Elsevier

Toxicology Letters

Volume 158, Issue 3, 15 September 2005, Pages 225-236
Toxicology Letters

Topical exposure to carbon disulfide induces epidermal permeability alterations in physiological and pathological changes

https://doi.org/10.1016/j.toxlet.2005.03.017Get rights and content

Abstract

Carbon disulfide (CS2) has been suggested its possible skin toxicity. Neither a dose-response relationship nor any mechanism of CS2-exposure regarding epidermal permeability alterations has been postulated. The objectives of this study were to evaluate the dose-dependent association and the pathological changes with CS2 topically applied to mouse epidermis. Four concentrations of CS2 (0% (controls), 10%, 15%, and 20% in ethanol) were topically applied to a 1.8 cm2 area of the lateral abdomen of female nude mice for 10 min. Time-series transepidermal water loss (TEWL) profile, morphological examinations by both light microscopy (hematoxylin/eosin stain and Nile Red stain) and electronic microscopy, and lipid analysis by high performance thin-layer chromatography (HPTLC) were used to evaluate the epidermal impairment. We found no recovery occurred within 72 h exposure to 20% CS2 in contrast to substantial recovery found in 10% and 15% CS2-exposure. Clear dose-dependent fashions were shown in TEWL elevations, recovery retardation, and lipid extraction across the ethanol (control), 10%, 15%, and 20% CS2 exposures. Two mechanistic pathways were raised to account for CS2-induced epidermal alterations: intercellular lipid depletion and keratinocyte damage. A study with different test animal species is warranted owing to the discrepancies in epidermis between nude mice and other species.

Introduction

Numerous environmental stresses and industrial toxicants such as UV radiation and organic solvents have documented to pose skin toxicity (Tsai et al., 2001, Kanikkannan et al., 2002, Heck et al., 2004, Monteiro-Riviere et al., 2004). Carbon disulfide (CS2) has widely been used as a solvent in industries and has raised great public attention owing to its easy re-contamination in the general environment from the primary pollution sources. In western countries, CS2 has been one major concern for the American population because it has been identified in more than 200 of the 1430 current or former USEPA National Priorities List (NPL) hazardous waste sites since 1996 (ATSDR, 1996a). In Asia, CS2 has been in the list of the detectable chemicals in the effluent from wastewater treatment plants in Tokyo, Japan (Hwang et al., 1995). CS2 has exerted great toxicity in neurological, cardiovascular, reproductive, and hepatic systems (Beauchamp et al., 1983, Graham et al., 1995, Luo et al., 2003). Despite speculation for more than three decades that CS2 might be a strong skin toxicant because of its high lipophilicity and reactivity (Pirila et al., 1971), there is little data about its dermatological toxicity. Our recent study revealed that skin contact with CS2 among occupationally exposed workers could result in hand dermatitis, and that the toxicity could be aggravated by simultaneous co-exposure to sulfuric acid. An alarmingly high prevalence (61.5%) of irritant hand dermatitis has been observed in those exposed to CS2 in the rayon manufacturing process (Chou et al., 2004a). Another study carried out in the occupational settings also demonstrated the chronic and repeated exposure to rayon manufacturing chemicals containing saturated CS2 aqueous solution can pose significant elevation of basal transepidermal water loss (TEWL) (Chou et al., 2004b). There is a need to explore the underlying mechanism behind skin impairment after topical application of CS2, and to establish the dose-response relationship between CS2 and skin damage.

TEWL has been extensively used to evaluate the skin barrier impairment resulting from contact with solvents, tape-stripping, and pathological conditions (Grubauer et al., 1989a; Aalto-Korte and Turpeinen, 1993, Gfesser et al., 1997). It is generally believed that the change of basal TEWL is a sensitive indicator for evaluating skin disease (Seidenari and Giusti, 1995), and that the dynamics of barrier recovery after impairment can provide an in-depth understanding of the functional difference of skin barriers that depart from basal conditions (Denda et al., 2003). Morphological examination by light and electron microscopy can obtain the information of pathological and ultrastructure changes on skin after contact with irritants (Fartasch, 1997, Ahn et al., 2001). Barrier disruption and recovery, however, are reportedly associated with the removal and synthesis of lipids enriched within stratum corneum interstices (Elias and Feingold, 1992). Nude mice model has been extensively documented in percutaneous absorption studies (van den Akker et al., 2000, Sheu et al., 2002, Venter et al., 2001, Tsai et al., 2002). In the present study, nude mice were topically exposed at various levels of CS2 to determine the dose-response relationship, to measure TEWL immediately after topical exposure to evaluate the change of barrier function (Aalto-Korte and Turpeinen, 1993), and to measure the time-series changes of TEWL within 72 h to determine barrier recovery rates (Taljebini et al., 1996). The exposed skin was further examined by light and electron microscopy and CS2-extracted lipids were further analyzed to investigate the possible components responsible for skin impairment and recovery.

Section snippets

Experiments in topical exposure to CS2 and TEWL determination

CS2 and ethanol (HPLC grade) were obtained from Tedia Company Inc. (Fairfield, OH, USA). Female nude mice (BALB/c-nu, 8–12 w/o; Taiwan National Animal Laboratory Center, Taipei) were topically exposed to 1 mL of four levels of CS2/ethanol solutions (0/100, 10/90, 15/85, and 20/80, % in v/v) on a 1.8 cm2 area of the lateral abdomen epidermis for 10 min (n = 3 for each experiment). The exposure concentrations were designed based on findings in previous pioneer experiments: a plateau of TEWL over 50 g m−2 h

Effects of CS2-exposure on TEWL

The TEWL differences between post- and pre-exposure were 3.5 ± 1.1, 9.8 ± 0.9, 14.5 ± 1.6, and 38.3 ± 4.0 g m−2 h−1 (mean ± S.E.M.) for ethanol, 10%, 15%, and 20% CS2-exposed, respectively (Table 1). Although there were no significant pre-exposure differences in TEWL between four groups (P = 0.10), all post-exposure TEWL measurements showed significant elevation from their pre-exposure ones (P < 0.05), suggesting that both ethanol and CS2 are epidermal permeability barrier disruptors. In addition, clear linear

Discussion

CS2, used worldwide in a great number of industries, is strongly toxic to the neurological, cardiovascular, reproductive, and hepatic systems (Stetkiewicz and Wronska-Nofer, 1998, Luo et al., 2003). Our previous studies have demonstrated CS2 could be a potent skin toxicant by the findings of an alarmingly high prevalence (61.5%) of irritant hand dermatitis and significant elevation of basal TEWL observed in those who chronically and repeatedly exposed to CS2 in the rayon manufacturing process (

Acknowledgements

This study was financially supported by grant NSC-92-2320-B-285A-001 from the National Science Council, Taiwan. We thank Ms. Shu-Miao Chen, Ms. Li-Ching Shen, Mr. Ming-Kai Lin, and Ms. Yu-Jung Cheng for their technical assistance.

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