Soap Salts Human Health Risk Assessment D399690

Page 2 of 8 1.0 Executive Summary 3

2.0 Regulatory Recommendations 3

3.0 Introduction 4

4.0 Hazard Identification and Dose-Response Assessment 4

5.0 Dietary Exposure and Risk Assessment 6

5.1 Food Residue Profile 6

5.2 Dietary Exposure and Risk Assessment 6

6.0 Residential (Non-Occupational) Exposure/Risk Characterization 6

7.0 Aggregate Exposure/Risk Characterization 6

8.0 Cumulative Exposure/Risk Characterization 7

9.0 Occupational Exposure/Risk Characterization 7

10.0 References 8Soap Salts Human Health Risk Assessment D399690

Page 3 of 8 1.0 Executive Summary HED has prepared a human health risk assessment to support registration review for the uses of sodium, potassium, and ammonium soap salts as ac tive ingredients in pestic ides. Because of the limited uses, minimal potential for exposure, and lo w toxicity, HED determined that a qualitative risk assessment is appropriate for the soap salts.

Potassium and ammonium salts are currently exempt from the requirement of a tolerance. An exemption for sodium salts is not needed, as th ere are no uses on/near food crops. There are no concerns for residential and occupational exposures since the labels spec ify adequate protection from the irritating effects of soap.

Fatty acids are normally metaboli zed by the cells, where they ar e oxidized to simple compounds for use as energy sources and as structural comp onents utilized in al l living cells. Sodium, potassium, and ammonium are normally part of the body’s metabolism and electrolyte balance. Oral exposure to soaps is generally self-limiting because the taste of soap is unpleasant. Also, the ammonium soap salts have a notable ammoni a odor that is self-limiting. To date, EPA has waived all generic mammalian toxicity data requirements for the soap salts. No in vivo toxicity testing studies relevant to HED’s human health ri sk assessments were identified in a literature

screen.

HED continues to believe that it is appropriate to waive all generic mammalian toxicity data requirements for the soap salts, due to the lack of effects at high doses in the available toxicity studies, the nature of the chemicals (fatty acids ) and their ubiquity in nature, and the limited exposure via the oral route resu lting from established uses.

While exposure to soap salts is possible via dietary exposur e, HED has not identified any toxicological endpoints for human health risk as sessment. Therefore, HED concludes that no quantitative dietary assessments are needed.

Soap salts do not belong to a common mech anism group, and therefore there are no cumulative

risk concerns. No human studies were used in the soap salts risk assessment.

2.0 Regulatory Recommendations Sufficient data are available to support HED’ s decision to waive generic mammalian toxicity data requirements for the soap salts.

Residues of potassium soap salts are exempt fr om the requirement of a tolerance in 40 CFR § 180.1068 when used in accordance with good agricultu ral practice. Similarly, residues of ammonium soap salts are except from the re quirement of a tolerance in 40 CFR § 180.1284 when used in accordance with good agricultural pr actices. Further, the potassium and sodium salts are generally recognized as safe (GRAS) in food and in the manufacture of food, as described in 21 CFR § 172.863.

Codex has not established ma ximum residue limits for any of the soap salts.

HED has no objection to the continuing regi stration of soap salts for current uses.Soap Salts Human Health Risk Assessment D399690

Page 4 of 8 3.0 Introduction The soap salt registration review case is comprised of three activ e ingredients which are currently associated with active product registra tions. These chemicals are (1) ammonium salts

of C 8 - C 18 saturated and C 18 unsaturated fatty acids; (2) potassium salts of C 12 —C 18 saturated fatty acids; and (3) sodium salts of mixed fatty acid esters. Potassium salts are produced by adding potassium hydroxide to fatty acids found in an imal fats and in plant oils, such as palm, coconut, olive, castor, and cottonseed oils. A similar process is used for producing ammonium and sodium soap salts.

The potassium salts are used as insecticides, herb icides, fungicides, and al gaecides in a variety of settings, including food crops and residences. The ammonium salts are used as herbicides and deer and rabbit repellents, also in a wide variety of settings including agricu ltural settings. The

sodium salts are used as a deer re pellent in residential settings only.

Potential areas of environmental ju stice concerns, to the extent po ssible, were considered in the human health risk assessment, in accordance w ith U.S. Executive Order 12898, "Federal Actions

to Address Environmental Justice in Minor ity Populations and Lo w-Income Populations 1 ." The Office of Pesticide Programs (OPP) typically cons iders the highest potenti al exposures from the legal use of a pesticide when conducting human health risk assessments, including, but not limited to, people who obtain drinking water from s ources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should these highest exposures indicate potenti al risks of concern, OPP further refines the risk assessments to

ensure that the risk estimates are ba sed on the best available information.

4.0 Hazard Identification and Dose-Response Assessment The toxicology database for soap salts is ad equate to support reregistration eligibility. To date, EPA has waived all generic mammalian t oxicity data requirements for the soap salts due to the lack of effects at high doses in the ava ilable studies, the nature of the chemicals (fatty acids) and their ubiquity in natu re, and the limited potential for human exposure via the oral route from established uses. The ammonium, pot assium, and sodium salts demonstrate similar toxicity, so that they are groupe d in the same EPA case. With no systemic toxicity observed, HED did not select endpoints for human hea lth risk assessment and waived all mammalian toxicity data. For the current action, a search of the open litera ture was conducted through Google Scholar to identify any new toxici ty studies since HED’s 2008 memorandum “Soap

Salts

. Revised Human Health Assessment Scopi ng Document in Support of Registration Review.” (D352949, C. Olinger, September 03, 2008). None were identified. According to peer review literature, no single do se or repeated dose study available produced a systemic toxic effect up to or near the limit dose in any exposure route.

Soap salts caused mutagenic effects when admi nistered to laboratory animals at high doses. Unscheduled DNA synthesis was found in m ouse cells with 35 mg/kg of oleic acid 2

. Cytogenetic analysis was positive for 2500 ug/L of oleic acid with hamster fibroblasts and for

1 Available: http://www.eh.doe.gov/nepa/tools/guidance/Volume1/2-6-EO_12898envjustice.pdfSoap Salts Human Health Risk Assessment D399690

Page 5 of 8 100 mg/L with Saccaromyces cerevisiae 2 . As noted earlier, the potassi um and sodium soap salts are GRAS compounds, and the three soap salt s compounds are either exempt from the requirement of a tolerance or a tolerance does not apply. Fatty acids lik e the soap salts are ubiquitous in nature and exposures to high dietary or residentia l doses of the soap salts are unlikely given the pesticidal use patterns.

No toxicological points of depart ure were selected for soap salts based on the available toxicity data. As a result, no dietary, residential, occ upational, or aggregate exposure assessments are required at this time.

Fatty acids are normally metaboli zed by the cells, where they ar e oxidized to simple compounds for use as energy sources and as structural comp onents utilized in al l living cells. Sodium, potassium, and ammonium are normally part of the body’s metabolism and electrolyte balance. Oral exposure to soaps is generally self-limiting because the taste of so ap is unpleasant. The ammonium soap salts also have a notable ammo nia odor that is self-limiting. Eye irritation for ammonium, potassium, and sodium salts is addr essed through product labe ling (See Section 9.0).

Potassium salts of fatty acids have low acute to xicity by oral, dermal, or inhalation routes of exposure and are considered to be severe eye irritants, based on corneal involvement. Potassium salts of fatty acids are corrosive to the skin ba sed on severe erythema at both intact and abraded sites and cracking and fissuring of epithelial layers, but ar e not dermal sensitizers.

Ammonium and sodium salts of fatty acids have low acute toxicity by oral, dermal, or inhalation routes of exposure. Ammonium and sodium salts of fatty acids are considered to be mild skin irritants, dermal sensitizers, and are corrosive to the eye.

In an open literature report, potassium salt of co coa fatty acids was examined for developmental effects following percutaneous administration to mice and rats (Palmer et al, 1975). Solutions containing 0.3, 3 and 30% of a soap salts were a pplied to shaved skin during pregnancy days 2-

13 in mice and 2-15 in rats. The treated area was not occluded or washed. Dosages employed were 0.5 mL/rat or mouse/day. These doses we re equivalent to 50, 500 and 5000 mg/kg/day for mice and 6, 60, and 600 mg/kg/day for rats. In mice treated with 500 and 5000 mg/kg/day, the maternal mice demonstrated marked skin reaction, irritability, weight loss and failure to maintain pregnancy. In young mice at 500 mg/kg/ day, the incidences of fetal loss, malformations, visceral

or skeletal anomalies and skeletal variants we re within the historical control range (0-4.4%)

. In young mice at 5000 mg/kg/day (a dose level 5X of limit dose), the assessments of these effects were impossible due to the negligible num bers of litters and young mice available for

examination. In rats treated w ith 600 mg/kg/day (highest dose tested), the maternal animals demonstrated erythema and edema. The incide nces of fetal loss, li tter size, malformations,

visceral or skeletal anomalies and skeletal varian ts in all treated rats were comparable to the control group.

A developmental toxicity study in rats dosed with ammonium nonanoic acid (C9 fatty acid) (MRID 43843508), reported that the treatment had no adverse effects. No fetal toxicity was

2 Sax, N. I., and Lewis, R. J. SR, 1989. Dangerous properties of Industrial Materials, 7th Edition. Van Nostrand Reinhold, New York.Soap Salts Human Health Risk Assessment D399690

Page 6 of 8 observed. The no observed adverse effect leve l (NOAEL) for maternal and developmental toxicity was 1,500 mg/kg/day and the lowest obs erved adverse effect level (LOAEL) was > 1,500 mg/kg/day. The developmental toxicity study for ammonium nonanoic acid showed no

effects at dose levels belo w the limit dose (1,000 mg/kg/day).

5.0 Dietary Exposure and Risk Assessment

5.1 Food Residue Profile Residues of ammonium soap salts are except from the requirement of a tolerance in 40 CFR § 180.1284 when used in accordance with good agricu ltural practices. Similarly, residues of potassium soap salts are exempt from the requi rement of a tolerance in 40 CFR § 180.1068 when used in accordance with good agricu ltural practice. Further, the potassium and sodium salts are generally recognized as safe in food and in th e manufacture of food, as described in 21 CFR §

172.863.

5.2 Dietary Exposure and Risk Assessment While exposure to soap salts (potassium, amm onium) could occur via the diet, HED has not identified any toxicological endpo ints to conduct a human health risk assessment. Therefore, no additional data are required and no quantitative dietary assessments are needed. The soap salts have a low acute toxicity via the oral route of exposure and residue s from the pesticides uses are not likely to exceed the levels of naturally o ccurring fatty acids in commonly eaten foods.

There is a tolerance exemption for potassium ol eate acid related C12- C18 fatty acid potassium salts [40 CFR §180.1068] when used under good agri cultural practic es. A tolerance exemption for the ammonium salts of higher fatty acids (C8–C18 saturated; C8–C12 unsaturated) was recently established in 40 CFR §180.1284 ( Federal Register , Vol. 73, No. 132, pp. 39264- 39269) when applied for the suppression and control of a wide variety of grasses and weeds. However, there are product labels for the ammonium salts with instructions for use in agricultural settings as a deer repellent to growing crops and or chards with fruit present.

A 2009 revision to the ammonium so ap salts tolerance exemption [ Federal Register , Vol. 74, 47457) exempted ammonium salts of C8-C18 satu rated and C8-C12 unsaturated higher fatty acids from the requirement of a tolerance for re sidues in or on all food commodities when used in accordance with good agricultural practice. An exemption for sodium salts is not needed, as there are no food uses. Residue chemistry st udies have not been submitted, and none are required.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization While exposure to soap salts could occur in the residential environment, HED has not identified any toxicological endpoint s to conduct a human health risk assessment.

HED has no objection to the continuing registrati on of soap salts because there are adequate label recommendations regarding potential eye and sk in irritation. Curr ent product labels require protective eyewear while applying the ammonium salts of fa tty acids to prevent permanent eye injury. These requirements are appropriate and should be retained.

7.0 Aggregate Exposure/Risk CharacterizationSoap Salts Human Health Risk Assessment D399690

Page 7 of 8 HED has no concern for aggregate risk resulting from the existing uses of soap salts given the lack of toxicity and in light of the natural prevalence of thes e compounds in the environment. While both residential and dietary exposures ar e possible given the use pattern, HED has not identified any toxicological poi nts of departure needed to co nduct a quantitative human health

risk assessment.

8.0 Cumulative Exposure/Risk Characterization Unlike other pesticides for which EPA has fo llowed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to the soap salts and any othe r substances and soap salts do not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that soap salts have a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate th e cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and proc edures for cumulating effects from substances found to have

a common mechanism on EPA’s website 3

.

9.0 Occupational Exposure/Risk Characterization Occupational exposure to soap salts is possible due to their registered use pattern. While exposure to soap salts could occur in occ upational settings, HED has not identified any toxicological endpoints to conduct a human health risk assessment.

Potassium salts of fatty acids are used on vegetabl es up to the day of harvest, indoor plants, and unspecified domestics dwellings. Products are typi cally applied with spray bottles or hand held sprayers. Ammonium salts of higher fatty acids are used as an herbicide or rabbit and deer repellent on forage and grain crops, vegetables, nursery stock, flower s, fruit trees and vines. The

sodium salts are used as a deer repellent on trees and shrubs.

All ammonium salts of fatty ac ids liquid concentrat e products contain the warning “Wear eye protection (goggles, face shield, or safety glasses), long sleeved shirt, long pants, socks, shoes and rubber gloves. After this product is dilu ted in accordance with label directions, eye protection, gloves and long sleeves are not required.” Additionall y, the instructions (e.g., “Avoid contact with eyes or clothing. Wash thoroughly with soap and wa ter after handling” and “Causes substantial, but temporary eye inju ry. Causes skin irritation. Do not get on skin, in eyes, or on clothing. Wear goggles or safety glasses. Wash thoroughly with soap an d water after handling”) on the product label are ad equate for applicators.

3 Available: at http://www.epa.gov/pesticides/cumulative/

.Soap Salts Human Health Risk Assessment D399690

Page 8 of 8 10.0 References
Table 7.1. Memoranda Relevant to Registration Review Risk Assessment

Author Barcode Date Title

Literature Study N/A 1975 Palmer, A. K., Readshaw, M. A., Neuff, A. M., 1975. Assessment of the teratogenic potential of surfactants. Part III—Dermal application of LAS and soap. Toxicology, 4 (1975) 171-181. L. Kutney None 6/12/92 Human Health Risk Assessment for the Reregistration Eligibility Document (RED) C. Swartz D171289 5/26/92 Soap. Potassium Salts of Fatty Acids /Ammonium Salts of Fatty Acids Chemistry Branch Input (Product and Residue Chemistry) to the Reregistration Eligibility Document (RED)

P. McLaughlin None 4/22/92 Toxicology Review for the Reregistration Eligibility Document on Soap and Soap Salts J. Yowell None 6/8/92 Review of Potential Occupational and Residential Exposure to Soaps for the Reregistration Eligibility Document (RED) C. Olinger D352949 9/3/08 Soap Salts. Revised Human Health Assessment Scoping Document in Support of Registration Review.