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Direct laser acceleration (DLA) of electrons in plasmas of near-critical density (NCD) is a very advancing platform for high-energy PW-class lasers of moderate relativistic intensity supporting Inertial Confinement Fusion research. Experiments conducted at the PHELIX sub-PW Nd:glass laser demonstrated application-promising characteristics of DLA-based radiation and particle sources, such as ultra-high number, high directionality and high conversion efficiency. In this context, the bright synchrotron-like (betatron) radiation of DLA electrons, which arises from the interaction of a sub-ps PHELIX laser pulse with an intensity of 10 19 W/cm 2 with pre-ionized low-density polymer foam, was studied. The experimental results show that the betatron radiation produced by DLA electrons in NCD plasma is well directed with a half-angle of 100-200 mrad, yielding (3.4 ± 0.4)·10 10 photons/keV/sr at 10 keV photon energy. The experimental photon fluence and the brilliance agree well with the particle-in-cell simulations. These results pave the way for innovative applications of the DLA regime using low-density pre-ionized foams in high energy density research., (© 2024. The Author(s).)

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2  mg/cm^{3} density and 1 mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17  eV and n_{e}=4×10^{20}  cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.

Intense particle beams generated from the interaction of ultrahigh intensity lasers with sample foils provide options in radiography, high-yield neutron sources, high-energy-density-matter generation, and ion fast ignition. An accurate understanding of beam transportation behavior in dense matter is crucial for all these applications. Here we report the experimental evidence on one order of magnitude enhancement of intense laser-accelerated proton beam stopping in dense ionized matter, in comparison with the current-widely used models describing individual ion stopping in matter. Supported by particle-in-cell (PIC) simulations, we attribute the enhancement to the strong decelerating electric field approaching 1 GV/m that can be created by the beam-driven return current. This collective effect plays the dominant role in the stopping of laser-accelerated intense proton beams in dense ionized matter. This finding is essential for the optimum design of ion driven fast ignition and inertial confinement fusion.

More than 2500 chemically defined substances are approved as drugs in Germany. Unlike agricultural pesticides, these biologically active structures are not used in open environmental compartments and therefore their environmental toxicological data base is not nearly as complete. Nevertheless, some of them become environmental contaminants after their intended use. Therefore, from the viewpoint of environmental health protection, there are gaps in their health-related environmental risk assessment. Organic trace compounds that lack an adequate toxicological database, and their mixtures, in drinking water can be safely regulated and provisionally assessed by combining the "similar joint action" addition rule with the recommendation of the Federal Environment Agency of March 2003 "Assessing the presence of substances in drinking water without (adequate) toxicological database from the health point of view". The general precautionary value (Gesundheitlicher Orientierungswert GOW1=0.10 microg/l), which is a recommendation for weakly to not genotoxic compounds, re presents a workable compromise between preventive health protection, water management considerations and aesthetic quality claims (purity). Compliance with this value in the long term will only be possible if the chemical and biological degradation of pharmaceuticals and their metabolites in waste water and waste water treatment plants is effectively improved. Alternatively, there is the risk of drinking water degenerating into a sink for highly mobile, polar and persistent compounds. Their elimination at a stage as late as technical drinking water treatment would be neither close to the initial cause nor justifiable in terms of technical effectiveness. The risk assessment of their byproducts would give rise to further uncertainties. Possible conflicts with the therapeutic quality must be solved by developing substitute products which are environmentally sound.

Nitro compounds are important industrial chemicals with a broad range of applications. During their commercial production or practical use and through leaching from military waste sites they may be released into the environment and thus lead to a contamination of drinking water resources. In the last 15-20 years, the wider public first became aware of nitro compounds as contaminants in groundwater and drinking water resources that originated from manufacturing and processing of secondary explosives during World War II. In 1980, the former Bundesgesundheitsamt (BGA; Federal Health Office) had based its first risk assessment of monocyclic nitro compounds in drinking water on the known carcinogenicity of some aromatic amines in the working environment. On this basis, the BGA recommended for metabolites of aromatic nitro compounds a guide value of 0.1 mug/l for the sum of aromatic amines. From the beginning to the middle of the 1990s, the BGA established a more specific health-related assessment for the individual compounds, but not on the basis of tolerable or acceptable body doses but of dimensionless risk assessment scores ranking their combined toxic and carcinogenic potential on a scale from 1 to 100. In this contribution, we derived new health-based drinking water guide values for 19 nitro(aromatic) compounds and nitramines, including hexogen, octogen, and tetryl as well as the O-nitro compound PETN. All compounds under consideration have been detected within the last 15 years in Germany at contaminated sites close to or directly in groundwater resources for drinking water. For toxicological evaluation and derivation of guideline values for the nitro compounds of interest, the tolerable daily intake (TDI) approach was used for chemicals exhibiting a threshold for toxic effects. This was done by using established tolerable body doses for humans based on an identified NOAEL/LOAEL for the most sensitive toxic endpoint. In the case of non-threshold chemical substances, suitable estimates of excess lifetime cancer risk have been applied.

In order to secure a safe drinking water supply, the setting of tolerable/acceptable ceilings of drinking water hygiene is required with regard to xenobiotics resulting from several anthropogenic impacts. This is done in practice by using drinking water guidelines or standards as quantitative objectives. The list of the new EU Directive or the German drinking-water standards is limited to those parameters that have the highest relevance for drinking water quality; nitro compounds (NCs) are not regulated. Because other substances contained in water can also represent a hazard for human health, the German Drinking Water Ordinance clarifies that specific actions must be implemented if compounds other than those regulated appear at concentrations that may be a cause for concern regarding human health. NCs serve as intermediates for dyes, pharmaceuticals, and synthetic materials; they themselves are used as solvents, explosives, and pesticides. During their commercial production or from their use, they may be released to the environment and lead to a contamination of aquatic systems and thus also of drinking water resources. In practice, therefore, a need for assessment is frequently given for relevant NCs. For 19 nitro-, amino-, and aminonitroaromatics, nitramines, and nitrate esters health-based drinking water guide values have been derived. For toxicological evaluation and derivation of guideline values for the NCs of interest, the tolerable daily intake approach was used for chemicals exhibiting a threshold for toxic effects. This was done by using established tolerable body doses for humans based on an identified no-observed-adverse-effect level/low-observed-effect-level for the most sensitive indicator for toxicity. In the case of nonthreshold chemical substances, suitable estimates of excess lifetime cancer risk have been applied.

A method for beam shaping based on fitting the power moments of the final beam intensity distribution and independent of the optical system particularities is suggested. It is shown how one can analytically calculate any moment of the final phase space distribution using the moments of the initial distribution and the optical system transfer map. Numerical tests carried out for a final focus system have demonstrated the usefulness of the approach developed here.

Copper (Cu) is an essential trace element with many physiological functions. Homeostatic mechanisms exist to allow Cu to act as a cofactor in enzymatic processes and to prevent accumulation of Cu to toxic levels. The aim of this commentary is to better understand the role of dietary Cu supply in deficiency and under physiological and pathological conditions. The essentiality of Cu can be attributed to its role as a cofactor in a number of enzymes that are involved in the defence against oxidative stress. Cu, however, has a second face, that of a toxic compound as it is observed with accumulating evidence in hepatic, neurodegenerative and cardiovascular diseases. The destructive potential of Cu can be attributed to inherent physico-chemical properties. The main property is its ability to take part in Fenton-like reactions in which the highly reactive and extremely deleterious hydroxyl radical is formed. Diseases caused by dietary Cu overload could be based on a genetic predisposition. Thus, an assessment of risk-groups, such as infants with impaired mechanisms of Cu homeostasis regarding detoxification, is of special interest, as their Cu intake with resuspended formula milk may be very high. This implies the need for reliable diagnostic markers to determine the Cu status. These topics were introduced at the workshop by the participants followed by extensive group discussion. The consensus statements were agreed on by all members. One of the conclusions is that a re-assessment of published data is necessary and future research is required.

Copper is an essential element for the activity of a number of physiologically important enzymes. Enzyme-related malfunctions may contribute to severe neurological symptoms and neurological diseases: copper is a component of cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide-dismutase which plays a key role in the cellular response to oxidative stress by scavenging reactive oxygen species. Furthermore, copper is a constituent of dopamine-beta-hydroxylase, a critical enzyme in the catecholamine biosynthetic pathway. A detailed exploration of the biological importance and functional properties of proteins associated with neurological symptoms will have an important impact on understanding disease mechanisms and may accelerate development and testing of new therapeutic approaches. Copper binding proteins play important roles in the establishment and maintenance of metal-ion homeostasis, in deficiency disorders with neurological symptoms (Menkes disease, Wilson disease) and in neurodegenerative diseases (Alzheimer's disease). The Menkes and Wilson proteins have been characterized as copper transporters and the amyloid precursor protein (APP) of Alzheimer's disease has been proposed to work as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological observations in neurodegenerative disorders like Alzheimer's disease and in the genetically inherited copper-dependent disorders Menkes and Wilson disease are summarized. This could provide a rationale for a link between severely dysregulated metal-ion homeostasis and the selective neuronal pathology.

In a multicentric retrospective clinical study with 16 pediatric centres we identified 103 cases of histologically confirmed early childhood cirrhosis (ECC) in Germany for the years 1984-1994. The most prominent diagnoses were congenital bile duct anomalies (47.5%), inborn metabolic disorders (17.5%) and unclear etiologies (17.5%). Chronic and excessive intake of copper might be discussed as an etiological factor in 8 other cases. 5 of these were proven to have coincided with very high hepatic copper contents and copper plumbing/acid well water. Their connection with copper exposure must be considered as probable, whereas 3 others were only suspected copper cases, mainly due to reliable exclusion of other etiologies. High corrosivity (base capacity) values and copper levels in the water for infants formula of 9-26.4 mg/L were determined in those probable cases for which exposure conditions could be exactly reproduced. Additional reports on copper associated ECC, either Indian Childhood Cirrhosis (ICC) from outside India or so-called Idiopathic Copper Toxicosis ( ICT ), originate from Austria, Australia, Germany, Ireland, USA.

Limit values (LVs) are legal concentration limits for constituents, residues and contaminants in consumer products or for emissions from production processes into environmental compartments. They are a traditional regulatory aid to manage chemicals in human environments. To make them proactive, LVs should become enforced by means of a transparent and informed decision process whose starting point is the Basic Rule of Environmental Hygiene, BREH:Avoid useless exposure as far as possible, minimize useful exposure in a reasonable manner, and prevent that exposure which is dangerous. The BREH calls upon minimizing exposure not only according to on site risk potentials and acceptance, but also to off site avoidability and acceptability.

The Basic Rule of Environmental Hygiene BREH (Dieter 1996;1998b) is a suitable starting point for proactive chemicals management.Three definitions (==> LV) for corresponding proactive LVs can be derived from the BREH: (1) Functional anthropogenic exposure of the type residues = substance group B is accepted at least at a minimal technical threshold FB > 0 to maintain desired functionality distinctly below the most sensitive adverse effect threshold Ea, (0 < FB ==> LVB < Ea). (2) Group C exposure = non functional contaminants (F c = 0) is to be tolerated only at technically low if not "zero" levels Tc, hence 0 = Fc < Tc ==> LVC < or= 0). It may be accepted or tolerated up to its upper limit NA LVA

Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administered orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group, liver damage was established. In the combined group, liver injury was more frequent and more severe compared to the aflatoxin B1 group and biliary copper excretion was diminished compared with the copper group. Histologically, only the livers of this group exhibited degeneration, atrophy and steatosis of liver cells, inflammatory processes and a more or less prominent fibrosis. For childhood cirrhosis (ICC and ICT) a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.

This paper proposes a procedure to establish coherence between the toxicological and the legal definition of hazardous exposure situations to substances with effect threshold. This procedure is useful for defining unsafe body doses or exposure levels at and above which such situations would appear to be "sufficiently probable" in the toxicological as well as the legal sense. We propose the unsafe exposure level to be F-times higher than the safe level. F is the geometric mean of those default factors which are intended to relate the experimental or epidemiological database to the human target population. Our proposal for defining "sufficiently probable unsafe exposures" is based entirely on widely accepted toxicological conventions. It is conservative and, at the same time, flexible enough to allow F to be corrected in concert with improvements of the database. The German Federal Environmental Agency has officially adopted this proposal and is recommending it for risk assessment of environmental contaminants.

Legally recoverable protection of human health against pollutant effects must have for the enforcement in practice a technically comprehensible toxicological basis, i.e., a coherence or connection between the toxicological and legal definition of a dangerous situation must be found. For this purpose toxicological and socially accepted reference points in the unit "mg of pollutant amount absorbed per kg of weight per day" (mg/[kg of weight x d]) may be used to assess a danger in the sense a sufficient probability a damage to human health exists after exposure to certain pollutant concentrations. Based on the plausible toxicological assumption that above this reference point in case of an undisturbed course of action and by giving consideration to all exposure pathways a threshold of harmlessness including all groups of the population would be exceeded, criteria both for non-carcinogenic and carcinogenic substances or for substances suspected to cause cancer are being developed. These criteria allow to determine from which point the existence of a danger would be assessable as "sufficiently probable", and hence the required coherence between legal and toxicological view to be established.

The problem of lead in drinking water with regard to sensitive groups of the general population (e.g. unborn, babies that are not breast-fed, infants and children) is discussed. In respect of children in nurseries, the question regarding the relation of blood-lead levels to neurobehavioural deficits due to lead as well as a theoretical "tolerable" daily intake of lead is discussed. A provisional daily intake of approx. 1.2-1.3 micrograms Pb/kg body weight for children and pregnant women is proposed. For non-pregnant adults a double to three times higher intake may be tolerated (base: high blood pressure). These doses are well three times below the still recognised Provisional Tolerable Weekly Intake of led (PTWI-values, WHO), when related to daily intake. Considering the water consumption as well as the proportionate share of other exposure routes which result in the total lead exposure of risk groups, a toxicologically tolerable level of 10 micrograms Pb/l in drinking water is suggested. A reduction of the actual limiting value in drinking water (40 micrograms Pb/l) is advised. A special problem arises from lead tubes within the water distribution system. Water in stagnation as well as in use in these tubes may have enhanced lead concentrations. Therefore, it is recommended to exchange lead tubes preferentially in areas of sensitive use (e.g. as in the kitchen).

Organochlorine compounds are widely used in Germany although the inland production of chlorinated solvents has greatly decreased since 1985. Data on groundwater contamination are incomplete, but there are some regional data sets from the States (Länder). Approximately 25% of the groundwater samples contain more than 1 microgram/l of a single solvent, the most prominent ones being tri- and tetrachloroethene, 1,1,1-trichloroethane and dichloromethane, but also chloroform. The most important causes for contaminations of the groundwater are unprotected storage and leaking sewage systems. Abandoned waste sites are, besides chlorinated compounds, also a source of many other contaminants. A ranking procedure according to their exposure potential (concentration, incidence, toxicology) is proposed. The compound of greatest concern is vinyl chloride, which is formed from tri- and tetrachloroethene under reducing conditions in the subsoil. The most important contaminant in drinking water is tetrachloroethene followed by 1,1,1-trichloroethane and trichloroethane. Chlorobenzene may also be present on occasion, while only about 20% of the finished drinking waters contain more chloroform after treatment than before. Only about 10% of all analyses of drinking water derived from groundwater shows the presence of organochlorine solvents and most of these show total concentrations less than 2 micrograms/l. The degradation product, vinyl chloride, was found up to now only in different groundwaters. To stabilize and to improve the situation, which still is much more favorable for drinking than for groundwater, precautions are going to be taken which should assure that these and other problematic substances which endanger water are used only in closed systems and rigid safety measures be imposed on their disposal and transport.

The limit values prescribed by German drinking water regulations for "pesticides and their toxic main metabolites" (PBSM) protect the consumer from imponderable toxicological risks. It therefore complies with the "principle of concern" which is part of several statutory instruments of the FRG to protect ground and drinking water. Moreover, for about 10% of the permissible active ingredients, health-based limit concentrations in drinking water can be derived which are of the same order of magnitude as the legal limit value for PBSM. The main purpose of the "PBSM Recommendation" of the Federal Health Office of July 1989 is to preserve and to restore a pesticide-free ground and drinking water situation mainly by agricultural measures with at the same time maximum possible health protection for the consumers of drinking water. The bureaucratic handling of this "Recommendation" by the Commission of the EC and the standardised pesticide admittance procedure as envisaged by the EC could seriously endanger this purpose. A consequence would be that, as already in the USA, the same situation could arise in Europe that more and more active ingredients are found in ground water in concentrations which are up to 1,000 fold higher than the respective toxicological limit values for drinking water.

Three known teratogenic agents--methoxyethanol (ME), cyclophosphamide (CP) and cadmium (Cd)--are possible inducers of metallothionein (MT) in the embryo and/or in the fetus. Their effect on the MT levels of forelimbs, brain and liver during prenatal development and in dam's liver was studied in the mouse to elucidate whether MT could be used as an early biochemical indicator of teratogenicity. Pregnant mice were injected with 2 doses of each teratogen at different days of the middle gestational phase and their embryos and fetuses were obtained thereafter. Quantitative estimation of MT in the S9 from homogenates of the embryo/fetal tissues and organs and maternal liver showed major alterations in the dam's hepatic MT content but only small changes in prenatal MT levels. These results do not support MT as an early indicator of teratogenicity. However, a causal relationship between the maternal MT changes induced by the tested agents and their teratogenic effect could be possible.

Cases of chronic copper intoxication of infants via the ingestion of water, as investigated recently in certain regions of Bavaria and the EMs district, have been prompting a quest for additional risk factors which enhance the effect of copper, even though they do limit its frequency rate. The water from water wells, which had been incriminated, was never of a quality standard that would classify it as "drinking water", i.e. as potable water, so that one must consider not only physiological/biochemical but also water-conditioned/chemical causes. Copper alone as the sole risk factor--and in the concentrations considered to be suspect so far--will not suffice to explain the number of cases recorded to date. Basing on the established knowledge in toxicology and essentially of copper we arrive at the following points of attack for further research on the causes: Special kinds of copper ingestion of a chemical nature; unusual reaction of the intestinal mucosa to copper; development-conditioned variable coeruloplasmin synthesis or elimination of copper via the bile; delayed degradation of metallothioneine. Until the causes have been definitely clarified, we believe that suitable prophylactic measures should be taken in accordance with the short communication by Eife and Müller-Höcker (Dt. Arztebl. 85 (1988) 11: A 693) or the press release by the Federal Public Health Service dated 18 March 1988.

A variety of compounds that can arise from the metabolism of progesterone in vivo stimulate the 16 alpha-hydroxylation of progesterone as catalyzed by highly purified, reconstituted preparations of cytochrome P-450 3b obtained from rabbit strain IIIVO/J. In general, reduction of the 20-keto moiety of progesterone or related compounds increases the extent of stimulation. Reduction of the 3-keto group also results in increased stimulatory activity in most cases. The resulting 3 beta-hydroxy derivatives are more active than the corresponding 3 alpha-isomers. In a similar fashion, 5 beta-pregnanes exhibit greater activity than the corresponding 5 alpha-pregnanes. The effect of these allosteric effectors is saturable at relatively low concentrations when compared to other positive effectors of P-450-mediated metabolism. These compounds increase the apparent ratio of Vmax/Km without altering the amount of reductase required for half-maximal activity when reconstituted with the cytochrome. In contrast, many of these compounds do not affect or inhibit the 6 beta-hydroxylation of progesterone catalyzed by a subform of P-450 3b that is expressed in New Zealand White rabbits but not in strain IIIVO/J. Many of the compounds investigated here are metabolites of progesterone and, therefore, may modulate P-450 3b-mediated metabolism during pregnancy.

Mice were treated intraperitoneally over 20 days with 0,30; 0,10 and 0,03 mg Cd+2/kg.day. Subsequent induction of microsomal metabolism by 50 mg phenobarbital/kg.day over 5 days revealed increased microsomal cytochrome P 450 content in Cd+2-pretreated animals as compared to animals treated only with phenobarbital. The microsomal cadmium content of animals having received cadmium plus phenobarbital was about 5 times higher than that of animals treated with cadmium alone. The only enzyme activity found to be changed by cadmium in induced microsomes was ethylmorphine-N-deethylation. In phenobarbital-free animals no microsomal changes by cadmium could be detected.

The presence of the low molecular weight protein metallothionein (MT) has been investigated in fetal forelimbs, brain and liver from the mouse with the aim of using the protein as a biochemical marker for the early recognition of potential teratogenic agents in the future. Forelimbs, brain and liver were taken from mouse fetuses at ages ranging from 12 to 18 d. Each type of organ was homogenized and centrifuged at 9000 x g. The analysis of MT in the supernatants (S9) with the Cd-heme saturation method detected in all three cases the presence of a low molecular weight, Cd-binding protein whose concentration increased with the age of the fetus. Analysis of the S9 fractions using gel- and anion exchange-chromatography and polyacrylamide gel electrophoresis demonstrated the existence of a protein analogue to the hepatic MT in forelimbs and brain.

The dose-dependence of the effect of Cadmium chloride (Cd) on the induction by 3-methylcholanthrene (MC) of the microsomal cytochromes b5 and P-450, seven monooxygenase activities and the arylepoxide hydrase was investigated in the livers of male random bred mice (NMRI Hannover). The animals were treated with 6.0; 3.0; 1.0 and 0.3 mumoles Cd++/kg/day for 20 days and subsequently with MC for three days (20 mg MC/kg/day). Cytochrome P-450 of control animals receiving MC only was not induced, and presumably kinetic inhibition of three monooxygenase activities was observed at the highest Cd-dosage. However, treatment with the two intermediate Cd-dosages resulted in induction by MC of both microsomal cytochromes and of 5 hydroxylating activities, leaving unaffected only the arylhydrocarbon hydroxylase. Previous work had shown that Cd alone in this dose range is without effect on microsomal enzymes. Therefore, Cd exerts a stabilizing or permissive effect on the phenotypic expression of some microsomal enzymes, but not of the arylhydrocarbon hydroxylase, within the MC-dependent induction process in mouse liver.

The present report describes several characteristics of rabbit microsomal cytochrome P-450 form 3b isolated from liver microsomes prepared from an incipient inbred strain, IIIVO/J. Whereas most preparations of P-450 3b isolated from outbred New Zealand White (NZW) rabbits catalyze both 6 beta- and 16 alpha-hydroxylation of progesterone, form 3b prepared from strain IIIVO/J exhibits a greatly diminished 6 beta-hydroxylase activity. This difference is attributable to a large difference in Km for progesterone, and similar differences are seen when the metabolism of progesterone by microsomes prepared from each rabbit source is examined. The dependence of the rate of 16 alpha-hydroxylation of progesterone and similar differences are seen when the metabolism of progesterone by microsomes prepared from each rabbit source is examined. The dependence of the rate of 16 alpha-hydroxylation of progesterone on the initial substrate concentration also differs in that most preparations from NZW rabbits contain two enzymatically distinct forms and that one of these forms is apparently absent from the preparations of P-450 3b obtained from strain IIIVO/J. The two enzymatic subforms are differentially inhibited by 16 alpha-methylprogesterone. In contrast, the rates of 4-hydroxylation of biphenyl and of the 7-hydroxylation of 2-acetylaminofluorene catalyzed by form 3b prepared from strain IIIVO/J are similar to those catalyzed by the cytochrome obtained from NZW rabbits. When the two types of P-450 3b were compared by peptide mapping, they displayed similar yet distinguishable peptide closely related yet distinct. The selective loss of 6 beta-hydroxylase activity in the preparations of P-450 3b is suggestive of the genetically determined absence of a subform of the cytochrome that catalyzes this reaction and that is normally expressed in New Zealand White rabbits.

Progesterone 21-hydroxylase activity varies extensively among liver microsomes prepared from individual New Zealand White (NZW) rabbits. The 21-hydroxylase activities are distributed between two groupings that differ by more than tenfold in mean activity. Both male and female animals are represented in the two groupings. However, females exhibited the higher activity more frequently than males. The 21-hydroxylation of progesterone is catalyzed by one of the liver microsomal cytochrome P-450 isozymes, form 1, and these differences in activity are suggestive of differences in the occurrence of this isozyme among NZW rabbits.

Five methods of metallothionein (MT) estimation in biological materials (Hg-saturation assay, Cd-saturation assay, thiolate group determination, Sephadex G-75 gel chromatography with subsequent Cd determination by Zeeman-AAS, and a radioimmunoassay (RIA) were compared for their ability to recover standard MT(rabbit Cd-MTI) from liver or kidney S9. Uniform molar calibration of all assays was achieved using the known amino acid composition of standard MT and the nitrogen content of the standard MT stock solution as measured after complete Kjeldahl digestion. Known molar amounts of standard MT were added exogenously to rat liver- or kidney-S9 samples and recoveries measured using the methods indicated. In an overall rating, RIA and Cd-saturation assay performed best with recoveries of 97 +/- 12.0 and 105 +/- 9.7%, respectively. On the other hand, the remaining methods either underestimated (thiolate group determination, G-75/Cd-AAS) or overestimated (Hg-saturation assay) the theoretical expectation by up to 44%.

Five current methods of metallothionein (MT)-estimation in biological materials (Hg/TCA-, Cd/heme-, SH-assay, G 75-method and RIA) were compared. Uniform calibration was ensured by measuring the nitrogen-content of the standard-apoprotein after "Kjeldahl-digestion". Known amounts of rabbit standard Cd-MT I were recovered from identical rat S9-samples. In an overall rating, RIA and Cd/heme-assay performed best, whereas the other methods either underestimated (SH-, G 75) or overestimated (Hg/TCA) the 100%-expectation.