Skin absorption, pesticides

For most chemicals, inhalation is the main route of entry into the body. However, certain chemicals (e.g. phenol, aniline, certain pesticides) can penetrate intact skin and so become absorbed into the body. This may occur through local contamination, e.g. from a liquid splash, or through exposure to high vapour concentrations. Special precautions to avoid skin contact are required with these chemicals and potential exposure via skin absorption has to be taken into account when assessing the adequacy of control measures. Chemicals able to penetrate intact skin are listed in Table 4.2. 

Colorless to white hygroscopic crystals that are odorless. Pesticide grade is often dyed blue. This material is hazardous through inhalation, skin absorption, penetration through broken skin, and ingestion, and produces local skin/eye impacts. 

The skin absorption of nicotine and subsequent adverse effects make it an effective pesticide. Nicotine poisoning occurs primarily by children coming into contact with nicotine insecticides or tobacco products. 

One of the most notorious cases of industrial disaster took place in 1984 in Bhopal, India. A plant with a license from the Union Carbide company was making methyl isocyanate (MIC), CH3NCO, which is an intermediate for the manufacture of pesticides. MIC boils at 39 °C, and the vapor density is heavier than air and very toxic by inhalation and skin absorption. The maximum allowable air concentration is 0.02 ppm by volume over 8 h. MIC also reacts with water and produces heat, which must be removed to prevent boiling over. On that day in 1984, the cooling system failed during... 

The answer is D. Organophosphates react with the active site serine residue of hydrolases such as acetylcholinesterase and form a stable phosphoester modification of that serine that inactivates the enzyme toward substrate. Inhibition of acetylcholinesterase causes overstimulation of the end organs regulated by those nerves. The symptoms manifested by this patient reflect such neurologic effects resulting from the inhalation or skin absorption of the pesticide diazinon. 

Dermal Exposure Of the three major routes of exposure, the dermal (skin) route constitutes nearly 90% of chemical exposure, particularly of pesticides. Dermal exposure is common whenever chemicals are mixed or handled. Certain types of dry materials, (e.g., pesticide dusts, wet or dry powders, granules, liquid pesticides) enter the body through quick skin absorption. Many factors influence the rate of dermal exposure of a chemical these may be as follows ... 

There is a wealth of literature showing significant differences in the acute toxicity values of chemicals (particularly pesticides) by oral and dermal routes of exposure. In a majority of instances, chemicals (particularly pesticides) are more toxic by ingestion than by skin absorption. However, it should be remembered that workers handling pesticides invariably can be affected through all three routes of exposure (oral, dermal, inhalation) and must exercise extreme caution (Table 2-9). 

OPs cause adverse effects in poisoned animals and humans, which are based on the dose and durabon of exposure. Examples of the effects include nausea, coma, convulsions, respiratory failure, and death. Workers in pesticide manufacturing industries and farming industries may contract OP poisoning via skin absorption. The inhibition of AChE results in accumulahon of ACh, causing the wide variety of Henry s symptoms. 

Herbicides, or weed killers, may be classified as pesticide chemicals. They can kill plants on contact, or they can be translocated (i.e absorbed by one part of the plant and carried to other parts where they exert their primary toxic effect). Most commonly used herbicides have a low toxicity and have caused few adverse effects in users. Some herbicides pose more serious problems to the central nervous system (CNS) and can cause depression. The skin absorption of herbicides also may cause skin irritation, dermatitis, and photosensitization in addition to peripheral motor neuropathies. 

It is commonly known that the skin contains a large range of enzymes capable of metabolizing topically applied compounds. Eor pesticides, esterase activity is among the most important (van de Sandt et al, 1993 Hewitt et al, 2000). Although the stratum comeum is generally accepted as the most important barrier in skin absorption, there are some indications that skin metabolism in other skin layers influences the percutaneous absorption of compounds (Potts etal, 1989). The interrelation between metabolism and absorption rate, however, has not been unequivocally established. 

Many of the formulations for plant protection are designed to help the active substance to penetrate the cuticle of plant leaves or insects. It is therefore not surprising that these formulations sometimes enhance the skin absorption in humans. To account for this in Europe, EC Directive 91/414 for pesticides requires testing of both the active substance and the formulated product (EEC, 1991). The United States Environmental Protection Agency (USEPA) requires that the vehicle system duplicates that used in the field (USEPA, 1998). Since many pesticides are... 

In addition to in vivo and in vitro experimentation, mathematical models and quantitative structure-permeability relationship (QSAR) methods have been used to predict skin absorption in humans. These models use the physico-chemical properties of the test compound (e.g. volatility, ionization, molecular weight, water/lipid partition, etc.) to predict skin absorption in humans (Moss et al 2002). The models are particularly attractive because of the low cost and rapidity. However, because of the above-mentioned factors influencing dermal absorption, mathematical models are of limited use for risk assessment purposes. Since these models are currently not accepted by regulatory agencies involved in pesticide evaluations, they will not be further discussed in this chapter. 

This chapter provides an overview of factors affecting dermal absorption. Factors influencing absorption are among others related to the skin (e.g. anatomical site, difference between species, metabolism, etc.) and the exposure conditions (e.g. area dose, vehicle, occlusion and exposure duration). In order to provide relevant information for the risk assessment of pesticides, dermal absorption studies should take these aspects into account. With respect to the methods being used nowadays for the assessment of dermal absorption, it is important to realize that neither in vitro nor in vivo animal studies have been formally validated. Available data from various in vitro studies, however, indicate that the use of the total absorbed dose (i.e. the amount of test substance in the receptor medium plus amount in the skin) could be used in a quantitative manner in risk assessment. Tape stripping of the skin can be adequate to give a good indication of test chemical distribution, and hence its immediate bioavailability. 

Hydrocyanic acid, HCN, is corrosive in addition to toxic. It is also a dangerous fire and explosion risk. It has a wide flammable range of 6 to 41% in air. The boiling point is 79 F, the flash point is 0°F, and the ignition temperature is 1004°F. It is toxic by inhalation, ingestion, and through skin absorption. The TLV of hydrocyanic acid is 10 ppm in air. It is used in the manufacture of acrylonitrile, acrylates, cyanide salts, dyes, rodenticides, and other pesticides. 

Extremely toxic carbamate pesticide routes of entry—ingestion, skin absorption, and inhalation of vapors although the vapor pressure is very low [0.00002 torr at 33°C (91.4°F)], because of high toxicity, even trace inhalation could be harmful can cause death if swallowed, absorbed through skin or inhaled ingestion of about 0.5- to 2-g... 

Highly toxic by ingestion and moderately toxic by inhalation and skin absorption cholinesterase inhibitor exhibits acute, delayed, and chronic toxicity toxic effects are those of organophosphorus pesticides and carbamate esters the symptoms include excessive salivation, lacrimation, blurred vision, headache, labored breathing, twitches of muscle, loss of reflexes, headache, weakness, sweating, nausea, giddiness, vomiting, cramps, diarrhea, convulsions, and coma U.S. EPA-listed extremely hazardous substance. 

Heptachlor (CAS 76-44-8) CNS convulsant. Skin absorption is rapid and has caused convuisions and death. Hepatotoxic. Stored in fatty tissues, Limited evidence fcr adverse effects on fetai deveiop-ment in test animais at high doses, A carcinogen in test animais. See aiso p 151, 0.05 mg/m S,A3 35 mg/m White or light tan, waxy solid with a camphor-like odor. Vapor pressure is 0.0003 mm Hg at 20 C (68°F). Thermal-breakdown products include hydrogen chloride. Not combustible. Pesticide use banned byEPAin 1988. 

Many of these are phosphate or thiophosphate esters. Some organophosphorus insecticides and other pesticide products are almost immediately toxic to humans, while others appear to be nontoxic, at least in the short and medium term. Specialised references need to be consulted. Best known of the extremely toxic varieties are Parathion and tetraethylpyrophosphate (TEPP), both of which can be rapidly fatal by inhalation, ingestion or skin absorption. Potential long-term hazards from residual traces of relatively non-toxic pesticides (or their breakdown products) are currently the subject of much investigation and concern. 

OECD, 2004c, Guidance Document for the Conduct of Skin Absorption Studies. Environment Directorate Joint Meeting of the Chemicals Committee and The Working Party on Chemicals, Pesticides and Biotechnology. OECD series on testing and assessment (nnmber 28). 

Skin is also important as an occupational exposure route. Lipid-soluble solvents often penetrate the skin, especially as a liquid. Not only solvents, but also many pesticides are, in fact, preferentially absorbed into the body through the skin. The ease of penetration depends on the molecular size of the compound, and the characteristics of the skin, in addition to the lipid solubility and polarity of the compounds. Absorption of chemicals is especially effective in such areas of the skin as the face and scrotum. Even though solid materials do not usually readily penetrate the skin, there are exceptions (e.g., benzo(Lt)pyrene and chlorophenols) to this rule. 

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