Predictive identification of human skin sensitization thresholds

Basketter, David A.; Clapp, Catherine; Jefferies, Donna; Safford, Bob; Ryan, Cindy A.; Gerberick, Frank; Dearman, Rebecca J.; Kimber, Ian

doi:10.1111/j.0105-1873.2005.00707.x

Cited by 130 publications

(76 citation statements)

References 40 publications

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“…In view of these properties also in the skin, a prolonged presence of formaldehyde can be expected after exposure. Our results on the EC3 value (0.96%) of formaldehyde are on the same order of magnitude as previously published (EC3 of 0.54% and 0.65%, Griem et al, 2003;Basketter et al, 2005a). For the formaldehyde donors investigated, we did not reach a stimulation index of 3 in the dose-response experiments (Table 1).…”

Section: Exposure To Chemicalsupporting

confidence: 90%

“…In order to investigate the effects of such an accumulation, the induction of cellular proliferation in draining lymph nodes was compared after short and repeated prolonged exposure to formaldehyde releasers. We used the stimulation index of 3 as a benchmark response as this value is used as cutoff to conclude sensitizing ability (Kimber and Basketter, 1992;Basketter et al, 1999a;Haneke et al, 2001) and, in addition, can be used to compare potency of various chemicals (Van Och et al, 2000;De Jong et al, 2002b;Kimber et al, 2003;Basketter et al, 2005a).…”

Section: Exposure To Chemicalmentioning

confidence: 99%

“…Using the EC3 value (the effective concentration inducing a threefold increase in lymph node cell proliferation compared to 240 DE JONG ET AL. controls, SI = 3), various chemicals can be compared with each other for their sensitizing potency, and a ranking order can be determined (Basketter et al, 1999a(Basketter et al, , 1999b(Basketter et al, , 2005aVan Och et al, 2000;De Jong et al, 2002b). Based on such ranking, chemicals might be classified according to their potency in various categories instead of the two categories currently used-sensitizer and non-sensitizer (Dearman et al, 1999;Kimber et al, 2003;Schneider and Akkam, 2004;Basketter et al, 2005a).…”

Section: Introductionmentioning

confidence: 99%

“…Based on such ranking, chemicals might be classified according to their potency in various categories instead of the two categories currently used-sensitizer and non-sensitizer (Dearman et al, 1999;Kimber et al, 2003;Schneider and Akkam, 2004;Basketter et al, 2005a). For the manufacturing of consumer products, chemicals can be chosen with a high EC3 value that is indicative for a low(er) sensitizing potency.…”

Section: Introductionmentioning

confidence: 99%

“…The quantitative data obtained in the LLNA might be of use as a starting point for the risk assessment of individual chemicals rather then an identification as sensitizer or non-sensitizer (Kimber et al, 2001;Basketter et al, 2005aBasketter et al, , 2005b. This opens the possibility for sensitizers to perform a more in-depth risk assessment to estimate relatively safe exposure levels for ingredients in consumer products.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Prolonged Repeated Exposure to Formaldehyde Donors with Doses Below the EC3 Value on Draining Lymph Node Responses

Jong

Klerk

Beek

et al. 2007

Journal of Immunotoxicology

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In the Local Lymph Node Assay (LLNA), a stimulation index of 3 (SI = 3) is established as a threshold value for hazard identification of sensitization. The corresponding EC3 value, the effective concentration inducing a threefold increase compared to controls, can possibly predict threshold levels for sensitization in humans. Exposure to a dose below the threshold dose would not result in an induction of an immune response. Each repeated contact would be considered and viewed as a new contact and as long as the dose is below the threshold there will be no response, even after repeated exposures. However, repeated exposure may result in local accumulation eventually resulting in a dose that induces a response above the threshold for immunization. We investigated lymph node responses after short and prolonged exposure to formaldehyde donors, chemicals that are highly reactive with proteins and may thus persist in the skin. The studies were performed with formaldehyde and formaldehyde releasers (formaldehyde, paraformaldehyde, Quaternium-15, 2-Chloro-N-(hydroxymethyl)acetamide, and hexamethylenetetramine), at concentrations that induce a SI = 2, i.e., below the threshold for hazard identification. For all test chemicals investigated enhanced lymph node responses were obtained when comparing long-term prolonged exposure to short-term exposure, while three of five chemicals induced responses above SI = 3. Our results show that repeated and prolonged exposure to doses below the EC3 value can induce reactions above the SI = 3, the hazard identification threshold for sensitization in mice. So, when discussing the possible use of the EC3 as benchmark for risk assessment, one should consider duration of exposure and the possibility of local accumulation of the chemical under investigation.

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Section: Exposure To Chemicalsupporting

confidence: 90%

Section: Exposure To Chemicalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effect of Prolonged Repeated Exposure to Formaldehyde Donors with Doses Below the EC3 Value on Draining Lymph Node Responses

Jong

Klerk

Beek

et al. 2007

Journal of Immunotoxicology

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Dermal Toxicology of Cosmetics and Body‐Care Products

Basketter

Lea

2009

General, Applied and Systems Toxicology

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There is a tendency in both regulatory thinking and in public perception towards the view that cosmetics are in some way different from other products. The reality of course is that they are formed from a combination of chemical ingredients, raw materials which, in fact, can be found in a very wide range of products. Consequently, the toxicology considerations which apply to other products also apply to cosmetics and body‐care products. Application of appropriate toxicological review of product ingredients and of the final formulation is key to meeting the requirement that such products do not cause harm to the consumer. Failure to undertake such a review to an adequate standard gives rise to a risk of adverse reactions. In this chapter, we set out some general thoughts on how a review of product safety generally should be approached for these types of product. Wherever possible, emphasis has been placed on the minimization and/or elimination of the need for in vivo testing.

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