Mortality Among Titanium Dioxide Workers at Three DuPont Plants

Ellis, Elizabeth D.; Watkins, Janice P.; Tankersley, William G.; Phillips, Joyce; Girardi, David J.

doi:10.1097/jom.0b013e3181d0bee2

Cited by 28 publications

(16 citation statements)

References 14 publications

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“…TiO 2 is classified by the International Agency for Research on Cancer (IARC) as being possible carcinogen to humans by inhalation (Group 2B), based on sufficient evidence in experimental animals and inadequate (little) evidence from epidemiological studies (5), and the European Chemicals Agency recently opened for commenting a proposition for classifying TiO 2 as a carcinogen (Carc 1B) in Europe (available at: ). There is, however, no conclusive evidence of TiO 2 -related cancer after the occupational exposure (6,7), and it has been proposed that it is carcinogenic only after massive prolonged inhalation exposure. The National Institute for Occupational Safety and Health (NIOSH) has proposed an occupational exposure limit of 0.3mg/m 3 for ultrafine TiO 2 particles (8), compared with the current occupational exposure limit of 10mg/m 3 TiO 2 or 6mg/m 3 titanium (Ti) in Denmark (available at: ).…”

Section: Introductionmentioning

confidence: 99%

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice

Wallin

Kyjovska

Poulsen

et al. 2016

MUTAGE

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The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mRNA levels in liver tissue by real-time quantitative polymerase chain reaction. Instillation of NRCWE-001 and -002 both induced a dose-dependent neutrophil influx into the lung lining fluid and Saa3 mRNA levels in lung tissue at all assessed time points. There was no statistically significant difference between NRCWE-001 and NRCWE-002. Exposure to both TiO2 NPs induced increased levels of DNA strand breaks in lung tissue at all doses 1 and 28 days post-exposure and NRCWE-002 at the low and middle dose 3 days post-exposure. The DNA strand break levels were statistically significantly different for NRCWE-001 and -002 for liver and for BAL cells, but no consistent pattern was observed. In conclusion, functionalisation of reactive negatively charged rutile TiO2 to positively charged did not consistently influence pulmonary toxicity of the studied TiO2 NPs.

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Section: Introductionmentioning

confidence: 99%

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice

Wallin

Kyjovska

Poulsen

et al. 2016

MUTAGE

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“…1). Upon further evaluation, seven studies were determined to fulfill the inclusion criteria and quantitatively characterized carcinogenic endpoints in humans (Boffetta et al, 2001(Boffetta et al, , 2004Chen and Fayerweather, 1988;Ellis et al, 2010Ellis et al, , 2013Fryzek et al, 2003;Ramanakumar et al, 2008). These studies were all epidemiologic assessments of workers in TiO 2 production facilities in Europe and in the United States.…”

Section: Human Datamentioning

confidence: 99%

Development of linear and threshold no significant risk levels for inhalation exposure to titanium dioxide using systematic review and mode of action considerations

Thompson

Suh

Mittal

et al. 2016

Regulatory Toxicology and Pharmacology

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“…In humans, a potential relationship between exposure to TiO 2 and the occurrence of cancers was assessed in seven epidemiological studies . An increase in death due to lung cancer was reported in most of these studies, although no causal relationship could be established.…”

Section: Toxicitymentioning

confidence: 99%

Safety of titanium dioxide nanoparticles in cosmetics

Dréno¹,

Chuberre

et al. 2019

Acad Dermatol Venereol

177

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Titanium dioxide (TiO2) is widely used in a variety of products including cosmetics. TiO2 in its nanoparticle form (nano‐TiO2) is now the only form used as an ultraviolet (UV) filter in sunscreens, but also in some day creams, foundations and lip balms. While its efficacy as a UV filter is proven in the prevention of skin cancers and sunburns, some concerns have been raised about its safety. Indeed, considering its small size, nano‐TiO2 is suspected to penetrate dermal, respiratory or gastrointestinal barriers, disseminate in the body and therefore constitute a potential risk to the consumer. At the skin level, most studies performed in humans or animals showed that nano‐TiO2 did not penetrate beyond the outer layers of stratum corneum to viable cells and did not reach the general circulation, either in healthy or in compromised skin. The Scientific Committee on Consumer Safety (SCCS) considers nano‐TiO2 as a non‐sensitizer and as mild‐ or non‐irritant to skin and concludes in no evidence of carcinogenicity (supported by the European Chemicals Agency), mutagenicity or reproductive toxicity after dermal exposure to nano‐TiO2. According to the SCCS, nano‐TiO2 from sunscreens does not present any health risk when applied on the skin at a concentration up to 25%. However, the SCCS does not recommend the use of nano‐TiO2 in formulations that may lead to exposure of the consumer's lungs by inhalation (sprayable products and powders). Indeed, even if human data are sparse and inconsistent, lung inflammation was reported in animals. In 2016, the EU Cosmetic Regulation made nano‐TiO2 as an authorized UV filter, except in products that could lead to exposure of the lungs. After oral exposure, nano‐TiO2 absorption and toxicity are limited. The incidental oral exposure to nano‐TiO2 contained in lip balms is thus not expected to induce adverse health effects.

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Mortality Among Titanium Dioxide Workers at Three DuPont Plants

Abstract: The mortality rates are comparable with the general US population. Increasing SMRs with length of plant operation is indicative of waning healthy worker effect with time since first employment. The results are comparable with other titanium dioxide cohort studies.

Cited by 28 publications

References 14 publications

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice

Development of linear and threshold no significant risk levels for inhalation exposure to titanium dioxide using systematic review and mode of action considerations

Safety of titanium dioxide nanoparticles in cosmetics

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Mortality Among Titanium Dioxide Workers at Three DuPont Plants

Abstract: The mortality rates are comparable with the general US population. Increasing SMRs with length of plant operation is indicative of waning healthy worker effect with time since first employment. The results are comparable with other titanium dioxide cohort studies.

Cited by 28 publications

References 14 publications

Surface modification does not influence the genotoxic and inflammatory effects of TiO2nanoparticles after pulmonary exposure by instillation in mice

Surface modification does not influence the genotoxic and inflammatory effects of TiO2nanoparticles after pulmonary exposure by instillation in mice

Development of linear and threshold no significant risk levels for inhalation exposure to titanium dioxide using systematic review and mode of action considerations

Safety of titanium dioxide nanoparticles in cosmetics

Contact Info

Product

Resources

About

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice