Document ID: EPA-HQ-OPP-2016-0259-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2017-08-29T04:00Z

Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations for 1-Triacontanol

                    Docket ID Number: EPA-HQ-OPP-2016-0259
                              Date: June 13, 2017
                                       
Section 408(c)(2)(A)(i) of FFDCA allows the U.S. Environmental Protection Agency (EPA or the Agency) to establish an exemption from the requirement for a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if the EPA determines that the exemption is "safe." Section 408(c)(2)(A)(ii) of FFDCA defines "safe" to mean that "there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information." This includes exposure through drinking water and in residential settings but does not include occupational exposure. Pursuant to FFDCA section 408(c)(2)(B), in establishing or maintaining in effect an exemption from the requirement of a tolerance, the EPA must take into account the factors set forth in FFDCA section 408(b)(2)(C), which require the EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance exemption, and to "ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue...." Additionally, FFDCA section 408(b)(2)(D) requires that the EPA consider "available information concerning the cumulative effects of [a particular pesticide's] . . . residues and other substances that have a common mechanism of toxicity."
The EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. First, the EPA determines the toxicity of pesticides. Second, the EPA examines exposure to the pesticide through food, drinking water, and through other exposures that occur as a result of pesticide use in residential settings.
I.  Summary of Petitioned-for Tolerance Exemption
In the Federal Register of August 18, 2016 (81 FR 55191) (FRL-9950-22), EPA issued a notice pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance petition (PP 6F8459) by CH Biotech R&D, Co., LTD. (the Petitioner), c/o Spring Trading Company, 203 Dogwood Trail, Magnolia, TX 77354. The petition requested that 40 CFR part 180 be amended by establishing an exemption from the requirement of a tolerance for residues of 1-triacontanol (TA) in or on food commodity crops or in products to treat animals. The notice referenced a summary of the petition prepared by the Petitioner, which is available in Docket ID Number EPA-HQ-OPP-2016-0259 via http://www.regulations.gov.
II. Toxicological Profile
Consistent with section 408(b)(2)(D) of FFDCA, the EPA reviewed the available scientific data and other relevant information on TA, and considered its validity, completeness, and reliability, as well as the relationship of this information to human risk. The EPA also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

A.  Overview of 1-Triacontanol	

1-Triacontanol, a long chain fatty alcohol (LCOH), is a naturally occurring plant growth regulator (PGR) existing in plant wax and insect wax widely. As a PGR, it is used to promote germination, root, stem and leaf growth and flowering (early ripening), improve the seed quality, enhance the plant's capacity for cold and drought resistance, increase production and improve quality of product grown. In terms of the mechanism of action, TA is absorbed through the plant's stem and leaf, and may promote plant growth, increase accumulation of dry matter, improve the permeability of cell membranes, increase chlorophyll content, improve photosynthetic intensity, and increase activity of amylase, oxidase and peroxidase.

TA is ubiquitous in the environment and constitutes a regular part of the human diet as it is found in plant and insect waxes. TA occurs in concentrations of 11-62% in grains and sugarcane (Ref. 1). Additionally, policosanols, fatty acids containing TA, can be found up to 10% as a solidifying agent in gel like substances such as olive oil (Ref. 2). TA is used for its health benefits and is incorporated into pharmaceuticals for its anti-inflammatory properties and to protect against gastric ulcers (Ref. 3). Policosanols lower total cholesterol by 17-21% when taken at doses of 10-20 mg per day (Ref. 4). Additionally, TA constitutes the majority of long chain alcohols found in beeswax, naturally secreted through the bee's abdomen (Ref. 5).
      
Significant residues of TA on treated commodities are not anticipated as a result of its use as a pesticide especially given the rapid biodegradation of TA. Moreover, residues of TA in drinking water are unlikely given its insolubility in water.  

There is a history of human exposure to TA due to its use in the cosmetic and pharmaceutical industries, surface lubricants, and its occurrences in a variety of plants for human consumption, such as tea leaves, sugarcane and grain wax. The Organization for Economic Co-operation and Development (OECD) noted that the sum of C14 - C18 chain length fatty alcohols [including octadecanol (C18), hexadecanol (C16), and tetradecanol (C14)] ranged from 217 to 1825 micrograms per gram human waste (μg/g) sent to sewage treatment (Ref.6). These measurements of long chain alcohol in environmental matrices reflect the combination of both natural and anthropogenic sources to these chemicals. 
      
An aggregate risk assessment for TA for dietary (food and drinking water) exposures was not conducted as no toxicological endpoints have been identified in the toxicity database.  EPA has determined under the FFDCA that there is reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to TA. 
	
There are no human health or environmental risks of concern associated with this assessment.  Therefore, EPA has no objection to the registration of the proposed MP and EP, and proposes to establish an exemption from the requirement of a tolerance for residues of 1-triacontanol in or on food commodities when used in accordance with label directions and good agricultural practices. 
	
For a summary of the data upon which EPA relied, and its review and conclusions based on that data, please refer to the sections below. 

Based on the data submitted in support of this petition (summarized in Unit II. B., below) and the comprehensive risk assessment conducted by the Agency, EPA concludes that there is a reasonable certainty of no harm from aggregate exposures to TA, including the consumption of food treated with this active ingredient in accordance with label directions and good agricultural practices. EPA has made this determination because available toxicology data indicate that the active ingredient is of low acute toxicity and is not a developmental toxicant, a mutagen, or toxic via repeat oral exposure.

B.  Biochemical Pesticide Toxicology Data Requirements
Based on the submitted data and the results of studies using comparable long chain fatty alcohols, there are no human health risks of concern associated with TA, and there is sufficient information to justify an exemption from the requirement of a tolerance for this compound when used as a plant growth regulator on all food commodities. Acute studies on TA show that this long chain fatty alcohol is Toxicology Category IV for Acute Oral Toxicity, Acute Dermal Toxicity, Acute Eye irritation, and Primary Dermal irritation. TA is not a dermal sensitizer. All applicable mammalian toxicology data requirements supporting the request for an exemption from the requirement of a tolerance for residues of TA when used pre-harvest to fruiting vegetables, cereal grains, stone fruits, nut crops, and cotton have been fulfilled with data or waiver requests/rationales submitted by the petitioner. Waivers were submitted and accepted for sub chronic toxicology studies including the 90-Day Oral study (OSCPP 870.2600); Developmental Toxicity study (OSCPP 870.3700); Genetic toxicity testing (OSCPP 870.5100, 870.5300, 870.5375, 870.5395, 870.5450, 870.5900). Data was bridged with long chain alcohols (structurally similar to TA), including 1-Docosanol (C22), Policosanol (C24 to C34), and D-002 a substance purified from beeswax, containing a mixture of the higher aliphatic alcohols (C24, C26, C28, C30, C32, and C34) the major component of D-002 is TA (C30), followed by Octacosanol (C28) and Docotriacontanol (C32). The following is a summary of EPA's review of the toxicity profile of this biochemical:
  
Acute Toxicity: Acute toxicity studies on TA confirm a low toxicity profile. The acute toxicity data are of low toxicity for all routes of exposure, with the exception of eye irritation and dermal sensitization.

1.	OCSPP Guideline 870.1100: TA was evaluated for acute oral toxicity potential in female albino rats when administered as a gavage dose at 5,000 mg/kg. The study was terminated following stopping rules of this procedure. No mortality occurred during the study. There were no clinical signs of toxicity during the study. Animals exhibited weekly weight gain during the study. Gross necropsy conducted at terminal sacrifice revealed no observable abnormalities. The acute oral LD50, indicated by the data, was determined to be greater than 5,000 mg/kg. 1-Triacontanol is classified as Toxicity Category IV for acute oral toxicity. 
									
2.	OCSPP Guideline 820.1200: TA was evaluated for dermal toxicity potential and relative skin irritancy when a single dose moistened with 1.0 mL of com oil/g test substance, at 5050 mg/kg, was applied to the intact skin of albino rats. No mortality occurred during the study. The only clinical sign was emaciation in one animal on Day 7. There were no signs of dermal irritation at any time throughout the study. Animals exhibited weekly weight gain, except for two that lost weight between Days 0 and 7. Gross necropsy conducted at study termination revealed no observable abnormalities. The LD50 was determined to be greater than 5,050 mg/kg. 1-Triacontanol is classified as Toxicity Category IV for acute dermal toxicity.

    OCSPP Guideline 870.1300: The acute inhalation median lethal concentration (LC50) in rats cannot be generated as TA is insoluble in water. In an attempt to conduct such a study, an aerosol was generated by pumping test substance into a pressure operated Spraying System Company air atomizer (1/4 JSS), and then spraying the resulting aerosol directly into the exposure chamber. Chamber air flow was maintained through use of a calibrated orifice plate, sufficient to ensure an oxygen content of at least 19% of the exposure atmosphere. Concentration of test substance in the exposure atmosphere was determined gravimetrically during the assay. Gravimetric concentration was determined by passing a known volume of exposure air through a pre-weighed filter and dividing the amount of test substance deposited on the filter by volume of air which passed through the filter. Exposure concentrations are calculated from these data by a computer program utilizing Probit analysis. Particle size and MMAD were not determined. The exposure concentrations ranged from 0.22 - 0.58 mg/L. These levels would not provide meaningful acute inhalation toxicity data. The OECD noted that inhalation of vapors of long chain alcohols in the range of C6-C22 at levels up to the saturated vapor pressure is unlikely to be associated with significant toxicity.  The OECD provides unique tools and protocols for assessing human health and the environment that are accepted by the Environmental Protection Agency. Based on the weight of evidence (WOE) approach, considering all the available TA hazard and exposure data, EPA has determined that an acute inhalation study is not required at this time. This approach included the following considerations: (1) low vapor pressure of 7.11x10[-11] mm Hg limits vapor exposure; (2) the weight of evidence provided by OECD (Ref. 6): SIDS Initial Assessment Report for SIAM 22 (long chain alcohols) and (3) the acute toxicology studies (Toxicology Category IV), suggest that this compound, which is like comparable LCOH, is of low toxicity.
 
4.    OCSPP Guideline 870.2400: For primary eye irritation, EPA has classified TA as minimally irritating.
   An acute eye irritation study was conducted on three albino rabbits using test substance 1-Triacontanol. 
   Test substance, 0.1 mL by volume (99.9 mg), was placed into the conjunctival sac of the right eye of
   each animal selected for testing. All treated eyes were washed with room temperature deionized (DI)
   water for one minute after recording the 24-hour observation. There were no positive effects exhibited
   in any eye after treatment to rats. TA is minimally irritating and is assigned Toxicity category IV. 
 
 5.	OCSPP Guideline 870.2500: A primary dermal irritation study for TA was conducted on rabbits. There was one intact test site per animal. Each test site was treated with 500 mg of test substance moistened with 0.5 mL of corn oil and covered with semi-permeable dressing. TA was maintained in contact with the skin for 4 hours. Observations for dermal irritation and defects were made at 1, 24, 48 and 72 hours after removal of the dressings. Based on 0.2 PII, TA is rated as slightly irritating. TA is regarded as Toxicity category IV. 
 6.	OCSPP Guideline 870.2600: A dermal sensitization study was conducted on short-haired albino guinea pigs to determine if test substance TA produced a sensitizing reaction. Naive control group animals remained untreated during induction phase of the study. Test group animals were treated with 400 mg of test substance moistened with 0.4 mL of corn oil (selected from range-finding). Test animals were treated once weekly for three weeks, for a total of three treatments. After a two-week rest period, all animals (both groups) were challenged at a virgin test site with an application of 400 mg of test substance moistened with 0.4 mL of corn oil. The test substance produced no reaction in either Test animals or Naive control animals after the challenge treatment.  TA is not a dermal sensitizer. 
 
Mutagenicity, OCSPP Guidelines 870.5100, 870.5300, 870.5375: TA did not show a positive response with any of the tester strains either in the presence or absence of microsomal enzymes prepared from Aroclor induced rat liver. Studies on docosanol, policosanol, and D-002 also showed negative effects of these fatty alcohols on Bacterial Reverse Mutation and Ames Testing.

Based on a WOE approach, considering all the available TA hazard and exposure data, EPA had determined that a Bacterial Reverse Mutation study is not required at this time. This approach included the following considerations: (1) study on similar compound, 1-Docosanol (C22), showed negative results; and (2) For long chain alcohols that are C15 or greater, it is unlikely that they would exhibit chronic toxicity because the relationship between carbon number and chronic toxicity suggests that the solubility of the alcohol would limit the bioavailable dissolved fraction to sub-toxic concentrations (Ref. 6).

Subchronic Toxicity: 

 OCSPP Guideline 870.3100: 90-day oral data requirement is required to be addressed for uses of a pesticide on foods. Policosanol (C24-C34) was reviewed in the long chain alcohol study submitted. After 12 months of treatment to Sprague-Dawley rats (20/group), by gavage at dosage levels of 0, 250, 500, and 1,000 mg/kg/day, there were no treatment related effects on body weight gain, food consumption, hematology and clinical chemistry parameters or organ weights. No difference between groups was observed upon microscopic examination of tissue. The determined NOAEL was > 1,000 mg/kg/day. Based on a WOE approach, considering all the available TA hazard and other LCOH (bridging data) and exposure data, EPA has determined that a 90-Day Oral study on TA is not required at this time.  This approach included the following considerations: (1) 90-day Oral Toxicity study conducted on a mixture of long chain fatty alcohols, Policosanol (C24 to C34) that have similar chemistry as 1-Triacontanol (C30) showed NOAEL > 1,000 mg/kg/day; and (2) the acute toxicology studies demonstrate Toxicology Category IV, suggesting that the compound is of low toxicity on an acute basis.
   
 OCSPP Guideline 870.3250: The 90-day dermal data requirement is conditionally required to support uses involving purposeful application to the human skin or uses that would result in prolonged dermal exposure and if data from a 90-day oral study are not required, or the active ingredient is known or expected to be metabolized differently by the dermal route of exposure than by the oral route and the metabolite is of toxicological concern. The Agency has waived this data requirement for TA at this time. During use of the pesticide, applicators and handlers are required to wear appropriate PPE (long-sleeved shirt, long pants, shoes, socks, gloves and chemical resistant gloves). These PPE requirements mitigate the potential for repeated dermal exposure. Additionally, prolonged dermal exposure is also not anticipated as TA is expected to degrade rapidly once introduced into the environment. There were no significant differences from control in any treatment group for the absolute organ weights, the organs weight relative to brain weight or the organ weights relative to body weights for dermal testing. There were no other abnormal observations recorded for any animal at necropsy. The histopathology examination revealed no microscopic test-article related findings. The effects of the administration of TA on mortality, body weights, food consumption, in-life observations, hematology, clinical chemistry, gross pathology, organ weights and histopathology indicate the no-observable adverse effect level (NOAEL) of TA is greater than 1,000 mg/kg body weight when administered dermally over 92 days for 5 days a week. 
   
 OCSPP Guideline 870.3465: 90-day inhalation data requirement is conditionally required if there is a likelihood of significant levels of repeated inhalation exposure to the pesticide as a gas, vapor or aerosol. Previously, EPA's Office of Pesticide Programs (OPP) used a set of criteria to determine whether or not an inhalation study could be waived. These criteria considered the scientific information available for the chemical, including the following: (1) severe irritation and corrosivity, (2) low volatility, and (3) large aerosol particle size. In 2009, OPP developed an issue paper on risk assessment approaches for semi-volatile pesticides. As part of that issue paper, an analysis was conducted on a comparison of oral and inhalation experimental toxicology studies.  In general, this analysis showed that the degree to which oral PODs were protective of potential inhalation toxicity varied.  In many cases the oral POD was protective, but in some, the inhalation PODs were significantly more sensitive. Currently, OPP uses a WOE approach which builds upon experience using the previously used criteria listed above and informed by the 2009 Science Advisory Panel (SAP).  As approaches for route to route extrapolation evolve and improve in the future, OPP may, if appropriate, bring additional considerations into the WOE analysis.  Inhalation exposure can be to vapors, droplets, and/or particles/dusts.  The form of this exposure is determined by a number of factors including physical-chemical properties, use pattern, and exposure scenario.  Based on a WOE approach, considering all the available TA hazard and exposure data, EPA has determined that a 90-Day Inhalation study is not required at this time.  This approach included the following considerations: (1) TA is insoluble in water (1.35 x 10[-5] mg/L at 25[0]C) and a liquid aerosol could not be generated in an attempt at assessing acute toxicity; (2) The exposure concentrations for the Acute Inhalation study ranged from 0.22 - 0.58 mg/L. These levels, however, could not provide meaningful acute inhalation toxicity data; (3) TA has a low vapor pressure (7.1x10[-11] mm Hg) and cannot be aerosolized to obtain an exposure concentration high enough to determine the acute toxicity potential; (4) WOE (Ref. 6) suggest that inhalation of vapors of long chain alcohols in the range C6 - C22 at levels up to the saturated vapor pressure (the pressure at which fluid passes from gaseous to liquid phase for a given temperature) is unlikely to be associated with significant toxicity.  Gravimetric concentration was determined by passing a known volume of exposure air through a pre-weighed filter and dividing the amount of test substance deposited on the filter by volume of air which passed through the filter. Exposure concentrations are calculated from these data by a computer program utilizing Probit analysis; (5) the acute toxicology studies demonstrate Toxicology Category IV; and (6) Potential low exposure in the environment. 

Developmental Toxicity, OCSPP Guideline 870.3700:  The developmental study requirement was satisfied by the submission of two existing studies from the peer reviewed scientific literature. One study administered 10% aqueous gum acacia by gavage to female Sprague-Dawley rats at dose levels of 0, 5.00, 50.0, and 500.0 mg/kg/day from day 6 to day 15 of gestation. A second study administered policosanol to pregnant rabbits at dose levels of 0, 500, and 1000 mg/kg/day from gestation day 6 through day 18. Based on a WOE approach, considering all the available TA hazard and exposure data, EPA has determined that a Prenatal Development study is not required at this time. This approach included the following considerations: (1) Oral Toxicity studies conducted on a mixture of long chain alcohols, Policosanol (C24 to C34) that have similar chemistry as 1-Triacontanol (C30) (OECD, 2006) in both rats and rabbits; (2) Bridging data using Policosanol show that no adverse effects were found on dams and fetuses regarding body weights, the mean number of corpora lutea, implantations, resorption or dead and live fetuses and no treatment related visceral or skeletal findings were observed. The NOAEL (rabbit) for maternal and developmental toxicity was > 1,000 mg/kg/day and for rats > 500 mg/kg/day; (3) the acute toxicology studies demonstrate Toxicology Category IV, suggesting that the compound is of low toxicity on an acute basis. These studies followed OECD protocols for assessing the potential effects of chemicals on human health and the environment. These standard methods are accepted by the U.S. Environmental Protection Agency and (4) Residues at harvest should be low given application timing.  

III.  Aggregate Exposure

In examining aggregate exposure, FFDCA section 408 directs the EPA to consider available information concerning exposures from the pesticide residue in food and all other non-occupational exposures, including drinking water from ground water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses). An aggregate risk assessment for TA for dietary (food and drinking water) exposures was not conducted as no toxicological endpoints have been identified in the toxicity database.  Furthermore, there is reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to TA.

Other Non-occupational Exposure: Other non-occupational exposure to 1-triacontanol from pesticidal use is not expected to occur as the TA biodegrades rapidly and is applied at low application rates. There are no residential uses for TA that would result in non-occupational exposure.

IV.  Cumulative Effects from Substances with a Common Mechanism of Toxicity

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the EPA consider "available information concerning the cumulative effects of [a particular pesticide's] . . . residues and other substances that have a common mechanism of toxicity."

The EPA has not found TA to share a common mechanism of toxicity with any other substances, and TA does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, the EPA has assumed that TA does not have a common mechanism of toxicity with other substances. Following from this, the EPA concludes that there are no cumulative effects associated with TA that need to be considered. For information regarding the EPA's efforts to determine chemicals that have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the EPA's website at http://www.epa.gov/pesticides/cumulative. 

V.  Determination of Safety for the United States Population, Infants and Children
	
FFDCA section 408(b)(2)(C) provides that, in considering the establishment of a tolerance or tolerance exemption for a pesticide chemical residue, the EPA shall assess the available information about consumption patterns among infants and children, special susceptibility of infants and children to pesticide chemical residues, and the cumulative effects on infants and children of the residues and other substances with a common mechanism of toxicity. In addition, FFDCA section 408(b)(2)(C) provides that the EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure, unless the EPA determines that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the Food Quality Protection Act Safety Factor. In applying this provision, the EPA either retains the default value of 10X, or uses a different additional or no safety factor when reliable data are available to support a different additional or no safety factor. 

There are no human health or environmental risks of concern associated with this assessment. Furthermore, there is reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to TA.

EPA has determined that there are no foreseeable dietary risks to the U.S. population, including infants and children, from the use of TA as a pesticide (plant growth regulator) in or on food commodities when used in accordance with label directions and good agricultural practices.

The available data and information indicate that the chemical is of low toxicity, minimal eye irritant, not a dermal sensitizer and not a developmental toxicant. Therefore, EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to the residues of TA when it is used as labeled and in accordance with good agricultural practices. Such exposure includes all anticipated dietary exposures and all other exposures for which there is reliable information. EPA has arrived at this conclusion because the data and information available on TA do not demonstrate significant toxic potential to mammals, including infants and children. 

VI.  Conclusions
EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to residues of 1-triacontanol (TA). Therefore, an exemption is established for residues of the biochemical pesticide 1-triacontanol in or on food commodities when used in accordance with label directions and good agricultural practices. 

VII.  References
   
 University of the Ryukysus (2008). Determination of Long-chain Alcohol and Aldehyde
      Contents in the Non-Centrifuged Cane Sugar Kokuto. Okinawa, Japan, August 2008. 583-588pp. (Available at: https://www.jstage.jst.go.jp/article/fstr/14/6/14_6_583/_pdf).
      
 Trends in Food Science & Technology (2016). Edible Oleogels for the Oral Delivery of
      Lipid Soluble Molecules" Composition and Structural Design Considerations. Ontario, Canada, August 2016. 59-73pp. (Available at: https://www.journals.elsevier.com/trends-in-food-science-and-technology).
      
 The Japanese Society of Pharmacognosy and Springer (2011). Evaluation of anti
      inflammatory and antinociceptive effects of D-002 (beeswax alcohols). Havana, Cuba, January 2011. 330-335pp. (Available at: https://link.springer.com/content/pdf/10.1007%2Fs11418-010-0496-4.pdf)
      
 American Heart Journal (2002). Policosanol: Clinical Pharmacology and Therapeutic
      Significance of a New Lipid-Lowering Agent. Rotenburg an der Fulda and Bonn, Germany, February 2002. 356-365pp. (Available at: http://www.sciencedirect.com/science/article/pii/S0002870302585008?via%3Dihub)
      
 USDA (2005). Isolation of Long-Chain Aliphatic Alcohols from Beeswax Using Lipase
      Catalyzed Methanolysis in Supercritical Carbon Dioxide. Peoria, Illinois, August 2005. 173-177pp. (Available at: http://www.sciencedirect.com/science/article/pii/S0896844605001713).
      
   
 OECD  2006. SIDS Initial Assessment
      Report for SIAM 22. Organisation for Economic Cooperation and Development (OECD). Paris, France, 18-21 April 2006. TOME 1: SIAR. Category: Long Chain Alcohols, 294pp. (Available at: http://www.oecd.org/documents/63/0,2340,en_2649_34379_1897983_1_1_1_37465,00.html).