Topical exposure to carbon disulfide induces epidermal permeability alterations in physiological and pathological changes
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.
References (45)
- et al.
Beta2-adrenergic receptor antagonist accelerates skin barrier recovery and reduces epidermal hyperplasia induced by barrier disruption
J. Invest. Dermatol.
(2003) - et al.
Transepidermal water loss: the signal for recovery of barrier structure and function
J. Lipid. Res.
(1989) - et al.
Lipid content and lipid type as determinants of the epidermal permeability barrier
J. Lipid. Res.
(1989) - et al.
Solar ultraviolet radiation as a trigger of cell signal transduction
Toxicol. Appl. Pharmacol.
(2004) - et al.
Identification and quantification of sulfur and nitrogen containing odorous compounds in wastewater
Water. Res.
(1995) - et al.
Percutaneous absorption and skin irritation of JP-8 (jet fuel)
Toxicology
(2001) - et al.
Effect of jet fuels on the skin morphology and irritation in hairless rats
Toxicology
(2002) - et al.
Lamellar body secretory response to barrier disruption
J. Invest. Dermatol.
(1992) - et al.
Skin toxicity of jet fuels: ultrastructural studies and the effects of substance P
Toxicol. Appl. Pharmacol.
(2004) - et al.
The biochemistry and function of stratum corneum lipids
Adv. Lipid. Res.
(1991)