Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats

Xu, Jiegou; Sagawa, Yoko; Futakuchi, Mitsuru; Fukamachi, Katsumi; Alexander, David B.; Furukawa, Fumio; Ikarashi, Yoshiaki; Uchino, Tadashi; Nishimura, Takuya; Morita, Akimichi; Suzui, Masumi; Tsuda, Hiroyuki

doi:10.1016/j.fct.2011.03.011

Cited by 26 publications

(18 citation statements)

References 21 publications

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“…the epidermis and reach the underlying tissue (Xu et al, 2011). This speculation is consistent with a report by Newman et al (2009) demonstrating an absence of penetration of TiO 2 through the epidermis and hair follicles (Newman et al, 2009).…”

Section: Introductionsupporting

confidence: 80%

“…Thus, the lack of skin promotion/carcinogenesis effects is probably due to lack of penetration of the particles through the epidermis to the dermis where cytogenetic cells of skin carcinogenesis reside. In another study, we found no promoting effect of TiO 2 particles in a UVB-initiated long-term (52 weeks) skin carcinogenesis study and no penetration of TiO 2 particles through the epidermis (Xu et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that alveolar macrophages play an important role in promotion of lung carcinogenesis when TiO 2 particles are inhaled into the lung (Xu et al, 2011). Because of this, TiO 2 particles, especially nano-sized particles, are deemed to have the potential to induce skin tumors after long-term topical application should the particles penetrate into the epidermis and subcutaneous tissue and interact with macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Based on our previous study showing lack of TiO 2 penetration through the normal skin (Xu et al, 2011), ncTiO 2 was applied to damaged skin, which is postulated to be more susceptible to particle penetration. The back skin of 10-week-old female SD rats (24 rats) was shaved (3 × 3 cm area) and the epidermis was removed by stripping the epidermis off with a fresh piece of adhesive tape (3M's No.…”

Section: Skin Penetration Study Of Non-coated Tio 2 (Nctio 2 ) In Sd mentioning

confidence: 99%

“…In 12 wells: 4 wells had silicone oil alone applied directly to the human skin epidermis keratinocytes for 48 hr; 4 wells had 100 mg/ml sTiO 2 suspended in silicone oil applied directly to the human skin epidermis keratinocytes for 48 hr; and 4 wells had 200 mg/ml sTiO 2 suspended in silicone oil applied directly to the human skin epidermis keratinocytes for 48 hr. The medium in the receiving chamber was collected for elemental titanium analysis by an inductively coupled plasma/mass spectrometry (ICP-MS) (HP-4500, Hewlett-Packard Co., Houston,TX, USA) as described previously (Xu et al, 2011).…”

Section: Skin Penetration Study Of Silicone Coated Tio 2 (Stio 2 ) Inmentioning

confidence: 99%

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Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice

Sagawa

Futakuchi

et al. 2012

J. Toxicol. Sci.

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Nano-sized titanium dioxide (TiO 2 ) particles are used in sunscreen formulations to protect against skin lesions caused by exposure to UV light (Gelis et al., 2003;Rouabhia et al., 2002;Suzuki, 1987). Nano and larger scale titanium dioxide particles are known to be carcinogenic to the rat lung (Baan et al., 2006;Baan, 2007). Recently, we demonstrated a promoting effect on rat lung carcinogenesis by nano-size TiO 2 particles administered by a novel intrapulmonary spraying method (Xu et al., 2010). The mechanism of promotion of lung carcinogenesis involved the induction of MIP1α protein expression by ncTiO 2 -laden alveolar macrophages (Xu et al., 2010).We also examined the carcinogenic effect of TiO 2 (mean manufacturer's particulate diameter of 20 nm) on the skin in a UVB-initiated two-stage rat carcinogenesis model and found that topical application of TiO 2 did not promote skin carcinogenesis in this model. This result is probably due to the inability of TiO 2 to penetrate through Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice ABSTRACT -Nano-sized titanium dioxide particles (TiO 2 ) are widely used in cosmetics, sunscreens and food additives. We previously reported that topical application of non-coated rutile type TiO 2 did not exhibit a promoting effect on ultraviolet B-initiated skin carcinogenesis in rats, and that this was likely due to lack of penetration of TiO 2 into the epidermis. In the present study, we examined the promoting effect of silicone coated TiO 2 (sTiO 2 ) suspended in silicone oil and non-coated TiO 2 (ncTiO 2 ) suspended in Pentalan 408 on a two-stage skin chemical carcinogenesis model: sTiO 2 suspended in silicon oil forms smaller particles than ncTiO 2 suspended in Pentalan because of the smaller sizes of aggregates formed. The model used skin carcinogenesis-sensitive human c-Ha-ras proto-oncogene transgenic mice (rasH2) and rats (Hras128) and their wild-type counterparts and CD-1 mice to test the effects of topical application of TiO 2 . Animals were initially treated with a single dose of 7,12-dimethylbenz[a]anthracene (DMBA) and then with 0, 10, or 20 mg sTiO 2 (mice) or 0, 50, or 100 mg ncTiO 2 (rats). The incidence and multiplicity of skin tumors (squamous cell papilloma and carcinoma) did not increase over DMBA alone controls in skin carcinogenesis-sensitive mice or rats or wild-type animals. Analysis of rat skin indicated that sTiO 2 and ncTiO 2 did not penetrate though either healthy or damaged skin. Furthermore sTiO 2 did not penetrate an in vitro human epidermis model. Our results indicate that treatment with sTiO 2 or ncTiO 2 did not promote skin carcinogenesis in mice or rats, probably due to lack of penetration through the epidermis.

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Section: Introductionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Skin Penetration Study Of Non-coated Tio 2 (Nctio 2 ) In Sd mentioning

confidence: 99%

Section: Skin Penetration Study Of Silicone Coated Tio 2 (Stio 2 ) Inmentioning

confidence: 99%

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Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice

Sagawa

Futakuchi

et al. 2012

J. Toxicol. Sci.

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Titanium Dioxide

Battersby,

Warheit

2023

Patty's Toxicology

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Titanium is a naturally occurring element. The commercially most important titanium compound is pigmentary TiO 2 , whereas nano‐scaled TiO 2 represents only a small amount on the market. Since humans are exposed to TiO 2 at workplace or through consumer products, a thorough evaluation of its potential toxicity has been summarized herein. Dermal absorption of TiO 2 is deemed to be negligible, whereas oral and inhalation absorption has been reported but is assumed to be very low. TiO 2 has been shown to be of low acute oral, dermal, and inhalation toxicity and is considered to be void of skin and eye‐irritating properties. It also does not show any potential for skin and respiratory sensitization. Oral long‐term toxicity studies in rats report no adverse effects, and due to lack of dermal absorption of TiO 2 , it is assumed that dermal exposure is also not a hazard. TiO 2 does not show any primary mutagenicity and is also void of reproductive or developmental toxicity. However, in long‐term inhalation toxicity studies in rats, inflammation, fibroproliferative effects, and lung tumor formation has been observed but only under conditions of excessive particle lung overload. Carcinogenicity under such extreme conditions with complete cessation of lung clearance is considered to not imply a cancer hazard for humans, which is in line with epidemiological studies showing no causative link between TiO 2 particle exposure and cancer risk in humans. However, based on the available animal database, IARC in the past classified TiO 2 as possibly carcinogenic to humans, and the Risk Assessment Committee of ECHA also concluded that TiO 2 warrants a Category 2 classification for carcinogenicity.

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Toxicity ofTiO₂Nanoparticles

Dar

Saeed

2020

TiO2 Nanoparticles

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Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats

Cited by 26 publications

References 21 publications

Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice

Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice

Titanium Dioxide

Toxicity ofTiO₂Nanoparticles

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Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats

Cited by 26 publications

References 21 publications

Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice

Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice

Titanium Dioxide

Toxicity ofTiO2Nanoparticles

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Product

Resources

About

Toxicity ofTiO₂Nanoparticles