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Biomedical subjects

R Roll

Publications and source records attributed to R Roll.

At least 37 records · Page 2Linked to original sources

A differentiated approach to testing skin sensitization. Proposal for a new test guideline skin sensitization.

The present EEC and OECD Guidelines for testing skin sensitization have been reviewed in light of scientific evidence demonstrating that those methods which use Freund's Complete Adjuvant (FCA) are likely to be more accurate in predicting a probable skin-sensitizing effect of a new substance in humans than those methods not employing Freund's Complete Adjuvant. In this new test guideline, therefore, the primary testing of a substance should be carried out using one of the recommended Adjuvant methods. In special cases a non-adjuvant method may be performed in addition. Not all of the seven methods in the EEC Guideline or eight methods in the OECD Guideline have been included, but in a proposal for an updated test protocol two Adjuvant tests (Maximization test by Magnusson and Kligman and Optimization test by Maurer), and two non-Adjuvant tests (Open Epicutaneous test by Klecak and Buehler test) are suggested. The criteria for selecting these methods are based on the fact that they are well validated and widely used on a broad basis by the scientific community. Furthermore, it is considered appropriate to permit the use of a lower number of animals than presently recommended for the testing of skin sensitization. This is also in agreement with aspects of animal welfare.

Animals↗

Eye, head and skeletal muscle spindle feedback in the elaboration of body references.

Evidence is presented to support the notion that the sensory feedback originating in muscles is of major importance in the central elaboration of motor representation. The muscle spindle messages during movement and postural performance may be processed in order to elaborate continuously updated static and dynamic body references. These may then form the basis for the interpretation of retinal information in terms of spatial coordinates. The main arguments supporting this view are as follows. Experimental manipulation of muscle spindle proprioceptive feedback by tendon vibration induced segmental or postural kinaesthetic illusory movements in the direction of stretch of the vibrated muscles. By modifying the spatial distribution (agonists and/or antagonists), the frequency and the duration of the vibratory stimuli it is possible to induce simple or complex kinaesthetic illusions the parameters of which may be predicted. Microneurographic recordings confirmed that vibration rather selectively excited spindle Ia afferents, eliciting 1:1 driving up to 80-100 Hz. Moreover painless vibration, applied at increasing frequency (from 10 to 80 Hz) to either the medial, lateral, superior or inferior rectus of a subject's eye, was found to induce directional perceptual and motor effects which were closely related to the postural context. Likewise, the subjects reported illusory directional shifts of a visually fixed target in darkness during extraocular muscle vibration. These data suggest that extraocular proprioception contributes to the coding of eye, head and body position in relation to postural and environmental conditions. As with eye muscle stimulation, directional visual and postural effects were induced by vibration of neck and/or ankle postural muscles. These effects were found to summate when vibrations were applied simultaneously to the eye, neck and ankle muscles. The likely involvement of extraocular proprioception in interrelating body space with extrapersonal space in oriented behaviour is discussed.

Head↗

Thallium determinations in fetal tissues and maternal brain and kidney.

The transfer of T1+ cations through the placental barrier of pregnant mice and rats was studied by comparing the thallium concentrations in the maternal brain and kidney and those in fetal tissue at times of 10 min to 50 h after dosage of the animals with 10 mg/kg body wt. T1(2)SO4. The quantitative determinations were performed with field desorption mass spectrometry after dilution of the homogenised tissue samples with enriched stable isotopes of thallium. The total sample quantity required for one complete assay is 1-3 micrograms, the analysis time for one determination about 30 min.

Animals↗

[Comparative studies on the embryotoxicity of 2-methyl-4-chlorophenoxyacetic acid, mecoprop and dichlorprop in NMRI mice].

From the group of herbicidal phenoxy carbonic acids, 2-methyl-4-chlorophenoxyacetic acid (MCPA; 0-500 mg/kg), 2-(4-chloro-2-methyl-phenoxy) propionic acid (mecoprop/MCPP; 0-700 mg/kg) and 2-(2,4-dichlorophenoxy) propionic acid (dichlorprop/2,4-DP; 0-500 mg/kg) as well as the dextrorotatory compounds of MCPP (MCPPD; 0-500 mg/kg) and 2,4-DP (2,4-DPD; 0-500 mg/kg) were studied in NMRI mice after oral administration between days 6-15 of pregnancy. All five substances proved to be embryotoxic and teratogenic in varying intensity. MCPA proved to be most effective: it was embryotoxic from doses of 100 mg/kg and teratogenic from 200 mg/kg. The remaining compounds (MCPP, MCPPD, 2,4-DP, 2,4-DPD) were embryotoxic from doses of 300 mg/kg and caused malformations of the skeleton from 400 mg/kg. The embryocidal and teratogenic potencies of the dextrorotatory components of MCPA and 2,4-DP exceeded those of the corresponding racemates. Influences of MCPPD and 2,4-DPD upon postimplantative loses, frequency of cleft palates and wavy ribs appeared already at dosages being 100-200 mg/kg below those of the racemates given to the respective groups of experimental animals. Additional alterations of the skeleton were observed which did not occur following administration of the racemic mixtures: deformed centrums of thoracic vertebra and exencephaly.

2,4-Dichlorophenoxyacetic Acid↗

Effect of sensorimotor cortical ablation on the placing reaction in the standing cat.

The placing reaction in the standing cat permits the analysis of a movement, the placing movement, together with its postural support. It is provoked by one of two moving plates coming into contact with one forelimb. Each limb rests on a platform equipped with strain gauges which permit changes in force exerted by each limb to be recorded. The placing reaction is characterized by two phases, an early isometric phase lasting until the lift-off of the stimulated limb occurs. It is then that a diagonal postural support on one forelimb and the opposite hindlimb takes place so that the placing movement can take place. Performance of this movement corresponds to the second phase. Four cats underwent an unilateral lesion in sensorimotor cortex. Two animals had a large lesion extending to the pre- and post-cruciate regions and from the midline to the coronal sulcus, including a large part within the depth of that sulcus. Two other cats had a restricted lesion covering mainly the forelimb part of area 4. After extensive cortical lesions, permanent changes in the contralateral placing reaction were observed. The isometric phase increased in duration, without marked changes of the pattern of postural support whereas the movement was prolonged and usually hypermetric. On the contrary, ipsilateral placing with its associated postural support was unmodified. After restricted cortical lesions, only temporary changes were observed. Recuperation was complete within 30 postoperative days. It was concluded that motor cortex on one side controls, as a whole, the contralateral placing movement and its associated postural adjustment, whereas it does not significantly modify the ipsilateral placing and its associated postural responses notwithstanding the use of the contralateral limbs in this adjustment.

Animals↗

[Studies on the embryotoxicity of monolinuron and buturon in NMRI-mice (author's transl)].

The acute LD50 in virginal NMRI-Mice was found to be 2528 mg/kg for monolinuron and 1791 mg/kg for buturon. Pregnant female mice of the NMRI strain were administered orally 25--1000 mg monolinuron/kg (I) and 100-400 mg buturon/kg (II) on days 6--15 of gestation and, during defined phases of fetal development (days 10--13 after conception), 500 mg I/kg and 350 mg II/kg. Following administration of 10 doses, an increase of postimplantative losses and clear retardation of development in the upper dose range from 100 mg I/kg and 300 mg II/kg as well as a dose-dependent increase of the rate of cleft palates could be observed. High doses of both substances given from day 6--15 of pregnancy produced minor numbers of wavy and fused ribs as well as hypoplasia of the upper jaw after application of monolinuron and exenteria and exencephaly after buturon. Administration of monolinuron between days 10 and 13 of gestation resulted a minor and that of buturon a clear increase of the number of cleft palates. To evaluate postnatal development 200 and 500 mg I/kg, and 200 and 300 mg II/kg were administered orally on days 6--15 of gestation. In the higher doses, both substances produced an increased mortality among the offspring up to 3 weeks after birth, and a clear increase of the rate of cleft palates.

Abnormalities, Drug-Induced↗

[Letter: Herbicides].

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2,4-Dichlorophenoxyacetic Acid↗