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Biomedical subjects

R A Ford

Publications and source records attributed to R A Ford.

14 recordsLinked to original sources
PubMed1992

Safety evaluation of dibenzyl ether.

Dibenzyl ether (FEMA No. 2371, CAS No. 103-50-4) was given in the diet to rats at a rate of 62, 196 or 620 mg/kg/day for 91 consecutive days. Body weights and food consumption were measured weekly; haematological, clinical chemistry and urinalysis values were obtained at wk 6 and 12. Gross and microscopic pathological changes were observed and organ weights recorded. The high-dose females had increased absolute and relative liver weights; this was considered to be related to dose. Other statistically significant events that occurred sporadically within the test groups were unrelated to dose and were considered to be normal adaptive change. No toxicological or pathological effects were noted at any of the dose levels after 91 consecutive days of feeding dibenzyl ether. A no-effect level was achieved at 196 mg/kg/day. In a 60-kg human, this would be equivalent to approximately 11.8 g/day, assuming a direct relationship between dose and body weight across species. Based on the possible average daily intake of 19.2 mg/day, this would confer a safety factor of 600. The safety factor based on the more realistic consumption per capita of 23.6 micrograms/day would be approximately 500,000.

Administration, Oral↗
PubMed1992

A controlled study of 99mTc-HMPAO single-photon emission imaging in chronic schizophrenia.

Regional cerebral blood flow (rCBF) during a word fluency task was compared in twenty-five male, right-handed, medicated schizophrenic patients and twenty-five age-matched male, right-handed healthy volunteers, using 99mtechnetium-HMPAO multidetector single-photon emission tomography. Increased rCBF in caudate and thalamus was found in patients, probably secondary to neuroleptic medication. Patients showed decreased rCBF in left frontal cortical regions and increased rCBF in left posterior cortical regions, compared to controls. Patterns of left-sided frontal rCBF dominance in controls were reversed in patients, as were normal patterns of right-sided parietal rCBF dominance. Negative symptom score correlated inversely with mesial frontal rCBF, particularly on the left.

Adult↗
PubMed1992

Ventricular size and regional cerebral blood flow in schizophrenia: an attempted replication.

We attempted to replicate the finding of Berman et al. (1987) that frontal cortical blood flow correlated inversely with ventricular size in schizophrenia. Computed tomography and high-resolution 99m-Tc-HMPAO single photon emission computed tomography were performed in 25 right-handed chronic schizophrenic men engaged in a word-fluency task. Weak, nonstatistically significant inverse correlations were found between the ventricle-brain ratio (VBR) and frontal cortical blood flow. The VBR was significantly inversely correlated with the ratio of left to right medial frontal blood flow.

Adult↗
PubMed1991

Safety evaluation of benzophenone.

Benzophenone (FEMA No. 2134; CAS No. 119-61-9) was administered in the diet to rats at target dose levels of 20 mg/kg body weight/day for 90 days and 100 or 500 mg/kg/day for 28 days. Body weights and food consumption were measured weekly; haematology, clinical chemistry and urinalysis values were obtained at 4 wk and at the end of the study. Gross and microscopic pathological examinations were conducted and organ weights were recorded. Treatment-related changes occurred in erythrocyte count, haemoglobin, haematocrit, bilirubin, total protein and albumin at the mid- and high-dose levels, although all changes did not occur in both groups in both sexes. There were indications of increased absolute and relative liver and kidney weights in the mid- and high-dose groups, but this was not statistically consistent for absolute kidney weights. Histopathology of the liver in the mid- and high-dose groups showed hepatocellular enlargement with an associated clumping of cytoplasmic basophilic material around the central vein. A no-effect level was demonstrated at 20 mg/kg/day for 90 days of administration. This would be equivalent to an intake of 1200 mg/day for a 60-kg human. On the basis of the calculated Possible Average Daily Intake of 0.33 mg/day, a safety factor of greater than 3600 is demonstrated. The safety factor based on the more realistic per capita consumption of 0.32 microgram/day would be approximately 3.7 million.

Administration, Oral↗
PubMed1990

90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat.

Musk ketone, musk xylene, musk tibetene and moskene, synthetic musks used in fragrances, were applied dermally to rats in daily doses of 240 (musk ketone and musk xylene only), 75, 24 or 7.5 mg/kg body weight for 90 days. The chemically related musk ambrette, a known neurotoxin in rats, was used as a positive control. While musk ambrette was clearly neurotoxic and caused testicular atrophy, as had been previously reported, the other compounds tested caused neither effect. The only effects of application of these materials were some organ weight changes at the higher doses, but these were not associated with histopathological changes in any of the tissues. The no-effect levels were: musk ketone, 75 mg/kg for males and females; musk xylene, 75 mg/kg for males and 24 mg/kg for females; moskene, 24 mg/kg for males and 75 mg/kg (highest dose administered) for females; and musk tibetene, 75 mg/kg (highest dose) for males and females.

Administration, Topical↗
PubMed1989

The psychopathology of echophenomena.

Repetition of other person's activities is, to some extent, part of normal human behaviour. However, in some circumstances it becomes pathological and symptomatic of an underlying disease process. The pathogenesis of this type of behaviour is very diverse. The circumstances in which echoing can be expected to occur are reviewed.

Aphasia↗
PubMed1985

Influence of dose and sex on the disposition and hepatic effects of cinnamyl anthranilate in the B6C3F1 mouse.

Cinnamyl anthranilate is a synthetic food flavouring and fragrance agent, formerly used at very low levels. There is currently some concern over the potential risk to man from its use, since it has been found to cause liver tumours in mice, following the administration of very large doses. This paper reports studies of its disposition and hepatic effects in B6C3F1 mice in relation to dose. Following a single oral dose of 500 mg cinnamyl anthranilate/kg body weight to B6C3F1 mice peak plasma levels of unchanged compound were reached in 30 min, and were higher in males than in females. Unchanged cinnamyl anthranilate in the urine accounted for 0.3-0.4% of the dose. Anthranilic acid (c. 17%) and hippuric acid (35%; the major metabolite of cinnamyl alcohol) were present in the urine, and recoveries of both were higher in females. Groups of male and female B6C3F1 mice were given 0, 10, 100, 1000, 5000, 15,000 and 30,000 ppm cinnamyl anthranilate in the diet. After 4 days, the diet was removed and urine collected for 24 hr. This contained cinnamyl anthranilate (more in males) hippuric and anthranilic acids (more in females) in concentrations that increased with dose. Other animals were given these diets for 19 days and then killed. Relative liver weight and hepatic microsomal cytochrome P-450 increased with increasing dose above 1000 ppm cinnamyl anthranilate, more markedly in males than in females although the maximum response (roughly twofold) was very similar in the two sexes. SDS-PAGE examination of the microsomes revealed the induction of a cytochrome P-450 isozyme of 53.1 kDa, but the aniline hydroxylase and p-nitroanisole O-demethylase activities of the 9000 g supernatant of liver were not induced. The data are discussed in terms of their significance for the human safety evaluation of cinnamyl anthranilate. It is important to note that liver hypertrophy, microsomal enzyme induction and the excretion of unchanged cinnamyl anthranilate all have the same dose-threshold for their appearance. This suggests that the hepatic effects of cinnamyl anthranilate may be mediated by unhydrolysed cinnamyl anthranilate, which is present only at very high doses due to the saturation of its hydrolysis.

Animals↗
PubMedDate not supplied

Allergic contact sensitization potential of hydroxycitronellal in humans.

Hydroxycitronellal, an important ingredient in fragrances, was studied for its sensitizing potential in human skin. Fifteen human maximization tests were conducted with hydroxycitronellal obtained from four different sources at induction concentrations from 5 to 12%. No reactions were induced at 5% in two separate panels while 10% sensitized 2/25 panelists in one test but none in a second. Induction at 12% produced sensitization in 8 of 11 tests. Impurities do not appear to be a sensitizing factor. There is some evidence that the l-stereoisomer is a less potent sensitizer than the d-stereoisomer. In an initial modified human repeat-insult patch-test two positive reactions to challenge were observed among 197 panelists, one at a concentration of 5% and the other at 7.5%. When 100 of the non-reacting panelists were re-exposed in the same way, allergic sensitization reactions appeared during the induction period with concentrations as low as 2.5%. When 28 sensitized panelists were exposed to 1% concentrations in a simulated use test, there were three reactors. A no-effect level for sensitization has not been determined although the lowest concentrations tested were in the product usage range.

Adolescent↗