ESCP
Empire State Consumer Project, Inc.
Protecting children, consumers, and the environment since 1971.
July 12, 2019
Ms. Mary K. Engle, Associate Director
Division of Advertising Practices
U.S. Federal Trade Commission
[email protected] (7 pages)
Petition to Disallow the Use of Terms ‘Natural’ and ‘Works Naturally’ in Polyethylene Glycol 3350 Product Advertising
Empire State Consumer Project, Inc. (ESCP) is a registered 501c3 not-for-profit organization dedicated to reducing the use of unsafe products and chemicals toxic to human and environmental health. We accomplish this by educating consumers and industry, conducting product testing and reporting, and by advocating for regulation where needed to protect the public interest.
We are petitioning the Federal Trade Commission (FTC) to disallow the use of the terms ‘natural’ and ‘works naturally’ in polyethylene glycol 3350 (PEG 3350) advertising. We are asking the Commission to take the following action to protect the health and safety of consumers as soon as possible.
A. Action Requested
Disallow use of the terms ‘natural’ and ‘works naturally’ to describe product ingredients and actions in polyethylene glycol 3350 laxative product advertising as false and misleading.
B. Statement of Grounds
‘Natural’ Advertising Claim
According to a survey by Consumer Reports, 62% of shoppers said they usually buy foods labeled ‘natural,’ but nearly two thirds believe the label means more than it does and nearly half incorrectly believe that natural claims on labels have been independently verified.
https://www.consumerreports.org/food-safety/peeling-back-the-natural-food-label/
Although the FDA has not engaged in rulemaking to establish a formal definition of the term ‘natural’ in food labeling, it has a longstanding policy concerning use of the word ‘natural’ in human food labeling. The FDA has considered the term ‘natural’ to mean that nothing artificial or synthetic has been included in or added to a food that would not normally be expected to be in that food.
https://www.fda.gov/food/food-labeling-nutrition/use-term-natural-food-labeling
A recent class action suit was decided in favor of consumers with a $1,250,000 settlement against Utz and Bachman brand foods for using “All Natural” in their labeling of products that contain artificial ingredients.
http://www.utzsettlement.com/index.html
No such guidance exists for the use of the terms ‘natural’ or ‘works naturally’ in drug product labeling or advertising. Bayer, maker of the world’s best-selling laxative, Miralax, advertises that the product “unblocks your system naturally.”
https://www.ispot.tv/ad/Iqqv/miralax-hydrates-and-softens
https://www.ispot.tv/ad/wDIx/miralax-switch-laxatives
https://www.ispot.tv/ad/AgZc/miralax-unblock-naturally
https://www.youtube.com/watch?v=JcgPZTZPDNs
https://www.miralax.com/
https://www.miralax.com/faqs
This commercial recommends Miralax to “Restore your body’s natural rhythm.”
https://www.ispot.tv/ad/7VkH/miralax-constipation-relief
PEG 3350 is Synthetic
Miralax, like other polyethylene glycol laxatives, is made of 100% polyethylene glycol 3350 (PEG 3350), a polymer derived from petroleum. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+5159.
PEG is not found in the human body, is not found in any food required by humans, and cannot be considered a natural substance by any scientific or consumer definition. Polyethylene glycol is a synthetic substance made from a chain of ethylene oxide (EO) molecules through a manufacturing process and may break down into ethylene glycol (EG) and/or diethylene glycol (DEG) in the body. EG and DEG are key ingredients in antifreeze, and are toxic to humans. Potential for PEG 3350 to break down into EG and/or DEG is being studied by the U.S. Food and Drug Administration (FDA) as a result of our 2012 FDA petition regarding PEG 3350 safety in children.
https://www.regulations.gov/searchResults?rpp=25&po=0&s=fda-2012-p-0566&fp=true&ns=true
The FDA Adverse Event Reporting System (FAERS) shows 31,252 adult and child adverse event reports related to at least one PEG 3350 product, including 117 deaths. The number of reports rose from 2,257 in 2012, when our FDA Citizen petition was filed.
Pharmaceutical manufacturers market products in a way that convinces consumers to believe that drugs act in targeted ways to produce particular outcomes (not only newer drugs used in targeted gene therapy). The term ‘side effect’ is used to describe any unwanted effect a drug has, as though the drug knows its intended action and also carries incidental actions that cannot be avoided. In this case, Miralax is marketed as an osmotic laxative that is purposefully designed to pull water into the intestines to produce a bowel movement. In fact, the pulling of water from the body is an action that many synthetic chemicals share – they cause a bowel movement or diarrhea because the body is attempting to rid the body of them. Describing the body’s natural response to ingesting a petroleum product as the product working ‘naturally’ is both false and misleading advertising.
PEG 3350 and Children
Due to the serious safety concerns raised in our FDA Citizen Petition, in 2013, the FDA agreed to study the effects of polyethylene glycol 3350 laxative use in children and issued a grant to the Children's Hospital of Philadelphia (CHOP) to conduct the study.
ESCP submitted the petition in 2012 on behalf of parents who say their children have been harmed by polyethylene glycol 3350 drug products. The Parents Against Miralax Facebook group, now over 33,000 members is a group of parents sharing the same shocking stories of neuropsychiatric and other adverse events acknowledged by the FDA in 2009. In a split decision, the FDA felt that “no action was required” at that time:
“The Drug Safety Oversight Board discussed reports of metabolic acidosis, metabolic acidosis with increased anion gap, and neuropsychiatric adverse events in children using polyethylene glycol (PEG) products. Metabolic acidosis is a disturbance in the body's acid-base balance and causes too much acid in the blood. In some situations, metabolic acidosis can be a mild, chronic condition; however, it may lead to shock or death in severe cases. Neuropsychiatric adverse events may include seizures, tremors, tics, headache, anxiety, lethargy, sedation, aggression, rages, obsessive-compulsive behaviors including repetitive chewing and sucking, paranoia and mood swings.” “It is unknown if prolonged duration in solution would change the chemical properties of PEG-3350, and what the actual content of ethylene glycol or diethylene glycol or other low molecular weight PEG would be under such conditions.”
https://docs.google.com/document/d/1bZ5SuSYQ4OqpE6MPycg9bWckyf2xxHNe-12qtqeukcQ/edit
Miralax and other PEG laxatives are not approved for use in children, and are not approved for more than seven days use in adults for occasional constipation. Many children are prescribed multiple daily adult doses by doctors off-label, often for months or years at a time, some beginning in infancy. The medical community is convincing parents that PEG is safe for children while Miralax television ads describe the product as working ‘naturally’ with no adult warnings or warnings against use in children. Large bottles of Miralax have a fold-out label with age warnings on the innermost panel that is not opened until after purchase. Off-label prescribing to children has become normalized, so that even doctors do not question the possible effects on children, despite the urgent claims of parents.
Although PEG 3350 laxatives have been studied for their effectiveness in producing a bowel movement, no study has ever been conducted on neuropsychiatric effects in children and no study has ever been done on the long term use of these products in children. The study being conducted in response to our petition is limited in scope and does not include research into the effects of PEG 3350 on the gut microbiome or nutrient absorption and depletion, which may be likely contributors to neuropsychiatric events in children.
This FDA document, updated in 2016 shows that the FDA acknowledged years ago that Miralax causes seizures (45th page): http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203595Orig1s000OtherR.pdf
Doctors at the National Taiwan University Hospital in Taipei have concluded “that bowel preparation with PEG lavage solution may be associated with severe renal complications, and that physicians should be aware of possible adverse effects when administering the agent.” http://www.ntuh.gov.tw/pmr/lists/list14/attachments/164/10253009-200903-37-1-45-50-a.pdf
Researchers at Copenhagen University Hospital in Denmark have concluded that Immediate-type Hypersensitivity Reactions (HSRs) do occur with PEG use, and that doctors have no knowledge of PEG and do not suspect it as a cause of hypersensitivity reactions.
https://documentcloud.adobe.com/link/track?uri=urn%3Aaaid%3Ascds%3AUS%3Ad9b8bccb-71f2-4370-9c9f-60dfab5a728d
Our FDA petition calls for an investigation into the effects of PEG 3350 on children and a boxed warning on PEG 3350 products. The boxed warning was not granted, but the FDA decided to update the labeling of prescription PEG 3350 bowel preparations with more stringent warnings and precautions for patients with certain health conditions. Our request for a Drug Safety Communication issued to doctors was denied, pending the results of the study, which, according to the FDA, has been delayed due to technical difficulties in producing the blood tests. Meanwhile, the effects of chronic PEG 3350 use on the microbiome and nutrition in children are not being studied.
At our request, in 2016, the same researcher(s) from the Research Institute at National Children’s Hospital in Columbus, Ohio working on the child study at CHOP agreed to conduct a study of the effects of PEG 3350 on the behavior and gut biology of mice. Results are due to be published this year.
Impurities/Breakdown
The PEG 3350 safety concerns acknowledged by the FDA include symptoms similar to those of ethylene glycol toxicity. Empire State Consumer Project’s FDA Citizen Petition grant includes an agreement by the FDA to study the potential for PEG 3350 to degrade into ethylene glycol (EG) and diethylene glycol (DEG), and to study the long term effects of PEG 3350 products on pediatric patients. Ethylene glycol and diethylene glycol are synthetic chemicals used to make antifreeze. Both are toxic to the central nervous system, liver, and kidneys when ingested. In recent history, DEG contaminated cough and acetaminophen syrups killed hundreds of adults and children. In 2007, the FDA issued a warning for consumers not to buy toothpaste from China, as some brands were made with DEG.
In addition to the ethylene glycol and diethylene glycol children may be exposed to through the degradation of PEG 3350, the FDA has tested 8 lots of polyethylene glycol 3350 and found ethylene glycol and diethylene glycol contaminants in the product itself… “To better understand the level of polyethylene glycol impurities in PEG, the FDA Chemistry and Manufacturing group evaluated PEG 3350. This analysis of eight lots of PEG 3350 confirmed the presence of small amounts of ethylene glycol and diethylene glycol in all lots tested. Based upon the recommended daily adult dose of 17g daily dose PEG 3350, the maximum daily exposure of ethylene glycol would be 0.005 mg/kg/day for a 60 kg patient, or 0.015 mg/kg/day for a 20 kg pediatric patient (approx 5 years of age). Other low molecular weight (LMW) PEGs were not included in this analysis. However, it is not known if any of these LMW species are absorbed and if so to what extent. Understanding the human absorption profile of LMW species is the first step needed in trying to understand the possible contribution of PEG 3350 use to the development of adverse events in children using this product chronically.”
https://grants.nih.gov/grants/guide/rfa-files/RFA-FD-14-088.html
Although another FDA test did not show the presence of EG and DEG, we have asked the FDA to perform ongoing testing of PEG 3350 products to show whether EG and DEG are contaminants, as one test is not a comprehensive study, nor an assurance of safety. Our request was denied.
The US Environmental Protection Agency (EPA) recommends that children not be exposed to more than 20 mg/L or 20 parts per million (ppm) of ethylene glycol in drinking water per one day or 6 mg/L or 6 ppm per day over 10 days. The daily drinking water consumption for the 22 lb child is assumed to be 1 L/day.
https://www.atsdr.cdc.gov/csem/csem.asp?csem=12&po=7
https://www.epa.gov/sites/production/files/2018-03/documents/dwtable2018.pdf
The adult doses of PEG 3350 tested were found to contain 0.3 mg of ethylene glycol of daily exposure for a 44 lb. child. This exposure is in addition to any EG and DEG exposure that may be found to occur from PEG 3350 degradation of the laxative products. The health effects of long term exposure of children to PEG 3350 are not known, although risks from short term exposure to EG and DEG are well documented in humans.
Empire State Consumer Project has since petitioned the FDA to issue a Drug Safety Communication regarding the finding of ethylene glycol and diethylene glycol in all lots of PEG 3350 it tested, so that parents of study participants and all parents can be made aware of the potential for PEG 3350 to contain ethylene glycol and diethylene glycol. This petition for a Drug Safety Communication was denied.
PEG is also known to contain carcinogens ethylene oxide (EO) and 1,4-dioxane, among other toxic chemicals. Ethylene oxide also causes reproductive harm; 1,4-dioxane causes reproductive harm in animals. Ethylene oxide can harm the brain and nervous system. Studies show that breathing air containing elevate ethylene oxide levels over many years increases the risks of some types of cancers of the white blood cells (including Non-Hodgkin’s Lymphoma, myeloma, and lymphocytic leukemia), and breast cancer in females. Recently, ethylene oxide has been in the news as the EPA shut down the Sterigenics facility in Willowbrook, Illinois for the toxic levels of ethylene oxide emitted by the company causing an “imminent and substantial endangerment to the community.”
The U.S. Environmental Protection Agency (EPA) has established a 1 day health advisory of 4.0 mg/L (4 ppm) and a 10 day health advisory of .4 mg/L (.4 ppm) for 1,4-dioxane for a 22 lb. (10 kg) child and a lifetime health advisory of .2 mg/L (.2 ppm) in drinking water. The daily drinking water consumption for the 22 lb child is assumed to be 1 L/day.
https://www.atsdr.cdc.gov/phs/phs.asp?id=953&tid=199
https://www.epa.gov/sites/production/files/2014-03/documents/ffrro_factsheet_contaminant_14-dioxane_january2014_final.pdf
https://www.epa.gov/sites/production/files/2018-03/documents/dwtable2018.pdf
https://www.epa.gov/hazardous-air-pollutants-ethylene-oxide/fact-sheet-epa-taking-steps-address-emissions-ethylene-oxide
The federal government has not set overall limits on ingestion of ethylene oxide; the FDA has only set a limit in ground spices, 50 ppm.
https://www.atsdr.cdc.gov/phs/phs.asp?id=732&tid=133
At least one pharmaceutical grade PEG 3350 product properly carries the California Proposition 65 warning for containing EO and 1,4-dioxane. The product may contain up to 1 ppm of ethylene oxide and 10 ppm of 1,4-dioxane.
https://www.spectrumchemical.com/OA_HTML/SCI_DOCS/PO125_SD.pdf
The California Office of Environmental Health Hazard Assessment (OEHHA) has established Proposition 65 (Prop 65) thresholds for requiring the Prop 65 toxicity warning on products on products sold in California - No Significant Risk Levels (NSRLs) and Maximum Allowable Dose Levels (MADLs). These are adult levels, not levels allowed for children.
Chemical No Significant Risk Level Maximum Allowable Dose Level
Ethylene Glycol 8700 ug/day or 8.7 mg/day
(ingested)
Ethylene Oxide 2 ug/day or .002 mg/day 20 ug/day or .02 mg/day
1,4-Dioxane 30 ug/day or .03 mg/day
https://oehha.ca.gov/proposition-65/general-info/current-proposition-65-no-significant-risk-levels-nsrls-maximum
PEG 3350 is also known to contain degradation products acetaldehyde, formaldehyde, and formic acid.
https://patentimages.storage.googleapis.com/f4/a3/e9/9dda8bcafbd410/US20140080918A1.pdf
Child PEG 3350 Dosing
As stated in our petition, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) has created guidelines for off-label prescribing of PEG 3350 laxatives to children. These guidelines are not approved by the FDA. Parents report that many doctors are prescribing even higher doses. Children are often given multiple adult doses daily for months and years at a time beginning in infancy. Advertising Miralax as working ‘naturally’ only serves to commit parents to a regimen that has undergone no long term safety studies on the effects of PEG 3350 on the brains, nervous systems, kidneys, and microbiomes of children.
Based on NASPGHAN dosing, one gram of PEG 3350 per kg of body weight is 10 grams of PEG for a 22 lb. child, or more than half of the 17 gram adult dose.
http://journals.lww.com/jpgn/fulltext/2006/09000/evaluation_and_treatment_of_constipation_in.28.aspx
In an example of a constipation treatment recommendation from a large children’s hospital in the US, dosing is 3 times per day for 3 days during the cleanout phase and a duration of 6-12 months or more for the maintenance phase. In this case, a 10 year old child would receive 3 adult daily doses per day for 3 days, then 1-2 adult daily doses per day for up to a year or more. Again, much younger children are also routinely given adult doses of PEG 3350 daily for months and years at a time… “As soon as they complete the first cleanout, give polyethylene glycol once daily at the following dosages. Mix in juice or water, not milk. It needs to be taken daily for at least 6-12 months and often longer. You can increase the dose slightly if needed.
Children 18 months to 5 years old – Give 2 teaspoons, mixed in 4 to 6 ounces of fluid
Children 5 to 10 years old – Give 1 capful (17 gms) mixed in 6-8 ounces of fluid
10 years old and older – Give 1 to 2 capfuls mixed in 8 ounces of fluid”
Note that the FDA’s own website warns parents to read product labels and to follow the directions exactly, to look for those approved for the age of the child and warns against giving adult medications to children. It also warns parents never to guess the weight of the child or to guess about dosing from the adult dose instructions, which is what doctors on their own or following unproven NASPGHAN protocols are doing. Again, no study has ever been conducted on neuropsychiatric events in children. As we stressed in our first FDA petition and the FDA agrees here, children are not small adults and adult dosing cannot be converted for children.
https://www.fda.gov/drugs/drug-information-consumers/kids-arent-just-small-adults-medicines-children-and-care-every-child-deserves?fbclid=IwAR14-WSNeJzXgfXA-rb5tz4V6WadQa4bTH5SfDOXXbnmV3SlHELqA0On-3s
Conclusion
Drug advertising that falsely claims a product works ‘naturally’ is intended to make consumers feel the product is safe for the purpose of selling more product. In the case of PEG 3350 products, which are prescribed widely by pediatricians off-label for use by children, parents are being seduced into believing, against scientific evidence (or lack thereof) that these products are safe even for children and are shocked to find that they are being prescribed by doctors off-label.
The effectiveness of a polyethylene glycol laxative is measured by the number of stools produced or the ‘cleanliness’ of the bowel after use. All the while, the unnatural work of the chemical and its component chemicals circulating through the bodies of children over a prolonged duration, including their effects on the brain, nervous system, kidneys, and microbiome have not been tested. The over 33,000 members of the parent group, Parents Against Miralax offer a convincing body of knowledge about their children’s health and wellbeing. While most parents and doctors do not file FDA Adverse Event Reports, these tens of thousands of unreported adverse events added to the number on file in the FDA FAERS system rate pediatric PEG 3350 use and adverse events as a nationwide children’s healthcare crisis.
Empire State Consumer Project asks the FTC to disallow the use of the terms ‘natural’ and ‘works naturally’ in PEG 3350 product advertising, to prevent consumers being misled as to the safety of these products and their potential for harm to children while we wait for answers that will help the medical community understand the mechanisms by which harm may occur.
C. Environmental Impact
Some studies have shown PEG 3350 carcinogenic changes and teratogenicity (ability to cause birth defects) in animals. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+5159
Ethylene glycol, ethylene oxide, and 1,4-dioxane have additional environmental effects.
https://toxnet.nlm.nih.gov/
D. Economic Impact
Based on one source, the global laxative market was valued at almost $5.3 billion in 2017 and is expected to reach over $8.7 billion by 2026. Off-label prescribing to children represents a large segment of this market. PEG laxative manufacturers have much to gain by marketing their products as ‘natural’ and working ‘naturally.’
https://www.globenewswire.com/news-release/2018/03/19/1441968/0/en/Global-Laxatives-Market-is-Expected-to-Reach-US-8-734-2-Million-By-2026-Credence-Research.html
Sincerely,
Carol Chittenden, Director
Empire State Consumer Project
[email protected]
Empire State Consumer Project, Inc. (ESCP) is a registered 501c3 Not-for-Profit Organization dedicated to reducing the use of unsafe products and chemicals toxic to human and environmental health. We accomplish this by educating consumers and industry, conducting product testing and reporting, and by advocating for regulation where needed to protect the public interest. ESCP is represented by Joel Kupferman, Esq., NY Environmental Law & Justice Project, [email protected].
www.empirestateconsumerproject.blogspot.com
FTC response to our petition:
https://documentcloud.adobe.com/link/track?uri=urn:aaid:scds:US:768d363b-5cec-426d-b48b-9b70c78565a0#pageNum=1
Empire State Consumer Project, Inc.
Protecting children, consumers, and the environment since 1971.
July 12, 2019
Ms. Mary K. Engle, Associate Director
Division of Advertising Practices
U.S. Federal Trade Commission
[email protected] (7 pages)
Petition to Disallow the Use of Terms ‘Natural’ and ‘Works Naturally’ in Polyethylene Glycol 3350 Product Advertising
Empire State Consumer Project, Inc. (ESCP) is a registered 501c3 not-for-profit organization dedicated to reducing the use of unsafe products and chemicals toxic to human and environmental health. We accomplish this by educating consumers and industry, conducting product testing and reporting, and by advocating for regulation where needed to protect the public interest.
We are petitioning the Federal Trade Commission (FTC) to disallow the use of the terms ‘natural’ and ‘works naturally’ in polyethylene glycol 3350 (PEG 3350) advertising. We are asking the Commission to take the following action to protect the health and safety of consumers as soon as possible.
A. Action Requested
Disallow use of the terms ‘natural’ and ‘works naturally’ to describe product ingredients and actions in polyethylene glycol 3350 laxative product advertising as false and misleading.
B. Statement of Grounds
‘Natural’ Advertising Claim
According to a survey by Consumer Reports, 62% of shoppers said they usually buy foods labeled ‘natural,’ but nearly two thirds believe the label means more than it does and nearly half incorrectly believe that natural claims on labels have been independently verified.
https://www.consumerreports.org/food-safety/peeling-back-the-natural-food-label/
Although the FDA has not engaged in rulemaking to establish a formal definition of the term ‘natural’ in food labeling, it has a longstanding policy concerning use of the word ‘natural’ in human food labeling. The FDA has considered the term ‘natural’ to mean that nothing artificial or synthetic has been included in or added to a food that would not normally be expected to be in that food.
https://www.fda.gov/food/food-labeling-nutrition/use-term-natural-food-labeling
A recent class action suit was decided in favor of consumers with a $1,250,000 settlement against Utz and Bachman brand foods for using “All Natural” in their labeling of products that contain artificial ingredients.
http://www.utzsettlement.com/index.html
No such guidance exists for the use of the terms ‘natural’ or ‘works naturally’ in drug product labeling or advertising. Bayer, maker of the world’s best-selling laxative, Miralax, advertises that the product “unblocks your system naturally.”
https://www.ispot.tv/ad/Iqqv/miralax-hydrates-and-softens
https://www.ispot.tv/ad/wDIx/miralax-switch-laxatives
https://www.ispot.tv/ad/AgZc/miralax-unblock-naturally
https://www.youtube.com/watch?v=JcgPZTZPDNs
https://www.miralax.com/
https://www.miralax.com/faqs
This commercial recommends Miralax to “Restore your body’s natural rhythm.”
https://www.ispot.tv/ad/7VkH/miralax-constipation-relief
PEG 3350 is Synthetic
Miralax, like other polyethylene glycol laxatives, is made of 100% polyethylene glycol 3350 (PEG 3350), a polymer derived from petroleum. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+5159.
PEG is not found in the human body, is not found in any food required by humans, and cannot be considered a natural substance by any scientific or consumer definition. Polyethylene glycol is a synthetic substance made from a chain of ethylene oxide (EO) molecules through a manufacturing process and may break down into ethylene glycol (EG) and/or diethylene glycol (DEG) in the body. EG and DEG are key ingredients in antifreeze, and are toxic to humans. Potential for PEG 3350 to break down into EG and/or DEG is being studied by the U.S. Food and Drug Administration (FDA) as a result of our 2012 FDA petition regarding PEG 3350 safety in children.
https://www.regulations.gov/searchResults?rpp=25&po=0&s=fda-2012-p-0566&fp=true&ns=true
The FDA Adverse Event Reporting System (FAERS) shows 31,252 adult and child adverse event reports related to at least one PEG 3350 product, including 117 deaths. The number of reports rose from 2,257 in 2012, when our FDA Citizen petition was filed.
Pharmaceutical manufacturers market products in a way that convinces consumers to believe that drugs act in targeted ways to produce particular outcomes (not only newer drugs used in targeted gene therapy). The term ‘side effect’ is used to describe any unwanted effect a drug has, as though the drug knows its intended action and also carries incidental actions that cannot be avoided. In this case, Miralax is marketed as an osmotic laxative that is purposefully designed to pull water into the intestines to produce a bowel movement. In fact, the pulling of water from the body is an action that many synthetic chemicals share – they cause a bowel movement or diarrhea because the body is attempting to rid the body of them. Describing the body’s natural response to ingesting a petroleum product as the product working ‘naturally’ is both false and misleading advertising.
PEG 3350 and Children
Due to the serious safety concerns raised in our FDA Citizen Petition, in 2013, the FDA agreed to study the effects of polyethylene glycol 3350 laxative use in children and issued a grant to the Children's Hospital of Philadelphia (CHOP) to conduct the study.
ESCP submitted the petition in 2012 on behalf of parents who say their children have been harmed by polyethylene glycol 3350 drug products. The Parents Against Miralax Facebook group, now over 33,000 members is a group of parents sharing the same shocking stories of neuropsychiatric and other adverse events acknowledged by the FDA in 2009. In a split decision, the FDA felt that “no action was required” at that time:
“The Drug Safety Oversight Board discussed reports of metabolic acidosis, metabolic acidosis with increased anion gap, and neuropsychiatric adverse events in children using polyethylene glycol (PEG) products. Metabolic acidosis is a disturbance in the body's acid-base balance and causes too much acid in the blood. In some situations, metabolic acidosis can be a mild, chronic condition; however, it may lead to shock or death in severe cases. Neuropsychiatric adverse events may include seizures, tremors, tics, headache, anxiety, lethargy, sedation, aggression, rages, obsessive-compulsive behaviors including repetitive chewing and sucking, paranoia and mood swings.” “It is unknown if prolonged duration in solution would change the chemical properties of PEG-3350, and what the actual content of ethylene glycol or diethylene glycol or other low molecular weight PEG would be under such conditions.”
https://docs.google.com/document/d/1bZ5SuSYQ4OqpE6MPycg9bWckyf2xxHNe-12qtqeukcQ/edit
Miralax and other PEG laxatives are not approved for use in children, and are not approved for more than seven days use in adults for occasional constipation. Many children are prescribed multiple daily adult doses by doctors off-label, often for months or years at a time, some beginning in infancy. The medical community is convincing parents that PEG is safe for children while Miralax television ads describe the product as working ‘naturally’ with no adult warnings or warnings against use in children. Large bottles of Miralax have a fold-out label with age warnings on the innermost panel that is not opened until after purchase. Off-label prescribing to children has become normalized, so that even doctors do not question the possible effects on children, despite the urgent claims of parents.
Although PEG 3350 laxatives have been studied for their effectiveness in producing a bowel movement, no study has ever been conducted on neuropsychiatric effects in children and no study has ever been done on the long term use of these products in children. The study being conducted in response to our petition is limited in scope and does not include research into the effects of PEG 3350 on the gut microbiome or nutrient absorption and depletion, which may be likely contributors to neuropsychiatric events in children.
This FDA document, updated in 2016 shows that the FDA acknowledged years ago that Miralax causes seizures (45th page): http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203595Orig1s000OtherR.pdf
Doctors at the National Taiwan University Hospital in Taipei have concluded “that bowel preparation with PEG lavage solution may be associated with severe renal complications, and that physicians should be aware of possible adverse effects when administering the agent.” http://www.ntuh.gov.tw/pmr/lists/list14/attachments/164/10253009-200903-37-1-45-50-a.pdf
Researchers at Copenhagen University Hospital in Denmark have concluded that Immediate-type Hypersensitivity Reactions (HSRs) do occur with PEG use, and that doctors have no knowledge of PEG and do not suspect it as a cause of hypersensitivity reactions.
https://documentcloud.adobe.com/link/track?uri=urn%3Aaaid%3Ascds%3AUS%3Ad9b8bccb-71f2-4370-9c9f-60dfab5a728d
Our FDA petition calls for an investigation into the effects of PEG 3350 on children and a boxed warning on PEG 3350 products. The boxed warning was not granted, but the FDA decided to update the labeling of prescription PEG 3350 bowel preparations with more stringent warnings and precautions for patients with certain health conditions. Our request for a Drug Safety Communication issued to doctors was denied, pending the results of the study, which, according to the FDA, has been delayed due to technical difficulties in producing the blood tests. Meanwhile, the effects of chronic PEG 3350 use on the microbiome and nutrition in children are not being studied.
At our request, in 2016, the same researcher(s) from the Research Institute at National Children’s Hospital in Columbus, Ohio working on the child study at CHOP agreed to conduct a study of the effects of PEG 3350 on the behavior and gut biology of mice. Results are due to be published this year.
Impurities/Breakdown
The PEG 3350 safety concerns acknowledged by the FDA include symptoms similar to those of ethylene glycol toxicity. Empire State Consumer Project’s FDA Citizen Petition grant includes an agreement by the FDA to study the potential for PEG 3350 to degrade into ethylene glycol (EG) and diethylene glycol (DEG), and to study the long term effects of PEG 3350 products on pediatric patients. Ethylene glycol and diethylene glycol are synthetic chemicals used to make antifreeze. Both are toxic to the central nervous system, liver, and kidneys when ingested. In recent history, DEG contaminated cough and acetaminophen syrups killed hundreds of adults and children. In 2007, the FDA issued a warning for consumers not to buy toothpaste from China, as some brands were made with DEG.
In addition to the ethylene glycol and diethylene glycol children may be exposed to through the degradation of PEG 3350, the FDA has tested 8 lots of polyethylene glycol 3350 and found ethylene glycol and diethylene glycol contaminants in the product itself… “To better understand the level of polyethylene glycol impurities in PEG, the FDA Chemistry and Manufacturing group evaluated PEG 3350. This analysis of eight lots of PEG 3350 confirmed the presence of small amounts of ethylene glycol and diethylene glycol in all lots tested. Based upon the recommended daily adult dose of 17g daily dose PEG 3350, the maximum daily exposure of ethylene glycol would be 0.005 mg/kg/day for a 60 kg patient, or 0.015 mg/kg/day for a 20 kg pediatric patient (approx 5 years of age). Other low molecular weight (LMW) PEGs were not included in this analysis. However, it is not known if any of these LMW species are absorbed and if so to what extent. Understanding the human absorption profile of LMW species is the first step needed in trying to understand the possible contribution of PEG 3350 use to the development of adverse events in children using this product chronically.”
https://grants.nih.gov/grants/guide/rfa-files/RFA-FD-14-088.html
Although another FDA test did not show the presence of EG and DEG, we have asked the FDA to perform ongoing testing of PEG 3350 products to show whether EG and DEG are contaminants, as one test is not a comprehensive study, nor an assurance of safety. Our request was denied.
The US Environmental Protection Agency (EPA) recommends that children not be exposed to more than 20 mg/L or 20 parts per million (ppm) of ethylene glycol in drinking water per one day or 6 mg/L or 6 ppm per day over 10 days. The daily drinking water consumption for the 22 lb child is assumed to be 1 L/day.
https://www.atsdr.cdc.gov/csem/csem.asp?csem=12&po=7
https://www.epa.gov/sites/production/files/2018-03/documents/dwtable2018.pdf
The adult doses of PEG 3350 tested were found to contain 0.3 mg of ethylene glycol of daily exposure for a 44 lb. child. This exposure is in addition to any EG and DEG exposure that may be found to occur from PEG 3350 degradation of the laxative products. The health effects of long term exposure of children to PEG 3350 are not known, although risks from short term exposure to EG and DEG are well documented in humans.
Empire State Consumer Project has since petitioned the FDA to issue a Drug Safety Communication regarding the finding of ethylene glycol and diethylene glycol in all lots of PEG 3350 it tested, so that parents of study participants and all parents can be made aware of the potential for PEG 3350 to contain ethylene glycol and diethylene glycol. This petition for a Drug Safety Communication was denied.
PEG is also known to contain carcinogens ethylene oxide (EO) and 1,4-dioxane, among other toxic chemicals. Ethylene oxide also causes reproductive harm; 1,4-dioxane causes reproductive harm in animals. Ethylene oxide can harm the brain and nervous system. Studies show that breathing air containing elevate ethylene oxide levels over many years increases the risks of some types of cancers of the white blood cells (including Non-Hodgkin’s Lymphoma, myeloma, and lymphocytic leukemia), and breast cancer in females. Recently, ethylene oxide has been in the news as the EPA shut down the Sterigenics facility in Willowbrook, Illinois for the toxic levels of ethylene oxide emitted by the company causing an “imminent and substantial endangerment to the community.”
The U.S. Environmental Protection Agency (EPA) has established a 1 day health advisory of 4.0 mg/L (4 ppm) and a 10 day health advisory of .4 mg/L (.4 ppm) for 1,4-dioxane for a 22 lb. (10 kg) child and a lifetime health advisory of .2 mg/L (.2 ppm) in drinking water. The daily drinking water consumption for the 22 lb child is assumed to be 1 L/day.
https://www.atsdr.cdc.gov/phs/phs.asp?id=953&tid=199
https://www.epa.gov/sites/production/files/2014-03/documents/ffrro_factsheet_contaminant_14-dioxane_january2014_final.pdf
https://www.epa.gov/sites/production/files/2018-03/documents/dwtable2018.pdf
https://www.epa.gov/hazardous-air-pollutants-ethylene-oxide/fact-sheet-epa-taking-steps-address-emissions-ethylene-oxide
The federal government has not set overall limits on ingestion of ethylene oxide; the FDA has only set a limit in ground spices, 50 ppm.
https://www.atsdr.cdc.gov/phs/phs.asp?id=732&tid=133
At least one pharmaceutical grade PEG 3350 product properly carries the California Proposition 65 warning for containing EO and 1,4-dioxane. The product may contain up to 1 ppm of ethylene oxide and 10 ppm of 1,4-dioxane.
https://www.spectrumchemical.com/OA_HTML/SCI_DOCS/PO125_SD.pdf
The California Office of Environmental Health Hazard Assessment (OEHHA) has established Proposition 65 (Prop 65) thresholds for requiring the Prop 65 toxicity warning on products on products sold in California - No Significant Risk Levels (NSRLs) and Maximum Allowable Dose Levels (MADLs). These are adult levels, not levels allowed for children.
Chemical No Significant Risk Level Maximum Allowable Dose Level
Ethylene Glycol 8700 ug/day or 8.7 mg/day
(ingested)
Ethylene Oxide 2 ug/day or .002 mg/day 20 ug/day or .02 mg/day
1,4-Dioxane 30 ug/day or .03 mg/day
https://oehha.ca.gov/proposition-65/general-info/current-proposition-65-no-significant-risk-levels-nsrls-maximum
PEG 3350 is also known to contain degradation products acetaldehyde, formaldehyde, and formic acid.
https://patentimages.storage.googleapis.com/f4/a3/e9/9dda8bcafbd410/US20140080918A1.pdf
Child PEG 3350 Dosing
As stated in our petition, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) has created guidelines for off-label prescribing of PEG 3350 laxatives to children. These guidelines are not approved by the FDA. Parents report that many doctors are prescribing even higher doses. Children are often given multiple adult doses daily for months and years at a time beginning in infancy. Advertising Miralax as working ‘naturally’ only serves to commit parents to a regimen that has undergone no long term safety studies on the effects of PEG 3350 on the brains, nervous systems, kidneys, and microbiomes of children.
Based on NASPGHAN dosing, one gram of PEG 3350 per kg of body weight is 10 grams of PEG for a 22 lb. child, or more than half of the 17 gram adult dose.
http://journals.lww.com/jpgn/fulltext/2006/09000/evaluation_and_treatment_of_constipation_in.28.aspx
In an example of a constipation treatment recommendation from a large children’s hospital in the US, dosing is 3 times per day for 3 days during the cleanout phase and a duration of 6-12 months or more for the maintenance phase. In this case, a 10 year old child would receive 3 adult daily doses per day for 3 days, then 1-2 adult daily doses per day for up to a year or more. Again, much younger children are also routinely given adult doses of PEG 3350 daily for months and years at a time… “As soon as they complete the first cleanout, give polyethylene glycol once daily at the following dosages. Mix in juice or water, not milk. It needs to be taken daily for at least 6-12 months and often longer. You can increase the dose slightly if needed.
Children 18 months to 5 years old – Give 2 teaspoons, mixed in 4 to 6 ounces of fluid
Children 5 to 10 years old – Give 1 capful (17 gms) mixed in 6-8 ounces of fluid
10 years old and older – Give 1 to 2 capfuls mixed in 8 ounces of fluid”
Note that the FDA’s own website warns parents to read product labels and to follow the directions exactly, to look for those approved for the age of the child and warns against giving adult medications to children. It also warns parents never to guess the weight of the child or to guess about dosing from the adult dose instructions, which is what doctors on their own or following unproven NASPGHAN protocols are doing. Again, no study has ever been conducted on neuropsychiatric events in children. As we stressed in our first FDA petition and the FDA agrees here, children are not small adults and adult dosing cannot be converted for children.
https://www.fda.gov/drugs/drug-information-consumers/kids-arent-just-small-adults-medicines-children-and-care-every-child-deserves?fbclid=IwAR14-WSNeJzXgfXA-rb5tz4V6WadQa4bTH5SfDOXXbnmV3SlHELqA0On-3s
Conclusion
Drug advertising that falsely claims a product works ‘naturally’ is intended to make consumers feel the product is safe for the purpose of selling more product. In the case of PEG 3350 products, which are prescribed widely by pediatricians off-label for use by children, parents are being seduced into believing, against scientific evidence (or lack thereof) that these products are safe even for children and are shocked to find that they are being prescribed by doctors off-label.
The effectiveness of a polyethylene glycol laxative is measured by the number of stools produced or the ‘cleanliness’ of the bowel after use. All the while, the unnatural work of the chemical and its component chemicals circulating through the bodies of children over a prolonged duration, including their effects on the brain, nervous system, kidneys, and microbiome have not been tested. The over 33,000 members of the parent group, Parents Against Miralax offer a convincing body of knowledge about their children’s health and wellbeing. While most parents and doctors do not file FDA Adverse Event Reports, these tens of thousands of unreported adverse events added to the number on file in the FDA FAERS system rate pediatric PEG 3350 use and adverse events as a nationwide children’s healthcare crisis.
Empire State Consumer Project asks the FTC to disallow the use of the terms ‘natural’ and ‘works naturally’ in PEG 3350 product advertising, to prevent consumers being misled as to the safety of these products and their potential for harm to children while we wait for answers that will help the medical community understand the mechanisms by which harm may occur.
C. Environmental Impact
Some studies have shown PEG 3350 carcinogenic changes and teratogenicity (ability to cause birth defects) in animals. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+5159
Ethylene glycol, ethylene oxide, and 1,4-dioxane have additional environmental effects.
https://toxnet.nlm.nih.gov/
D. Economic Impact
Based on one source, the global laxative market was valued at almost $5.3 billion in 2017 and is expected to reach over $8.7 billion by 2026. Off-label prescribing to children represents a large segment of this market. PEG laxative manufacturers have much to gain by marketing their products as ‘natural’ and working ‘naturally.’
https://www.globenewswire.com/news-release/2018/03/19/1441968/0/en/Global-Laxatives-Market-is-Expected-to-Reach-US-8-734-2-Million-By-2026-Credence-Research.html
Sincerely,
Carol Chittenden, Director
Empire State Consumer Project
[email protected]
Empire State Consumer Project, Inc. (ESCP) is a registered 501c3 Not-for-Profit Organization dedicated to reducing the use of unsafe products and chemicals toxic to human and environmental health. We accomplish this by educating consumers and industry, conducting product testing and reporting, and by advocating for regulation where needed to protect the public interest. ESCP is represented by Joel Kupferman, Esq., NY Environmental Law & Justice Project, [email protected].
www.empirestateconsumerproject.blogspot.com
FTC response to our petition:
https://documentcloud.adobe.com/link/track?uri=urn:aaid:scds:US:768d363b-5cec-426d-b48b-9b70c78565a0#pageNum=1