Biomedical subjects

D Jonker

Publications and source records attributed to D Jonker.

25 records · Page 2Linked to original sources

PubMed1993

The relationship between sexual abuse and female suicidal behavior.

This study investigated the relationship between suicide attempts and a history of sexual abuse. In a sample of 158 female suicide attempters aged 20 years or older, 50% of the subjects reported having been sexually abused at some time. Sexually abused suicide attempters had shown more suicidal behavior in the past than their non-sexually abused counterparts (even though they were significantly younger), and were characterized by a more severe problem history. In the past, as well as shortly after the index attempt, they had experienced more serious problems in their relationships with significant others, with sexuality, and with self-fulfillment. At follow-up 1 year later, significantly more sexually abused women had attempted suicide during the intervening period than the women without a history of sexual abuse, and they also had more serious sexual problems. It is concluded that within a group of female suicide attempters, those with a history of sexual abuse are disproportionately vulnerable to repeated suicidal behavior.

Adolescent↗

PubMed1992

21-day intravenous toxicity study with feline interferon in rats.

The toxicity of recombinant feline interferon, a prospective antiviral drug for cats, was examined in a subacute study. Groups of five male and five female Wistar rats were given iv feline interferon in 20 mM-NaCl at doses of 0, 5, 15 and 50 MU/kg body weight/day for 21 consecutive days. Criteria to assess toxicity included clinical observations, ophthalmoscopy, growth, food and water intake, haematology, clinical chemistry, urinalysis, organ weights, gross examination at autopsy and microscopic examination of the liver, kidneys, spleen, adrenals, heart, mesenteric lymph nodes and thymus. No treatment-related were observed even at the highest dose level. The no-observed-adverse-effect level for feline interferon in this study was therefore 50 MU/kg body weight/day.

Animals↗

PubMed1990

4-week oral toxicity study of a combination of eight chemicals in rats: comparison with the toxicity of the individual compounds.

In a 4-wk oral toxicity study, 4-wk-old male and female Wistar rats were exposed to a combination of arbitrarily chosen chemicals comprising sodium metabisulphite, Mirex, Loperamide, metaldehyde, di-n-octyltin dichloride, stannous chloride, lysinoalanine and potassium nitrite. The dose levels used were based on the "no-observed-adverse-effect level" (NOAEL) and the "minimum-observed-adverse-effect level" (MOAEL) of the individual compounds obtained in similar studies with Wistar rats previously performed at TNO-CIVO, and comprised 0 (controls), 1/10 and 1/3 of the NOAEL, the NOAEL and the MOAEL. In comparison with the adverse effects of the individual compounds, both more severe and less severe adverse effects were observed at the MOAEL of the combined compounds, indicating interaction of effects at this exposure level. Slightly decreased haemoglobin content and slightly increased relative kidney weight were the only treatment-related adverse effects seen in the NOAEL group. In the 1/10 and 1/3 NOAEL groups no untoward effects were found that could be related to treatment. The present study clearly demonstrates absence of a simple additive effect, and provides some, but no convincing, evidence for an increased risk from exposure to a combination of chemicals when each chemical is administered at its own individual NOAEL. At lower dose levels no increased risk appears to exist. These generalizations may not be fully justifiable from a purely scientific point of view but are the most important practical lesson learnt from the present study.

Administration, Oral↗

PubMed1988

Comparison of the effects of ascorbyl palmitate and L-ascorbic acid on paracetamol-induced hepatotoxicity in the mouse.

The effects of ascorbyl palmitate (ASCP) and free L-ascorbic acid (LAA) on the hepatotoxicity of paracetamol (acetaminophen) and the in vivo covalent binding of reactive paracetamol metabolites to hepatic proteins has been studied in male MF1 mice. The oral administration of [3H(G)]paracetamol (600 mg/kg) resulted in covalent binding to hepatic proteins, a depletion of hepatic non-protein sulphydryl (NPS) groups after 2 h, and a marked elevation of plasma alanine aminotransferase (ALAT) activity after 24 h. The co-administration of paracetamol and ASCP (1412 mg/kg, equivalent to 600 mg/kg free LAA), but not paracetamol and LAA (600 mg/kg), significantly reduced covalent binding of paracetamol metabolites at 2 and 4 h after treatment. In addition ASCP, but not LAA, significantly reduced the depletion of NPS groups and the elevation of plasma ALAT activity. ASCP also completely prevented the 35% mortality observed at 24 h in paracetamol treated mice. These results demonstrate that ASCP, but not LAA, when co-administered orally with the analgesic is an effective inhibitor of paracetamol-induced hepatotoxicity in the mouse. The mechanism by which ASCP prevents liver injury appears to involve destruction of reactive paracetamol metabolites which is associated with a sparing action on hepatic reduced glutathione levels.

Acetaminophen↗

PubMedDate not supplied

Toxicity of mixtures of nephrotoxicants with similar or dissimilar mode of action.

The toxicity of mixtures of chemicals with the same target organ was examined in rats using nephrotoxicants with similar or dissimilar modes of action. In a 4-wk feeding study, lysinoalanine, mercuric chloride, hexachloro-1,3-butadiene and d-limonene, each affecting renal proximal tubular cells but through different modes of action, were administered simultaneously at their individual lowest-observed-nephrotoxic-effect level (LONEL), no-observed-nephrotoxic-effect level (NONEL) and NONEL/4. Combined exposure at the LONEL resulted in increased growth depression and increased renal toxicity in male but not in female rats. Co-exposure at the NONEL produced only weak signs of toxicity (slightly retarded growth and increased renal weight), and rats co-exposed at the NONEL/4 did not show any treatment-related changes. The absence of an obviously increased hazard on combined exposure at the NONEL suggested absence of synergism and probably also of additivity. In a subsequent study the additivity assumption (dose addition) was tested, using the similarly acting nephrotoxicants tetrachloroethylene, trichloroethylene, hexachloro-1,3-butadiene and 1,1,2-trichloro-3,3,3-trifluoropropene. The compounds were given to female rats by daily oral gavage for 32 days either alone, at the LONEL and NONEL (= LONEL/4), or in combinations of four (at the NONEL and LONEL/2) or three (at the LONEL/3). Relative kidney weight was increased on exposure to the individual compounds at their LONEL and, to about the same extent, on combined exposure at the NONEL or the LONEL/3. As assessed by this endpoint, the renal toxicity of the mixtures corresponded to the effect expected on the basis of the additivity assumption. The other endpoints were not (or hardly) affected on combined exposure.

Administration, Oral↗

PubMedDate not supplied

Experimental designs and risk assessment in combination toxicology: panel discussion.

Advancing our knowledge on the toxicology of combined exposures to chemicals and implementation of this knowledge in guidelines for health risk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A prerequisite for successful research and fruitful discussions on the toxicology of combined exposures (mixtures of chemicals) is the use of defined terminology implemented by an authoritative international body such as, for example, the International Union of Pure and Applied Chemistry (IUPAC) Toxicology Committee. The extreme complexity of mixture toxicology calls for new research methodologies to study interactive effects, taking into account limited resources. Of these methodologies, statistical designs and mathematical modelling of toxicokinetics and toxicodynamics seem to be most promising. Emphasis should be placed on low-dose modelling and experimental validation. The scientifically sound so-called bottom-up approach should be supplemented with more pragmatic approaches, focusing on selection of the most hazardous chemicals in a mixture and careful consideration of the mode of action and possible interactive effects of these chemicals. Pragmatic approaches may be of particular importance to study and evaluate complex mixtures; after identification of the 'top ten' (most risky) chemicals in the mixture they can be examined and evaluated as a defined (simple) chemical mixture. In setting exposure limits for individual chemicals, the use of an additional safety factor to compensate for potential increased risk due to simultaneous exposure to other chemicals, has no clear scientific justification. The use of such an additional factor is a political rather than a scientific choice.

Hazardous Substances↗

PubMedDate not supplied

Safety evaluation of chemical mixtures and combinations of chemical and non-chemical stressors.

Recent developments in hazard identification and risk assessment of chemical mixtures are reviewed. Empirical, descriptive approaches to study and characterize the toxicity of mixtures have dominated during the past two decades, but an increasing number of mechanistic approaches have made their entry into mixture toxicology. A series of empirical studies with simple chemical mixtures in rats is described in some detail because of the important lessons from this work. The development of regulatory guidelines for the toxicological evaluation of chemical mixtures is discussed briefly. Current issues in mixture toxicology include the adverse health effects of ambient air pollution; the application of such modern, sophisticated methodologies as genomics, bioinformatics, and physiologically based pharmacokinetic modeling; and databases for mixture toxicity. Finally, the state of the art of our knowledge on the potential adverse health effects of combined exposures to chemicals and non-chemical stressors (noise, heat/cold, microorganisms, immobilization, restraint, or transportation), research initiatives in these fields, and the development of an indicator for the cumulative health impact of multiple environmental exposures are discussed.

Dose-Response Relationship, Drug↗