Reflections on the OECD guidelines for in vitro skin absorption studies.

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16-18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments.

Short contact with nickel causes allergic contact dermatitis: an experimental study.

BACKGROUND: Knowledge about the required duration of exposure for elicitation of allergic nickel dermatitis in nickel-allergic individuals is limited. However, it often has been proposed that short skin contact is safe. OBJECTIVES: To examine whether repeated skin contact with nickel over short time periods (3 × 10 min) can elicit allergic nickel dermatitis. METHODS: Sixteen nickel-allergic adults and 10 controls were exposed to, respectively, nickel- and aluminium-containing discs on each volar forearm and on each earlobe for 3 × 10 min. One arm was pretreated for 24 h with sodium lauryl sulfate (SLS) 0·5% under occlusion before exposure. One aluminium and one nickel exposure site were clinically evaluated, and blood flow was measured with laser Doppler flowmetry at day 2 and day 4. RESULTS: Ten of 16 (63%) nickel-allergic participants developed allergic nickel dermatitis on SLS-pretreated arm skin and three of 16 (19%) developed it on normal skin on the earlobe. On the SLS-pretreated arms of nickel-allergic participants, blood flow increased significantly more on the nickel-exposed skin than on the aluminium-exposed skin on days 2 and 4. No change in clinical reactivity or blood flow was found on normal forearm skin in nickel-allergic participants or on any skin in controls. CONCLUSIONS: This experimental study showed that relatively short repeated skin contact (3 × 10 min) with metallic nickel elicits allergic nickel dermatitis in irritated skin and at sites with previous dermatitis. The results support the restrictions in current nickel regulation.

Levels of brominated flame retardants in blood in relation to levels in household air and dust.

Levels of tri- to decabrominated diphenyl ethers (BDEs), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and 1,2-bis(pentabromophenyl)ethane (DeBDethane) were determined in air, sedimentary dust and human plasma from five households in Sweden. The levels of the individual BDEs in the plasma samples were in the same order of magnitude as in other studies of the general population in Scandinavia, and varied between non-detectable (<0.41 ng g(-1) l.w.) to 17 ng g(-1) (l.w.). BDE#28 and #47 were present in all air samples, with mean values of 0.015 and 0.12 ng m(-3), respectively, except for one sample where the BDE#47 concentration was below the limit of detection (<0.17 ng m(-3)). BDE#209 was found in one of the five air samples at a concentration of 0.26 ng m(-3). DeBDethane was also detected in one sample, in which the BDE#209 level was below LOD (<0.021 ng m(-3)), at a level of 0.023 ng m(-3). All the target compounds were found in the sedimentary dust samples at levels from 0.51 to 1600 ng g(-1), the highest concentration representing BDE#209. The most abundant components in plasma, air and dust were BDE#47, #99 and #209. In the plasma samples BDE#207 and #206 were also present at similar concentrations as BDE#47. In the sedimentary dust samples, DeBDethane was also among the most abundant BFRs. A positive relationship was found for the sumBDE concentrations in dust and plasma, although the relationship was strongly dependent on one of the five observations. BFR levels in dust and air were not dependent on the house characteristics such as living area, floor material or number of electronic devices.

Polybrominated diphenyl ethers--plasma levels and thyroid status of workers at an electronic recycling facility.

OBJECTIVES: Personnel working with electronic dismantling are exposed to polybrominated diphenyl ethers (PBDEs), which in animal studies have been shown to alter thyroid homeostasis. The aim of this longitudinal study was to measure plasma level of PBDEs in workers at an electronic recycling facility and to relate these to the workers' thyroid status. METHODS: PBDEs and three thyroid hormones: triiodothyronine (T(3)), thyroxin (T(4)) and thyroid stimulating hormone (TSH) were repeatedly analysed in plasma from 11 workers during a period of 1.5 years. RESULTS: Plasma levels of PBDEs at start of employment were <0.5-9.1 pmol/g lipid weight (l.w.). The most common congener was PBDE #47 (median 2.8 pmol/g l.w.), followed by PBDE #153 (median 1.7 pmol/g l.w.), and PBDE #183 had a median value of <0.19 pmol/g l.w. After dismantling the corresponding median concentrations were: 3.7, 1.7 and 1.2 pmol/g l.w., respectively. These differences in PBDE levels were not statistically significant. PBDE #28 showed a statistically significantly higher concentration after dismantling than at start of employment (P=0.016), although at low concentrations (start 0.11 pmol/g l.w. and dismantling 0.26 pmol/g l.w.). All measured levels of thyroid hormones (T(3), T(4) and TSH) were within the normal physiological range. Statistically significant positive correlations were found between T(3) and #183 in a worker, between T(4) and both #28 and #100 in another worker and also between TSH and #99 and #154 in two workers. CONCLUSIONS: The workers' plasma levels of PBDEs fluctuated during the study period. Due to small changes in thyroid hormone levels it was concluded that no relevant changes were present in relation to PBDE exposure within the workers participating in this study.