 synapses, and required transient sharp wave-concurrent population field-burst activity generated by the autoassociative CA3 network. Exogenous long theta-frequency stimulation of Schaffer collateral axons erased LTPOX in intact hippocampal slices but not mini slices devoid of the CA3 region. Pharmacological analysis revealed that LTPOX requires co-activation of ionotropic and metabotropic glutamatergic, GABAergic, as well as noradrenergic and cholinergic receptors. Together these data indicate that OX-A induces a state-dependent metaplasticity in the CA1 region associated with sharp-wave and theta rhythm activity as well as glutamatergic, GABAergic, aminergic, and cholinergic transmission. Thus, orexins not only regulate arousal threshold and body weight but also threshold and weight of synaptic connectivity, providing a molecular prerequisite for homeostatic and behavioral state-dependent control of neuronal plasticity and presumably memory functions.

Taurine-induced long-lasting enhancement of synaptic transmission in mice: role of transporters.

Taurine, a major osmolyte in the brain evokes a long-lasting enhancement (LLETAU) of synaptic transmission in hippocampal and cortico-striatal slices. Hippocampal LLETAU was abolished by the GABA uptake blocker nipecotic acid (NPA) but not by the taurine-uptake inhibitor guanidinoethyl sulphonate (GES). Striatal LLETAU was sensitive to GES but not to NPA. Semiquantitative PCR analysis and immunohistochemistry revealed that taurine transporter expression is significantly higher in the striatum than in the hippocampus. Taurine transporter-deficient mice displayed very low taurine levels in both structures and a low ability to develop LLETAU in the striatum, but not in the hippocampus. The different mechanisms of taurine-induced synaptic plasticity may reflect the different vulnerabilities of these brain regions under pathological conditions that are accompanied by osmotic changes such as hepatic encephalopathy.

Ethanol differentially enhances hippocampal GABA A receptor-mediated responses in protein kinase C gamma (PKC gamma) and PKC epsilon null mice.

Ethanol intoxication results partly from actions of ethanol at specific ligand-gated ion channels. One such channel is the GABA(A) receptor complex, although ethanol's effects on GABA(A) receptors are variable. For example, we found that hippocampal neurons from selectively bred mice and rats with high hypnotic sensitivity to ethanol have increased GABA(A) receptor-mediated synaptic responses during acute ethanol treatment compared with mice and rats that display low behavioral sensitivity to ethanol. Here we investigate whether specific protein kinase C (PKC) isozymes modulate hypnotic and GABA(A) receptor sensitivity to ethanol. We examined acute effects of ethanol on GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) in mice lacking either PKCgamma (PKCgamma(-/-)) or PKCepsilon (PKCepsilon(-/-)) isozymes and compared the results to those from corresponding wild-type littermates (PKCgamma(+/+) and PKCepsilon(+/+)). GABA(A) receptor-mediated IPSCs were evoked in CA1 pyramidal neurons by electrical stimulation in stratum pyramidale, and the responses were recorded in voltage-clamp mode using whole-cell patch recording techniques. Ethanol (80 mM) enhanced the IPSC response amplitude and area in PKCgamma(+/+) mice, but not in the PKCgamma(-/-) mice. In contrast, ethanol markedly potentiated IPSCs in the PKCepsilon(-/-) mice, but not in PKCepsilon(+/+) littermates. There was a positive correlation between ethanol potentiation of IPSCs and the ethanol-induced loss of righting reflex such that mice with larger ethanol-induced increases in GABA(A) receptor-mediated IPSCs also had higher hypnotic sensitivity to ethanol. These results suggest that PKCgamma and PKCepsilon signaling pathways reciprocally modulate both ethanol enhancement of GABA(A) receptor function and hypnotic sensitivity to ethanol.

Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor.

Caffeine is believed to act by blocking adenosine A(1) and A(2A) receptors (A(1)R, A(2A)R), indicating that some A(1) receptors are tonically activated. We generated mice with a targeted disruption of the second coding exon of the A(1)R (A(1)R(-/-)). These animals bred and gained weight normally and had a normal heart rate, blood pressure, and body temperature. In most behavioral tests they were similar to A(1)R(+/+) mice, but A(1)R(-/-) mice showed signs of increased anxiety. Electrophysiological recordings from hippocampal slices revealed that both adenosine-mediated inhibition and theophylline-mediated augmentation of excitatory glutamatergic neurotransmission were abolished in A(1)R(-/-) mice. In A(1)R(+/-) mice the potency of adenosine was halved, as was the number of A(1)R. In A(1)R(-/-) mice, the analgesic effect of intrathecal adenosine was lost, and thermal hyperalgesia was observed, but the analgesic effect of morphine was intact. The decrease in neuronal activity upon hypoxia was reduced both in hippocampal slices and in brainstem, and functional recovery after hypoxia was attenuated. Thus A(1)Rs do not play an essential role during development, and although they significantly influence synaptic activity, they play a nonessential role in normal physiology. However, under pathophysiological conditions, including noxious stimulation and oxygen deficiency, they are important.

In vitro tolerance to inhibition by ethanol of N-methyl-D-aspartate-induced depolarization in locus coeruleus neurons of behaviorally ethanol-tolerant rats.

Intracellular recordings were made in pontine slice preparations of the rat brain containing the locus coeruleus (LC). Ethanol at 100 mM, but not at 10 or 30 mM inhibited depolarizing responses to pressure-applied N-methyl-D-aspartate (NMDA) in LC neurons of ethanol-naive rats. Ethanol (100 mM) had a similar effect in LC neurons of ethanol-naive rats, of rats treated with ethanol for 14 days (3 g/kg daily, i.p.) and of rats treated with equicaloric amounts of saccharose (5 g/kg daily, i.p.). The blood concentration of ethanol was markedly decreased at 4 h, and was below the detection limit at 24 h after the last injection. Behavioral measurements in the open-field system demonstrated the development of tolerance in rats receiving ethanol for 14 days. Moreover, an anxiety-related reaction was shown to develop when the acute effect of the last ethanol injection vanished. Therefore, in subsequent in vitro experiments, ethanol (10 mM) was continuously present in the superfusion medium in order to mimic a steady blood concentration and to prevent a withdrawal-like situation. Under these conditions, ethanol (100 mM) still continued to inhibit the NMDA-induced depolarization in slices of untreated rats, but became ineffective in slices of ethanol-treated rats at 4 h after the last injection. By contrast, a supersensitivity to ethanol developed in brain slices at 24 h after the last ethanol injection. In conclusion, in vitro tolerance between systemically and locally applied ethanol at LC neurons could only be demonstrated when a low concentration of ethanol was added to the superfusion medium to simulate the blood concentration of this compound.

Co-transmitter function of ATP in central catecholaminergic neurons of the rat.

Intracellular recordings were made in a mid-pontine slice preparation of the rat brain containing the nucleus locus coeruleus. Focal electrical stimulation evoked biphasic synaptic potentials consisting of early depolarizing (d.p.s.p.) and late hyperpolarizing (i.p.s.p.) components. The alpha(2)-adrenoceptor antagonist idazoxan inhibited the i.p.s.p. without altering the d.p.s.p. All of the following experiments were carried out in the presence of kynurenic acid and picrotoxin to block the glutamatergic and GABAergic fractions of the d.p.s.p., respectively. Guanethidine, which is known to inhibit noradrenaline and ATP release from nerve terminals of postganglionic sympathetic nerves, depressed both the d.p.s.p. and the i.p.s.p. in a concentration-dependent manner. Damage of catecholaminergic nerve terminals by 6-hydroxydopamine also decreased both the d.p.s.p. and the i.p.s.p. The P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) depressed the d.p.s.p., whereas the i.p.s.p. remained unaffected. The further application of PPADS did not increase the depression of the d.p.s.p. by guanethidine. Superfusion with the mixed alpha-adrenoceptor agonist noradrenaline or the selective P2 receptor agonist adenosine 5'-O-(2-thiodiphosphate) inhibited both the d.p.s.p. and the i.p.s.p. The inhibitory effects of these agonists were prevented by the respective antagonists idazoxan or suramin. In the presence of suramin noradrenaline failed to inhibit the residual d.p.s.p. Superfused noradrenaline potentiated rather than inhibited responses to pressure-applied alpha,beta-methylene-ATP; superfused adenosine 5'-O-(2-thiodiphosphate) did not interact with pressure-applied noradrenaline. In conclusion, we present electrophysiological evidence for the co-release of ATP and catecholamines in the CNS. At the cell somata of neurons in the locus coeruleus, noradrenaline and ATP activate inhibitory alpha(2)-adrenoceptors and excitatory P2 receptors, respectively. In addition, inhibitory presynaptic autoreceptors of the alpha(2) and P2 types appear to regulate release of the two co-transmitters.

Single-cell RT-PCR analysis of N-methyl-D-aspartate receptor subunit expression in rat locus coeruleus neurones.

Whole-cell patch-clamp recordings were performed on 12- to 15-day-old rat locus coeruleus neurones in a midpontine slice preparation. Application of noradrenaline (100 microM) and N-methyl-D-aspartate (NMDA; 100 microM) induced a small outward current and a distinct inward current, respectively. Single-cell reverse transcriptase-polymerase chain reaction (scRT-PCR), used to analyse the expression pattern of NMDA receptor subunits 2A, 2B, and 2C (NR2A-C) subsequent to electrophysiological characterization, demonstrated differences in the capacity of individual locus coeruleus neurones to express NR2A-C mRNA. NR2C mRNA expression predominated over those of NR2A and NR2B mRNA in most neurones. In addition, in neurones containing NR2C mRNA NMDA induced significantly larger currents than in cells lacking expression of this gene. RT-PCR studies performed on tissue preparations of adult rats also revealed a distinct expression of NR2C mRNA. In conclusion, the present data demonstrate differences in the mRNA expression pattern of NR2A-C of individual locus coeruleus neurones with a predominant NR2C mRNA expression in the majority of the cells.

The in vitro ethanol sensitivity of hippocampal synaptic gamma-aminobutyric acid(A) responses differs in lines of mice and rats genetically selected for behavioral sensitivity or insensitivity to ethanol.

Previous work has demonstrated that in the hippocampal CA1 region of Sprague-Dawley rats, there are ethanol-sensitive and ethanol-insensitive populations of GABAergic synapses on pyramidal neurons. The present experiments characterized the ethanol sensitivity of these pathways in lines of rats and mice genetically selected for sensitivity or insensitivity to the behavioral effects of ethanol. In ethanol-sensitive inbred long sleep mice, GABA(A) IPSCs induced by stimulation of proximal (probably somatic) synapses were enhanced by 80 mM ethanol, whereas the distal (i.e., dendritic) pathway was unaffected. Thus, the relative sensitivity of these pathways (proximal > distal) is the same in both Sprague-Dawley rats and in inbred long sleep mice. However, in the ethanol-insensitive inbred short sleep mice, neither proximal nor distal IPSCs were affected by 80 mM ethanol. The ethanol sensitivity of the proximal pathway was also examined in replicate lines of rats selected for either high ethanol sensitivity or low ethanol sensitivity. GABA(A) IPSCs in the high ethanol sensitivity lines were significantly enhanced by 80 mM ethanol, whereas IPSCs in the low ethanol sensitivity lines were unaffected. Thus, IPSCs evoked via the proximal pathway were enhanced by ethanol in all the sensitive mouse and rat lines, and unaffected in all the insensitive lines. These experiments demonstrate that GABA(A) synapses in brain differ in their sensitivity to enhancement by ethanol, and the sensitivity to such enhancement is under the control of genes that can be selected for using classical genetic selective breeding based on a behavioral phenotype.

Mechanism of inhibition by ethanol of NMDA and AMPA receptor channel functions in cultured rat cortical neurons.

The effect and mode of action of ethanol on N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors of rat cortical neurons in primary culture were compared by means of the patch-clamp technique. The maxima of the concentration-response curves for both NMDA and AMPA were markedly depressed by ethanol without an apparent shift of the curves to the right. Ethanol inhibited the effects of NMDA and AMPA concentration-dependently and equally well. Excitatory amino acid (EAA) currents were depressed to the largest extent when ethanol was continuously superfused during and between agonist applications; a smaller inhibitory effect was observed when ethanol was intermittently superfused during agonist applications only. There was no inhibition by ethanol, when its superfusion was between two agonist applications. According to expectations, the analysis of the ratios of plateau to peak currents failed to suggest a use-dependent blockade by ethanol. In addition, comparison of the voltage-current curves of NMDA and AMPA in the absence and presence of ethanol indicated a voltage-independent effect and no change in the reversal potential of the two agonists. Finally, the measurement of activation and deactivation time constants for the ethanol-induced inhibition of NMDA and AMPA responses confirms the failure of ethanol to cause an open-channel block. In conclusion, these findings as a whole indicate that ethanol inhibits NMDA and AMPA currents by a noncompetitive mechanism. The mode of action appears to be similar for both NMDA and AMPA; under the conditions of the present study, a selective interference with structural motifs of the NMDA receptor is unlikely.

Ethanol-induced inhibition of NMDA receptor channels.

Ethanol is a potent inhibitor of the N-methyl-D-aspartate (NMDA)-receptor subtype of glutamate receptor in a number of brain areas. The mechanism of ethanol action has been investigated by means of patch-clamp recording of ionic currents and fura-2 measurement of intracellular Ca2+ concentration in cell culture systems; the subunit composition of NMDA receptors and their influence on the effect of ethanol was determined by molecular biology methods. Ethanol does not appear to interact with NMDA either at the glutamate recognition site of the receptor, or at any of the hitherto known multiple modulatory sites, such as the glycine or polyamine site. Moreover, ethanol does not cause an open channel block by itself and fails to interact with Mg2+ at the site where it causes open channel block. The ability of ethanol to inhibit responses to NMDA is dependent on the subunit combination of NMDA receptors. The NR1/NR2A and NR1/NR2B combinations are preferentially sensitive to ethanol inhibition. Chronic treatment with ethanol leads to an increase of the NMDA receptor number at the transcriptional and posttranscriptional level; the receptor function is also facilitated. This causes withdrawal-type seizures after termination of chronic treatment with ethanol. The inhibition of NMDA receptors by ethanol leads to the depression of excitatory synaptic potentials mediated by this type of excitatory amino acid receptor. Ethanol-induced disturbances in certain regions of the brain, i.e. hippocampus, nucleus accumbens or locus coeruleus may lead to cognitive disorders or drug dependence. Brain slices containing the locus coeruleus may be used as an in vitro test system to investigate the addictive properties of ethanol.

Effect of extracellular adenosine 5'-triphosphate on principal neurons of the rat ventral tegmental area.

Intracellular recordings were made in a midbrain slice preparation of the rat brain containing the ventral tegmental area (VTA). Dopaminergic principal cells were identified by their electrophysiological properties and their hyperpolarizing responses to dopamine. Superfusion with dopamine (100 microM) caused hyperpolarization and a decrease of the apparent input resistance. By contrast, two structural analogues of ATP, 2-methylthio ATP (2-MeSATP; 10 microM) and alpha,beta-methylene ATP (alpha, beta-meATP; 30 microM) had no effect, when added to the superfusion medium. Pressure applied dopamine also hyperpolarized the membrane, while both 2-MeSATP and alpha,beta-meATP were ineffective. Hence, dopaminergic principal neurons of the VTA do not possess somatic P2 purinoceptors present on peripheral and central noradrenergic neurons.

Inhibition by ethanol of excitatory amino acid receptors in rat locus coeruleus neurons in vitro.

Intracellular recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus (LC). In a first series of experiments, various parameters of spontaneous action potentials were evaluated. It turned out that ethanol (100 mM) does not alter the firing rate, the spike amplitude and the afterhyperpolarization following a spike. In subsequent experiments, the generation of action potentials was prevented by passing continuous hyperpolarizing current via the recording electrode. Under these conditions, ethanol (100 mM) had no effect on the membrane potential or input resistance. Pressure-applied N-methyl-D-aspartate (NMDA), (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and alpha,beta-methylene ATP (alpha,beta-meATP) reproducibly depolarized LC neurons. While ethanol (100 mM) depressed the NMDA- and AMPA-induced depolarization to a similar extent, it did not interact with alpha,beta-meATP. Lower concentrations of ethanol (10 and 30 mM) had no effect on depolarizing responses to NMDA or AMPA. Noradrenaline applied by pressure pulses reproducibly hyperpolarized LC cells. These hyperpolarizations were unchanged by ethanol (100 mM). Biphasic synaptic potentials consisting of early depolarizing (PSP) and late hyperpolarizing (IPSP) components were evoked by electrical stimulation. Ethanol (100 mM) depressed the PSP and increased the IPSP. Glutamatergic PSPs recorded in the combined presence of picrotoxin (100 microM) and suramin (100 microM) were also inhibited by ethanol (100 mM). However, IPSPs recorded under these conditions were insensitive to ethanol (100 mM). In conclusion, ethanol may interfere with the AMPA (or NMDA) receptor-mediated fraction of the PSP and slightly facilitate the alpha2 adrenoceptor-mediated fraction of the IPSP.

Role of ATP in fast excitatory synaptic potentials in locus coeruleus neurones of the rat.

1. Intracellular recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus (LC). The pressure application of alpha,beta-methylene ATP (alpha,beta-meATP) caused reproducible depolarizations which were depressed by suramin (30 microM) and abolished by suramin (100 microM). Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10, 30 microM) also concentration-dependently inhibited the alpha,beta-meATP-induced depolarization, although with a much slower time-course than suramin. Almost complete inhibition developed with 30 microM PPADS. Reactive blue 2 (30 microM) did not alter the effect of alpha,beta-meATP, while reactive blue 2 (100 microM) slightly depressed it. 2. Pressure-applied (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) also depolarized LC neurones. Kynurenic acid (500 microM) depressed and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM) abolished the response to AMPA. Suramin (100 microM) potentiated the AMPA effect. 3. Pressure-applied noradrenaline hyperpolarized LC neurones. Suramin (100 microM) did not alter the effect of noradrenaline. 4. Focal electrical stimulation evoked biphasic synaptic potentials consisting of a fast depolarization (p.s.p.) followed by a slow hyperpolarization (i.p.s.p.). A mixture of D(-)-2-amino-5-phosphonopentanoic acid (AP-5; 50 microM), CNQX (50 microM) and picrotoxin (100 microM) depressed both the p.s.p. and the i.p.s.p. Under these conditions suramin (100 microM) markedly inhibited the p.s.p., but did not alter the i.p.s.p. In the combined presence of AP-5 (50 microM), CNQX (50 microM), picrotoxin (100 microM), strychnine (0.1 microM), tropisetron (0.5 microM) and hexamethonium (100 microM), a high concentration of suramin (300 microM) almost abolished the p.s.p. without changing the i.p.s.p. 5. In the presence of kynurenic acid (500 microM) and picrotoxin (100 microM), PPADS (30 microM) depressed the p.s.p. Moreover, the application of suramin (100 microM) to the PPADS (30 microM)-containing medium failed to cause any further inhibition. Neither PPADS (30 microM) nor suramin (100 microM) altered the i.p.s.p. 6. It was concluded that the cell somata of LC neurones are endowed with excitatory P2-purinoceptors. ATP may be released either as the sole transmitter from purinergic neurones terminating at the LC or as a co-transmitter of noradrenaline from recurrent axon collaterals or dendrites of the LC neurones themselves.

Tolerance to inhibition by ethanol of N-methyl-D-aspartate-induced depolarization in rat locus coeruleus neurons in vitro.

Intracellular recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus. The pressure application of N-methyl-D-aspartate (NMDA) produced reproducible depolarizations of stable amplitude. Superfusion with ethanol (100 mM) for 15 min inhibited the depolarizing response to NMDA: the effect of ethanol was rapidly reversed on washout. When the superfusion time of ethanol (100 mM) was increased to 60 min, its inhibitory effect disappeared after 50 to 60 min. Moreover, after the subsequent washout of ethanol a withdrawal-like increase in the sensitivity to NMDA became evident. Hence, adaptive mechanisms of locus coeruleus neurons during the long-time contact with ethanol may be modelled in an in vitro system.

Effect of long-term ethanol pretreatment on the metabolism of dichloromethane to carbon monoxide in rats.

The present study investigates the influence of long-term ethanol (ETOH) treatment of rats [10% (v/v) for 4, 12, and 36 weeks] on the metabolism of DCM after its oral and inhalative uptake to CO. Biotransformation of DCM to CO as measured by carboxyhemoglobin (COHb) formation was stimulated after long-term ETOH treatment in rats. A single oral dose of DCM (6.2 mmol/kg body mass) caused a significant increase of COHb, the maximum of about 9% occurring approximately 6 hr after DCM administration. In comparison to this control, in the blood of rats pretreated with ETOH (10% v/v) for 4, 12, and 36 weeks COHb values of 18, 17, and 13%, respectively, were measured. Long-term ETOH treatment followed by inhalation of 100, 500, and 2500 ppm DCM for 4 hr stimulated the formation of COHb, compared to controls. The elevation of COHb level was accompanied by decreased concentrations of DCM in the blood. The reason for the elevated biotransformation of DCM was ascertained by means of the determination of p-nitrophenol and aniline hydroxylation in liver microsomes of rats after long-term ETOH treatment to be an increase in cytochrome P450-dependent enzyme activities.

Influence of long-term ethanol treatment on rat liver aniline and p-nitrophenol hydroxylation.

The present study investigates the influence of long-term ethanol (EtOH) treatment of rats [10% (v/v) for 1, 4, 12, and 36 weeks] on hepatic microsomal cytochrome P450 (P450) content and liver aniline and p-nitrophenol hydroxylation. Total P450 per liver was stimulated after EtOH treatment for 1, 4, and 12 weeks. In the case of longer EtOH treatment no additional stimulation in P450 content was observed. Aniline and p-nitrophenol hydroxylase activity increased in direct relation with the duration of EtOH consumption. The stimulation of both enzymatic activities was different. In comparison to controls, in rats treated with 10% (v/v) EtOH for 1, 4, 12, and 36 weeks, an increase in nitrocatechol formation (1.1-, 1.2-, 2.2-, and 2.8-fold, respectively) was found. In contrast, no effect was observed on the metabolism of aniline after 1 and 4 weeks of EtOH consumption. Aniline hydroxylation increased after 12 and 36 weeks of EtOH treatment only. Addition of EtOH in vitro had an inhibitory effect on both aniline and p-nitrophenol hydroxylation. With liver microsomes from controls as well as EtOH-treated rats the inhibition of p-nitrophenol hydroxylation was competitive in nature (Ki = 5.6 mM and Ki = 5.9 mM). In contrast, there was a competitive inhibition of aniline hydroxylation with liver microsomes from controls only. With microsomes from EtOH-treated rats a mixed inhibition was found.

[Analytical comparison of "paraffin" labeled highly toxic lamp oils with paraffinum perliquidum (DAB 10)]. / Analytischer Vergleich "Paraffin"-deklarierter hochtoxischer Lampenöle mit dem Paraffinum perliquidum (DAB 10).

Coloured and odoriferous lamp oils available as household articles repeatedly lead to ingestion intoxications in children in some cases resulting in a bad course. Labels on containers of lamp oils are misleading, e.g. "pure liquid paraffin" or "without noxious substances", causing considerable misconceptions during therapeutic use by treating doctors. Analyses of four arbitrary chosen lamp oils by GC and GC/MS show that the main components (approx. 98%) are the unbranched saturated hydrocarbons n-decane, n-undecane, n-dodecane, n-tridecane, n-tetradecane. Tests according to the German Pharmacopoeia 10th ed. prove also that "paraffin"-labelled products are not at all identical with medical/pharmaceutical paraffinum perliquidum or liquidum. Lamp oils are low viscous and high toxic petroleum distillates and should be labelled "toxic to humans".