Lack of nephrotoxicity and renal cell proliferation following subchronic dermal application of a hydroquinone cream.
Hydroquinone (HQ) is used in over-the-counter formulations of skin-lightening creams sold in the United States and European Union. HQ was introduced into these formulations to provide a safe and effective alternative to mercury and other less effective ingredients. Recent studies involving subchronic oral exposure of male F344 rats to HQ have shown nephrotoxicity and renal tubule cell proliferation (English et al., 1994), while chronic exposures of male F344 rats were reported to cause renal cell adenomas (NTP, 1989). Previous subchronic dermal toxicity studies (CTFA, 1986; NTP, 1989) with HQ failed to detect nephrotoxicity; however, these studies were not specifically designed to assess renal structure and function. More sensitive endpoints were used in the present subchronic study to address concerns over potential toxicity from repeated dermal exposure to HQ. Male and female F344 rats were given topical applications with 0, 2.0, 3.5, or 5.0% HQ in an oil-in-water emulsion cream for 13 wk (5 days/wk). Body weights, feed consumption and water consumption were monitored, and animals were observed for clinical signs of toxicity and dermal irritation. Blood taken at termination was analysed for haematological and clinical chemistry effects. Erythema, which abated when exposure stopped, was the only dermatological effect seen at the HQ-cream application sites. Cell proliferation in the kidneys was evaluated after 3, 6 and 13 wk of treatment using bromodeoxyuridine (BrdU) labelling, but no changes indicative of sustained cell proliferation were seen. The renal histopathological lesions noted after oral exposure to HQ were not present after dermal exposure. Thus, topical exposure to HQ does not result in the renal toxicity observed in previous studies with F344 rats given HQ orally.
Health and Environment Laboratories, Eastman Kodak Company, Rochester, NY 14652-6272, USA.
R M
RM
David
J C
JC
English
L C
LC
Totman
C
C
Moyer
J L
JL
O'Donoghue
D000279:Administration, Cutaneous; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004890:Erythema / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006873:Hydroquinones / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D008297:Male; D004366:Nonprescription Drugs; D009824:Ointments; D009842:Oligopeptides / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000187:drug effects / Q000473:pathology; D016482:Urinalysis; D005723:gamma-Glutamyltransferase / Q000652:urine
D006873:Hydroquinones; D004366:Nonprescription Drugs; D009824:Ointments; D009842:Oligopeptides; D011837:Radiation-Protective Agents; C029579:antiarrhythmic peptide; D005723:gamma-Glutamyltransferase; C031927:hydroquinone