Measurement of Cell Proliferation in the Kidneys of Fischer 344 and Sprague-Dawley Rats after Gavage Administration of Hydroquinone

English, J. Caroline; Perry, L.G.; Vlaovic, Milan S.; MOYER, CAROLYN; O’Donoghue, John L.

doi:10.1093/toxsci/23.3.397

Cited by 7 publications

(9 citation statements)

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“…37 In agreement with the National Toxicology Program (NTP) study findings and other reports, the male F-344 rats developed a mild renal tubular nephropathy that was associated with an increase in cell proliferation in renal tubular epithelial cells. 37 Female F-344 rats and male Sprague-Dawley rats did not develop nephropathy or demonstrate an increase in the proliferation of tubular epithelial cells. These results are consistent with other work that shows that HQ induces a sex-, species-, and strain-specific nephropathy in male F-344 rats.…”

Section: Human Health Effects Studies With Hq Have Shown a Lack Of Sysupporting

confidence: 86%

“…The relationship between HQ dose, renal toxicity, and renal cell proliferation was examined in an oral gavage study in which male and female F‐344 and male Sprague‐Dawley rats were given 0, 2.5, 25, or 50 mg/kg HQ by gavage for up to 6 weeks 37 . In agreement with the National Toxicology Program (NTP) study findings and other reports, the male F‐344 rats developed a mild renal tubular nephropathy that was associated with an increase in cell proliferation in renal tubular epithelial cells 37 . Female F‐344 rats and male Sprague‐Dawley rats did not develop nephropathy or demonstrate an increase in the proliferation of tubular epithelial cells.…”

Section: Experimental Animal Exposure Studies With Hqmentioning

confidence: 99%

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Hydroquinone and its analogues in dermatology – a risk‐benefit viewpoint

O’Donoghue

2006

J of Cosmetic Dermatology

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Hydroquinone (HQ) has been used since the 1950s in commercially available over-the-counter skin lightener products and since the 1960s as a commercially available medical product. It is also used in cosmetic products such as hair dyes and products for coating finger nails. Beginning in 2001, HQ is no longer authorized for use in cosmetic skin lightening formulations in European Union countries, although products containing arbutin, an analogue of HQ, and botanicals, including plants that naturally contain HQ and arbutin, continue to remain available in European countries. The potential toxicity of HQ is dependent on the route of exposure, and toxicity in rodents is highly sex-, species-, and strain-specific. Subchronic and chronic toxicity in experimental animals is primarily limited to nephrotoxicity in male F-344 rats. Dermal toxicity studies, even those conducted in the sensitive male F-344 rat, are essentially devoid of systemic toxicity. Developmental and reproductive toxicity studies with HQ in rats and rabbits have not demonstrated significant effects. Cancer bioassay data for HQ demonstrate limited effects and are not sufficient to classify HQ for human carcinogenicity. Epidemiology and occupational studies of workers with extensive exposure to HQ have not reported any evidence of adverse systemic health effects or carcinogenicity. A risk-benefit approach is recommended for assessing the available data for HQ, arbutin, and other materials in use as, or proposed for use as, skin lighteners to provide optimal therapeutic benefits to patients with pigmentary changes of the skin.

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Section: Human Health Effects Studies With Hq Have Shown a Lack Of Sysupporting

confidence: 86%

Section: Experimental Animal Exposure Studies With Hqmentioning

confidence: 99%

Hydroquinone and its analogues in dermatology – a risk‐benefit viewpoint

O’Donoghue

2006

J of Cosmetic Dermatology

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“…It is of interest that female F-344 rats were markedly more sensitive to hydroquinone-induced nephrotoxicity compared to male F-344 rats. Surprisingly, in a chronic 2-yr study, English et al (17) found that hydroquinone induced an increased incidence of renal tubule adenomas, enzymuria, and tubular degeneration, measured histopathologically, in male but not female F-344 rats. SD rats were also resistant to the acute and chronic nephrotoxic actions of hydroquinone.…”

Section: Kidneymentioning

confidence: 94%

“…Although it is difficult to ascertain the basis for the reversal in toxicity in F-344 rats from acute nephrotoxicity seen in female vs chronic toxicity seen in males, it should be noted that male F-344 rats are more susceptible to chemical-induced intestinal carcinoma (3,86) and chloroform-induced nephrotoxicity (68). Because the male F-344 rat in general is more sensitive than the female to carcinogens (29) and tumorigenesis is seen in male rats chronically administered hydroquinone (17), it would appear that susceptibility to nephrotoxicity is reversible in the female and that sensitivity in-creases with age in the male F-344 rat. It would be of interest to determine the role of testosterone in hydroquinone-induced nephrotoxicity.…”

Section: Kidneymentioning

confidence: 99%

Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals

Kacew

Ruben

McConnell³

1995

Toxicol Pathol

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The beneficial effects derived from the use of chemicals in agriculture, energy production, transportation, pharmaceuticals, and other products that improve the quality of life are clearly established. However, continued exposure to these chemicals is only advantageous in conditions where the benefit far outweighs toxic manifestations. By law, determination of risk of toxicity necessitates the use of laboratory animals to establish whether chemical exposure is safe for humans. To simulate the human condition, it is incumbent upon investigators to choose a species in which pharmacokinetic and toxicokinetic principles are established and resemble those of humans. Some of the advantages to the use of rat in chemical toxicity testing include (a) similarities in metabolism, anatomy, and physiological parameters to humans; (b) the short life span, especially for carcinogenesis study; (c) the availability, ease of breeding, and maintenance at a relatively low cost; and (d) the existence of a large database to enable comparison of present to reported literature findings. However, the choice of rat can be complicated by several factors such as sex, age, and nutrition, but especially strain, where currently there are over 200 different strains of rat known to exist. The aim of this review is to demonstrate that there are differences in the responsiveness of rat strains to chemicals and that the susceptibility observed is dependent on the tissue examined. It is evident that the genotype differs among strains, and this may be responsible for differences in sensitivities to chemicals. Awareness of strain as a factor in susceptibility to toxicant action needs to be taken into account in interpretation of relevance of risk of toxicity for humans.

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“…22 Subchronic treatment (6 weeks) of male F344 rats with 25 and 50 mg/kg HQ (via gavage) produced increased cell proliferation in the kidneys, and dose-dependent and statistically significant increases in the incidence of degenerative and regenerative foci in the tubules. 41 This same treatment regimen using 2.5 mg/kg HQ did not produce these effects in male F344 rats and none of the tested doses (2.5, 25 or 50 mg/kg) produced these effects in female F344 rats or in male SD rats. Glutathione metabolites can be reabsorbed in the proximal tubules of the kidney and metabolized by g-glutamyl transferase (also g-GT) where the released compound could generate ROS or covalently bond to cellular targets (ie, proteins or DNA).…”

Section: Smentioning

confidence: 78%

Final Amended Safety Assessment of Hydroquinone as Used in Cosmetics

Andersen¹,

Bergfeld²,

Belsito³

et al. 2010

Int J Toxicol

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Hydroquinone is an aromatic compound that functions in cosmetics as an antioxidant, fragrance, reducing agent, or polymerization inhibitor. Hydroquinone is also used as a skin bleaching agent. Safety and toxicity information indicate that hydroquinone is dermally absorbed in humans from both aqueous and alcoholic formulations and is excreted mainly as the glucuronide or sulfate conjugates. Hydroquinone is associated with altered immune function in vitro and in vivo in animals and an increased incidence of renal tubule cell tumors and leukemia in F344 rats, but the relevance to humans is uncertain. Quantitatively, however, the use of hydroquinone in cosmetics is unlikely to result in renal neoplasia through this mode of action. Thus, hydroquinone is safe at concentrations of ≤1% in hair dyes and is safe for use in nail adhesives. Hydroquinone should not be used in other leave-on cosmetics.

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Measurement of Cell Proliferation in the Kidneys of Fischer 344 and Sprague-Dawley Rats after Gavage Administration of Hydroquinone

Cited by 7 publications

References 0 publications

Hydroquinone and its analogues in dermatology – a risk‐benefit viewpoint

Hydroquinone and its analogues in dermatology – a risk‐benefit viewpoint

Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals

Final Amended Safety Assessment of Hydroquinone as Used in Cosmetics

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