ARTICLE

Cough and Cold Medication Use by US Children, 1999 2006: Results From the Slone Survey
Louis Vernacchio, MD, MSc, Judith P. Kelly, MS, David W. Kaufman, ScD, Allen A. Mitchell, MD Slone Epidemiology Center, Boston University, Boston, Massachusetts
Financial Disclosure: The analyses presented in this article were funded internally by the Slone Epidemiology Center at Boston University; the center has received funding from McNeil Consumer Healthcare for other analyses related to the pediatric use of cough and cold medications.

Whats Known on This Subject

Pediatric OTC CCMs are readily available in the United States and are widely promoted for the treatment of childrens upper respiratory tract infections. Recent reports have linked these products to serious adverse effects and deaths among children.

What This Study Adds

This study documents the prevalence and patterns of use of CCMs among US children and provides a baseline against which to measure any changes in use that occur as a result of marketing or regulatory actions.

ABSTRACT
OBJECTIVE. Pediatric cough and cold medications are widely marketed in the United States, but the precise patterns of use among children are not known. Such information is especially important given recent reports suggesting that these medications are responsible for previously underappreciated serious adverse events and deaths among children. We sought to describe the prevalence and patterns of pediatric use of cough and cold medications, with particular attention to use among young children. METHODS. We analyzed data on the use of cough and cold medications, dened as any oral medication that contains 1 antitussive, decongestant, expectorant, and/or rst-generation antihistamine active ingredients, among 4267 US children who were younger than 18 years and enrolled during 1999 2006 in the Slone Survey, a national random-digit-dial telephone survey of medication use by the US population. RESULTS. In a given week, a cough and cold medication was used by 10.1% of US

www.pediatrics.org/cgi/doi/10.1542/ peds.2008-0498 doi:10.1542/peds.2008-0498

Key Words cough and cold medications, over-the-counter medications Abbreviations CCM cough and cold medication OTC over-the-counter FDAFood and Drug Administration CI condence interval
Accepted for publication Apr 16, 2008 Address correspondence to Louis Vernacchio,

children. Exposure was highest to decongestants (6.3%; mostly pseudoephedrine) MD, Slone Epidemiology Center at Boston University, 1010 Commonwealth Ave, Boston, and rst-generation antihistamines (6.3%; most common were chlorpheniramine, MA 02115. E-mail: lvernacchio@slone.bu.edu diphenhydramine, and brompheniramine), followed by antitussives (4.1%; mostly PEDIATRICS (ISSN Numbers: Print, 0031-4005; dextromethorphan) and expectorants (1.5%; almost exclusively guaifenesin). MulOnline, 1098-4275). Copyright 2008 by the tiple-ingredient products accounted for 64.2% of all cough and cold medications American Academy of Pediatrics used. Exposure to antitussives, decongestants, and rst-generation antihistamines was highest among 2- to 5-year-olds (7.0%, 9.9%, and 10.1%, respectively) followed by children who were younger than 2 years (5.9%, 9.4%, and 7.6%, respectively); expectorant use was low in all age groups. The use of cough and cold medications declined from 1999 through 2006.
CONCLUSIONS. Approximately 1 in 10 US children uses a cough and cold medication in a given week. The especially high prevalence of use among children of young age is noteworthy, given concerns about potential adverse effects and the lack of data on the efcacy of cough and cold medications in this age group. Pediatrics 2008;122:e323e329

EDIATRIC COUGH AND cold medications (CCMs), which typically include antitussives, decongestants, expectorants, and/or rst-generation antihistamines, are readily available over the counter (OTC) in the United States and are widely promoted for the treatment of childrens upper respiratory tract infections. Many of these medications are also approved for the treatment of allergic diseases and may be used for those conditions as well. Reports of adverse effects that are associated with these products (particularly inadvertent overdose) have increased in recent years, especially among very young children. For example, the Toxic Exposure Surveillance System documented nearly 90 000 calls and 3 accidental deaths associated with CCM among US children in 2004,1 and 7000 annual emergency department visits were attributed to CCM in a recent study.2 Among children who were younger than 2 years, the Centers for Disease Control and Prevention linked CCMs to 1500 emergency department visits in 2004 2005 and 3 additional deaths in 2005.3 The US Food and Drug Administration (FDA) recently enforced measures against unapproved marketing of the antihistamine carbinoxamine to young children because of reports of 21 deaths that were associated with use of this drug in children who were younger than 2 years.4 In a number of case series, CCM overdoses have been linked to neurologic impairment, cardiovascular instability, and death among young children.59 Concerns about these toxicities, especially in light of data that CCMs have not been proved effective in treating symptoms of cough and the common cold in young children,1016 led to the ling of a citizen petition with the FDA

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on March 1, 2007,17 which prompted an FDA review of the safety and efcacy of CCMs for children. In October 2007, the Consumer Healthcare Products Association announced a voluntary withdrawal of infant cough and cold preparations targeted to children who are younger than 2 years.18 In the meantime, the FDAs Nonprescription Drugs and Pediatric Advisory committees voted to ban OTC CCMs that are intended for children who are younger than 6 years,19 and the FDA is currently considering the committees advice. Although the potential for harm has been documented, understanding the risks of CCMs to children requires information on the prevalence and patterns of use of these medications. It is difcult, however, to identify usage patterns for what are primarily OTC products. Unlike prescription drugs, purchases of OTC medications are not captured in insurance and pharmacy claims data; in addition, data on patterns of exposure can be obtained only directly from patients or their parents. As a result, very few data exist on the prevalence and patterns of CCM use among children. One US study from 1994, relying on interview data from the Longitudinal Follow-up to the National Maternal and Infant Health Survey, found that approximately one third of 3-year-old children had used an OTC CCM within the previous 30 days,20 and a 2007 study from England based on mail survey data from the Avon Longitudinal Study of Parents and Children identied use of CCMs in the previous year by two thirds of children 3.0 to 4.5 years of age and by approximately half of children 5.5 to 7.5 years of age.21 A national telephone survey conducted in November 2007 reported that 56% of parents of children who were younger than 2 and 79% of parents of children who were aged 2 to 6 years had ever given their children a CCM, but no additional information on types of products or patterns of use was collected22; therefore, to characterize the current prevalence and patterns of use of CCMs by US children and to provide a baseline against which to measure any changes in use that occur as a result of marketing and regulatory actions, we analyzed data from the Slone Survey, a random-digit-dial telephone survey of medication use among the US population. METHODS Detailed methods of the Slone Survey have been published.23 Briey, this random-digit-dial telephone survey targeted households in the 48 contiguous states and the District of Columbia and was conducted continuously between February 1998 and April 2007. Once a household was successfully contacted, 1 individual from the household was randomly selected for interview and informed consent was obtained. All medication use (including prescription and OTC products, vitamins/minerals, and herbals/supplements) by the selected individual within the past week was ascertained by structured interview. Medications were linked to their active ingredients through the Slone Epidemiology Centers Drug Dictionary.24 Details of use were obtained, including drug form (eg, tablet, liquid), duration and frequency of
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use, and reason for use. For children who were younger than 14 years, a parent/guardian was interviewed; for children who were 14 to 17 years of age, either the child or a parent/guardian was interviewed (82.2% of interviews in this age range were completed by a parent/ guardian). The study was approved by the Boston University Medical Campus Institutional Review Board. This analysis used data derived from all individuals who were younger than 18 years for the complete years 1999 2006. We included in the analysis all oral medications, both OTC and prescription, that contained 1 antitussive, decongestant, expectorant, or rst-generation antihistamine active ingredients (we excluded rstgeneration antihistamines such as dimenhydrinate and cyproheptadine that do not carry an indication for the common cold). Response rates were calculated according to the American Association for Public Opinion Research RR3 denition.25 Estimates of the weekly prevalences of use were weighted by household size to adjust for the probability of selection. Prevalence comparisons were performed by 2 analysis. SAS 9.1 (SAS Institute, Cary, NC) was used for all analyses. RESULTS The response rate to the survey during the period 1999 2006 was 61.9%, and 4267 individuals who were aged 0 to 17 years were enrolled. The median age was 9 years (25th, 75th percentiles: 4, 13), and 48.9% were female (both similar to the 2000 US census26). In terms of race/ ethnicity, 65.2% were white non-Hispanic (69.1%, census); 14.3% were Hispanic (12.5%, census); 11.7% were black non-Hispanic (12.1%, census); 1.9% were Asian non-Hispanic (3.6%, census); and 7.0% were of other, mixed, or unknown race/ethnicity (2.7%, census). According to US census regions, 19.4% were from the Northeast (18.0%, census), 25.9% from the South (35.4%, census), 25.0% from the Midwest (23.1%, census), and 29.8% from the West (23.5%, census). Of the 4267 children surveyed, 439 had used a CCM in the previous week, for a weighted prevalence of use of 10.1% (95% condence interval [CI]: 9.211.0). The 1-week prevalences of exposure to specic CCM active ingredients are shown in Table 1; 4.1% of individuals were exposed to antitussives (primarily dextromethorphan), 6.3% to decongestants (primarily pseudoephedrine), 1.5% to expectorants (nearly all guaifenesin), and 6.3% to a variety of rst-generation antihistamines. A summary of the 489 products used by the 439 study subjects is shown in Table 2. Among those products, 175 (35.8%) were single-ingredient products, the most common of which were rst-generation antihistamines (19.4% of all products) and decongestants (7.2%). A total of 314 (64.2%) products contained multiple active ingredients; those most commonly used were decongestant/ rst-generation antihistamine combinations (15.5%) and antitussive/decongestant/rst-generation antihistamine combinations (10.4%). Of note, 100 (20.4%) of the CCM products also contained an analgesic (acetaminophen, in all but 7). We asked the reason for the use of each medication, but many responses were not clearly

TABLE 1 One-Week Prevalence of Exposure to Any CCM, Categories of Active Ingredients, and Specic Active Ingredients Among 4267 US Children: 1999 2006
Parameter Any CCMb Antitussives Dextromethorphan Codeine Hydrocodone Carbetapentane Decongestants Pseudoephedrine Phenylpropanolamine Phenylephrine Expectorants Guaifenesin Guaiacolsulfate First-generation antihistamines Chlorpheniramine Diphenhydramine Brompheniramine Doxylamine Carbinoxamine Pyrilamine Promethazine Hydroxyzine Phenyltoxamine Triprolidine Pheniramine Dexbrompheniramine Phenindamine
a Weighted b Dened

n 439 174 161 8 4 1 278 214 53 21 68 67 1 271 99 83 50 14 10 9 8 5 4 3 2 1 1

Weighted Prevalence, % (95% CI)a 10.1 (9.211.0) 4.1 (3.54.7) 3.8 (3.24.4) 0.2 (0.10.4) 0.1 (0.00.2) 0.0 (0.00.1) 6.3 (5.67.1) 4.9 (4.25.6) 1.1 (0.81.4) 0.5 (0.30.7) 1.5 (1.11.9) 1.5 (1.11.8) 0.0 (0.00.1) 6.3 (5.57.0) 2.2 (1.82.6) 2.0 (1.52.4) 1.1 (0.81.5) 0.4 (0.20.6) 0.3 (0.10.4) 0.2 (0.10.3) 0.2 (0.00.3) 0.1 (0.00.2) 0.1 (0.00.2) 0.1 (0.00.1) 0.1 (0.00.1) 0.0 (0.00.1) 0.0 (0.00.1)

for household size as an oral medication that contains 1 antitussive, decongestant, expectorant, or rst-generation antihistamine active ingredients.

related to cough, cold, or allergy (eg, sleep, pain) or were difcult to classify specically (eg, runny nose, congestion, sinus). For the 489 products used, the stated reason for use was cough in 116 (23.7%); cold in 106 (21.7%); allergy in 96 (19.6%); and not related to cough, cold, or allergy or unclear in 171 (35.0%). The forms of the products used stratied by age are shown in Fig 1. Among children who were younger than 2 years, 94.6% were liquid preparations, a frequency that decreased with age to 23.3% among adolescents. The 1-week prevalences of use of specic active ingredients stratied by age are shown in Fig 2. Exposure to antitussives, decongestants, and rst-generation antihistamines was highest among 2- to 5-year-olds (7.0%, 9.9%, and 10.1%, respectively) followed by children who were younger than 2 years (5.9%, 9.4%, and 7.6%, respectively). Expectorant use was relatively low in all age groups. Among all ages combined, the 1-week prevalence of use of any CCM declined signicantly throughout the course of the study, from a high of 12.3% in 1999 2000 to a low of 8.4% in 20052006 (P .003 for trend; Fig 3). The prevalence of exposure to antitussive and expectorant active ingredients did not change signicantly over time (P .3 and P .2 for trend, respectively). In contrast, decongestant use declined from 7.2% in 1999 2000 to 5.1% in 20052006 (P .03 for trend), with a steep decline in phenylpropanolamine use, from 2.8% in 1999 2000 to 0.3% in 20052006 (P .0001 for trend). In addition, rst-generation antihistamine use declined from 8.5% in 1999 2000 to 5.3% in 20052006 (P .002 for trend). The use of antihistamines did not vary signicantly according to season, but antitussives, de-

TABLE 2 List of 489 Cough and Cold Product Types Used by 439 Study Subjects
Product Type n (%) of All Products 95 (19.4) 76 (15.5) 51 (10.4) 36 (7.4) 35 (7.2) 28 (5.7) 24 (4.9) 23 (4.7) 22 (4.5) 20 (4.1) 18 (3.7) 17 (3.5) 9 (1.8) 8 (1.6) 8 (1.6) 7 (1.4) 4 (0.8) 4 (0.8) 2 (0.4) 1 (0.2) 1 (0.2) Reason for Usea Cough 4 15 21 10 1 22 2 10 11 0 7 1 2 5 0 2 2 0 0 0 1 Cold 3 25 14 13 8 2 7 6 6 1 8 4 6 0 0 0 2 0 1 0 0 Allergy 52 15 3 0 3 1 1 0 0 17 0 3 0 0 0 0 0 0 0 1 0 Other 36 21 13 13 23 3 14 7 5 2 3 9 1 3 8 5 0 4 1 0 0

First-generation antihistamine Decongestant rst-generation antihistamine Antitussive decongestant rst-generation antihistamine Antitussive decongestant rst-generation antihistamine analgesic Decongestant Antitussive expectorant Decongestant analgesic Antitussive Expectorant Decongestant second-generation antihistamineb Antitussive decongestant Decongestant rst-generation antihistamine analgesic Antitussive decongestant analgesic Antitussive decongestant expectorant First-generation antihistamine analgesic Decongestant expectorant Antitussive rst-generation antihistamine Antitussive analgesic Antitussive decongestant expectorant analgesic Antitussive decongestant expectorant rst-generation antihistamine Expectorant rst-generation antihistamine

a Reason for use was reported by the patient or parent; other includes responses that were not specically related to cough, cold, or allergy (eg, sleep, pain ), or were difcult to classify specically (eg, runny nose, congestion, sinus ). b Indicated for allergic diseases only, not common cold.

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100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%

2.7% 2.7%

0.7%

7.6%

0.7%

2.3%

Other/unknowna Tablet/capsule Liquid

33.8%

74.4%

94.6%

91.7%

65.4%

23.3%

<2 y

25 y

611 y

1217 y

FIGURE 1 Form of cough and cold products used by children, stratied according to age group.

congestants, and expectorants each were used less frequently in the summer and more frequently in the winter (data not shown). We examined the overall use of CCM stratied by the childs gender and race/ethnicity, parental education, household income, census region, and household size and found no appreciable differences (data not shown), except for a borderline higher prevalence of use among individuals from the South and Midwest compared with

the Northeast (odds ratio for South: 1.5 [95% CI: 1.1 2.0]; odds ratio for Midwest: 1.5 [95% CI: 1.12.0]). We also examined the duration of use of CCMs on at least 1 day per week among study subjects. As shown in Fig 4, the majority of CCM use was for 1 week. For antitussives and expectorants, 15% of use was for 1 to 4 weeks, with virtually no use lasting 4 weeks. In contrast, 22.9% of rst-generation antihistamine use was for 1 week (including 12.2% for 4 weeks), and

12% Under 2 years 10% 2-5 years 6-11 years 8% 12-17 years

6%

4%

2%

0% Antitussives Decongestants Expectorants First-generation antihistamines

FIGURE 2 Prevalence of exposure to antitussive, decongestant, expectorant, and rst-generation antihistamine active ingredients according to age group. Bars represent 95% CIs.

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14% 12% 10% 8%

FIGURE 3 Prevalence of exposure to any CCM and specic active ingredients according to 2-year intervals.

Any cough/cold medication Antitussives Decongestants Expectorants First-generation antihistamines

6% 4% 2% 0% 1999-2000 2001-2002 2003-2004 2005-2006

22.5% of decongestant use was for 1 week (including 10.4% for 4 weeks). Of the 56 individuals who used a CCM for 4 weeks, 22 used a rst-generation antihistamine alone, 14 used a decongestant plus a secondgeneration antihistamine, and 9 used a decongestant plus a rst-generation antihistamine; the majority took them on a daily basis. The reasons for using a CCM for 4 weeks included allergies in 37 (66.1%), sleep in 4 (7.1%), cough in 2 (3.6%), cold in 1 (1.8%), and other reasons in 12 (21.4%). Among those who took a CCM for 4 weeks, there were 11 children who were younger than 6 years. Four of them used a rst-generation antihistamine alone; 4 used a decongestant plus rst-gener-

ation antihistamine; and 1 each used a decongestant alone, a decongestant plus a second-generation antihistamine, and a rst-generation antihistamine plus an analgesic. DISCUSSION This study documents that CCMs are used widely by US children for the treatment of coughs, colds, allergies, and a variety of other reasons, with 1 in 10 children, or just over 7 million individuals, exposed to at least 1 CCM in a given week. Our estimate of the weekly prevalence of exposure is consistent with a monthly prevalence of approximately one third among 3-year-olds in the only other published US study to examine this issue.20 We found exposure to be particularly high among young children, raising a potential safety concern because nearly all published reports of CCM-associated serious adverse events and deaths have involved very young children.1,39 Although the high prevalence of use together with the relatively small number of reported serious adverse events may suggest that the absolute magnitude of risk associated with pediatric CCM use is small, the important clinical and public health question is whether any serious risk is justied by the benets of treatment. Despite widespread parental belief that pediatric CCMs are effective for treating coughs and colds,22 there are no data supporting the efcacy of CCMs for such uses in young children; the few available randomized, controlled trials have found no signicant benets in this age group.1016 In addition to lack of evidence of efcacy for cough and the common cold, CCM use in young children is fraught with the potential for dosing errors. First, because of the lack of clinical and pharmacologic studies of children, most pediatric dosages are extrapolated from adult data, and many CCMs lack formal dosing recommendations for young children.27,28 Second, concentrations and dosages for young children are not standardized across products, dosage delivery devices differ from product to product, and products with different ingrediPEDIATRICS Volume 122, Number 2, August 2008 e327

A
>4 wk, 1.1% 14 wk, 14.3%

B
>4 wk, 10.4% 14 wk, 12.1%

1 wk, 77.5% 1 wk, 84.6%

C
>4 wk, 1.5% 14 wk, 14.9%

D
>4 wk, 12.2% 14 wk, 10.8%

1 wk, 77.1% 1 wk, 83.6%

FIGURE 4 Duration of use on at least 1 day per week for antitussive (A), decongestant (B), expectorant (C), and rst-generation antihistamine (D) active ingredients.

ents can have similar names. Finally, as our data point out, well over half of pediatric CCM use involves multiple-ingredient products (with as many as 5 separate active ingredients), a situation that increases the risk for a child inadvertently receiving 1 product with the same active ingredient. The prevalence of use of any CCM among children declined somewhat over the years of the study, with the decline most notable for decongestants and rst-generation antihistamines. The decline in decongestant use seems largely attributable to the removal of phenylpropanolamine from the market in 2000 2001 because of its association with hemorrhagic stroke in adults.29 We speculate that pseudoephedrine use may likewise decline in the coming years as a result of the 2005 Combat Methamphetamine Act, which requires pseudoephedrine-containing products to be kept behind pharmacy counters.30 More broad, the prevalence and patterns of pediatric CCM use are likely to change substantially given the media attention being paid to the issue of CCM safety, the Consumer Healthcare Products Associations voluntary recall of CCMs that are marketed for children who are younger than 2 years,18 and any regulatory changes that the FDA may make in response to its advisory panels recommendations. It will be important to track secular trends in pediatric CCM use as these changes take effect. Not surprising, we found that the duration of use of CCMs varies substantially by components. Antitussives and expectorants are used almost exclusively for brief periods of time, whereas decongestants and rst-generation antihistamines are more commonly used for extended durations. Most long-term use is for allergic diseases, and the predominant products used long-term are antihistamines or decongestant-antihistamine combinations, which are indicated for allergies as well as the common cold. Still, we identied a small number of children, including a few who were younger than 6 years, who were given other combination CCMs regularly for extended periods of time, and the risks that are associated with such long-term exposure are unknown. Our data suggest that CCM use is not strongly associated with personal and demographic factors such as gender, race/ethnicity, region, parental education, household income, or household size. That use is so widespread among US children suggests that efforts focused on educating the public about safe use of CCMs should be broadly targeted. Our study has several potential imitations. First, there is the possibility of response bias. Although our response rate was relatively high for a random telephone survey and our distributions of age, gender, and race/ethnicity approximate the 2000 US census data, our sample somewhat underrepresents children from the South and overrepresents those from the West. We cannot determine whether CCM exposure among nonresponders or undersampled populations differs from that of survey participants. A second potential limitation is the accuracy of the drug exposure information collected in the survey. We relied on parent (or patient) reports of products used, but we made signicant efforts to ensure that
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such information was compete and accurate. Individuals were asked to gather all relevant bottles and packages and to read medication names directly from the label; these were matched in real time to drug codes from the Slone Epidemiology Center Drug Dictionary, an electronic compendium of prescription, OTC, vitamin, and herbal/supplement medications.24 Because only very recent use (within the previous 7 days) was elicited, the possibility of recall errors was reduced. In most cases, parents acted as reporters of their childrens medication use, which may have led to underreporting of use in adolescents who may have obtained and used CCMs independently. Finally, our survey was not designed to capture illicit drug use or intentional misuse. CONCLUSIONS This study demonstrates that CCM use is common among US children despite a lack of demonstrated efcacy for treatment of cough and the common cold. Of particular concern are high rates of exposure among young children, for whom dosing recommendations are largely extrapolated from adults and the risk for adverse events is greatest. Regulatory changes (which are currently under consideration by the FDA) as well as efforts aimed at educating parents and caregivers about the safe use of CCMs may be needed to reduce inappropriate exposure to these medications and thereby minimize risks to children. ACKNOWLEDGMENTS We greatly appreciate the contributions of Theresa Anderson, study coordinator; Marie Berarducci and Marilyn Wasti, study supervisors; Gene Sun, information systems; and the interviewing staff. REFERENCES
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and the Pediatric Advisory Committee October 18 19, 2007. Available at: www.fda.gov/ohrms/dockets/ac/07/minutes/20074323m1-Final.pdf. Accessed December 20, 2007 Kogan MD, Pappas G, Yu SM, Kotelchuck M. Over-thecounter medication use among US preschool-age children. JAMA. 1994;272(13):10251030 Headley J, Northstone K. Medication administered to children from 0 to 7.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC). Eur J Clin Pharmacol. 2007;63(2): 189 195 Childrens OTC cold medicines: the public, and parents, weigh in. Available at: www.kff.org/kaiserpolls/upload/7725.pdf. Accessed February 14, 2008 Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002; 287(3):337344 Kelley KE, Kelley TP, Kaufman DW, Mitchell AA. The Slone Drug Dictionary: a research driven pharmacoepidemiology tool [Abstract]. Pharmacoepidemiol Drug Saf. 2003;12(S1): S168 S169 American Association for Public Opinion Research. Standard Denitions: Final Disposition of Case Codes and Outcome Research Rates for Surveys. 3rd ed. Lenexa, KS: American Association for Public Opinion Research; 2004 Census 2000 Gateway. Available at: www.census.gov/main/ www/cen2000.html. Accessed November 30, 2007 Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use. Fed Regist. 2002; 67(246):78158 78172 Sharfstein JM, North M, Serwint JR. Over the counter but no longer under the radar: pediatric cough and cold medications. N Engl J Med. 2007;357(23):23212324 Meadows M. FDA issues public health advisory on phenylpropanolamine in drug products. FDA Consum. 2001;35(1):9 Retail sales of scheduled listed chemical products: selfcertication of regulated sellers of scheduled listed chemical products. Interim nal rule with request for comment. Fed Regist. 2006;71(186):56008 56027

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