Sub-chronic and developmental toxicity of transdermal delivery of Renzhu ointment in young SD rats.

Purpose: Renzhu ointment (Renzhuqigao, RZQG) is a patented herbal drug derived from Chinese traditional medicine formula and modern clinical experience for the transdermal treatment of non-infectious infantile diarrhoea. The safety of RZQG in preclinical studies has not been reported.Materials and methods: In this study, the pups of parent rats were examined for sub-chronic toxicity and developmental toxicity. After 21 days of birth, they were exposed to RZQG through their abdominal skin at doses of 0.1, 0.3, and 0.9 g/kg/day for 4 weeks and then were observed for another four weeks during their recovery period.Results: During the administration period, RZQG had no significant toxicological effect on body weight, food consumption, external eye examination, urinalysis, bone marrow examination, histopathology, central nervous system, reproductive system, or skeletal development. However, in the 0.9 g/kg/day group, the skin of some rats became dry and cracked, red and swollen, forming a white scab, while the white blood cells (WBC) count in female rats was lower and cholesterol (CHOL), triglycerides (TG), and glutamyl-transferase (GGT) were higher (p < 0.05).Conclusions: Rats receiving 0.9 g/kg/day exhibited skin irritation and were suspected to have a mild liver injury. There was no evidence of delayed toxicity four weeks after withdrawal. Therefore, the no-observed adverse effect level of RZQG was 0.3 g/kg/day (30 times the clinical dose planned and 4.92 times the human equivalent dose).

Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice.

BACKGROUND: Recently, the Aldara-induced psoriasis-like skin inflammation model in mice has attracted increased attention, due to its dependence on the same immunological pathways and cell types as in human psoriasis. OBJECTIVES: To study the impact of constitutive deficiency of tumour necrosis factor (TNF)-α and its upstream regulator mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2, herein MK2) in the Aldara-induced psoriasis-like skin inflammation model. METHODS: TNF-α knockout (KO), MK2 KO and wild-type (WT) mice divided into separate groups received either 45-mg Aldara cream or control cream for 5 consecutive days. The skin inflammation was evaluated clinically, histologically, and by quantitative reverse transcription-polymerase chain reaction. RESULTS: We found that TNF-α KO mice developed significantly less skin inflammation compared with WT mice, as evaluated clinically and histologically. At the molecular level, we demonstrated that the Aldara-induced mRNA expression of the psoriasis-related inflammatory markers interleukin (IL)-17C, IL-23p19, IL-12p40, IL-17A, IL-22 and S100A8 was significantly decreased in TNF-α KO mice compared with WT mice. No significant difference in the mRNA expression of these inflammatory markers between MK2 KO mice and WT mice was found, although Aldara-treated MK2 KO mice showed a tendency towards a lower mRNA expression of IL-17A and IL-22 compared with WT mice. CONCLUSIONS: We were able to demonstrate significantly lower levels of inflammation in TNF-α KO mice compared with WT mice, supporting the use of this model in future studies characterizing the role of TNF-α in psoriasis.

Cytotoxicity testing of burn wound dressings, ointments and creams: a method using polycarbonate cell culture inserts on a cell culture system.

UNLABELLED: We have developed a method to test the cytotoxicity of wound dressings, ointments, creams and gels used in our Burn Centre, by placing them on a permeable Nunc™ Polycarbonate cell culture insert, incubated with a monolayer of cells (HaCaTs and primary human keratinocytes). METHODS: We performed two different methods to determine the relative toxicity to cells. (1) Photo visualisation: The dressings or compounds were positioned on the insert's membrane which was placed onto the monolayer tissue culture plate. After 24 h the surviving adherent cells were stained with Toluidine Blue and photos of the plates were taken. The acellular area of non-adherent dead cells which had been washed off with buffer was measured as a percentage of the total area of the plate. (2) Cell count of surviving cells: After 24 h incubation with the test material, the remaining cells were detached with trypsin, spun down and counted in a Haemocytometer with Trypan Blue, which differentiates between live and dead cells. RESULTS: Seventeen products were tested. The least cytotoxic products were Melolite™, White soft Paraffin™ and Chlorsig1% Ointment. Some cytotoxicity was shown with Jelonet™, Mepitel(®), PolyMem(®), DuoDerm(®) and Xeroform™. The most cytotoxic products included those which contained silver or Chlorhexidine and Paraffin Cream™ a moisturizer which contains the preservative Chlorocresol. CONCLUSION: This in vitro cell culture insert method allows testing of agents without direct cell contact. It is easy and quick to perform, and should help the clinician to determine the relative cytotoxicity of various dressings and the optimal dressing for each individual wound.

Some pharmacological properties of immunotropic preparation from porcine skin.

We studied pharmacological properties of immunotropic preparation from porcine skin (skin resorption effect and acute and chronic toxicity). It was demonstrated that the preparation did not damage the skin during evaluation of skin-resorption effect; evaluation of acute and chronic toxicity revealed no changes in the general state of experimental animals and histological structure of visceral organs and skin; evaluation of chronic toxicity showed that the preparation induced no changes in blood biochemical parameters compared to the control.

Reduced cellular toxicity of a new silver-containing antimicrobial dressing and clinical performance in non-healing wounds.

Bacterial colonisation of wounds may delay wound healing. Modern silver-containing dressings are antimicrobial, yet cellular toxicity is a serious side-effect. We provide data for a newly formulated silver-containing ointment dressing, Atrauman Ag, for antimicrobial activity and cytotoxicity. Atrauman Ag effectively killed a panel of commensal skin as well as pathogenic bacterial strains while cytotoxicity for HaCaT keratinocytes was only around 10%. With these favourable in vitro tests, Atrauman Ag was analysed in 86 patients with traumatic and non-healing wounds of different aetiologies. The wound state was evaluated for 3 subsequent dressing changes. The slough score was reduced from 59.2 to 35.8%, granulation tissue increased from 27 to 40% and epithelialisation went up from 12.1 to 24%. We conclude that Atrauman Ag has a superior profile of antimicrobial activity over cellular toxicity and the low silver ion release rate may prevent interference with wound-healing mechanisms.

Study on acute and subchronic toxicity of “thach vi gia giam” liquid ointment

Study was conducted in experimental mice to investigate acute and subchronic toxicity of “thach vi gia giam” remedy with liquid ointment form on their blood formation system and liver-kidney functions. The results showed that: LD50 toxic dose by oral route with maximum dose of 125 ml/kg mice weight could not been determined. With dose of “Thach vi gia giam” 50 ml/2kg (25 times higher than human dosage) during 2 months continuously, there was not a significant sigh of the changes in blood component, liver-kidney function compared with control group in a same condition.

Oral toxicity of topical preparations.

This chapter covers the hazards that some topical pharmaceutical preparations pose to animals who consume them. Included are medications containing calcipotriene, vitamins A and D, zinc oxide, 5-fluorouracil, brimonidine, imidazoline decongestants, local anesthetics, corticosteroids, antibiotics, salicylates, and benzoyl peroxide.

Estudio Toxicológico de un producto derivado de la Caña de Azúcar / Toxicity study of a product derived from sugar cane

Se presentan los resultados obtenidos en la evaluación toxicológica preclínica de un principio activo formulado en crema con propiedades cicatrizantes y antifúngicas a partir de un producto natural derivado de la caña de azúcar, al cual se le determinó su inocuidad en animales de experimentación mediante la estimación de la dosis letal media en conejos F1 y ratas albinas Wistar, utilizando niveles de dosis elevados. También se estudió el potencial irritante sobre la piel, mucosa ocular, vaginal y rectal, así como su potencial como agente sensibilizante. De forma general los síntomas tóxicos observados no fueron significativos y desaparecieron en un período corto, no se presentó mortalidad y se comprobó la ausencia de efectos irritantes sobre la piel y mucosas evaluadas. Se demostró que el producto no es un agente sensibilizante. Los resultados obtenidos en el estudio realizado permiten clasificar al producto de una baja toxicidad(AU)

Estudio Toxicológico de un producto derivado de la Caña de Azúcar / Toxicity study of a product derived from sugar cane

Se presentan los resultados obtenidos en la evaluación toxicológica preclínica de un principio activo formulado en crema con propiedades cicatrizantes y antifúngicas a partir de un producto natural derivado de la caña de azúcar, al cual se le determinó su inocuidad en animales de experimentación mediante la estimación de la dosis letal media en conejos F1 y ratas albinas Wistar, utilizando niveles de dosis elevados. También se estudió el potencial irritante sobre la piel, mucosa ocular, vaginal y rectal, así como su potencial como agente sensibilizante. De forma general los síntomas tóxicos observados no fueron significativos y desaparecieron en un período corto, no se presentó mortalidad y se comprobó la ausencia de efectos irritantes sobre la piel y mucosas evaluadas. Se demostró que el producto no es un agente sensibilizante. Los resultados obtenidos en el estudio realizado permiten clasificar al producto de una baja toxicidad

Prueba de irritabilidad dérmica primaria del Plantago major L / Primary dermal irritability test of Plantago major L

Se le realiza el test de Draize a una crema de Plantago major L. (llantén mayor) que se encontraba en una concentración de 20,7 g de sólidos por cada gramo de ungüento hidrófilo, el cual fue aplicado en dosis única en conejos. La crema resultó ser ligeramente irritante, lo cual no imposibilitó su uso en la terapeútica (AU)

Prueba de irritabilidad dermica primaria del Plantago major / Primary dermal irritability test of Plantago major

Se le realiza el test de Draize a una crema de Plantago major L. (llanten mayor) que se encontraba en una concentracion de 20,7 g de solidos por cada gramo de ungueento hidrofilo, el cual fue aplicado en dosis unica en conejos. La crema resulto ser ligeramente irritante, lo cual no imposibilito su uso en la terapeutica

Ocular toxicity following topical application of anesthetic cream to the eyelid skin.

BACKGROUND AND OBJECTIVE: The use of topical anesthetic cream in the periorbital region may be of clinical value. The potential for toxic effects from such use has not been studied in a controlled manner. This study was performed to evaluate the potential ocular toxicity of anesthetic cream topically applied to the eyelid in an animal model. MATERIALS AND METHODS: Ten rabbits underwent periorbital eutectic mixture of local anesthetics (EMLA) (2.5 percent lidocaine and 2.5 percent prilocaine) application and were observed for evidence of gross or microscopic ocular toxicity. Baseline external and anterior segment examinations were performed, including biomicroscopy and fluorescein staining, after which a standard quantity of EMLA cream (0.75 g) was applied along the upper eyelid and covered with an occlusive dressing. After 1 hour of treatment, the eyelid and anterior segment were examined for evidence of adverse reaction. The eyelids were excised and examined histopathologically. RESULTS: No significant adverse effects were noted on external lid and anterior segment examination. The histopathologic findings were within normal limits. CONCLUSIONS: This study suggests that external application of EMLA cream to the eyelid does not induce local toxicity in the rabbit model. The external application of EMLA cream may be safe in the periorbital region.

Pediatric dosing considerations in ophthalmology.

In almost all cases concerned with topically applied ophthalmic drugs, no distinction is made between adults and infants or children with regard to the concentration and amount of drug used. Even though maximal therapeutic effects are usually observed, there can be significant short- and long-term toxicity problems. Based on some modest assumptions it should be possible to reduce doses without sacrificing therapeutic effectiveness in infants and children up to three years of age. The overriding concern should be, however, potential toxicity problems which may exist in infants and children, in particular the neonate, due to their low body weight and the fact that in most cases, more than 90 percent of an instilled dose in potentially available to act systemically. Total body surface area can be used as a measure for determining potentially toxic doses in children. Especially for potent drugs, with both short- and long-term manifestations, toxicity considerations may necessitate some sacrifice in therapeutic effectiveness of a given drug or switching to an alternate drug in order to insure a reduction in toxic side effects.