Acceptable surface limits (ASLs) of skin sensitizers derived from the local lymph node assay (LLNA): BrdU‐ELISA EC1.6 values and their relationships to known sensitization potency information

Abstract

Skin sensitization is an extremely important risk factor for occupational health and safety, and it would be desirable to set health‐based exposure limits (HBELs) for the quantitative risk assessment (QRA) based on the skin sensitizing potencies of chemical. We attempted to set acceptable surface limits (ASLs) as HBELs for skin sensitizers in the workplace based on the local lymph node assay (LLNA): BrdU‐ELISA EC1.6 values. To calculate the ASLs, a safety assessment factor (SAF)interspecies value of 6, based on the EC1.6 values/human repeat insult patch test (HRIPT) NOEL ratios, a SAFinterindividual value of 10, and a SAFfrequency/duration value of 3 were applied, referring to previous literatures on SAFs for skin sensitization QRA, and the composite SAF was calculated as 180. The ASLs (mg/100 cm2) derived thus for 33 chemicals ranged from 0.001 to 10.417. Comparison of the ranges with known human sensitization potency classes and GHS subcategories revealed that use of GHS Category 1A chemicals needs to be controlled to ensure surface residue levels of less than 1 mg/100 cm2. To minimize sensitization risks, a quantitative sensitization risk assessment method for chemicals and appropriate risk management are necessary. This report provides a potentially useful ASL‐based method of managing sensitization risk derived from LLNA: BrdU‐ELISA EC1.6 values, comparison of the ASLs and known human sensitization potency data showed that GHS subcategorization results would be a primary information notifying ASL ranges to be required for minimizing the sensitization risk.

Retrospective quantitative risk assessment of skin sensitization caused by an antimicrobial agent used in a consumer product: 2,3,5,6‐Tetrachloro‐4‐(methylsulfonyl) pyridine

“…For the SAF interspecies , a factor of 6 was applied based on an analysis of the ratio of LLNA: BrdU‐ELISA EC1.6 values and HRIPT NOELs determined in a previous report 7 . For the SAF interindividual , a factor of 10 was applied, taking into account the default value that is consistently used in QRAs for the skin sensitization of cosmetics 6,9–11 …”

“…The SAFs for the consumer risk assessment of the chemical used in desk mats were considered by referring to a previous report, 7 in which appropriate SAFs were applied to EC1.6 values determined using LLNA: BrdU-ELISAs to derive acceptable surface limits for workers, and a previously reported QRA approach for skin sensitization caused by cosmetics. 6,[9][10][11] The components of the SAFs to be considered were decided as interspecies differences, interindividual differences, and the conditions characterising desk mat use.…”

“…For the SAF interspecies , a factor of 6 was applied based on an analysis of the ratio of LLNA: BrdU-ELISA EC1.6 values and HRIPT NOELs determined in a previous report. 7 For the SAF interindividual , a factor of 10 was applied, taking into account the default value that is consistently used in QRAs for the skin sensitization of cosmetics. 6,[9][10][11] As for the SAF use conditions , elements of the matrix/product, frequency/duration and skin condition/site were considered by referring to the 'Quantitative Risk Assessment for Fragrance Ingredients (QRA2)'.…”

“…Recently, a new approach for setting acceptable surface limits (ASLs) for chemicals on the surface of manufacturing equipment was reported to reduce the risk of skin sensitization in workers. 7 In this approach, the EC1.6 value obtained from an LLNA: BrdU-ELISA was used as the point of departure (POD), and the ASLs used for the risk assessment were derived using sensitization assessment factors (SAFs) that reflect interspecies differences, individual differences, and the conditions of use. This strategy for setting ASLs based on the EC1.6 value as the POD can also be applied to risk assessments for other targets or scenarios, such as the skin sensitization risk of chemicals in consumer products, by applying appropriate adjustment factors capable of reflecting the assessment purpose.…”

“…However, examples of QRAs for examining the sensitization risk of chemicals contained in other types of consumer products are limited, and further investigations of QRAs to avoid sensitization risk are needed for various types of consumer products. Recently, a new approach for setting acceptable surface limits (ASLs) for chemicals on the surface of manufacturing equipment was reported to reduce the risk of skin sensitization in workers 7 . In this approach, the EC1.6 value obtained from an LLNA: BrdU‐ELISA was used as the point of departure (POD), and the ASLs used for the risk assessment were derived using sensitization assessment factors (SAFs) that reflect interspecies differences, individual differences, and the conditions of use.…”