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Biomedical subjects

P G Brantom

Publications and source records attributed to P G Brantom.

At least 19 recordsLinked to original sources
PubMed2003

A study of the toxicity of five mineral hydrocarbon waxes and oils in the F344 rat, with histological examination and tissue-specific chemical characterisation of accumulated hydrocarbon material.

Five food-grade mineral hydrocarbon (MHC) materials; a low melting point wax (LMPW), a synthetic wax (C80W) and three white oils (N15H, N70H and P70H) were administered orally to female Fischer-344 rats for 28 and 90 days at a dose level of 2% in the diet. Tissues were examined at autopsy for any treatment-related histopathological changes. The histology of target organs was the same as found in previous studies on LMPW and mineral oils and similar effects were also observed from feeding C80W. Chemical analysis showed no detectable levels of MHCs in urine and no discernible differences in the MHC profile in faeces extracts compared to diets. The presence of MHCs in most tissues was not always associated with observable histological changes. The notable observations were MHC material was detected in all tissues of rats fed with diets containing LMPW and C80W. The levels found ranged from 0.04 to 1.52% by weight for the LMPW and from 0.01 to 0.75% for the C80W. MHC material was detected in all samples of small intestine, heart and kidney for all groups. Only the livers from rats administered with LMPW and C80W were analysed, which were found to contain MHC material. Preferential accumulation of MHCs was in the alkane range approximately C(20)-C(35). The findings indicate that the size and the structure of individual components play a role both in determining their propensity to accumulate in different tissues and in the severity of any response that they elicit once they have accumulated. The implication of these findings are discussed in the context of specifications for 'food-grade' mineral hydrocarbons such as used as food additives. The data presented here suggests that the current specifications are not prescriptively adequate in controlling the amount of MHC material between C(25) and C(35) that can accumulate.

Animals↗
PubMed1996

A 90-day feeding study of the alkaloids of Lupinus angustifolius in the rat.

Groups of 20 Sprague-Dawley rats of each sex were fed diets containing lupin alkaloid at dose levels of 0, 100, 330, 1000 and 5000 ppm supplemented with maltodextrin to attain a level of 4.5%, for 13 wk (equivalent to average daily intakes of lupin alkaloid of approximately 0, 10, 30, 100 and 500 mg/kg body weight/day, respectively, over the course of the study). A further group of rats was fed control (basal) diet over the same period. All control and high-dose animals underwent an ophthalmological examination before the start of the study and before autopsy. Blood samples were collected from all rats prior to the start of treatment, during wk 6 and prior to autopsy for haematological and clinical chemistry examination. All animals were monitored daily for change in clinical condition, and body weight and food intake were measured twice weekly. A range of tissues were preserved for histological examination at autopsy. There was an initial drop in food intake by all rats in the 1000 and 5000 ppm groups and thereafter the intake was between 90% and 95% of that of the controls. In general, no other effects related to treatment were seen. On the basis of the lower body weights and food intakes of the groups fed the alkaloid at levels of 1000 and 5000 ppm, a no-observed-adverse-effect level (NOAEL) of 330 ppm is seen under the conditions of this study. It is likely that these effects are entirely due to the antipalatability effect of the lupin alkaloids. In view of the growth rates, haematology, clinical chemistry and histological findings, a speculative NOAEL of 1000 ppm may be more appropriate.

Alkaloids↗
PubMed1992

A 28-day feeding study with methyl isoeugenol in rats.

Methyl isoeugenol was administered in rodent diet for a minimum of 28 consecutive days to groups of 16 male and 16 female rats (Sprague-Dawley strain) at levels of approximately 30, 100 and 300 mg/kg body weight/day. A further group of 16 male and 16 female rats was given the rodent diet as a control. The administration of methyl isoeugenol in the diet did not adversely affect the growth or general health of the animals or their food intakes. Although high dose animals of both sexes had increased lymphocyte and total white blood cell counts, these are not considered, in isolation, to be an adverse effect of treatment. None of the minor variations observed in the serum chemical analyses or urine analyses is considered to be indicative of a treatment-related toxic effect. An increase in liver weight, adjusted for body weight, was seen in male and female rats receiving 300 mg methyl isoeugenol/kg body weight. Few histopathological abnormalities were observed. Although the incidence of kidney and Harderian gland lesions was higher for high dose animals compared with the controls, the lesions are of a type that occurs spontaneously and are thus not considered to be attributable to treatment with methyl isoeugenol. While the increased liver weight and white blood cell counts of rats given 300 mg methyl isoeugenol/kg body weight may represent effects of treatment, it is not considered that there is any reason to regard these as adverse effects.

Alanine Transaminase↗
PubMed1992

A 28-day feeding study with ethyl acetoacetate in rats.

Ethyl acetoacetate encapsulated in gum arabic was administered in rodent diet for a minimum of 28 consecutive days to groups of 16 male and 16 female rats (Sprague-Dawley strain) at levels of approximately 100, 300 and 1000 mg/kg body weight/day. A further group of 16 male and 16 female rats was given rodent diet containing gum arabic as a control. The administration of ethyl acetoacetate in the diet did not adversely affect the growth or general health of the animals or their food intakes. None of the minor variations observed in the haematology, serum chemical analyses or urine analyses are considered to be indicative of a treatment-related toxic effect. Caecal enlargement was seen in male rats treated with the top dose of ethyl acetoacetate, but this was accompanied by a normal histopathology. Few histopathological abnormalities were observed. Proteinaceous casts were found in the bladder of approximately half the male rats given 1000 mg ethyl acetoacetate/kg, and nephrocalcinosis was a common occurrence in female rats in this dose group. Renal function was unimpaired in treated male and female rats, and the histopathological findings are common in the strain of rats chosen for this study. Although the caecal enlargement and the changes in kidney and bladder of rats given 1000 mg ethyl acetoacetate/kg are noted, it is considered that ethyl acetoacetate did not produce treatment-related adverse effects in rats during this study.

Acetoacetates↗
PubMed1987

Long-term toxicity study of Ponceau 4R in rats using animals exposed in utero.

Groups of 66 (treated) or 114 (control) rats of each sex were fed diets providing 0 (control), 50, 500 or 1250 mg Ponceau 4R/kg body weight/day for 60 days. The animals were then mated and allowed to rear their litters. At weaning, pups were selected for the long-term study to give treated groups of 54 (of each sex) and a control group of 96 (of each sex), with offspring always receiving the same treatment as their parents. Treatment continued until approximately 20% of animals survived, resulting in a duration of 114 wk for males and 118 wk for females. Body weight, food and water intake and clinical conditions were monitored regularly throughout the study. Blood and urine from 20 rats/sex/group from the high-dose and control groups were examined at months 3, 6, 12, 18 and 24. At the end of the study each animal was autopsied, selected organs were weighed, and a full range of tissues was preserved. High-dose animals showed a lower body-weight gain without any reduction in food intake. Water intake was higher than that of the controls in the medium- and high-dose groups and this was related to caecal enlargement and softening of faeces. No adverse changes were seen in the investigations of blood or urine apart from a higher incidence of females with higher levels of protein in urine at the 1250 mg/kg/day dose. No other findings of significance were seen and survival and tumour incidence were similar in all groups. A no-untoward-effect level was established at 500 mg Ponceau 4R/kg/day.

Animals↗
PubMed1987

A three-generation reproduction study of Ponceau 4R in the rat.

Ponceau 4R was fed to three generations of rats, at dietary concentrations to provide 0, 50, 500 or 1250 mg/kg body weight/day. In each generation treated groups consisted of 36 rats of each sex while 60 females served as controls. Apart from the F0 generation, which started treatment as weanlings, treatment was continued throughout the study, providing in utero exposure of all offspring. The F0 generation was bred twice, on the first occasion to provide animals for the next generation and for a long-term study, and a second time to provide data on in utero and post-partum development. In each generation approximately one third of the females from each group were killed before parturition to provide data on in utero development. The foetuses from these animals were examined for skeletal abnormalities. Remaining animals were allowed to litter and the offspring were monitored for 21 days after birth for survival and development. All animals were killed and subjected to a post-mortem examination which, for a proportion of each group in each generation, included recording of organ weights. Although a few adult rats died during the study these deaths were not associated with treatment. Fur of the treated animals was coloured pink, and faeces and caecal contents of animals from the two highest dose groups were yellow, the faeces also being softer than those of the controls. Treatment had no observed effect on clinical observations, body weight or food and water intake at any stage of the study. Animals fed the two highest doses for prolonged periods had enlarged caeca, but this effect was not seen in weanling animals on the same treatment. Neither the caecal enlargement nor the liver weights seen in the F2 and F3 offspring were considered to be an adverse effect of treatment. No treatment-related effects were seen in the uterine contents of females at any generation, but the skeletons of treated foetuses showed a slightly more advanced development than those of the controls. Postnatal development of offspring was not affected by treatment at any stage of the study. Tissues from the F3 animals were examined by light microscopy and revealed no treatment-related effects. It is concluded that the no-adverse-effect level for Ponceau 4R is 1250 mg/kg body weight/day.

Abnormalities, Drug-Induced↗
PubMed1987

Long-term toxicity study of Green S in mice.

Groups of 105 (control) or 65 (treated) female CD-1 mice were mated one to one with equal numbers of males after both sexes had received diets containing 0 (control), 0.033, 0.33 or 0.66% Green S for 9 wk. The number of animals pregnant, the number of young born and the number surviving were similar in all groups. One male and one female from each litter were used to provide groups of 85 (control) or 50 (treated) mice of each sex for the long-term study. Treatment with Green S continued throughout pregnancy and rearing. Body weight and condition were regularly monitored for each animal throughout the study. Blood was examined from groups of 20 mice from the control and highest treatment groups at wk 14, 28 and 51 and from all survivors at the end of the study. A post-mortem examination was carried out on all animals in the long-term study and a full range of tissues was preserved and examined by light microscopy. Organ weights were recorded at the autopsy of all mice reaching the end of the study. No effects that could be attributed to treatment were seen in any of the observations. The no-untoward-effect level of Green S fed to mice for 2 yr is concluded to be 0.66% of the diet, equivalent to intakes of approximately 530 and 660 mg/kg body weight/day in males and females, respectively.

Animals↗
PubMed1987

Three-generation toxicity study of rats ingesting Brown HT in the diet.

Brown HT was fed to rats of both sexes over three generations at dietary concentrations designed to provide daily intakes of 0, 50, 250 and 500 mg Brown HT/kg body weight/day. During the study a number of females died or failed to nurse their litters. This was so severe following the first mating of F1 adults that the animals were remated to provide the next generation. None of these effects were related to treatment. Body weight and food and water intakes were not adversely affected by treatment. No effects of treatment were seen on reproductive performance or foetal and pup development, apart from slight evidence of a treatment-related retarded ossification of the third sternebrae. Organ weights at autopsy showed two changes, one of which was increased kidney weights which, although not present in every generation, seemed to be related to treatment. The other, increased caecum weights, occurred in adult high-dose females of early generations, but not in males or later generations of the study. Apart from brown coloration of tissues, macroscopic and microscopic examination revealed no treatment-related changes. It was concluded that the no-untoward-effect level in the present study was 250 mg Brown HT/kg/day.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Studies on the effects of orally administered Di-(2-ethylhexyl) phthalate in the ferret.

A target-organ study of the effects of the phthalate ester di-(2-ethylhexyl) phthalate (DEHP) has been conducted in mature male albino ferrets. DEHP treatment caused a loss of body weight when administered as a 1% (w/w) diet for 14 months. Additionally marked liver enlargement with associated morphological and biochemical changes was observed. These changes consisted of liver cell enlargement, lysosomal changes, dilatation of the endoplasmic reticulum and the depression of a number of marker enzyme activities. The only other tissue observed to be affected by DEHP treatment was the testes where histological evidence of tissue damage was observed in some animals. Studies on the metabolism of [14C]DEHP in the ferret indicated that the diester was metabolised to derivatives of mono-(2-ethylhexyl) phthalate which were excreted in the urine both unconjugated and as glucuronides. The results obtained have been compared with previous studies in the rat and it is concluded that DEHP is hepatotoxic in both species.

Animals↗