Using structure to screen consumer product chemicals for asthma hazard potential

Using structure to screen consumer product chemicals for asthma hazard potential

Fragranced Products Information Network, 12602 Reed Rock Road, Amelia, Virginia 23002

Asthma rates in the general population have soared over the past several decades. While many factors have been implicated, none fully explain the rise. Children and women typically spend more time indoors and have been especially impacted; suggesting exposures in the indoor environment may play a role. Consumer products such as cleaners, air fresheners, and other scented products are frequently cited as triggering or exacerbating asthma. It is known that some chemicals even at low exposures can cause asthma in occupational settings. There has been limited focus on the possibility that chemicals commonly found in consumer products may contribute to the rise in asthma. Chemical structure–activity relationships are used to screen chemicals to assess for potential to cause health effects. A model program has been developed that allows comparison of structures of chemicals to those known or suspected of causing asthma in occupational settings. It was developed by James Jarvis and is freely available from his web page at the University of Edinburgh. EPA listed consumer products chemicals that were produced or imported at levels of one million pounds annually in 1990, a selection of high volume chemicals that are used in soaps and detergents, and common fragrance chemicals were assessed using this model program.

Asthma rates started increasing significantly during the mid-1970s and have more than doubled.The costs of asthma are high in terms of health, quality of life and economics. There are likely to be multiple factors involved in the increasing rates including hereditary, lifestyles, and environment. Environmental factors such as outdoor air pollution and second hand smoke have been considered. Improvements in outdoor air quality and decreases in exposure to second hand smoke have not produced corresponding decreases in asthma rates. This suggests other environmental factors are involved as well.

Children, women, blacks, and Hispanics of Puerto Rican descent have higher rates of asthma. Data on human exposures to common consumer products were collected by the Environmental Protection Agency (EPA) sponsored National Activity Pattern Survey (NHAPS).¹ According to the report, in a survey of 4723 participants:

Fragrance industry data also supports certain demographic groups have higher exposure to some common consumer products such as fragrances²; these groups also have higher asthma rates. Women are traditionally higher users of consumer products used in the home. Both women and children tend to spend more time indoors where many consumer products are used.

Products used and consumed by the general public have not been closely examined to determine the potential to cause asthma. It is known that consumer products such as home furnishings, items used to clean and maintain environments, as well as personal care products and cosmetics emit volatile organic compounds which can impact air quality³. Poor air quality is known to make existing respiratory conditions worse. The potential for the chemicals used in consumer products to cause asthma has not been closely examined.

There are literally thousands of chemicals used in making consumer products. Testing for harmful effects in all of them is a daunting task both in terms of time and cost. A means of rapidly and cost effectively screening large numbers of chemicals for potential for harm is needed to prioritize for further testing. Examining chemical structure to screen for potentially harmful effects is a promising method of economically and rapidly assessing potential for harm and is already being used.⁴

By examining the chemical structures of materials known to have specific actions, such as causing skin allergy, similarities in the chemicals’ structures can be found.⁴ When these structures are found in another chemical, it provides an alert that this chemical may have similar action. These structural-alerts as they are called are used in screening chemicals for possible skin effects such as sensitization and allergy.

Screening chemicals for respiratory effects such as asthma has inherent problems. There is more than one mechanism for development of asthma. High level irritant exposure can cause a form of asthma known as Reactive Airway Disease or RADS. Respiratory allergies to pollen, animal dander, and other protein substances can cause asthma as well. The mechanisms involved in respiratory sensitization to chemicals such as isocyanates are not known. There has been no recognized test to determine the potential of chemicals to cause asthma.

A model program developed at the University of Edinburgh allows comparison of structures of chemicals to the structures of those known or suspected of causing asthma in occupational settings. It was developed by James Jarvis and is freely available from his web page ( http://homepages.ed.ac.uk/jjarvis/research/hazassess/hazassess.html ) at the University of Edinburgh. This model is described in detail in the article Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds by J Jarvis, M J Seed, R Elton, L Sawyer and R Agius published in Occupational and Environmental Medicine 2005;62:243-250. The full text article is available online ( http://oem.bmjjournals.com/cgi/content/full/62/4/243#F2 ). This model program was used to assess potential asthma hazard of selected chemicals.

The Environmental Protection Agency (EPA) gathers information on chemicals used in the United States. Chemicals that are produced or imported at levels of one million pounds or more annually are know as High Production Volume (HPV) Chemicals. The EPA has asked industry to provide basic toxicity data on these chemicals. Further some chemicals are designated as Consumer Product Chemicals (CPC) meaning they are commonly found in consumer products. Information on HPV chemicals including which industries have volunteered to provide toxicity data is available from various databases found at the EPA’s High Production Volume Challenge website (http://www.epa.gov/chemrtk/volchall.htm)⁵.

There were 492 High Production Volume Chemicals that are designated as CPC⁶ and 122 that were sponsored by the soap and detergent industry⁷. There was overlap of twenty chemicals between the groups yielding a total of 594 chemicals. These chemicals will be referred to as HPV Consumer Chemicals.

Fragrance is added to almost all consumer products and some of these products are used specifically for their scent. Because fragrance formulations are considered trade secrets and the individual fragrance ingredients are not listed in the ingredients on labels, it is much more difficult to assess exposures. A listing of 483 materials used in scented products is provided in a fragrance industry's plan for safety assessment of fragrance chemicals⁴ These materials are representative of the classes and subclasses of chemicals used to scent products. This list will be referred to as the fragrance chemical list. Though there was some overlap in the HPV list and the fragrance chemical lists, the two lists will be assessed separately

In order to utilize the model asthma hazard assessment program, the structures of the chemicals must be in mol file format. ChemINDEX, an online commercial database was used to obtain structures in mol format. The chemicals were found by searching the database using Chemical Abstract Service (CAS) numbers which are unique identifying numbers. Some chemicals were not found in the database or structures were not available for all chemicals that were found. The chemical data files were saved and downloaded.

The chemical data files were opened in Word. The mol files for the structure of each chemical was copied and pasted into the Asthma Hazard Assessment program. The files were submitted and the program assigned a numerical index and a hazard assessment of that index.

Asthma hazard assessments were obtained on a total of 439 chemicals from the HPV list and 367 from the fragrance chemicals list.

The Asthma Hazard Assessment Program assigns a numerical index from “0” to “1” and gives a range to indicate asthma potential of chemicals. The findings are summarized below in Table 1.

Hazard Index	HPV Consumer Chemicals	Fragrance Chemicals
0.0 < 0.1 - low hazard index	194	77
0.1 < 0.3 - borderline hazard index	75	136
0.3 < 0.5 - probably hazardous.	34	72
0.5 < 0.7 - very probably hazardous.	30	55
0.7 to 1 - undoubtedly hazardous.	106	27
TOTAL	439	367

Chemicals that are commonly encountered in non-occupational settings have structure similarities to those known to or are suspected of causing asthma in occupational settings.

Chemicals with higher indexes are more likely to play a role in asthma. Over 30% of the HPV Consumer Chemicals and over 20% of the fragrance chemicals assessed are rated as very probably hazardous or undoubtedly hazardous.

The general public frequently uses and encounters multiple products that contain materials which have structures similar to those that are known and suspected of causing asthma. In occupational settings, it has been found that even low levels of some sensitizers can cause asthma. It well established that levels of fragrance encountered in consumer products can cause skin sensitization. It has not been established that such exposure can cause asthma, though there are clinical and anecdotal accounts of respiratory sensitivity to specific fragrances at relatively low levels suggesting sensitivity to specific materials in the products.

Research suggests that skin sensitizers may very well have the potential to cause respiratory sensitization as well. There are numbers of known skin sensitizers in these listings of commonly encountered consumer chemicals. Further it is known that combinations of similar materials may enhance or increase allergenic skin effects. Consumer products are often complex mixtures of volatile compounds which cause significant respiratory exposure. Whether these combinations enhance respiratory effects has yet to be determined.

While only time and use will confirm the validity of this model, it supports concerns in regards to the potential of consumer products to contain potent respiratory sensitizers. Consumers are frequently exposed to chemicals and combinations of chemicals that based on structure, have potential to cause respiratory sensitivity. Further research is needed to determine the accuracy of this model, refine it, or develop other models to assess potential for respiratory sensitization from chemicals.

More research is needed into the respiratory effects of chemicals and combinations of chemicals used in consumer products. Consumer education is needed to emphasize the need for careful reading and following directions such as “use with adequate ventilation” and increase the awareness that using multiple products may significantly increase exposure to materials which have the potential to cause asthma.

(1) U. S. Environmental Protection Agency "Exposure Factor Handbook: Chapter 16: Consumer Products," Office of Research and Development

(4) Bickers, D. R.; Calow, P.; Greim, H. A.; Hanifin, J. M.; Rogers, A. E.; Saurat, J. H.; Glenn Sipes, I.; Smith, R. L.; Tagami, H. Regul Toxicol Pharmacol 2003, 37, 218-73.