Chronic effects of agar, guar gum, gum arabic, locust-bean gum, or tara gum in F344 rats and B6C3F1 mice

Melnick, Ronald L.; Huff, James; Haseman, Joseph K.; Dieter, Michael P.; Grieshaber, Charles K.; Wyand, D. S.; Russfield, Agnes B.; Murthy, Anuradha; Fleischman, Robert W.; Lilja, Herman S.

doi:10.1016/0278-6915(83)90065-0

Cited by 40 publications

(30 citation statements)

References 8 publications

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“…The no-observed-adverse-effect level (NOAEL) was concluded to be 5.0% (3117 mg/kg body weights/day for males, and 3296 mg/kg body weights/day for males). This study further confirms a previous study of the chronic effects of gum arabic in F344 rats and B6C3F 1 mice (Melnick, Huff, Haaemman, Dieter, & Grieshaber, 1983). There were no adverse histophathological effects observed and bioassays showed that gum arabic was not carcinogenic.…”

Section: Synonymssupporting

confidence: 92%

The regulatory and scientific approach to defining gum arabic (Acacia senegal and Acacia seyal) as a dietary fibre

Phillips¹,

Ogasawara

Ushida

2008

Food Hydrocolloids

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Section: Synonymssupporting

confidence: 92%

The regulatory and scientific approach to defining gum arabic (Acacia senegal and Acacia seyal) as a dietary fibre

Phillips¹,

Ogasawara

Ushida

2008

Food Hydrocolloids

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“…Tara gum has been shown to induce LCTs in F344 rats after 103 weeks of treatment (Melnick et al, 1983). The incidence of LCTs was 83% (40/48), 100% (46/46), and 100% (48/48) in the 0, 25,000 (2.5% of diet), and 50,000 (5% of diet) ppm tara gum groups, respectively.…”

Section: Sugarsmentioning

confidence: 98%

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

Cook

Klinefelter

Hardisty

et al. 1999

Critical Reviews in Toxicology

175

122

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Leydig cells (LCs) are the cells of the testis that have as their primary function the production of testosterone. LCs are a common target of compounds tested in rodent carcinogenicity bioassays. The number of reviews on Leydig cell tumors (LCTs) has increased in recent years because of its common occurrence in rodent bioassays and the importance in assessing the relevance of this tumor type to humans. To date, there have been no comprehensive reviews to identify all the compounds that have been shown to induce LCTs in rodents or has any review systematically evaluated the epidemiology data to determine whether humans were at increased risk for developing LCTs from exposure to these agents. This review attempts to fill these deficiencies in the literature by comparing the cytology and ontogeny of the LC, as well as the endocrine and paracrine regulation of both normal and tumorigenic LCs. In addition, the pathology of LCTs in rodents and humans is compared, compounds that induce LC hyperplasia or tumors are enumerated, and the human relevance of chemical-induced LCTs is discussed. There are plausible mechanisms for the chemical induction of LCTs, as typified by agonists of estrogen, gonadotropin releasing hormone (GnRH), and dopamine receptors, androgen receptor antagonists, and inhibitors of 5alpha-reductase, testosterone biosynthesis, and aromatase. Most of these ultimately involve elevation in serum luteinizing hormone (LH) and/or LC responsiveness to LH as proximate mediators. It is expected that further work will uncover additional mechanisms by which LCTs may arise, especially the role of growth factors in modulating LC tumorigenesis. Regarding human relevance, the pathways for regulation of the hypothalamo-pituitary-testis (HPT) axis of rats and humans are similar, such that compounds that either decrease testosterone or estradiol levels or their recognition will increase LH levels. Hence, compounds that induce LCTs in rats by disruption of the HPT axis pose a risk to human health, except for possibly two classes of compounds (GnRH and dopamine agonists). Because GnRH and prolactin receptors are either not expressed or are expressed at very low levels in the testes in humans, the induction of LCTs in rats by GnRH and dopamine agonists would appear not to be relevant to humans; however, the potential relevance to humans of the remaining five pathways of LCT induction cannot be ruled out. Therefore, the central issue becomes what is the relative sensitivity between rat and human LCs in their response to increased LH levels; specifically, is the proliferative stimulus initiated by increased levels of LH attenuated, similar, or enhanced in human vs. rat LCs? There are several lines of evidence that suggest that human LCs are quantitatively less sensitive than rats in their proliferative response to LH, and hence in their sensitivity to chemically induced LCTs. This evidence includes the following: (1) the human incidence of LCTs is much lower than in rodents even when corrected for detection bias; (2) several ...

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“…GA administered to men for 3 weeks has no effect on glucose tolerance, but decreases serum cholesterol [19,21] In rats AG has no histopathology or hematological toxicity when administered for 13 weeks at doses as high as 5 g/k/day. Teratogenicity and carcinogenicity are also absent [21][22][23][24] There are no limitations on the use of AG as a food additive, as the experimental evidence required for international food safety has already been met [25][26][27][28] [ 40,41]. Figure 4 shows the urea-lowering mechanism of AG.…”

Section: Discussionmentioning

confidence: 98%

Six-year dialysis freedom in end-stage renal disease

Al-Mosawi

2009

Clin Exp Nephrol

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Chronic effects of agar, guar gum, gum arabic, locust-bean gum, or tara gum in F344 rats and B6C3F1 mice

Cited by 40 publications

References 8 publications

The regulatory and scientific approach to defining gum arabic (Acacia senegal and Acacia seyal) as a dietary fibre

The regulatory and scientific approach to defining gum arabic (Acacia senegal and Acacia seyal) as a dietary fibre

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

Six-year dialysis freedom in end-stage renal disease

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