Potency values from the local lymph node assay: Application to classification, labelling and risk assessment

Loveless, Scott E.; Api, A.M.; Crevel, René; Debruyne, E.; Gamer, Armin; Jowsey, Ian R.; Kern, Petra; Kimber, Ian; Lea, Linda J.; Lloyd, Peter; Mehmood, Zafar; Steiling, W.; Veenstra, G. E.; Woolhiser, Michael R.; Hennes, Christa

doi:10.1016/j.yrtph.2009.08.016

Cited by 57 publications

(31 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following dermal exposure to uITO, a dose-responsive increase in lymphocyte proliferation was observed (reaching statistical significance and SI >3 at both 5% and 10% levels). The EC3 calculated for uITO was 4.7%, resulting in its classification as a mild sensitizer (Loveless et al, 2010). This classification is similar to other metals including nickel, which are known human sensitizers.…”

Section: Discussionmentioning

confidence: 99%

Immune stimulation following dermal exposure to unsintered indium tin oxide

Brock

Anderson

Lukomska

et al. 2013

Journal of Immunotoxicology

View full text Add to dashboard Cite

In recent years, several types of pulmonary pathology, including alveolar proteinosis, fibrosis, and emphysema, have been reported in workers in the indium industry. To date, there remains no clear understanding of the underlying mechanism(s). Pulmonary toxicity studies in rats and mice have demonstrated the development of mediastinal lymph node hyperplasia and granulomas of mediastinal lymph nodes and bronchus-associated lymphoid tissues following exposure to indium tin oxide. Given the association between exposure to other metals and the development of immune-mediated diseases, these studies were undertaken to begin to investigate the immuno-modulatory potential of unsintered indium tin oxide (uITO) in a mouse model. Using modifications of the local lymph node assay, BALB/c mice (five animals/group) were exposed topically via intact or breached skin or injected intradermally at the base of the ear pinnae with either vehicle or increasing concentrations 2.5–10% uITO (90:10 indium oxide/tin oxide, particle size <50 nm). Dose-responsive increases in lymphocyte proliferation were observed with a calculated EC3 of 4.7% for the intact skin study. Phenotypic analysis of draining lymph node cells following intradermal injection with 5% uITO yielded a profile consistent with a T-cell-mediated response. These studies demonstrate the potential for uITO to induce sensitization and using lymphocyte proliferation as a biomarker of exposure, and demonstrate the potential for uITO to penetrate both intact and breached skin.

show abstract

Section: Discussionmentioning

confidence: 99%

Immune stimulation following dermal exposure to unsintered indium tin oxide

Brock

Anderson

Lukomska

et al. 2013

Journal of Immunotoxicology

View full text Add to dashboard Cite

show abstract

“…In the case of dermal irritation and sensitization where contact alone is a key parameter, the appropriate dose-metric is mass per unit area (European Commission, 2010;Kimber et al, 2008;Loveless et al, 2010). Otherwise, exposures are commonly expressed in units of mg/kg bw/day, the amount of material contacted (mg) per mean body weight (kg) of the subject per unit of time (day).…”

Section: Exposure Assessmentmentioning

confidence: 99%

“…Thus, the NOEL of 30 mM in Guinea pigs corresponds to a dermal sensitization threshold of about 17,000 ng/ cm 2 . Hilton et al (1995) determined an EC3 of 0.02% (w/v) 1 for dermal sensitization using the mouse LLNA, which has emerged as a preferred method for sensitization testing due to the pragmatic and scientific advantages it affords (Loveless et al, 2010). Based on the LLNA protocol (i.e., 25 ll applied to 1 cm 2 of skin on each ear), the EC3 of 0.02% corresponds to a dermal exposure of 5000 ng TDI/ cm 2 .…”

Section: Skin Sensitizationmentioning

confidence: 99%

Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam

Arnold

Collins²,

Graham

et al. 2012

Regulatory Toxicology and Pharmacology

View full text Add to dashboard Cite

Polyurethanes (PU) are polymers made from diisocyanates and polyols for a variety of consumer products. It has been suggested that PU foam may contain trace amounts of residual toluene diisocyanate (TDI) monomers and present a health risk. To address this concern, the exposure scenario and health risks posed by sleeping on a PU foam mattress were evaluated. Toxicity benchmarks for key non-cancer endpoints (i.e., irritation, sensitization, respiratory tract effects) were determined by dividing points of departure by uncertainty factors. The cancer benchmark was derived using the USEPA Benchmark Dose Software. Results of previous migration and emission data of TDI from PU foam were combined with conservative exposure factors to calculate upper-bound dermal and inhalation exposures to TDI as well as a lifetime average daily dose to TDI from dermal exposure. For each non-cancer endpoint, the toxicity benchmark was divided by the calculated exposure to determine the margin of safety (MOS), which ranged from 200 (respiratory tract) to 3×10(6) (irritation). Although available data indicate TDI is not carcinogenic, a theoretical excess cancer risk (1×10(-7)) was calculated. We conclude from this assessment that sleeping on a PU foam mattress does not pose TDI-related health risks to consumers.

show abstract

“…The test measures lymphocyte proliferation in lymph nodes draining the site where chemicals were applied. The method assumes that LNC proliferative responses are causally and quantitatively associated with the effectiveness of sensitization induction (ECETOC, 2003, 2008), yielding results that quantitatively describe relative sensitizing potency, which correlates with human sensitization thresholds (Loveless et al, 2010; van Loveren et al, 2008). Although initially used to evaluate induction of sensitization by skin exposure, recent studies describe its use for evaluating inhalation-induced sensitization (Arts et al, 2008; de Jong et al, 2009).…”

Section: In Vivo Animal Studiesmentioning

confidence: 99%

Methyl methacrylate and respiratory sensitization: A Critical review

Borak¹,

Fields²,

Andrews³

et al. 2011

Critical Reviews in Toxicology

View full text Add to dashboard Cite

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer.

show abstract

Potency values from the local lymph node assay: Application to classification, labelling and risk assessment

Cited by 57 publications

References 66 publications

Immune stimulation following dermal exposure to unsintered indium tin oxide

Immune stimulation following dermal exposure to unsintered indium tin oxide

Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam

Methyl methacrylate and respiratory sensitization: A Critical review

Contact Info

Product

Resources

About