From pfpc@istar.ca Tue Mar 21 12:02:12 2000 Date: Mon, 14 Feb 2000 23:50:29 -0800 From: PFPC To: brou@istar.ca Subject: PFPC: NEW RULE/POISON DATA According to this rule, green and black tea should be packaged in Child Resistant Packaging!!! (Also note posion data) The following excerpts are taken from Federal Register: June 2, 1998 (Volume 63, Number 105)] http://www.cpsc.gov/businfo/frnotices/fr98/fluoride.html ======================================================================= CONSUMER PRODUCT SAFETY COMMISSION 16 CFR Part 1700 Final Rule: Requirements for Child-Resistant Packaging; Household Products With More Than 50 mg of Elemental Fluoride and More Than 0.5 Percent Elemental Fluoride; and Modification of Exemption for Oral Prescription Drugs with Sodium Fluoride AGENCY: Consumer Product Safety Commission. ACTION: Final rule. ----------------------------------------------------------------------- SUMMARY: The Commission is issuing a rule to require child-resistant (``CR'') packaging for household products containing more than the equivalent of 50 mg of elemental fluoride and more than the equivalent of 0.5 percent elemental fluoride (on a weight-to-volume (``w/v'') or weight-to-weight (``w/w'') basis). For consistency, the Commission is also modifying the oral prescription drug exemption for sodium fluoride preparations. Instead of exempting drugs with no more than 264 mg of sodium fluoride per package as the current rule does, the Commission will exempt such drugs with either 50 mg or less of the equivalent of elemental fluoride (110 mg or less of sodium fluoride) per package or no more than the equivalent of 0.5 percent elemental fluoride on a w/v or w/w basis. The Commission determines that child-resistant packaging is necessary to protect children under 5 years of age from serious personal injury and serious illness resulting from handling or ingesting a toxic amount of elemental fluoride. The Commission takes this action under the authority of the Poison Prevention Packaging Act of 1970. DATES: The rule will become effective on March 2, 1999, and applies to products packaged on or after that date. SUPPLEMENTARY INFORMATION: A. Background 1. Household Products Containing Fluoride Fluorides are ingredients in such household products as cleaning solutions for metal, tile, brick, cement, wheels, radiators, siding, toilets, ovens and drains. Fluorides are also found in rust and water stain removers, silver solder and other welding fluxes, etching compounds, laundry sour, air conditioner coil cleaners and floor polishes. The fluorides that may be ingredients in these products and are potentially toxic are hydrofluoric acid (``HF''), ammonium bifluoride, ammonium fluoride, potassium bifluoride, sodium bifluoride, sodium fluoride and sodium fluosilicate. The Commission currently requires CR packaging for oral prescription drugs with fluoride, but it exempts those in liquid or tablet form that contain no more than 264 mg of sodium fluoride (equivalent to 120 mg fluoride) per package. The Commission based this exemption level on the lack of serious adverse human experience associated with such drugs at that time and a recommendation by the American Dental Association that no more than 264 mg of sodium fluoride should be dispensed at one time. As discussed below, the Commission is revising the exemption to a new level that is based on current information concerning the toxicity of fluoride and is consistent with the CR requirement for fluoride- containing household products. B. Toxicity of Fluoride Most available toxicity information on fluoride relates to acute toxicity of hydrofluoric acid (``HF''). However, other water soluble fluoride-containing compounds can cause fluoride poisoning. The fluoride ion is systemically absorbed almost immediately. It is highly penetrating and reactive and can cause both systemic poisoning and tissue destruction. Fluoride ions, once separated from either HF or fluoride salts, penetrate deep into tissues, causing burning at sites deeper than the original exposure site. The process of tissue destruction can continue for days.[2] Fluoride absorption can produce hyperkalemia (elevated serum potassium), hypocalcemia (lowered serum calcium), hypomagnesemia (lowered serum magnesium), and metabolic and respiratory acidosis. These disturbances can then bring on cardiac arrhythmia, respiratory stimulation followed by respiratory depression, muscle spasms, convulsions, central nervous system (``CNS'') depression, possible respiratory paralysis or cardiac failure, and death. Fluoride may also inhibit cellular respiration and glycolysis, alter membrane permeability and excitability, and cause neurotoxic and adverse GI effects.[2] When exposure is through inhalation, fluorides can cause severe chemical burns to the respiratory system. Inhalation can result in difficulty breathing (dyspnea), bronchospasms, chemical pneumonitis, pulmonary edema, airway obstruction, and tracheobronchitis. The severity of burns from dermal absorption can vary depending on the concentration of fluoride available, duration of the exposure, the surface area exposed, and the penetrability of the exposed tissue. Ocular exposure can result in serious eye injury.[2] Ingestion of fluoride can result in mild to severe GI symptoms. Reports suggest that ingesting 3 to 5 milligrams of fluoride per kilogram of body weight (mg/kg) causes vomiting, diarrhea, and abdominal pain. Ingestion of more than 5 mg/kg may produce systemic toxicity. A retrospective poison control center study of fluoride ingestions reported that symptoms, primarily safely tolerated GI symptoms that tended to resolve within 24 hours, developed following ingestions of 4 to 8.4 mg/kg of fluoride.[2] According to the medical literature, a safely tolerated dose (``STD'') and a certainly lethal dose (``CLD'') were determined from 600 fluoride poisoning deaths. The CLD was determined to be 32 to 64 mg/kg and the STD was estimated at one fourth that, or 8 to 16 mg/kg. These values were statistically determined and are not identical to the actual lowest toxic or lethal levels of fluoride. The lowest documented lethal dose for fluoride is 16 mg/kg in a 3-year-old child. There were complicating factors in this death. The child may have taken other medications and he suffered from Crohn's disease (an inflammatory disorder of the GI tract) that may have contributed to his death.[2] C. Injury Data Medical Literature. There are many reports in the medical literature of deaths and injuries involving fluoride-containing products. A retrospective study conducted by the American Association of Poison Control Centers (``AAPCC'') of hydrofluoric acid burns from rust stain removers applied to clothing found 619 such cases in 1990. Five of these required hospitalization.[2] Other reports gathered from the medical literature are discussed in the notice of proposed rulemaking and the accompanying briefing package. From 1988 to 1996, NEISS had reports of 31 incidents involving products documented to contain fluoride. Two of these were accidental ingestions by children under 5 years old. Most other injuries involved chemical burns of the hands.[2] In addition, 1997 NEISS reports show six adults experienced burns while using fluoride-containing products. In 1997, NEISS had reports of an additional five cases involving children under 5 years old ingesting products containing fluoride. For 1997, NEISS also reported an additional three cases of children under 5 years old involving products that might have contained fluoride.[7] The INDP files contain numerous injury reports. For example, a 50- year-old woman was using a water stain remover with 6 percent HF when it leaked through her rubber gloves and to her skin. She developed intense pain 4 hours later when the fluoride ion penetrated through to the bones of her forearm. Four months after the incident she had only partial use of her arm and hand. Three reports in the INDP files involve children under 5 years old who died after ingesting fluoride- containing products. A 3-year old child ingested an unknown product with HF. The second case involved a 2-year-old child who ingested a toilet bowl stain remover that contained 15.9 percent ammonium bifluoride. The most recent case was an 18-month-old child who ingested an unknown amount of air conditioner coil cleaner with 8 percent HF and 8 percent phosphoric acid.[2] Since 1995, there were six reports of fluoride poisoning in children under 5 years of age from a wheel cleaning product. The product contains ammonium bifluoride and ammonium fluoride salts, reportedly containing at least 15 percent fluoride. Before December, 1996, it was marketed for household use in non-CR packaging. Since that date it has been packaged in CR packaging, and in September 1997 it was recalled by the manufacturer.[2] Three deaths from fluoride-containing products were documented in 1997 after the staff had completed the briefing package for the proposed rule. Two involved children under 5 years old. In one case, a 3-year-old female died from cardiac arrest after ingesting the recalled wheel cleaner described above. The second death involved a 19-month-old female who ingested a rust remover with hydrofluoric acid and ammonium bifluoride. Finally, a 38-year-old male died from cardiac arrest after unintentional ingestion of a rust remover with ammonium bifluoride.[6] AAPCC Data. The staff reviewed AAPCC ingestion data involving children under 5 years old and products known to, or that may, contain fluoride. (The actual number of fluoride exposures cannot be determined because some products that contain fluoride are not identified as such and therefore may be coded to generic categories such as acidic cleaning products or other unknown cleaning products.) From 1993 to 1995, there were no reported fatalities in this age group. Out of a total of 499 exposures to products known to contain HF, there were 2 major \3\ outcomes and 24 moderate \4\ outcomes. The AAPCC data also show 23 major outcomes and 188 moderate outcomes for other acid household products. Some of these may have contained fluoride. The frequency of injury for dental treatments was much lower than that for household products containing HF. Of approximately 23,000 exposures to such dental products, there were 34 moderate outcomes, and the only documented major outcome was a miscoded incident where the child experienced an allergic reaction to the product rather than systemic toxicity from an overdose.[2] --------------------------------------------------------------------------- \3\ Major outcome--The patient exhibited signs or symptoms which were life-threatening or resulted in significant residual disability or disfigurement. \4\ Moderate outcome--The patient exhibited signs and symptoms that were more pronounced, more prolonged, or more of a systemic nature. Usually some form of treatment was required. Symptoms were not life-threatening and the patient had no residual disability or disfigurement. --------------------------------------------------------------------------- The 1996 AAPCC data report 136 exposures to products known to contain HF involving children under 5 years old. Four of these resulted in moderate outcomes. There were no major outcomes or deaths reported with this age group in 1996.[7] The staff also compiled data from AAPCC annual reports for all ages and all routes of exposure for the years 1985 to 1995. During this time period, there were about 25,000 exposures to products containing HF. Of these, 2,881 resulted in moderate outcomes and 275 in major outcomes. There were also injuries from dental products, fluoride mineral/ electrolyte products, and vitamins with fluoride. A total of 18 deaths were reported in the HF category. Two deaths involved children under 5 years old. One ingested an ammonium bifluoride toilet stain remover (described above) and the other child died after ingesting a toilet cleaner with HF. Generally, these AAPCC data suggest that household products with HF pose a more serious risk of injury than other classes of fluoride products. Moderate to serious outcomes developed in 12.8 percent of the exposures to HF compared to only 0.4 percent of the exposures to anticaries products.[2] The 1996 AAPCC data for all ages and all routes of exposure show that for 1996 there were about 2944 exposures to products containing HF. Of these, 742 resulted in moderate outcomes and 27 in major outcomes. Four deaths were reported involving HF.[7] D. Level of Regulation for Household Products Containing Fluoride The Commission is issuing a rule that requires special packaging for household products containing more than the equivalent of 50 mg of elemental fluoride and more than the equivalent of 0.5 percent elemental fluoride on a w/v basis for liquids or a w/w basis for non- liquids.[1,2&5] This is the same level as the Commission proposed. There is no well defined lethal dose for fluoride. In the medical literature, one source cites a minimum lethal dose in humans of 71 mg/ kg and another specifies a lethal oral dose in the range of 70 to 140 mg/kg. The staff considers these values too high based on documented cases of fluoride toxicity. There is one documented death from ingestion of 16 mg/kg fluoride, but as discussed above, other medical factors may have contributed to that death. Most evidence suggests that the lower limit of the calculated CLD of 32 mg/kg is a reasonable estimate for a minimum lethal dose.[2] Similarly, there is no established toxic dose for fluoride. Generally, greater than 6 percent HF can cause dermal burns and more than 0.5 percent can lead to serious eye injury. Several reports suggest ingestion of 3 to 5 mg/kg produces symptoms and that more than 5 mg/kg (50 mg in a 10 kg child) can produce systemic toxicity. Additionally, some medical professionals advise medical observation following ingestions of more than 5 to 8 mg/kg. Based on this information, the Commission determined a level for regulation that would include all household products with more than 50 mg of elemental fluoride and more than 0.5 percent elemental fluoride on a w/v basis for liquids or a w/w basis for non-liquids. There is no evidence that 50 mg or less of elemental fluoride or concentrations less than 0.5 percent cause serious systemic toxicity or serious burns.[1,2&5] E. Level of Regulation for Oral Prescription Drugs Containing Sodium Fluoride Based on the toxicity information discussed above, the Commission believes that the current exemption for oral prescription drugs with no more than 264 mg of sodium fluoride should be modified. To be consistent with the level for household products containing fluoride, the Commission is revising the level for the oral prescription drug exemption to exempt products that have either no more than the equivalent of 50 mg of elemental fluoride (110 mg sodium fluoride) per package or no more than a concentration of 0.5 percent elemental fluoride on a w/v basis for liquids or a w/w basis for non- liquids.[1,2&5] The Commission does not believe that changing the level of exemption for prescription drugs containing sodium fluoride will impact any of the currently exempted dental products with more than 50 mg of fluoride because these products have 0.5 percent or less fluoride.[1] In its comment, the American Dental Association confirmed this.[5] F. Statutory Considerations 1. Hazard to Children As noted above, the toxicity data concerning children's ingestion of fluoride demonstrate that fluoride can cause serious illness and injury to children. Moreover, it is available to children in common household products. Although some products currently use CR packaging, others do not. The Commission concludes that a regulation is needed to ensure that products subject to the regulation will be placed in CR packaging by any current as well as future manufacturers.[1,2&5] The same hazard posed to children by toxic amounts of fluoride in household products also exists from such levels of fluoride in oral prescription drugs. Therefore, the Commission is modifying the existing exemption for such drugs with sodium fluoride to reflect current toxicity data and be consistent with the level for fluoride-containing household products.[1&2] Pursuant to section 3(a) of the PPPA, 15 U.S.C. 1472(a), the Commission finds that the degree and nature of the hazard to children from handling or ingesting fluoride is such that special packaging is required to protect children from serious illness. The Commission bases this finding on the toxic nature of these products, described above, and their accessibility to children in the home. Some OTC fluoride-containing household products are packaged in containers with non-CR continuous threaded closures. The Commission also is aware of such products packaged in aerosols and mechanical pumps. Various types and designs of senior friendly CR packaging can be readily obtained that would be suitable for fluoride-containing products.[3&4] Two manufacturers currently use senior-friendly continuous threaded CR packaging for their fluoride-containing household products. Another manufacturer uses a senior-friendly trigger mechanical pump mechanism for its product. This shows that these types of CR packages are technically feasible, practicable and appropriate for fluoride- containing products. The Commission knows of at least one fluoride product that uses a non-CR aerosol package. The manufacturer of another regulated product is currently using a senior-friendly CR aerosol overcap. Thus, this kind of CR packaging could be used for fluoride- containing products. Finally, various designs of senior-friendly snap type reclosable CR packaging that would be appropriate for non-liquid fluoride-containing products are available. Thus, appropriate senior- friendly CR packaging is available for products marketed in continuous threaded, snap, aerosols, and trigger spray packaging.[4] Therefore, the Commission concludes that CR packaging for fluoride-containing products is technically feasible, practicable, and appropriate. Sec. 1700.14 Substances requiring special packaging. (a) Substances. The Commission has determined that the degree or nature of the hazard to children in the availability of the following substances, by reason of their packaging, is such that special packaging meeting the requirements of Sec. 1700.20(a) is required to protect children from serious personal injury or serious illness resulting from handling, using, or ingesting such substances, and the special packaging herein required is technically feasible, practicable, and appropriate for these substances: * * * * * (10) Prescription drugs. Any drug for human use that is in a dosage form intended for oral administration and that is required by Federal law to be dispensed only by or upon an oral or written prescription or a practitioner licensed by law to administer such drug shall be packaged in accordance with the provisions of Sec. 1700.15(a), (b), and (c), except for the following: * * * * * (vii) Sodium fluoride drug preparations including liquid and tablet forms, containing not more than 110 milligrams of sodium fluoride (the equivalent of 50 mg of elemental fluoride) per package or not more than a concentration of 0.5 percent elemental fluoride on a weight-to-volume basis for liquids or a weight-to-weight basis for non-liquids and containing no other substances subject to this Sec. 1700.14(a)(10). * * * * * (27) Fluoride. Household substances containing more than the equivalent of 50 milligrams of elemental fluoride per package and more than the equivalent of 0.5 percent elemental fluoride on a weight-to- volume basis for liquids or a weight-to-weight basis for non-liquids shall be packaged in accordance with the provisions of Sec. 1700.15(a), (b) and (c). ---------------------------------------------------------------------------- To subscribe to the PFPC NEWSLETTER, send message to pfpc@istar.ca and put "subscribe" in subject box. Likewise, to unsubscribe, put "cancel" in subject box.