In vitro metabolism of methiocarb and carbaryl in rats, and its effect on their estrogenic and antiandrogenic activities.

In this work, we examined the metabolism of the carbamate insecticides methiocarb and carbaryl by rat liver microsomes and plasma, and its effect on their endocrine-disrupting activities. Methiocarb and carbaryl were not enzymatically hydrolyzed by rat liver microsomes, but were hydrolyzed by rat plasma, mainly to methylthio-3,5-xylenol (MX) and 1-naphthol, respectively. When methiocarb was incubated with rat liver microsomes in the presence of NADPH, methiocarb sulfoxide was formed. The hydrolysis product, MX, was also oxidized to the sulfoxide, 3,5-dimethyl-4-(methylsulfinyl)phenol (SP), by rat liver microsomes in the presence of NADPH. These oxidase activities were catalyzed by cytochrome P450 and flavin-containing monooxygenase. Methiocarb and carbaryl both exhibited estrogen receptor α (ERα) and ERß agonistic activity. MX and 1-naphthol showed similar activities, but methiocarb sulfoxide and SP showed markedly decreased activities. On the other hand, methiocarb and carbaryl exhibited potent antiandrogenic activity in the concentration range of 1×10(-6)-3×10(-5) M. Their hydrolysis products, MX, and 1-naphthol also showed high activity, equivalent to that of flutamide. However, methiocarb sulfoxide and SP showed relatively low activity. Thus, hydrolysis of methiocarb and carbaryl and oxidation of methiocarb to the sulfoxide markedly modified the estrogenic and antiandrogenic activities of methiocarb and carbaryl.

Topical use of tea tree oil reduces the dermal absorption of benzoic acid and methiocarb.

Tea tree oil (TTO) is a complex mixture of terpene hydrocarbons. Intensive topical use of TTO in different cosmetics and investigations into its potential as an antimicrobial or anti-inflammatory agent has accentuated the need for studies on the toxicity of TTO. We have applied an experimental in vitro model using static diffusion cells with human skin to study penetration characteristics of terpinen-4-ol and the way TTO affects the barrier integrity of the skin and the percutaneous penetration of two chemicals covering a range of solubilities from 0.03 g/l (methiocarb) to 3.0 g/l (benzoic acid). Through GC-MS analysis we identified the major constituents of TTO. In our experimental set-up with full-thickness skin, only the least lipophilic ingredients of TTO penetrated the skin. Barrier integrity was evaluated through measurement of percutaneous penetration of tritiated water. Data indicate that 1% TTO does not affect barrier conditions. The Kp value for tritiated water was increased significantly at 5% TTO, which demonstrate that the barrier integrity is affected at this relatively low concentration of TTO. The barrier integrity is, however, not seriously damaged, but our data indicate an initiated and concentration-dependent effect on the barrier integrity. TTO changed the penetration characteristics for benzoic acid as well as for methiocarb. The general effect was that TTO reduced the maximal flux. For methiocarb, the lag-time was also prolonged by increasing the TTO concentration in the donor phase to 5%. Thus, TTO reduced the overall amount of benzoic acid as well as methiocarb entering the receptor chamber.

Percutaneous penetration through slightly damaged skin.

Guidelines for experimental studies of percutaneous penetration prescribe optimal barrier integrity of the skin. The barrier integrity of the skin exposed in occupational or household situations is, however, not always ideal, and skin problems are among the most dominant reasons for absence from work. We have therefore evaluated an experimental model for percutaneous penetration through slightly damaged skin. The influence of a slight damage to the skin was evaluated using five pesticides covering a wide range of solubilities. We used an experimental model with static diffusion cells mounted with human skin. A slight damage to the barrier integrity was induced by pre-treatment of the skin with sodium lauryl sulphate (SLS) before pesticide exposure. The experimental model with 3 h pre-treatment with SLS (0.1% or 0.3%) assured a significant but controlled damage to the barrier integrity, a damage that remained unchanged for an experimental period of 48 h. Based on the percutaneous penetration of five pesticides, we conclude that a slightly damaged skin may significantly affect the rate, lag-time as well as total penetration of chemicals covering a wide range of solubilities. The percutaneous penetration of the most hydrophilic compounds will be those most affected. These findings should be considered when setting standards for dermal exposure to chemicals.

Residues of methamidofos, malathion, and methiocarb in greenhouse crops.

The diminution of methamidofos, malathion, and methiocarb in different crops grown in greenhouses has been studied, including the presence of metabolites such as malaoxon, methiocarb sulfoxide, and methiocarb sulfone. The analytical method is based on dichloromethane extraction and GC-PFPD analysis. It has been validated establishing performance parameters such as recovery rates, precision, linear ranges, and limits of detection and quantification, which are low enough for ensuring that their corresponding MLRs can be adequately quantified. Samples of treated cucumbers and peppers grown in greenhouses were collected and analyzed during a 15-day period for obtaining the diminution rates of methamidofos and malathion. The behavior of methiocarb in treated green beans and tomatoes has been studied using analysis of variance (ANOVA) as the statistical tool, for establishing the influence of crop, season, application dose, and greenhouse design.

Dermal in vitro penetration of methiocarb, paclobutrazol, and pirimicarb: effect of nonylphenolethoxylate and protective gloves.

Dermal exposure has become the major route of human occupational exposure to pesticides. Detergents are used as part of formulated pesticide products and are known to change the barrier properties of human skin in vitro. However, studies on the influence of detergents as well as protective glove materials on dermal penetration of pesticides are scarce. In an experiment using in vitro static diffusion cells mounted with human skin, we evaluated the effect of nonylphenol-ethoxylate on dermal penetration of three extensively used pesticides--methiocarb, paclobutrazol, and pirimicarb--and the protection against dermal penetration offered by protective gloves made of latex or nitrile. There was a general tendency, though not statistically significant for all pesticides, for nonylphenolethoxylate to decrease the percutaneous penetration of the three pesticides. The nitrile generally offered better protection against percutaneous penetration of pesticides than did latex, but the degree of protection decreased over time and depended on the pesticides used.

Dermal in vitro penetration of methiocarb, paclobutrazol, and pirimicarb.

OBJECTIVES: The dominant route of occupational exposure to pesticides in horticulture is dermal. However, preventive measures are seldom used when handling plant cultures recently treated with pesticides, thus causing significant dermal exposure and potential absorption. Assessment of exposure often depends on biological monitoring of blood or urine samples. The skin often acts as a temporary reservoir for chemicals before absorption. Failure to consider the lag time between dermal exposure and appearance of pesticide or metabolites in the general circulation may lead to false conclusions about assessment of exposure. METHODS: In an experimental model in which in vitro static diffusion cells were mounted with human skin, dermal penetration of three extensively used pesticides (methiocarb, paclobutrazol, pirimicarb) was evaluated. RESULTS: Pirimicarb and paclobutrazol had comparable rates of dermal penetration and lag times of around 18 hours. Methiocarb had a considerably shorter lag time. Dermal penetration continued for extended periods after exposure had ended. CONCLUSIONS: With lag times sometimes considerably longer than a normal working day, biological monitoring at the end of exposure may seriously underestimate the actual exposure. There may be implications for regulatory guidelines, which often require only 24 hour observation periods.