SCREENING-LEVEL HAZARD CHARACTERIZATION OF HIGH PRODUCTION VOLUME CHEMICALS CHEMICAL CATEGORY NAME Rosin Adducts and Adduct Salts SPONSORED CHEMICALS High Production Volume Chemicals Branch Risk Assessment Division Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, DC 20460-0001 Rosin, fumarated Rosin, fumarated, sodium salt Rosin, fumarated potassium salt Rosin, maleated Rosin, maleated, potassium salt Rosin, maleated/fumarated CAS No. 65997-04-8 CAS No. 68201-59-2 CAS No. 68649-83-2 CAS No. 8050-28-0 CAS No. 85409-27-4 CAS No. 68554-16-5 October 2007 INTERIM Prepared by ------- SCREENING-LEVEL HAZARD CHARACTERIZATION OF HIGH PRODUCTION VOLUME CHEMICALS The High Production Volume (HPV) Challenge Program1 is a voluntary initiative aimed at developing and making publicly available screening-level health and environmental effects information on chemicals manufactured in or imported into the United States in quantities greater than one million pounds per year. In the Challenge Program, producers and importers of HPV chemicals voluntarily sponsor chemicals; sponsorship entails the identification and initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data do not exist, and making both new and existing data and information available to the public. Each complete data submission contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'2) endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the environment. The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored chemicals. OPPT is using a hazard- based screening process to prioritize review of the submissions. The hazard-based screening process consists of two tiers described below briefly and in more detail on the Hazard Characterization website3. Tier 1 is a computerized sorting process whereby key elements of a submitted data set are compared to established criteria to "bin" chemicals/categories for OPPT review. This is an automated process performed on the data as submitted by the sponsor. It does not include evaluation of the quality or completeness of the data. In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is performed according to established EPA guidance2'4 and is based primarily on hazard data provided by sponsors. EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar chemical structures, properties and biological activities may be grouped together and their data shared across the resulting category. This approach often significantly reduces the need for conducting tests for all endpoints for all category members. As part of Tier 2, evaluation of chemical category rationale and composition and data extrapolation(s) among category members is performed in accord with established EPA2 and OECD5 guidance. The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing chemicals review process. These hazard characterizations are technical documents intended to support subsequent decisions and actions by OPPT. Accordingly, the documents are not written with the goal of informing the general public. However, they do provide a vehicle for public access to a concise assessment of the raw technical data on HPV chemicals and provide information previously not readily available to the public. The public, including sponsors, may offer comments on the hazard characterization documents. The screening-level hazard characterizations, as the name indicates, do not evaluate the potential risks of a chemical or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the Inventory Update Reporting (IUR) rule. For the chemicals in the HPV Challenge Program, EPA will review the IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the screening-level hazard characterizations to develop screening-level risk characterizations4'6. The screening-level risk characterizations will inform EPA on the need for further work on individual chemicals or categories. Efforts are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk- based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action. 1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm. 2 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm. 3 U.S. EPA. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html). 4 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm. 5 OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf. 6 U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm. 2 ------- SCREENING-LEVEL HAZARD CHARACTERIZATION Rosin Adducts and Adduct Salts Introduction The sponsor, Pine Chemicals Association, Inc., submitted a Test Plan and Robust Summaries to EPA for the Rosin Adducts and Adduct Salts Category on September 18, 2001. EPA posted the submission on the ChemRTK HPV Challenge website on October 12, 2001 (http://www.epa.gov/chemrtk/pubs/summaries/rosinadd/cl3177tc.htm'). EPA comments on the original submission were posted to the website on March 26, 2002. Public comments were also received and posted to the website. The sponsor submitted updated/revised documents on March 19, 2002, August 29, 2002, September 26, 2002, and November 18, 2004, which were posted to the ChemRTK website on April 2, 2002, September 5, 2002, October 17, 2002 and December 21, 2004, respectively. The Rosin Adducts and Adduct Salts Category consist of the following substances: Rosin, fumarated CAS No. 65997-04-8 Rosin, fumarated, sodium salt CAS No. 68201-59-2 Rosin, fumarated potassium salt CAS No. 68649-83-2 Rosin, maleated CAS No. 8050-28-0 Rosin, maleated, potassium salt CAS No. 85409-27-4 Rosin, maleated/fumarated CAS No. 68554-16-5 This screening-level hazard characterization is based primarily on the review of the Test Plan and Robust Summaries of studies submitted by the sponsors) under the HPV Challenge Program. In preparing the hazard characterization, EPA considered its own comments and public comments on the original submission as well as the sponsor's responses to comments and revisions made to the submission. The structures of the sponsored chemicals are included in the appendix. Summary tables of SIDS endpoint data are included in the document. The screening- level hazard characterization for environmental and human health toxicity is based largely on SIDS endpoints and is described according to established EPA or OECD effect level definitions and hazard assessment practices. Category Justification The six members of the rosin adducts and adduct salts are derived from rosin. The substances in this category are complex mixtures; also called Class 2 substances, which means that they are composed of several chemicals with concentrations that vary depending on their source and methods of derivation. Each category member is derived from rosin that has been chemically reacted with either fumaric acid or maleic anhydride. A representative reaction between representative rosin and maleic anhydride to form a maleated rosin adduct is presented in the appendix. The sodium and potassium rosin adduct salts are simply the rosin adducts that have been reacted with either sodium hydroxide or potassium hydroxide. Therefore, all of the substances in this category are very similar in chemical composition being either fumarated or maleated adducts of rosin or rosin adduct salts. Rosin, fumarated (CAS# 65997-04-8) was selected as the representative substance in this category for ecotoxicity and mammalian toxicity testing. In addition, the fumarated rosin adduct is the most chemically and thermodynamically stable of the rosin adducts. Rosin is a naturally occurring substance found predominantly in pine trees and is obtained by chemical or distillation processes from the pulping of pine wood. There are three different types of rosins: gum, wood and tall oil rosin— the type depends on the way it is extracted from the pine tree. The composition of a typical tall oil rosin is provided in the appendix. Gum rosin is derived by slashing the tree and collecting the gummy exudates, which are further distilled; wood rosin is obtained by solvent extraction of pine wood; and tall oil rosin is obtained by distillation of tall oil (the Tall Oil and Related Substance Category has also been sponsored and characterized under the HPV Challenge Program). Rosin is composed primarily of resin acids, a class of tricyclic carboxylic acids, and contains minor amounts of dimerized rosin and unsaponifiable matter (the Rosin and Salts Category has also been sponsored and characterized under the HPV Challenge Program). Chemically, the three rosins are very similar, containing the same resin acids in slightly different ratios, and have the same CAS No. 8050-09-7. The sponsor reported typical compositions of the three types of rosins, as presented in the appendix. Representative resin acid structures are depicted in the appendix. 3 ------- In comments on the original test plan EPA questioned the justification of fumarated rosin as the representative compound for this category. The concern was that maleated rosin might be more biologically active than fumarated rosin. In the revised test plan, the sponsors explained that at the temperature where rosin/fumaric acid adduction occurs, isomerization and dehydration of a fraction of the fumaric acid to maleic anhydride invariably takes place. The result being that a portion (10-20%) of the adduct is the rosin/maleic anhydride reaction product and that any potential effects of the maleic anhydride adduct will be included in the testing of the fumaric acid adduct. The sponsors also stated that testing the fumaric acid adduct is equivalent to testing the maleic anhydride adduct because it is likely that the anhydride adduct will be readily hydrolyzed to the maleic acid adduct in an aqueous media and that since the maleic acid adduct and the fumaric acid adduct are cis-trans isomers, the hypothetical reactivity of the two adducts to proteins or other macromolecules should be equivalent. The sponsor also submitted additional data for maleated rosin (CAS # 68425-08-1) to demonstrate that the testing on fumarated rosin represents maleated rosin. EPA agrees that the rationale and additional test data support the assessment of the sponsored substances as a category. Sii mm;in-Conclusion The Ion k \ allies of rosm and rosm sails \ ai> rcfleclum I lie coniple\ nature of these Class 2 substances The upper raime of ilic Ion k \ allies for ilie calenors members indicates ilial llieir potential to hioaeeiiniulate is expected to he liinli I lie catenoix members are not readils biodeniadable. indicatum ilie> lia\e the potential to persist in the eu\ iroumeui I lie aquatic toxicits data submitted were ncucraled iismn the W ater \eeoniniodated Traction method. I lie e\ alualioii of a\ ailahlc toxicity data for fish and aquatic plants indicate the potential lia/ard to these aquatic ornauisnis is based on no effects obseix ed at the water solubility limn (saturation) of liiniai.ited rosin While the acute icstiun did not show toxicits mi aquatic ornauisnis. the ph\ sical-cheniical properties of the substances mi this catenoix indicate lhe> are soluble or niiscihle mi waleral concentrations that could cause chronic effects \cute oral toxicits of members of the rosm adducts and adduct salts catenoix is low Repeated dietaix exposures at 2(>n and 5ii(i nm kn-bw da> resulted mi decreases mi mean bod> wcmlit nam and food cousuniptioii Treatment with 5(>(> nm kn-bw da\ resulted in increases in total bilirubin mi both sexes. decreases mi henialolonical parameters mi males and decreased adrenal weinhts (absolute and relati\ei and th\ line atrophs m females kcproducli\ e effects were apparent at 5<»> nm kn-bw da> and included delated malum tune, increased nestalioiial time and decreased mean number of implants I )e\ clopnieuial effects seen at 5<>(> nm kn-bw da> included reduction m Inter si/e and weinlit I lie potential health lia/ard of rosm adducts and adduct salts is moderate based on the repeated-dose toxicits The chrome iu\ ertebrate to\icil> test remains a data uap under the I IPX" Challeuue I'romani Siibsequeui coiisideratiou of late and e\posure iiilormaliou w ill inform a determination olTlic need to obtain chrome aquatic lo\icil> data lor these substances 1. Physical-Chemical Properties and Environmental Fate A summary of physical-chemical properties and environmental fate data submitted is provided in Table 1. For the purpose of the screening-level hazard characterization, the review and summary of these data was limited to the octanol-water partition coefficient and biodegradation endpoints as indictors of bioaccumulation and persistence, respectively. Octanol-Water Partition Coefficient Because these substances in this category are Class 2 mixtures, the procedure (OECD 117) to determine the Kow yields a range of Kow values rather than a single value representative of the mixture. Thus, the results reflect the partition coefficients of the components rather than the mixture. 4 ------- Rosin, fumarated (CAS No. 64997-04-8) Log Kow: 4.4 - 7.0 at pH 2 (measured) Rosin, fumarated, sodium salt (CAS No. 68201-59-2) Log Kow: 1.5 - 6.6 at pH 2 (measured) Rosin, fumarated, potassium salt (CAS No. 68649-83-2) Log Kow: 3.2 - 6.6 at pH 2 (measured) Rosin, maleated (CAS No. 8050-28-0) Log Kow: 1.5 - 7.6 at pH 2 (measured) Rosin, maleated, potassium salt (CAS No. 85409-27-4) Log Kow: 1.4 - 7.9 at pH 2 (measured) Rosin, maleated/fumarated (CAS No. 68554-16-5) Log Kow: 1.5 - 6.6 at pH 2 (measured) Biodegradation Rosin, fumarated (CAS No. 65997-04-8) In a ready biodegradation test using secondary effluent collected from a domestic waste water treatment facility as inoculum, 15% of fumarated rosin had degraded after 28 days. Rosin, fumarated is not readily biodegradable. Rosin, fumarated, sodium salt (CAS No. 68201-59-2) An inherent biodegradation test was submitted for this substance. The inherent biodegradation test is not adequate for the purposes of the HPV Challenge Program. Therefore, ready biodegradation for rosin, fumarated (CAS No. 65997-04-8) was used to evaluate the biodegradation of rosin, fumarated sodium salt. Rosin, fumarated sodium salt is not readily biodegradable based on the data for rosin, fumarated. Rosin, fumarated, potassium salt (CAS No. 68649-83-2) An inherent biodegradation test was submitted for this substance. The inherent biodegradation test is not adequate for the purposes of the HPV Challenge Program. Therefore, ready biodegradation for rosin, fumarated (CAS No. 65997-04-8 ) was used to evaluate the biodegradation of rosin, fumarated potassium salt. Rosin, fumarated potassium salt is not readily biodegradable based on the data for rosin, fumarated. Rosin, maleated (CAS No. 8050-16-5) In a Modified Sturm test using activated sludge from a domestic waste water treatment facility as inoculum, 0.34% of maleated rosin had degraded after 29 days. Rosin, maleated is not readily biodegradable. Rosin, maleated,potassium salt (CASNo. 85409-27-4) An inherent biodegradation test was submitted for this substance. The inherent biodegradation test is not adequate for the purposes of the HPV Challenge Program. Therefore, ready biodegradation for rosin (CAS No. 8050-09-7) was used to evaluate the biodegradation of rosin, potassium salt. Rosin, maleated potassium salt is not readily biodegradable based on the data for rosin, maleated. Rosin maleated/fumarated (CAS No. 68554-16-5) In a Modified Sturm test using activated sludge from a domestic waste water treatment facility as inoculum, 18.9% of fumatated/maleated rosin had degraded after 29 days. Rosin, maleated/ fumarated is not readily biodegradable. 5 ------- Conclusion: The log Kow values of rosin and rosin salts vary reflecting the complex nature of these Class 2 substances. The upper range of the log Kow values for the category members indicates that their potential to bioaccumulate is expected to be high. The category members are not readily biodegradable, indicating they have the potential to persist in the environment. Table 1. Summary (if Physical-Chemical Properties and Environmental Fate Data Endpoints Rosin, fumarated (68997-04-8) Rosin, fumarated, sodium salt (68201-59-2) Rosin, fumarated, potassium salt (68649-83-2) Rosin, maleated (8050-28-0) Rosin, maleated, potassium salt (85409-27-4) Rosin, maleated/ fumarated (68554-16-5) Melting Point (°C) Melting point and boiling points were not determined because these substances are complex mixtures and will either not give a sharp melting point when heated or will decompose before they melt or boil. Boiling Point (°C) Vapor Pressure (hPa at 25°C) Under ambient conditions, accurate measurement of vapor pressure of these mixtures is difficult; based on their physical characteristics (solid at room temperature), their vapor pressure is expected to be negligible. Log K„w 4.4 - 7.0 (m) 1.5 - 6.6 (m) 3.2 - 6.6 (m) 1.5 - 7.6 (m) 1.4 - 7.9 (m) 1.5 - 6.6 (m) Water Solubility (mg/L at 25°C) 9.0 (m) Miscible Miscible 1.38 (m) Miscible 0.58 (m) Direct Photodegradation Direct photolysis is not expected to contribute to degradation. Indirect (OH ) Photodegradation Half-life (t1/2) Not expected to undergo photodegradation as the vapor pressure is negligible. Stability in Water (Hydrolysis) (t1/2) Based on low water solubility (<10 ppm), test was not conducted. Fugacity (Level in Model) Not estimated due to inability to obtain input values for the required model because the substances complex mixtures. Biodegradation at 28 days (%) 15 (m) Not Readily Biodegradable No Data1 Not Readily Biodegradable (RA) No Data1 Not Readily Biodegradable (RA) 0.34 (m) Not Readily Biodegradable No Data1 Not Readily Biodegradable (RA) 18.9 (m) Not Readily Biodegradable (m) = measured data (i.e., derived from experiment); 1 Inherent biodegradation test submitted. 2. Environmental Effects - Aquatic Toxicity A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 2. The table also indicates where data for tested category members are read-across (RA) to untested members of the category. Acute Toxicity to Fish Rosin, fumarated (CAS No. 65997-04-8) Fathead minnows (Pimephales promelas) were exposed to the test substance as water accommodated fractions (WAFs) under static conditions for 96 hours. The loading rates were 0, 1, 10, 100 or 1000 mg/L and no analytical measurements were made on the WAFs. No effects were noted at any of the WAF loading rates. EPA does not consider the loading rate as the no effect concentration when the concentration exceeds the water solubility of the substance. Assuming exposure concentration in the WAF is the water solubility limit (saturation) for rosin, the no effect concentration would be approximately 9.0 mg/L. No effects at saturation 6 ------- Acute Toxicity to Aquatic Invertebrates Rosin, fumarated (CAS No. 65997-04-8) Daphnia magna were exposed to the test substance as water accommodated fractions (WAFs) under static conditions for 48 hours. The loading rates were 0, 1, 10, 100 or 1000 mg/L and no analytical measurements were made on the WAFs. No effects were noted at any of the WAF loading rates. EPA does not consider the loading rate as the no effect concentration when the concentration exceeds the water solubility of the substance. Assuming exposure concentration in the WAF is the water solubility limit (saturation) for rosin, the no effect concentration would be approximately 9.0 mg/L. No effects at saturation Toxicity to Aquatic Plants Rosin, fumarated (CAS No. 65997-04-8) Green algae (Pseudokirchneriella subcapitata) were exposed to the test substance as water accommodated fractions (WAFs) under static conditions for 72 hours. The loading rates were 0, 1, 10, 100 or 1000 mg/L and no analytical measurements were made on the WAFs. No effects were noted at any of the WAF loading rates. EPA does not consider the loading rate as the no effect concentration when the concentration exceeds the water solubility of the substance. Assuming exposure concentration in the WAF is the water solubility limit (saturation) for rosin, the no effect concentration would be approximately 9.0 mg/L. No effects at saturation Conclusion: The available aquatic toxicity data submitted were generated using the Water Accommodated Fraction method. The evaluation of available aquatic toxicity data for fish, aquatic invertebrates and algae indicates no effects were observed at the water solubility limit (saturation) of fumarated rosin. In comments on the original test plan, EPA recommended that the sponsor conduct chronic toxicity testing on invertebrates (i.e. the daphnid 21-day reproduction test). While the acute testing did not show toxicity in aquatic organisms, the physical-chemical properties of the substances in this category indicate they are soluble or miscible in water at concentrations that could cause chronic effects. Therefore, the chronic invertebrate toxicity test remains a data gap under the HPV Challenge Program. Subsequent consideration of fate and exposure information will inform a determination of the need to obtain chronic aquatic toxicity data for these substances. Table 2. Summary of Environmental Effects - Aquatic Toxicity Data Endpoints Rosin, fumarated 68997-04-8) Rosin, fumarated, sodium salt 68201-59-2) Rosin, fumarated, potassium salt (68649-83-2) Rosin, maleated (8050-28-0) Rosin, maleated, potassium salt (85409-27-4) Rosin, maleated/ fumarated 68554-16-5) Fish 96-h LCS0 (mg/L) NES1 No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) Aquatic Invertebrates 48-h ECS„ (mg/L) NES1 No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) Aquatic Plants 72-h ECS0 (mg/L) NES1 No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) No Data NES1 (RA) 1NES = No effects at saturation (water solubility limit); (RA) = Read Across 3. Human Health Effects A summary of health effects data submitted for SIDS endpoints is provided in Table 3. The table also indicates where data for tested category members are read-across (RA) to untested members of the category. 7 ------- Acute Oral Toxicity Rosin, fumarated (CAS No. 65997-04-8) Female Sprague-Dawley rats were administered a single oral dose of rosin, fumarated via gavage at 2000 mg/kg-bw and observed for 14 days. No mortality or signs of toxicity reported. LDS0 (females) > 2000 mg/kg-bw Rosin, maleated (CAS No. 8050-16-5) Female Sprague-Dawley rats administered a single oral dose of rosin, maleated via gavage at 2000 mg/kg-bw and observed for 14 days. No mortality or signs of toxicity reported. LDS0 (females) > 2000 mg/kg-bw Repeated-Dose Toxicity Rosin, fumarated (CAS No. 65997-04-8) In a combined repeated-dose/reproductive/developmental toxicity screening test, Sprague-Dawley rats (10/sex/dose) were administered rosin, fumarated, via the diet at 0, 1000, 3000 or 10,000 ppm (approximately 91, 260 or 500 mg/kg-bw/day, respectively) daily for 4 weeks. Males were dosed for 4 weeks, starting from 2-weeks prior to mating. Females were dosed 2 weeks prior to mating and until day 6 of lactation. At 3000 and 10,000 ppm, there was a decrease in mean body weight gain and food consumption in both sexes. Also at this dose total bilirubin was markedly increased in both sexes, hemoglobin; red blood cells and hematocrit were slightly decreased in males and adrenal weights (absolute and relative) were decreased in females. In females, results of histopathology revealed thymic atrophy. Clinical observations associated with treatment were abnormal colored urine at all treatment levels and soft fecal output at 3000 and 10,000 ppm. LOAEL ~ 260 mg/kg-bw/day (based on decreased body weight and food consumption) NOAEL ~ 91 mg/kg-bw/day Reproductive Toxicity Rosin, fumarated (CAS No. 65997-04-8) In the combined repeated-dose/reproductive/developmental toxicity screening test described previously, there were slight increases in time to mating and in the duration of gestation and decreases in the mean number of implants per pregnancy noted at the 10,000 ppm dose. LOAEL (systemic toxicity) ~ 260 mg/kg-bw/day (based on decreased body weight and food consumption) NOAEL (systemic toxicity) ~ 91 mg/kg-bw/day LOAEL (reproductive toxicity) ~ 500 mg/kg-bw/day (based on increased time to successful mating and decreased mean number of implants) NOAEL (reproductive toxicity) ~ 260 mg/kg-bw/day Developmental Toxicity Rosin, fumarated (CAS No. 65997-04-8) In the combined repeated-dose/reproductive/developmental toxicity screening test described previously, dams showed decreased body weight gain and food consumption at 3000 and 10,000 ppm. A reduction in litter size and litter weight was evident at 10,000 ppm. LOAEL (maternal toxicity) ~ 260 mg/kg-bw/day (based on decreased body weight gain and food consumption) NOAEL (maternal toxicity) ~ 91 mg/kg-bw/day LOAEL (developmental toxicity) ~ 500 mg/kg-bw/day (based on reduced litter size and weight) NOAEL (developmental toxicity) ~ 260 mg/kg-bw/day 8 ------- Genetic Toxicity - Gene Mutation In vitro Rosin, fumarated (CAS No. 65997-04-8) In a reverse mutation test, Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA were exposed to rosin, fumarated at concentrations of 17, 50, 167, 600, 1667 and 5000 (ig/plate in the presence and absence of metabolic activation. Positive controls were employed (responses were not reported). No increases in mutation frequency were reported at any concentration of fumarated rosin with or without metabolic activation. Rosin, fumarated was not mutagenic in this assay. Genetic Toxicity - Chromosomal Aberrations In vitro Rosin, fumarated (CAS No. 65997-04-8) In a cytogenetic test, Chinese hamster ovary cells were exposed to rosin, fumarated at concentrations of 20 - 200 (ig/mL without metabolic activation and 5-80 (ig/mL with S9 mix. No increase in the number of aberrations in exposed cells was measured in either the presence or absence of metabolic activation. Positive controls were employed (responses were not reported). Rosin, fumarated was not clastogenic in this assay. Conclusion: Acute oral toxicity of members of the rosin adducts and adduct salts category is low. Repeated dietary exposures at ~ 260 and ~ 500 mg/kg-bw/day resulted in decreases in mean body weight gain and food consumption. Treatment with ~ 500 mg/kg-bw/day resulted in increases in total bilirubin in both sexes, decreases in hematological parameters in males and decreased adrenal weights (absolute and relative) and thymic atrophy in females. Reproductive effects were apparent at ~ 500 mg/kg-bw/day and included delayed mating time, increased gestational time and decreased mean number of implants. Developmental effects seen at ~ 500 mg/kg-bw/day included reduction in litter size and weight. The potential health hazard of rosin adducts and adduct salts is moderate based on the repeated-dose toxicity. Table 3. Summary of Health Effects Data Endpoints Rosin, fumarated (68997-04-8) Rosin, fumarated, sodium salt (68201-59-2) Rosin, fumarated, potassium salt (68649-83-2) Rosin, maleated (8050-28-0) Rosin, maleated potassium salt (85409-27-4) Rosin, maleated/ fumarated (68554-16-5) Acute Oral Toxicity LDS0 (mg/kg-bw) >2000 No Data >2000 (RA) No Data >2000 (RA) >2000 No Data >2000 (RA) No Data >2000 (RA) Repeated-Dose Toxicity Oral (mg/kg-bw/day) NOAEL-91 LOAEL ~ 260 No Data NOAEL-91 LOAEL -260 (RA) No Data NOAEL-91 LOAEL -260 (RA) No Data NOAEL-91 LOAEL -260 (RA) No Data NOAEL-91 LOAEL -260 (RA) No Data NOAEL - 91 LOAEL -260 (RA) Reproductive/ Developmental Toxicity (mg/kg-bw/day) Systemic and Maternal Toxicity NOAEL-91 LOAEL-260 No Data NOAEL-91 LOAEL -260 No Data NOAEL-91 LOAEL -260 No Data NOAEL-91 LOAEL -260 No Data NOAEL-91 LOAEL -260 No Data NOAEL - 91 LOAEL -260 Reproductive and Developmental Toxicity NOAEL - 260 LOAEL-500 NOAEL -260 LOAEL -500 (RA) NOAEL -260 LOAEL -500 (RA) NOAEL -260 LOAEL -500 (RA) NOAEL -260 LOAEL -500 (RA) NOAEL -260 LOAEL -500 (RA) 9 ------- Tabic 3. Summary of Health Effects Data Endpoints Rosin, fumarated (68997-04-8) Rosin, fumarated, sodium salt (68201-59-2) Rosin, fumarated, potassium salt (68649-83-2) Rosin, maleated (8050-28-0) Rosin, maleated potassium salt (85409-27-4) Rosin, maleated/ fumarated (68554-16-5) Genetic Toxicity - Gene Mutation In vitro Negative No Data Negative (RA) No Data Negative (RA) No Data Negative (RA) No Data Negative (RA) No Data Negative (RA) Genetic Toxicity - Chromosomal Aberrations In vitro Negative No Data Negative (RA) No Data Negative (RA) No Data Negative (RA) No Data Negative (RA) No Data Negative (RA) Bold = measured data; (RA) = Read Across 4. Hazard Characterization The log Kow values of rosin and rosin salts vary reflecting the complex nature of these Class 2 substances. The upper range of the log Kow values for the category members indicates that their potential to bioaccumulate is expected to be high. The category members are not readily biodegradable, indicating they have the potential to persist in the environment. The aquatic toxicity data submitted were generated using the Water Accommodated Fraction method. The evaluation of available toxicity data for fish and aquatic plants indicate the potential hazard to these aquatic organisms is low based on no effects observed at the water solubility limit (saturation) of fumarated rosin. While the acute testing did not show toxicity in aquatic organisms, the physical-chemical properties of the substances in this category indicate they are soluble or miscible in water at concentrations that could cause chronic effects. Acute oral toxicity of members of the rosin adducts and adduct salts category is low. Repeated dietary exposures at ~ 260 and ~ 500 mg/kg-bw/day resulted in decreases in mean body weight gain and food consumption. Treatment with ~ 500 mg/kg-bw/day resulted in increases in total bilirubin in both sexes, decreases in hematological parameters in males and decreased adrenal weights (absolute and relative) and thymic atrophy in females. Reproductive effects were apparent at ~ 500 mg/kg-bw/day and included delayed mating time, increased gestational time and decreased mean number of implants. Developmental effects seen at ~ 500 mg/kg-bw/day included reduction in litter size and weight. The potential health hazard of rosin adducts and adduct salts is moderate based on repeated-dose toxicity. 5. Data Gaps The chronic invertebrate toxicity test remains a data gap under the HPV Challenge Program. Subsequent consideration of fate and exposure information will inform a determination of the need to obtain chronic aquatic toxicity data for these substances. 10 ------- APPENDIX Members of this category are derived from rosin and either fumaric acid or maleic anhydride. The figure below depicts the reaction between representative rosin and maleic anhydride to form a maleated rosin adduct. The sodium and potassium rosin adduct salts are simply the rosin adducts that have been reacted with the appropriate base, either sodium hydroxide or potassium hydroxide. ch-c: S NCOOH LEVOPIMARIC MALEIC ANHYDRIDE ch~ c: "COOH MAUEOPIMARIC ACID General Composition of Gum. Wood and 1 all Oil Romiuj Components Gum Wood Tall Oil Abietic acid 20% 45% 35% Palustric acid 18% 10% 10% Isopimaric acid 18% 11% 7% Dehydroabietic acid 4% 8% 20% Neoabietic acid 18% 7% 4% Pimaric acid 2% 3% 3% 11 ------- The figures below are general representative structures found in rosin (as rosin is a mixture). Details of composition can be found in Rosin and Rosin Salts Hazard Characterization. *COCH MWIfcT»» V^-OOOH ~'NcOOH ""COOM •WLumrive giS5" 0^ / -tuoh < 'turn Pfetwrfc Tyixi KlWll Typa HOOC COMMtNNIC Figure 1. Representative' resin acids found in rosin and its deriwatives. 12 ------- |