Biomedical subjects

Mika Takahashi

Publications and source records attributed to Mika Takahashi.

8 recordsLinked to original sources

PubMed2006

Susceptibility of newborn rats to 3-ethylphenol and 4-ethylphenol compared with that of young rats.

Newborn rat studies were conducted with oral administration of 3-ethylphenol (3EP) and 4-ethylphenol (4EP) on postnatal days (PND) 4-21 to allow comparison of no observed adverse effect level (NOAEL) and unequivocally toxic level (UETL) with those from 28-day studies of young rats starting at 5-6 weeks of age. In the newborn rat studies, slightly lowered body weight was observed after 3EP treatment, and deaths, hypoactivity, Straub tail, deep respiration and delayed righting reflex were clearly observed after 4EP treatment. In the young rat studies, salivation, staggering gait, changes in the liver including high values of liver weight and alanine aminotransferase or total cholesterol and the lesions in the forestomach were clearly observed after 3EP and 4EP treatments. NOAELs of 3EP and 4EP in the newborn rat studies appeared to be almost 3 times lower than those in the young rat studies. As a clear toxicity of 3EP was not observed in newborn rats, UETLs were not established for 3EP. Regarding 4EP, UETL of young rats was 4-5 times higher than that of newborn rats. In conclusion, newborn rats were 3-5 times more susceptible to 3EP and 4EP than young rats.

Administration, Oral↗

PubMed2005

In silico assessment of chemical mutagenesis in comparison with results of Salmonella microsome assay on 909 chemicals.

Genotoxicity is one of the important endpoints for risk assessment of environmental chemicals. Many short-term assays to evaluate genotoxicity have been developed and some of them are being used routinely. Although these assays can generally be completed within a short period, their throughput is not sufficient to assess the huge number of chemicals, which exist in our living environment without information on their safety. We have evaluated three commercially available in silico systems, i.e., DEREK, MultiCASE, and ADMEWorks, to assess chemical genotoxicity. We applied these systems to the 703 chemicals that had been evaluated by the Salmonella/microsome assay from CGX database published by Kirkland et al. We also applied these systems to the 206 existing chemicals in Japan that were recently evaluated using the Salmonella/microsome assay under GLP compliance (ECJ database). Sensitivity (the proportion of the positive in Salmonella/microsome assay correctly identified by the in silico system), specificity (the proportion of the negative in Salmonella/microsome assay correctly identified) and concordance (the proportion of correct identifications of the positive and the negative in Salmonella/microsome assay) were increased when we combined the three in silico systems to make a final decision in mutagenicity, and accordingly we concluded that in silico evaluation could be optimized by combining the evaluations from different systems. We also investigated whether there was any correlation between the Salmonella/microsome assay result and the molecular weight of the chemicals: high molecular weight (>3000) chemicals tended to give negative results. We propose a decision tree to assess chemical genotoxicity using a combination of the three in silico systems after pre-selection according to their molecular weight.

Biological Assay↗

PubMed2005

Comparative susceptibility of newborn and young rats to six industrial chemicals.

To elucidate the comparative susceptibility of newborn rats to chemicals, newborn and young animals were administered six industrial chemicals by gavage from postnatal days (PND) 4 to 21, and for 28 days starting at 5-6 weeks of age respectively, under the same experimental conditions as far as possible. As two new toxicity endpoints specific to this comparative analysis, presumed no-observed-adverse-effect-levels (pNOAELs) were estimated based on results of both main and dose-finding studies, and presumed unequivocally toxic levels (pUETLs) were also decided. pNOAELs for newborn and young rats were 40 and 200 for 2-chlorophenol, 100 and 100 for 4-chlorophenol, 30 and 100 for p-(alpha,alpha-dimethylbenzyl) phenol, 100 and 40 for (hydroxyphenyl)methyl phenol, 60 and 12 for trityl chloride, and 100 and 300 mg/kg/day for 1,3,5-trihydroxybenezene, respectively. To determine pUETLs, dose ranges were adopted in several cases because of the limited results of experimental doses. Values for newborn and young rats were thus estimated as 200-250 and 1000 for 2-chlorophenol, 300 and 500 for 4-chlorophenol, 300 and 700-800 for p-(alpha,alpha-dimethylbenzyl) phenol, 140-160 and 1000 for (hydroxyphenyl)methyl phenol, 400-500 and 300 for trityl chloride, and 500 and 1000 mg/kg/day for 1,3,5-trihydroxybenzene, respectively. In most cases, newborn rats were 2-5 times more susceptible than young rats in terms of both the pNOAEL and the pUETL. An exception was that young rats were clearly more susceptible than their newborn counterparts for trityl chloride.

Animals↗

PubMed2005

Elevated susceptibility of newborn as compared with young rats to 2-tert-butylphenol and 2,4-di-tert-butylphenol toxicity.

In order to determine the susceptibility of newborn rats to 2-tert-butylphenol (2TBP) and 2,4-di-tert-butylphenol (DTBP) toxicity, studies were conducted with oral administration from postnatal days (PND) 4 to 21 and the findings were compared with results for young rats exposed from 5 or 6 weeks of age for 28 days. In the newborn rats, specific effects on physical and sexual development and reflex ontogeny were not observed. While there were no clear differences in toxicological profiles between newborn and young rats, the no-observed-adverse-effect levels (NOAELs) differed markedly. For 2TBP, clinical signs such as ataxic gait, decrease in locomotor activity and effects on liver, such as increase in organ weight, were observed and the NOAELs were concluded to be 20 and 100 mg/kg/day in newborn and young rats, respectively. Based on hepatic and renal toxicity (histopathological changes and increase in organ weight with blood biochemical changes), the respective NOAELs for DTBP were concluded to be 5 and 20 mg/kg/day. Therefore, the susceptibility of newborn rats to 2TBP and DTBP was found to be 4-5 times higher than that of young rats.

Age Factors↗

PubMed2005

[Progress on OECD chemicals programme (7)--SIAM 15 in Boston, 2002].

The 15th Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 15) was held in Boston, USA. The initial assessment documents of twelve substances at SIAM 15 (CAS numbers: 79-39-0, 88-60-8, 92-70-6, 102-76-1, 110-83-8, 135-19-3, 7647-01-0, 8007-18-9, 10043-52-4, 11070-44-3, 25321-09-9, 68186-90-3) were submitted by the Japanese Government with or without the International Council of Chemical Associations (ICCA) and all of them on the human health effect parts were agreed at the meeting. In this report, the human health effect parts in their 12 substance documents are introduced.

Animals↗

PubMed2004

Comparative toxicity study of 2,4,6-trinitrophenol (picric acid) in newborn and young rats.

The toxicity of oral 2,4,6-trinitrophenol (TNP) was determined in newborn rats, and compared with that in young rats. In newborn rats, males and females were given TNP at 0, 16.3, 81.4 or 407 mg/kg per day on postnatal days (PND) 4-17 for the dose-finding study, and at 0, 4.1, 16.3 or 65.1 mg/kg per day on PND 4-21 for the main study. Deaths, lower body weight (BW) and behavioral changes were found at 81.4 and 407 mg/kg per day in the dose-finding study, and lower BW was observed in males at 65.1 mg/kg per day during the dosing period of the main study. In young rats, 5-week-old males and females were given TNP at 0, 20, 100 or 500 mg/kg per day for 14 days as the dose-finding study and at 0, 4, 20 or 100 mg/kg per day for 28 days as the main study. Deaths were observed at 500 mg/kg per day in the dose-finding study. Deaths or changes in BW were not found at 100 mg/kg per day or less. At 100 mg/kg per day, hemolytic anemia and testicular toxicity were found. In conclusion, toxicity profiles induced by TNP were markedly different between newborn and young rats.

Animals↗

PubMed2004

Revision and establishment of Japanese drinking water quality guidelines for di(2-ethylhexyl) phthalate, toluene and vinyl chloride -- differences from the latest WHO guideline drafts.

The revision of the Japanese drinking water quality guidelines was established in May 2003. The WHO drinking water quality guidelines for the 3(rd) edition were also revised and the draft has been open to the public since last year. Most guideline values of each chemical in both Japan and WHO were quite similar; however, there are different overt values for three chemicals. In this short communication, we describe them and discuss the reason for taking the different toxicity endpoints and derivation method for these three chemicals, di(2-ethylhexyl) phthalate, toluene and vinyl chloride.

Diethylhexyl Phthalate↗

PubMed2004

[Progress on OECD chemicals programme].

The twelfth SIDS, the Screening Information Data Set, Initial Assessment Meeting (SIAM 12) was held at the Organisation for Economic Co-operation and Development (OECD) headquarters in Paris, France and SIAM 13 was held in Bern, Switzerland, hosted by the European Commission. Two substances at SIAM 12 (CAS No:91-15-6, 123-77-3) and 4 substances at SIAM 13 (CAS No:91-76-9, 112-85-6, 868-77-9, 1477-55-0) were submitted by the Japanese Government and/or International Council of Chemical Associations (ICCA). These substances were agreed at the meetings. In this report, the human health effects of 6 substances above-mentioned are introduced.

Animals↗