Science in the box

The four main exposure routes for detergents interacting with the human body are via skin contact, inhalation, ingestion and contact with the eyes.
For most consumer products or materials, there are three major routes of exposure, i.e., ways in which a material can interact with the human body: the material can be ingested, it can be inhaled, or it can come into contact with the skin. A fourth relevant route of exposure is through the mucosa, and for household laundry and cleaning products, that practically means only contact with the eyes. Not all of these exposure routes are relevant to all exposure situations. For example, most cleaning products come into contact with skin in a variety of ways during the normal use of the product. Household cleaning products are not intended for use in the eyes. If a person is exposed by this route, it is usually the result of an accident with the product (most frequently it is a single, not repeated event). Other exposure routes such as intravenous, intramuscular, or intradermal, are not relevant for consumer products other than drugs.

Cleaning products can come in contact with skin either through the hands during product use, or via wearing laundered clothes. P&G scientists have developed quantitative exposure assessments for scenarios for both skin contact situations.

Contact with the skin is by far the most common route of exposure for cleaning products. Almost every use of any cleaning product involves direct contact between the skin on the hands and the product itself or a solution of the product. For some types of products, such as laundry products and fabric softeners, additional exposure scenarios are also important, for example, exposure to the skin on other body sites that come into contact with residues of the product on laundered clothing. Quantitative exposure assessments can be developed for all possible exposure scenarios.
Two examples are given below:

• the potential exposure to hands during the use of a laundry detergent for hand laundry, and
• the potential exposure to product residue resulting from wearing clothing laundered with a fabric softener.

Example 1: The potential exposure to hands during the use of a laundry detergent for hand laundry.

There are two considerations for this type of exposure:


• the amount of the material in question on a given area of skin, and
• the systemic dose.

The amount of material in contact with a given area of skin is important when the toxic endpoints under consideration are skin irritation or contact sensitization (skin allergy) (Robinson, et al., 2000). The systemic dose, or the amount of material actually absorbed through the skin that could be available to have effects on the entire individual, is important when the toxic endpoints under consideration are from either a single, large exposure (acute dermal toxicity), or longer term exposures to lower amounts (subchronic dermal toxicity). For the following sample calculation, we have assumed that the material of interest is present at a level of 10% in the product formulation.
The mathematical equations that describe the exposure(s)
a) The amount of material on a given area of skin (mg/cm²)= C x F1 x L
Skin exposure = 1-10 mg / cm³ * 10% * 0,0024 cm = 0,00024 - 0,0024 mg/cm²
b) Systemic dose from this exposure (mg/kg/day) = (H x D x R) / W
Systemic dose = (960 cm² * 0,024 h / day * 0,00015 mg / cm² / hr) / 73 kg = 0,000047 mg / kg / day

Example 2: The potential exposure to product residue resulting from wearing clothing laundered with a fabric softener.
As with the previous example, there are two considerations for this type of exposure: a) the amount of the material in question on a given area of skin, and b) the systemic dose. The amount of material is contact with a given area of skin is important when the toxic endpoints under consideration are skin irritation or contact sensitization (skin allergy) (Robinson, et al., 2000). The systemic dose, or the amount of material actually absorbed through the skin that could be available to have effects on the entire individual, is important when the toxic endpoints under consideration are from either a single, large exposure (acute dermal toxicity), or longer term exposures to lower amounts (subchronic dermal toxicity).
The mathematical equations that describe the exposure(s)
a) The amount of material on a given area of skin (mg/cm²)= S x F2
Skin exposure = 0,05 mg / cm² * 2,8% = 0,0014 mg / cm²
b) Systemic dose from this exposure (mg/kg/day) = (S x F2 x F3 x B) / W

References:

• Robinson, M. K., G. F. Gerberick, C. A. Ryan, P. McNamee, I. R. White, and D. A. Basketter. 2000. The importance of exposure estimation in the assessment of skin sensitization risk. Contact Dermatitis 42:251-259.
• Exposure Factors Sourcebook for European Populations, with Focus on UK Data. May, 2000. Prepared by: ExxonMobil Biomedical Sciences, Inc.
• Exposure Factors Handbook, Volume I, General Factors. August, 1997. Office of Research and Development, United States Environmental Protection Agency.
Some factors that influence the uptake of materials by the skin
How the product mixes with water
Specific permeability of the skin on the particular body site
A number of references are available that discuss skin penetration of various materials. Two reference studies are:

• Cohen, D. E. and R. H. Rice. 2001. Toxic responses of the skin, in Casarett and Doull's Toxicology: The Basic Science of Poisons, ed. C. D. Klaassen, McGraw-Hill, New York. pp. 653-672.
• Dugard, P. H. 1987. Skin permeability theory in relation to measurements of percutaneous absorption in toxicology, in Dermatotoxicology, 3rd edition, eds. F. N. Marzulli and H. I. Maibach. pp. 95-120.

Cleaning products may become airborne and small particles can be inhaled by consumers during product use. P&G scientists have studied how respirable particles behave and under what scenarios people may be exposed.

Inhalation from normal product use
When a consumer dispenses product during use, some of this product can become airborne, and may be inhaled by the consumer in small quantities. A complete exposure assessment must consider this possible source of exposure for the potential to cause local or systemic toxic effects (respiratory tract irritation, acute inhalation toxicity and subchronic inhalation toxicity). This example considers the potential inhalation exposure to an ingredient in a laundry powder as that product is poured into the washing machine.
For the following sample calculation, we have assumed that the material of interest is present at a level of 10% in the product formulation, and when respired is 100% bioavailable (completely absorbed or available to induce irritation).
The mathematical equations that describe the exposure(s)
Inhalation exposure (µg/use) = (M x N x F1 x V x D) / W
Inhalation exposure (µg/use) = (4,14 µg / L / use * 0,2% * 10% *16,7 L/min * 2 min) / 73 kg = 0,00038 µg / kg / use

References:

• Hendricks, M. H. 1970. Measurement of enzyme laundry product dust levels and characteristics in consumer use. J Amer Oil Chemists Soc 47:207-11.
• Exposure Factors Sourcebook for European Populations, with Focus on UK Data. May, 2000. Prepared by: ExxonMobil Biomedical Sciences, Inc.
• Exposure Factors Handbook, Volume I, General Factors. August, 1997. Office of Research and Development, United States Environmental Protection Agency.

More about respirable particles
Only airborne particles or droplets below a certain size can be inhaled. If the particles are too big, they can't remain suspended in the air and, therefore, they are not available to breathe in. The precise spot where a particle will deposit in the lungs depends on the size of the particle. Particle size is expressed as the mean aerodynamic diameter, and is expressed in micrometers (1 millionth part of a meter). Generally, particles will deposit as displayed graphically: Localized, potential toxic effects (irritation) can occur at any place along the respiratory tract. Systemic effects (acute inhalation toxicity and subchronic inhalation toxicity) are more of a concern for particles that reach the lower respiratory tract since these particles are internalized as part of the clearance mechanism.
This discussion has focused primarily on the most common deposition type for small granular particles, namely impaction. Other respirable materials with different physiochemical properties may deposit in the lung through their preferential deposition mechanism, including sedimentation, interception, or diffusion. A number of reports are available that discuss evaluating potential toxicity to the respiratory tract, such as the 3 listed references.

• Hendricks, M. H. 1970. Measurement of enzyme laundry product dust levels and characteristics in consumer use. J Amer Oil Chemists Soc 47:207-11.
• Exposure Factors Sourcebook for European Populations, with Focus on UK Data. May, 2000. Prepared by: ExxonMobil Biomedical Sciences, Inc.
• Exposure Factors Handbook, Volume I, General Factors. August, 1997. Office of Research and Development, United States Environmental Protection Agency.

It is important to know the exposure levels of any thin residue of dishwashing product that may remain on dishware after the final rinse and whether this could have any short or long-term health effects.
Dishwashing products are designed to rinse clean, not leaving a residue behind that could be felt or tasted. However, a very small amount of dishwashing product residue can remain on the surfaces of dishware after washing the dishes. This residue may be absorbed into foods and beverages, and subsequently ingested in small amounts by the consumer. Once ingested, it is important to know the exposure amount, to assess the possibility that a material could have a short or long-term health effect.
Example
A typical automatic dishwasher cycle is composed of two wash cycles, each followed by a rinse, with an additional final rinse. Once the entire cycle is over, the final rinse water contains a very diluted amount of the dishwashing product that can remain on the surface of the dishware after the water is evaporated in the drying cycle.
The mathematical equations that describe the exposure(s) Oral exposure from residue on dishware (g/kg/day) = (C x F1 x F4 x J x U) / W
Solving this equation for a liquid product:
Oral exposure from residue on dishware = (105 g * 10% * 0,39% * 0,0023 g/cm² * 5400 cm²/day) / 58 kg = 0,0088 g/kg/day

We will assume for this example that the bioavailability (absorbable percentage) of the material (F1) is 100%.
Oral exposure from accidental ingestion (mg/kg/day) = (I x F1) / W
Oral exposure = (5 ml * 100 mg/ml) / 13,6 kg = 36,8 mg/kg

References:

• Exposure Factors Sourcebook for European Populations, with Focus on UK Data. May, 2000. Prepared by: ExxonMobil Biomedical Sciences, Inc.
• Exposure Factors Handbook, Volume I, General Factors. August, 1997. Office of Research and Development, United States Environmental Protection Agency

Example:
Assume a material is present in a wide range of down-the-drain consumer products. Because of the high volume of this material in the marketplace, residual quantities could potentially be found in drinking water. Drinking water levels are monitored and determined to be in the lower ppb range in some drinking water supplies (e.g. 10 ppb).

The human eye can accommodate about 0.0075 ml (7.5 µl) of material. (Chrai, et al. 1973) This amount is assumed for all accidental eye exposures.

References:

• Chrai, S. S., A. M. Patton and J. R. Robinson. 1973. Lacrimal and instilled fluid dynamics in rabbit eyes. J Pharm Sci 62:1112-1121.