# I UCLID

Data Set

Existing Chemical : ID: 108-19-0 CAS No. : 108-19-0 EINECS Name : biuret EC No. : 203-559-0 Molecular Formula C2H5N302 Producer related part Company : Epona Associates, LLC Creation date : 05.06.2007 Substance related part Company : Epona Associates, LLC Creation date : 05 .06.2007 Status . Memo : Fulfillment of data requirements under TSCA section 4 Printing date : 03.07 .2007 Revision date . Date of last update : 03.07 .2007 Number of pages : 64 Chapter (profile) : Chapter : 1, 2, 3, 4, 5, 6, 7, 8, 10 Reliability (profile) : Reliability: without reliability, 1, 2, 3, 4 Flags (profile) : Flags: without flag, confidential, non confidential, WGK (DE), TA-Luft (DE), Material Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDS



# CONTAINS NOCB1 1/64 371

## 1 . General Information

1 .0.1 APPLICANT AND COMPANY INFORMATION 1 .0.2 LOCATION OF PRODUCTION SITE, IMPORTER OR FORMULATOR 1 .0.3 IDENTITY OF RECIPIENTS 1 .0.4 DETAILS ON CATEGORY/TEMPLATE 1 .1 .0 SUBSTANCE IDENTIFICATION IUPAC Name . Smiles Code . Molecular formula : C2H5N302 Molecular weight : 103.09 Petrol class . 05.06.2007 1 .1 .1 GENERAL SUBSTANCE INFORMATION Purity type . Substance type . Physical status . Purity , Colour Odour : odorless 05.06.2007 1 .1 .2 SPECTRA 1 .2 SYNONYMS AND TRADENAMES AI3-14905 25.06.2007 Allophanamide 05.06.2007 Allophanic acid amide 05.06.2007 Id 108-19-0 Date 03.07 .2007

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## 1 . General Information Allophanimidic acid 25 .06 .2007 Allophanimidic acid (VAN) 05.06.2007 Biuret 25.06.2007 Biuret (ACN)(8C1) 05.06.2007 Carbamoylurea 25.06.2007 Carbamylurea 05 .06.2007 Caswelt No. 106A 25.06.2007 Caswell No. 159A 25.06.2007 Dicarbamylamine 05.06.2007 EPA Pesticide Chemical Code 206200 25 .06 .2007 Imidodicarbonic diamide (9C1) 05.06.2007 Isobiuret 25.06.2007 lsobiuret (VAN) 05.06.2007 L-101 05.06.2007 Id 108-19-0 Date 03 .07.2007

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## 1 . General Information NSC 8020 25.06 .2007 Urea, (aminocarbonyl)- 05 .06.2007 Ureidoformamide 05.06.2007 1 .3 IMPURITIES 1 .4 ADDITIVES 1 .5 TOTAL QUANTITY Quantity Remark

03 .07 .2007 1 .6.1 LABELLING 1 .6 .2 CLASSIFICATION 1 .6.3 PACKAGING 1 .7 USE PATTERN Type of use Category Remark 03.07 .2007 Id 108-19-0 Date 03.07.2007

0 - 0 tonnes produced in 2005 : Biuret is considered an impurity of urea with no commercial purpose for reporting under TSCA Section 8 Inventory Update Reporting (IUR), is not manufactured or processed for distribution in commerce as a chemical substances per se and, relative to the fertilizer industry, has no commercial purpose separate from the substance mixture or article of which they may be a part (40 CFR § 710.4(d) . biuret is not a commercial product ; it is produced incidentally during the production of urea fertilizers and as such is not reportable under the Inventory reporting Rule. The members of The Fertilizer Institute are not Tier 1 producers of biuret . (37)

. use : Biuret is produced incidentally in the production of urea fertilizers ; it is produced commercially by the members of The Fertilizer Institute. (37)

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## 1 . General Information Type of use : use Category . Remark ld 108-19-0 Date 03.07 .2007

Use: Feed Grade Food Additive: [Federal Register : May 22, 2003 (Volume 68, Number 99)] [Rules and Regulations] [Page 27904] Fromthe Federal Register Online via GPOAccess [wais .access .gpo.gov] [DOCID:fr22my03-5]

- --- - - -- --- - - - -- --- -- --- -- --- - - -- --- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 573 [Docket No . 02F-0327] Food Additive Permitted in Feed and Drinking Water of Animals; Feed-Grade Biuret AGENCY: Food and Drug Administration, HHS. ACTION: Final rule . -------------------- ------------- -- SUMMARY: The Food and Drug Administration (FDA) is amending the regulations for food additives to provide for the safe use of feedgrade biuret in lactating dairy cattle feed. This action is in response to a food additive petition filed by ADM Alliance Nutrition, Inc. DATES: This rule is effective May 22, 2003; written objections and request for hearing should be submitted by July 23, 2003. ADDRESSES: Submit written objections to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm . 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Sharon Benz, Center for Veterinary Medicine (HFV-228), Food and Drug Administration, 7500 Standish PI ., Rockville, MD 20855, 301-827-6656. SUPPLEMENTARY INFORMATION: I . Background In a notice published in the Federal Register of August 28, 2002 (67 FR 55269), FDA announced that a food additive petition (FAP 2248) had been filed by ADM Alliance Nutrition, Inc., 1000 North 30th St ., 5/64p. 6



## 1 . General Information Id 108-19-0 Date 03.07 .2007 P.O . Box C1 ., Quincy, IL 62305-7100 . The petition proposed to amend the food additive regulations in Part 573 Food Additives Permitted in Feed and Drinking Water of Animals (21 CFR part 573) to provide for the use of feed grade biuret in the diets of lactating dairy cows. The notice of filing provided for a 75-day comment period on the petitioner's environmental information . No substantive comments have been received . II . Conclusion FDA has evaluated data submitted by the sponsor of the petition and concludes that the data establish the safety and functionality of feedgrade biuret for use as proposed. III . Public Disclosure In accordance with Sec. 571 .1(h) (21 CFR 571 .1(h)), the petition and the documents that FDA considered and relied upon in reaching its decision to approve the petition are available for inspection at the Center for Veterinary Medicine by appointment with the information contact person listed above. As provided in Sec. 571 .1(h), the agency will delete fromthe documents any materials that are not available for public disclosure before making the documents available for inspection . IV . Environmental Impact The agency has determined under 21 CFR 25.32(r) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment . Therefore, neither an environmental assessment nor an environmental impact statement is required. V . Objections and Hearing Requests Any person who will be adversely affected by this regulation may at any time on or before July 23, 2003, file with the Dockets Management Branch (address above) written objections thereto. Each objection shall be separately numbered, and each numbered objection shall specify with particularity the provisions of the regulation to which objection is made and the grounds for the objection. Each numbered objection on which a hearing is requested shall specifically so state. Failure to request a hearing for any particular objection shall constitute a waiver of the right to a hearing on that objection . Each numbered objection for which a hearing is requested shall include a detailed description and analysis of the specific factual information intended to be presented in support of the objection in the event that a hearing is held. Failure to include such a description and analysis for any particular objection shall constitute a waiver of the right to a hearing on the objection. Three copies of all documents shall be submitted and shall be identified with the docket number found in brackets in the heading of this document . Any objections received in response to the regulation may be seen in the Dockets Management Branch between 9 a .m

. and 4 p.m

., Monday through Friday. List of Subjects in 21 CFR Part 573 Animal feeds, Food additives .p. 7



## 1 . General Information

Test substance 03.07 .2007 Id 108-19-0 Date 03.07.2007 0 Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs and redelegated to the Center for Veterinary Medicine, 21 CFR part 573 is amended as follows: PART 573--FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS 0 1 . The authority citation for 21 CFR part 573 continues to read as follows : Authority: 21 U.S .C. 321, 342, 348. Sec. 573.220 Feed-grade biuret . 0 2. Section 573 .220 Feed-grade biuret is amended by removing paragraph (c)(1)(iii) . Dated : May 14, 2003. Stephen F. Sundlof, Director, Center for Veterinary Medicine. [FR Doc. 03-12785 Filed 5-21-03; 8:45 am] Biuret Type of use : use Category , Remark (46) On April 15, 2002, the Environmental Protection Agency (EPA) issued its tolerance reassessment decision for the frost protectant pesticide urea, and is inviting public comment until May 15, 2002. EPA finds that urea poses no risk concerns within the limits of the existing tolerance exemptions . Therefore, no additional risk mitigation is needed, and no changes will be made to the 78 urea tolerance exemptions as a result of this reassessment decision. EPA regards the 78 exemptions as completed tolerance reassessments, contributing toward the Agency's goal of completing 66% of all required tolerance reassessment decisions by August 3, 2002. A naturally occurring compound in humans, urea is approved for several human therapeutic uses. In addition, urea is considered "Generally Recognized As Safe" (GRAS) as affirmed by the U. S. Food and Drug Administration for use in food. Urea is an active ingredient in only one registered pesticide product, Enfrost, which is registered for commercial application to a wide variety of field crops, vegetables, fruit trees, and ornamentals to reduce frost formation by ice-nucleating bacteria naturally present on leaf surfaces. Urea also is an inert ingredient included in pesticide products as a stabilizer, inhibitor, or intensifier . Outside the pesticide realm, urea is included in fertilizer, used as an animal feed supplement, and used in the manufacture of dyes, fire retardant paints, plasticizers, and stabilizers for explosives. The Federal Register notice is available on EPA's website at http://www

.epa .gov/fedrgstr. Risk assessments and related documents for urea also are available at http://www .epa .gov/oppsrrdl/reregistration/urea/

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## 1 . General Information Test substance : Urea 03.07 .2007 Type of use : use Category Remark : 21 C .F .R. § 184.1923 Urea . Title 21 - Food and Drugs

Test substance 03.07 .2007 Id 108-19-0 Date 03.07 .2007 (44)

Title 21 : Food and Drugs PART 184-DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZEDAS SAFE Subpart B-Listing of Specific Substances Affirmed as GRAS Browse Previous I Browse Next § 184.1923 Urea. (a) Urea (CO(NH2)2, CAS Reg. No. 57-13-6) is the diamide of carbonic acid and is also known as carbamide. It is a white, odorless solid and is commonly produced from C02 by ammonolysis or fromcyanamide by hydrolysis . (b) FDA is developing food-grade specifications for urea in cooperation with the National Academy of Sciences. In the interim, this ingredient must be of a purity suitable for its intended use. (c) In accordance with §184 .1(b)(1), the ingredient is used in food with no limitation other than current good manufacturing practice. The affirmation of this ingredient as generally recognized as safe as a direct human food ingredient is based upon the following current good manufacturing practice conditions of use: (1) The ingredient is used as a formulation aid as defined in §170.3(o)(14) of this chapter and as a fermentation aid. (2) The ingredient is used in yeast-raised bakery products; in alcoholic beverages as defined in §170.3(n)(2) of this chapter ; and in gelatin products. (d) Prior sanctions for this ingredient different from the uses established in this section do not exist or have been waived. (48 FR 51616, Nov. 10, 1983, as amended at 49 FR 19816, May 10, 1984) Urea (43) Type of use : use Category Remark

Test substance 03.07 .2007 Urea is approved for several therapeutic uses in humans with relatively few toxicities. Urea is used primarily as an osmotic agent for inducing diuresis and reducing intraoccular and intracranial pressure. Urea has also been used as a topical anesthetic for the treatment of mouth and throat inflammation (10-15%urea gel, liquid or solution), to debride necrotic and infected tissues, i .e. fingernails and toenails . It is also used in the treatment of sickle- cell anemia and to ammoniate dentrifices as well as a basic ingredient in the synthesis of medically important compounds such as barbiturates and urethanes . http://www

.epa .gov/oppsrrd1/REDs/urea_tred .htm; http://216.239.51 .104/search?q=cache:p1264Z8FFIJ :www

.fda .gov/cder/ogd/rld/12154s24 .pdf+FDA+category+C+ure a&hl=en&ct=clnk&cd=1 &gl=us Urea (45)

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## 1 . General Information 1 .7.1 DETAILED USE PATTERN 1 .7.2 METHODS OF MANUFACTURE 1 .8 REGULATORY MEASURES Id 108-19-0 Date 03.07 .2007

Remark : Fertilizers, fertilizer materials, and their manufacturing facilities are highly regulated at the federal and state level . At the federal level, standards are in place to govern: (I) air emissions fromfertilizer and fertilizer material manufacturing facilities [These regulations are found at : (1) 40 C.F .R. Part 60, Subpart G (standards of performance for nitric acid plants) ; (2) 40 C

.F .R. Part 60, Subpart H (standards of performance for sulfuric acid plants) ; (3) 40 C.F.R. Part 60, Subpart T (standards of performance for wet process phosphoric acid plants) ; (4) 40 C.F .R. Part 60, Subpart U (standards of performance for superphosphoric acid plants) ; (5) 40 C.F .R. Part 60, Subpart V (standards of performance for diammoniumphosphate plants) ; (6) 40 C.F .R. Part 60, Subpart W

(standards of performance for triple superphosphate plants) ; (7) 40 C .F .R. Part 60, Subpart X (standards of performance for granular triple supetphosphate storage facilities) ; (8) 40 C .F .R. Part 60 , Subpart NN (standards of performance for phosphate rock plants) ; (9) 40 C

.F .R. Part 60, Subpart PP (standards of performance for ammoniumsulfate plants) ; (10) 40 C .F .R. Part 61, Subpart R (national emission standards for radon emissions ftom phosphogypsumstacks) ; (11) 40 C .F .R.] ; (2) solid and hazardous waste generation, storage, transportation, and disposal [40 C .F .R. §§ 260-299.] ; (3) water discharges [40 C .F .R. Part 122.] ; (4) accident prevention and mitijation [40 C .F .R. Part 68 and 29 C.F .R. § 1910.119.] ; (5) release reporting [40 C.F .R. §§ 302.4, 355.40 and 40 C

.F .R. Part 372. ] ; (6) worker exposure [29 C .F .R. §§ 1910.1000 and 1910.1020.] ; (7) hazard communication [29 C .F .R. § 1910.1200] ; and (8) transportation [49 C.F .R.SubchapterC] . These regulations provide a comprehensive federal program to regulate fertilizers and fertilizer materials . In addition, and without conceding any arguments that could be made to the contrary, TSCA § 6 provides EPA with the authority to either prohibit or limit the manufacture of a chemical substance upon a finding that its manufacture, processing, distribution in commerce, use, or disposal "presents or will present an unreasonable risk of injury to health or the environment ." Also, under TSCA § 7, the Agency has the authority to take certain actions in response to an "imminently hazardous chemical substance or mixture." In addition to federal regulations, the states regulate fertilizers and fertilizer materials . As noted in the attached document, entitled Summary of State Fertilizer Laws, 48 states have laws and regulations in place to regulate fertilizers and fertilizers materials . Many of these states have an "adulteration" clause in their laws that enable the responsible state agency to stop the sale of 9/64p. 10



## 1 . General Information Id 108-19-0 Date 03.07 .2007 fertilizers and fertilizer materials that are dangerous to human health. Notably, five states have adopted comprehensive regulations to limit the amounts of nonnutritive elements in fertilizers . These states are Washington, California, Oregon, Florida and Texas. EPA, in response to a congressional inquiry, endorsed these programs. Other states are developing similar regulations fostered by the work of the Association of American Plant Food Control Officials (AAPFCO) . 03.07 .2007 1 .8.1 OCCUPATIONAL EXPOSURE LIMIT VALUES 1 .8.2 ACCEPTABLE RESIDUES LEVELS 1 .8.3 WATER POLLUTION 1 .8.4 MAJOR ACCIDENT HAZARDS 1 .8 .5 AIR POLLUTION 1 .8.6 LISTINGS E .G. CHEMICAL INVENTORIES 1 .9.1 DEGRADATION/TRANSFORMATION PRODUCTS 1 .9.2 COMPONENTS 1 .10 SOURCE OF EXPOSURE 1 .11 ADDITIONAL REMARKS 1 .12 LAST LITERATURE SEARCH Type of search

. External Chapters covered : 3, 4, 5 Date of search : 01 .06.2007 Remark : BibIioLine 03.07 .2007 10/64p. 11



## 1 . General Information

1 .13 REVIEWS Id 108-19-0 Date 03.07.2007

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## 2. Physico-Chemical Data

2.1 MELTING POINT Value Sublimation Method Year GLP Test substance Remark

Reliability 05.06.2007 Value

. = 190 °C Decomposition : yes, at = 190 °C Sublimation , Method : other Year ; 1979 GLP : no data Test substance : as prescribed by 1 .1 - 1 .4 Reliability 27.06.2007 2.2 BOILING POINT Value

. = 193 °C at 1013 .25 hPa Decomposition : yes Method : other Year : 1976 GLP : no data Test substance : as prescribed by 1 .1 - 1 .4 Remark : HYGROSCOPIC ; PYROLYSIS @

HIGH TEMP (GREATER THAN 193 DEG C) YIELDS MELAMINE =188-190°C other 2000 no data as prescribed by 1 .1 - 1 .4 Id 108-19-0 Date 03 .07.2007

This record originally appeared in the ISHOW database. ISHOW - Information Systemfor Hazardous Organics in Water Details : Sample Record ISHOW, sponsored by the Office of Toxic Substances of the EPA, was developed by the EPA laboratory in Duluth, Minnesota in conjunction with the University of Minnesota. This database of 17,159 records includes physical property data on more than 5,700 different chemicals with bibliographic references to the original sources. Not all properties are recorded for all substances. (2) valid with restrictions Handbook data

(2) valid with restrictions Handbook data (35) (36)

(11)

This record originally appeared in the ISHOW database . ISHOW - Information System

for Hazardous Organics in Water Details: Sample Record ISHOW, sponsored by the Office of Toxic Substances of the EPA, was developed by the EPA laboratory in Duluth, Minnesota in conjunction with the University of Minnesota. This database of 17,159 records includes physical property data on more than 5,700 different chemicals with bibliographic references to the original sources. Not all properties are recorded for all substances.

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## 2. Physico-Chemical Data Reliability : (2) valid with restrictions Handbook data 05.06.2007 2.3 DENSITY Type : relative density Value

. = 1 .467 at °C Method : other Year : 1976 GLP : no data Test substance : as prescribed by 1 .1 - 1 .4 Remark : Density/Specific Gravity: 1 .467 @ -5 DEG C/4 DEG C Reliability : (2) valid with restrictions Handbook data 05.06.2007 2.3 .1 GRANULOMETRY 2.4 VAPOUR PRESSURE Value . .000013599 hPa at °C Decomposition . Method : other (calculated) Year : 2007 GLP : no Test substance : as prescribed by 1 .1 - 1 .4 Method : SUMMARY MPBPW IN v1 .42 ----------------

Remark Result Boiling Point : 323.89 deg C (Adapted Stein and Brown Method) Melting Point : 309.34 deg C (Adapted Joback Method) Melting Point : 75.46 deg C (Gold and Ogle Method) Mean Melt Pt : 192.40 deg C (Joback; Gold,Ogle Methods) Selected MP

: 122.23 deg C (Weighted Value) No physical properties input by user SUMMARY MPBPWIN v1 .42 Vapor Pressure Estimations (25 deg C) : (Using BP: 323.89 deg C (estimated)) (Using MP

: 190.00 deg C (exp database)) VP: 6.39E-006 mmHg (Antoine Method) VP: 1 .02E-005 mmHg (Modified Grain Method) VP: 2.45E-005 mmHg (Mackay Method) Selected VP: 1 .02E-005 mmHg (Modified Grain Method) Subcooled liquid VP: 0.000544 mmHg (25 deg C, Mod-Grain method) -------+-----+------------------+---------+-------- TYPE I NUM

I BOIL DESCRIPTION I COEFF I VALUE -------+-----+---------------+----------+-------- Id 108-19-0 Date 03.07 .2007 (38)

(38)

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## 2. Physico-Chemical Data

Reliability 27.06.2007 Id 108-19-0 Date 03.07 .2007 I I Equation Constant ~ ~ 198.18 -------------+-----_____------__-_+_--------- ------------- ----- ------ - ----------+_________ RESULT-uncorrj BOILING POINT in deg Kelvin 1 658.96 RESULT- corr I BOILING POINT in deg Kelvin 1 597 .05 1 BOILING POINT in deg C 1 323 .89 Group 1 2 1 -C(=0)NH2 1 230.39 1 460.78



## ----------------------------

----- ----- -+---------------+--------+------ TYPE I NUM

I MELT DESCRIPTION I COEFF I VALUE --------------------------___+--------+-------- Group ~ 2 1 -C(=0)NH2 ~ 230.00 1 460.00 " I ~ Equation Constant ~ 1 122.50

-- RESULT I MELTING POINT in deg Kelvin 1 582.50 1 MELTING POINT in deg C 1 309.34 

## ----------------

------------------- - -- ---- (2) valid with restrictions - - Modeled data 2.5 PARTITION COEFFICIENT Partition coefficient Log pow pH value Method Year GLP Test substance Method

Remark Result : octanol-water

. -1 .399 at °C other (calculated) 2007 no as prescribed by 1 .1 - 1 .4 KOWWIN Program (v1 .67) SMILES : 0=C(NC(=0)N)N CHEM : Imidodicarbonic diamide MOL FOR: C2 H5 N3 02 MOL WT : 103.08 No physical properties input by user KOWWIN Program (v1 .67) Results: (7)

Log Kow(version 1 .67 estimate) : -1 .40 ------+-----+----------------------------------+------+-_--- TYPE I NUM

~ LOGKOW

FRAGMENT DESCRIPTION ~ COEFF ~ VALUE ------+-----+--------------------------------------+-------+---- Frag ~ 2 ~ -NH2 [aliphatic attach] 1-1 .4148 1-2.8296 Frag ~ 1 ~ -NH- [aliphatic attach] 1-1 .4962 1-1 .4962 Frag ~ 2 ~ -NC(=0)N- [urea] 11 .0453 1 2.0906 Factorl 1 1 -N-CO-N-CO- structure correction ~ 0 .6074 1 0.6074 Const I ~ Equation Constant ~ ~ 0.2290 -------+-----+---------------------------------+---------+----- = Reliability : (2) valid with restrictions Log Kow -1 .3988 14/64p. 15



## 2. Physico-Chemical Data Modeled data Id 108-19-0 Date 03 .07 .2007 27.06.2007 2.6.1 SOLUBILITY IN DIFFERENT MEDIA Solubility in : Water Value . 87.77 g/I at °C pH value . concentration . at °C Temperature effects . Examine different pol . . pKa . at 25 °C Description , Stable , Deg. product . Method : other Year ; 1992 GLP : no Test substance : as prescribed by 1 .1 - 1 .4 Method Water Sol from Kow(WSKOW v1 .41) SMILES : 0=C(NC(=0)N)N CHEM : Imidodicarbonic diamide MOL FOR

: C2 H5 N3 02 MOL WT : 103.08 Remark : No physical properties input by user Result : Water Sol from Kow (WSKOW

v1 .41) Results: Water Sol : 8.777e+004 mg/L

Reliability Experimental Water Solubility Database Match: Name : Imidodicarbonic diamide CAS Num : 000108-19-0 Exp WSol : 1 .52E+004 mg/L (15 deg C) Exp Ref : YALKOWSKY,SH & DANNENFELSER,RM (1992)

-------- WSKOW

v1 .41 Results ---------------_--- Log Kow (estimated) : -1 .40 Log Kow

(experimental) : not available fromdatabase Log Kow

used by Water solubility estimates : -1 .40 Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0 .854 log Kow - 0.00728 MW

+ Correction (used when Melting Point NOT available) Correction(s) : Value ------------------- Multi-Nitrogen Type -1 .310 Log Water Solubility (in moles/L) : -0.070 Water Solubility at 25 deg C (mg/L) : 8.777e+004 (2) valid with restrictions (7)

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## 2. Physico-Chemical Data

27 .06.2007 Handbook data Solubility in Value pH value concentration Temperature effects Examine different pol . pKa Description Stable Deg. product Method Year GLP Test substance Remark

Result Reliability Flag 27.06.2007 Solubility in Value pH value concentration Temperature effects Examine different pol . pKa Description Stable Deg. product Method Year GLP Test substance Reliability 27.06.2007 . Water

. =2.01 other : g/100 g at 25 °C at °C

. at 25 °C other 1976 no data as prescribed by 1 .1 - 1 .4 Id 108-19-0 Date 03 .07 .2007 (49)

: This record originally appeared in the ISHOW database . ISHOW - Information System

for Hazardous Organics in Water Details: Sample Record ISHOW, sponsored by the Office of Toxic Substances of the EPA, was developed by the EPA laboratory in Duluth, Minnesota in conjunction with the University of Minnesota. This database of 17,159 records includes physical property data on more than 5,700 different chemicals with bibliographic references to the original sources. Not all properties are recorded for all substances. : Solubility in 100 g water : 2.01 G@25DEGC 7G@50DEGC 20G@75DEGC 53.5G@105 .5DEGC (2) valid with restrictions Handbook data Critical study for SIDS endpoint (38) : other : rumen fluid

. =2.2 at °C at °C at 25 °C

. other : 1972

. no : as prescribed by 1 .1 - 1 .4 : (4) not assignable Original reference not reveiwed (40)p. 17



## 2. Physico-Chemical Data 2.6.2 SURFACE TENSION 2.7 FLASH POINT 2.8 AUTO FLAMMABILITY 2.9 FLAMMABILITY 2.10 EXPLOSIVE PROPERTIES 2.11 OXIDIZING PROPERTIES 2.12 DISSOCIATION CONSTANT 2.13 VISCOSITY 2.14 ADDITIONAL REMARKS Id 108-19-0 Date 03.07.2007

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## 3. Environmental Fate and Pathways Id 108-19-0 Date 03.07 .2007 3.1 .1 PHOTODEGRADATION Type . air Light source . Light spectrum . Relative intensity . INDIRECT PHOTOLYSIS Sensitizer . Conc. of sensitizer , Rate constant . Degradation . Deg. product . Method , Year . GLP Test substance . Method

Remark Result , nm based on intensity of sunlight OH 5000 molecule/cm3 .000000000003 cm3/(molecule"sec) 50 % after 3 .7 day(s) other (calculated) 2007 no as prescribed by 1 .1 - 1 .4 AOP Program (v1 .92) SMILES : 0=C(NC(=0)N)N CHEM : Imidodicarbonic diamide MOL FOR: C2 H5 N3 02 MOL WT : 103 .08 No physical properties input by user AOP Program (v1 .92) Results :

----------- - SUMMARY (AOP v1 .92) : HYDROXYL RADICALS ----------------- Hydrogen Abstraction = 0.0000 E-12 cm3/molecule-sec "*Reaction with N, S and -OH = 3.0000 E-12 cm3/molecule-sec Addition to Triple Bonds = 0.0000 E-12 cm3/molecule-sec Addition to Olefinic Bonds= 0.0000 E-12 cm3/molecule-sec Addition to Aromatic Rings= 0.0000 E-12 cm3/molecule-sec Addition to Fused Rings = 0.0000 E-12 cm3/molecule-sec OVERALL OH Rate Constant = 3.0000 E-12 cm3/molecule-sec HALF-LIFE= 3.565 Days (12-hr day; 1 .5E6 OH/cm3) HALF-LIFE = 42 .784 Hrs

. . . . . . . . . . . . . . . . . . . . . . . "' Designates Estimation(s) Using ASSUMED Value(s) ------------------ SUMMARY (AOP v1 .91) : OZONE REACTION ----------------

"""`"'* NOOZONE REACTION ESTIMATION *"`**" (ONLY Olefins and Acetylenes are Estimated) Reliability , 03.07 .2007 3.1 .2 STABILITY IN WATER Experimental Database: NO Structure Matches Fraction sorbed to airborne particulates (phi) : 0.00239 (Junge,Mackay) Note : the sorbed fraction may be resistant to atmospheric oxidation (2) valid with restrictions Modeled data (7)

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## 3. Environmental Fate and Pathways Type t112 pH4 t112 pH7 t1/2 pH9 Deg. product Method Year GLP Test substance abiotic at °C at °C at °C other (calculated) 2007 no as prescribed by 1 .1 - 1 .4 Id 108-19-0 Date 03 .07 .2007

Method : HYDROWIN Program (v1 .67) SMILES : 0=C(NC(=0)N)N CHEM : Imidodicarbonic diamide MOL FOR

: C2 H5 N3 02 MOL WT : 103.08 Result : HYDROWIN Program (v1 .67) Results:

------ ------ HYDROW

I N v1 .67 Results ------------------------- UREA: -N-C(=0)-NCompound has a urea group; C=0 located at SMILES atom # : 2 Hydrolysis Rate Extremely Slow or t1/2 > 1 Year """""` CALCULATION NOT PERFORMED *"*"

Reliability 27.06.2007 3.1 .3 STABILITY IN SOIL Type : laboratory Radiolabel , Concentration . Soil temperature . °C Soil humidity . Soil classification . Year Deg. product . Method : other Year : 1965 GLP : no Test substance : as prescribed by 1 .1 - 1 .4 Result UREA : -N-C(=0)-NCompound has a urea group; C=0 located at SMILES atom #: 4 Hydrolysis Rate Extremely Slow or t1/2 > 1 Year """""' CALCULATION NOT PERFORMED "`*' (2) valid with restrictions Modeled data

An enzyme tentatively named the biuret-hydrolyzing enzyme, capable of decomposing biuret into urea, ammonia, and carbon dioxide was isolated from Mycobacterium ranae and purified 28-fold was investigated . The properties of this enzyme were investigated in detail with the following results: (7)

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## 3. Environmental Fate and Pathways

03 .07 .2007 Type Radiolabel Concentration Soil temperature Soil humidity Soil classification Year Result The optimum pH of the enzyme is about 9.5. Id 108-19-0 Date 03.07 .2007

The most purified enzyme preparation is strictly specific for biuret, among the compounds tested . Heavy metal ions, such as Ag+, Hg2+, Pb2+ and Mn2+, inhibit the enzymatic activity more than 85% . A low concentration of p-chloromercuribenzoate completely inactivates the enzyme, and its activity is restored by addition of glutathione or cysteine. These results suggest that a sulfhydryl group is essential for the enzyme activity. Although magnesiumion has not been confirmed to be an activator, it shows a slight activating effect on the enzymatic activity and restores the activity after inhibition oby ethylenediaminetetraacetate . The Michaelis constant of this enzyme was calculated to be 6.1 x 10E-4 M . Results indicate that biuret is decomposed by the enzyme into urea, ammonia, and carbon dioxide. : laboratory

. °C (26)

Various fungi and bacteria capable of using biuret as nitrogren were isolated fromsoil and leaf material in selective media. Prominent among the fungi were Coniosporiumfuckelii, Penicillium spp. (particularly P. vermiculatumand P. lilacinum), and Auerobasidiumpululans, further Myrotheciumverrucaria, Humicola grisea, Alternaria sp . And Macrosporium sp. All grew

over a wide pH range with typical optima at pH 4.0 - 5 .0. Approximately 60 to 85%of the biuret-nitrogen could be recovered in the mycelium

. Biuret-grown and washed mycelia produced ammonia from urea although the urease did not appear to be a constitutive enzyme; ammonia formation frombiuret could not be detected with certainty. The most frequently encountered group of biuret-utilizing bacteria were strains of Pseudomonas trifolii . Pure cultures could under favorable conditions attain maximumgrowth in glucose-biuret mediumwithin less than 48 hours when 80-85%of the biuret nitrogen was assimilated in the cell material . Growth could be initiated from pH approx. 4 to 8, with apparent optimumat pH 5 to 6. Washed biuret-grown cells produced ammonia more rapidly from urea than frombiuret . Another group was represented by bacteria that culturally resembled the rapidly growing type of legume root nodule bacteria (Rhizobium) but were not definitely identifiable as such and were also different from Agrobacterium radiobacter . Two strains of these "quasi-rhizobia" grew even better with biuret than with urea as nitrogen source. Another series of experiments showed that many strains of genuine rhizobia were capable of utilizing biuret although this nitrogen source was mostly inferior to urea.

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## 3. Environmental Fate and Pathways Id 108-19-0 Date 03.07 .2007 Except for the rhizobia and certain strains of Aureobasidium pullulans, stock cultures of several fundi, actinomycetes and bacteria showed very little or no evident of metabolizing biuret . Experiments in soil showed that the total soil microflora was able to utilize biuret for the decomposition of straw and pure cellulose, as evidenced by the production of carbon dioxide, and that nitrogen in biuret added in doses of 50-100-200 ppmnot accompanied by other organic substances was nitrified to the extent of 80-100% in the course of two to three months . The results as a whole show that there can be no risk of the biuret from synthetic urea fertilizer accumulating in the soil . At the same time they seemto offer some explanation for the well-known fact that the phytotoxic effect of biuret is considerable greater by foliar application than by uptake through the root . 25.06.2007 (20) 3.2 .1 MONITORING DATA 3.2.2 FIELD STUDIES 3.3.1 TRANSPORT BETWEEN ENVIRONMENTAL COMPARTMENTS Type Media Air Water Soil Biota Soil Method Year Method fugacity model level III % (Fugacity Model Level I) % (Fugacity Model Level I) % (Fugacity Model Level I) % (Fugacity Model Level II/III) % (Fugacity Model Level II/III) other 2007 : Level III Fugacity Model ---------------------- ChemName : Imidodicarbonic diamide Molecular Wt : 103.08 Henry's LC : 2.03e-013 atm-m3/mole (Henryvirin program) Vapor Press : 1 .02e-005 mmHg (Mpbpwin program) Liquid VP : 9.34e-005 mmHg (super-cooled) Melting Pt : 122 deg C (Mpbpwin program) Log Kow :-1 .4 (Kowwin program) Soil Koc : 0.0163 (calc by model) Remark : No physical properties input by user Result : Level III Fugacity Model (Full-Output) : Mass Amount Half-Life Emissions (percent) (hr) (kg/hr) Air 4.83e-006 85 .6 1000 Water 39 360 1000

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## 3. Environmental Fate and Pathways

Reliability 03 .07 .2007 Type Media Air Water Soil Biota Soil Method Year Remark Soil 60.9 720 1000 Sediment 0.0713 3.24e+003 0 Id 108-19-0 Date 03.07 .2007 Fugacity Reaction Advection Reaction Advection (atm) (kg/hr) (kg/hr) (percent) (percent) Air 1 .97e-016 0.000679 0 .000839 2.26e-005 2 .8e-005 Water 6.67e-018 1 .3e+003 677 43 .5 22 .6 Soil 3.86e-016 1 .02e+003 0 34 0 Sediment 6.1e-018 0.265 0.0248 0.00883 0.000826 Persistence Time : 579 hr Reaction Time : 748 hr Advection Time: 2.57e+003 hr Percent Reacted: 77.4 Percent Advected : 22 .6 Half-Lives (hr), (based upon Biowin (Ultimate) and Aopwin) : Air : 85 .56 Water : 360 Soil : 720 Sediment : 3240 Biowin estimate : 2 .971 (weeks ) Advection Times (hr) : Air: 100 Water : 1000 Sediment : 5e+004 (2) valid with restrictions Modeled data other % (Fugacity Model Level I) % (Fugacity Model Level I) % (Fugacity Model Level I) % (Fugacity Model Level II/Ili) % (Fugacity Model Level II/III) (7)

Biuret does not accumulate in soil and is mineralized within a single growing season . Biuret is not retained in soil (Orgata, year) and is easily leached (Gadet et al ., 1959) . Nishihare et al . (1965) found an enzyme, biuret-hydrolyzing enzyme, capable of decomposing biuret into urea, ammonia, and carbon dioxide. Jensen (1966) found several widespread species of soil fungi and bacteria capable of degrading biuret . Jensen also reported that biuret at a concentration of 100 ppmwas almost completely nitrified after two to three months. Several studies have concluded that the rate of biuret mineralization depends on soil composition, temperature, and biuret concentration (Mithyantha et al ., 1977) . 03 .07 .2007 (10)(20)(24)(27)(28)

., . . . . . . . . .~. . . ., . .~. ., . .p. 23



## 3. Environmental Fate and Pathways 3.4 MODE OF DEGRADATION IN ACTUAL USE 3.5 BIODEGRADATION Contact time Degradation Result Deg. product Method Year GLP Test substance Method

Result (±) % after other : likely to be biodegradable other 2007 no as prescribed by 1 .1 - 1 .4 BIOWIN (v4.10) Program SMILES : 0=C(NC(=0)N)N CHEM : Imidodicarbonic diamide MOL FOR

: C2 H5 N3 02 MOL WT : 103.08 BIOWIN (v4 .10) Program Results :

------ BIOW

IN v4.10 Results ------------------------ Id 108-19-0 Date 03.07 .2007

Biowin1 (Linear Model Prediction) : Biodegrades Fast Biowin2 (Non-Linear Model Prediction) : Biodegrades Fast Biowin3 (Ultimate Biodegradation Timeframe) : Weeks Biowin4 (Primary Biodegradation Timeframe) : Days-Weeks Biowin5 (MITI Linear Model Prediction) : Does Not Biodegrade Fast Biowin6 (MITI Non-Linear Model Prediction) : Does Not Biodegrade Fast Biowin7 (Anaerobic Model Prediction) : Biodegrades Fast Ready Biodegradability Prediction: NO ------+-----+---------------------------------__+__---__+------ TYPE I NUM

~ Biowin1 FRAGMENT DESCRIPTION ~ COEFF ~ VALUE ------+-----+--------------------------------------+--------+------- MoIWtj " I Molecular Weight Parameter 1 I-0.0491 Constj " I Equation Constant I I 0.7475

--------- ---------___+_________________________------------------- ------------------- ------______+-_-----__-----------__-_- +_________+_________ ------------------ RESULT I Biowin1 (Linear Biodeg Probability) ~ ~ 0.6985

------+-----+------------------------------------+--------+-------- TYPE I NUM

~ Biowin2 FRAGMENT DESCRIPTION ~ COEFF ~ VALUE

------------ ------------+____________________ ~______---------------- ---------------- ------+-----+--------------------------------------+--------+-------- MoIWtj '" I Molecular Weight Parameter 1-1 .4638 ------------+---__--__-------_------- ------------------------ RESULT I Biowin2 (Non-Linear Biodeg Probability) 1 1 0.8242

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## 3. Environmental Fate and Pathways Id 108-19-0 Date 03.07.2007 A Probability Greater Than or Equal to 0.5 indicates --> Biodegrades Fast A Probability Less Than 0.5 indicates --> Does NOT Biodegrade Fast

---------------- ----------- ---------------------+-------+----__ TYPE INUM

I Biowin3 FRAGMENT DESCRIPTION I COEFF I VALUE ------+----+----------------------------------+--------+-------- MoIWtj " I Molecular Weight Parameter 1 1-0.2278 Constj " I Equation Constant 1 1 3.1992 ------------+-_---__-----__----------___-_---------_----- ------------ ----- ----- ---------- - --------- ----- RESULT I Biowin3 (Survey Model -Ultimate Biodeg) ~ ~ 2.9714 ------------+-_--_--____------------_--------- ----------- -----+----+------------------------------------+-----+------- TYPE INUM

I Biowin4 FRAGMENT DESCRIPTION I COEFF ~ VALUE ------+-----+--------------------------------------+-------+------- MoIWtj ' I Molecular Weight Parameter 1 I-0 .1487 Constj ` I Equation Constant 1 3.8477 ------------+-_-_--_____---------------------- --------------- RESULT I Biowin4 (Survey Model -Primary Biodeg) ~ ~ 3.6990 Result Classification : 5.00 -> hours 4.00 -> days 3.00 -> weeks (Primary & Ultimate) 2.00 -> months 1 .00 -> longer ------+-----+----------------------------------+-------+------- TYPE INUMI Biowin5 FRAGMENT DESCRIPTION I COEFF ~ VALUE MoIWtj ' ~ Molecular Weight Parameter I 1-0.3067 ------+-----+---------------------------------------+--------+------- ------------+-----------------_-------------- Constj ' I Equation Constant 1 1 0.7121

------------+-------------------------------- ---------------------___ RESULT I Biowin5 (MITI Linear Biodeg Probability) 1 1 0.4055

------+----+------------------------------------+------+------- TYPE I NUM

~ Biowin6 FRAGMENT DESCRIPTION ~ COEFF ~ VALUE ------+-----+---------------------------------------+--------+------ MoIWtj " I Molecular Weight Parameter I 1-2.9758 _-----______+___----____-_-------_-- ------- RESULT jBiowin6 (MITI Non-Linear Biodeg Probability)l 1 0.3893 A Probability Greater Than or Equal to 0.5 indicates --> Readily Degradable A Probability Less Than 0.5 indicates --> NOT Readily Degradable

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## 3. Environmental Fate and Pathways

Reliability 27 .06 .2007 Id 108-19-0 Date 03.07 .2007

------+----+---------------------------------+--------+------- TYPE INUM

I Biowin7 FRAGMENT DESCRIPTION ~ COEFF I VALUE ------+----+----------------------------------+--------+------- Constj * I Equation Constant ~ ~ 0 .8361 ------------+-----------_______-------------_------------ ------------ ----------- ------------- ------------ RESULT I Biowin7 (Anaerobic Linear Biodeg Prob) ~ ~ 0.8361 A Probability Greater Than or Equal to 0.5 indicates --> Biodegrades Fast A Probability Less Than 0.5 indicates --> Does NOT Biodegrade Fast (2) valid with restrictions Modeled data (7) 3.6 BOD5, COD OR BOD5/COD RATIO 3.7 BIOACCUMULATION 3.8 ADDITIONAL REMARKS

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## 4 . Ecotoxicity

4 .1 ACUTE/PROLONGED TOXICITY TOFISH 4 .2 ACUTE TOXICITY TOAQUATIC INVERTEBRATES 4.3 TOXICITY TOAQUATIC PLANTS E .G. ALGAE 4.4 TOXICITY TO MICROORGANISMS E .G. BACTERIA 4.5.1 CHRONIC TOXICITY TO FISH 4 .5.2 CHRONIC TOXICITY TOAQUATIC INVERTEBRATES 4 .6.1 TOXICITY TOSEDIMENT DWELLING ORGANISMS 4.6 .2 TOXICITY TO TERRESTRIAL PLANTS 4 .6.3 TOXICITY TO SOIL DWELLING ORGANISMS 4.6.4 TOX. TOOTHER NON MAMM . TERR . SPECIES 4.7 BIOLOGICAL EFFECTS MONITORING 4.8 BIOTRANSFORMATION AND KINETICS 4.9 ADDITIONAL REMARKS Id 108-19-0 Date 03.07 .2007

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## 5. Toxicity

5 .0 TOXICOKINETICS, METABOLISM AND DISTRIBUTION Method Year GLP Test substance Remark 1975 no as prescribed by 1 .1 - 1 .4 Id 108-19-0 Date 03.07 .2007

: It has been well established through the use of biuret as an non-protein nutrient, that in the rumen, biuret and urea are hydrolyzed to ammonia and simple carbon compounds . The complete hydrolysis and deamination of protein involves numerous enzymes . Biuret is decomposed by biuretase (within bacterial cells) to urea, ammonia, and carbon dioxide. Biuret is more slowly hydrolyzed than urea . Reliability : (2) valid with restrictions Provides basic data 03.07 .2007 Method . Year : 1958 GLP : no Test substance : as prescribed by 1 .1 - 1 .4 Remark : Biuret is not accumulated in the body of rats or chickens Reliability : (4) not assignable 27.06.2007 Method Year GLP Test substance Original reference not reveiwed 1968 no as prescribed by 1 .1 - 1 .4 (9)

(15)

Remark : Sheep, given 14C - biuret i .v. excreted 98%in the urine within 48 hours . Reliability : (4) not assignable 27 .06.2007 Original reference not reveiwed 5.1 .1 ACUTE ORAL TOXICITY Type : other Value Species : sheep Strain

. no data Sex : no data Number of animals . Vehicle Doses : 4, 8 and 16 g/kg Method : other Year , 1972 GLP : no Test substance : other TS Method Sheep were drenched (to administer a large oral dose of a liquid to an (8)

27/64p. 28



## 5. Toxicity Id 108-19-0 Date 03.07.2007 animal) with 4, 8 or 16 g/kg bw of feed grade Biuret . Result : No signs of toxicity observed in sheep administered 4 g/kg bw . Distress was observed in sheep treated with 8 g/kg bw . Death occurred in sheep treated with 16 g/kg bw . Test substance : Kedlor feed grade Biuret Reliability : (4) not assignable Original reference not reveiwed 27 .06.2007 Type : other Value . Species : sheep Strain : no data Sex : no data Number of animals . Vehicle . Doses . .6 g/kg bw Method : other Year . 1955 GLP : no Test substance : other TS (33)

Method : Sheep were drenched (to administer a large oral dose of a liquid to an animal) with crude Biuret at 0.68 g/kg bw and observed for signs of toxicity and death . Result : No signs of toxicity or death were reported . Test substance : crude Biuret Reliability : (4) not assignable Original reference not reveiwed 27.06.2007 Type : other Value . Species : sheep Strain : no data Sex : no data Number of animals . Vehicle . Doses : 6.9 g/kg bw Method : other Year . 1963 GLP : no Test substance : other TS (23)

Method : Sheep were drenched (to administer a large oral dose of a liquid to an animal) with feed grade Biuret at 6.9 g/kg bw (250 g) and observed for signs of toxicity and death. This massive dose of biuret was administered to sheep before and after an extended adaptation period. The animals were fed a low

protein, high roughage diet . Result : No signs of toxicity or death were reported irrespective of the period of adaptation. Test substance . Feed grade Biuret Reliability : (4) not assignable 27.06 .2007 Original reference not reveiwed (5)(6)(9) Type : other 28/64p. 29



## 5. Toxicity Value Species Strain Sex Number of animals Vehicle Doses Method Year GLP Test substance Method Result Reliability 27 .06 .2007 5.1 .2 ACUTE INHALATION TOXICITY 5.1 .3 ACUTE DERMAL TOXICITY 5 .1 .4 ACUTE TOXICITY, OTHER ROUTES 5.2.1 SKIN IRRITATION 5.2.2 EYE IRRITATION 5.3 SENSITIZATION 5.4 REPEATED DOSE TOXICITY Type Species Sex Strain Route of admin. Exposure period Frequency of treatm . Post exposure period Doses Control group Method Year GLP . sheep

. no data

. no data 4 .7 g/kg bw other 1959 no as prescribed by 1 .1 - 1 .4 Id 108-19-0 Date 03.07 .2007

4 .7 g/kg body weight of purified biuret was administered to sheep. The animals were observed for death and signs of toxicity. Signs of toxicity (not specified) were observed . (4) not assignable Original reference not reveiwed

. rat

. male : Sprague-Dawley oral feed 30 or 140 days : daily

. none

. Exp 1 : 0.2 - 1 .0%

; Exp 2: 5%

and 10% : yes, concurrent no treatment

. other : 1956

. no (9) (12)

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# 5. Toxicity

Test substance : other TS Method

Result

Test substance Reliability 27.06.2007 Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Id 108-19-0 Date 03.07 .2007 Experiment I : Male Sprague-Dawley rats (6/group) were fed a basal diet supplemented with Biuret at levels of 0.2, 0.4, 0.6, 0.8 and 1 .0%for 30 days . A control group (6 rats) was fed the basal diet without added Biuret . Animals were observed for signs of toxicity and body weights were recorded after 30 days . Experiment II : After 30 days it was evident that rats could tolerate Biuret in their diets up to 1 %

without any apparent toxic effects. Based on the lack of toxicity noted in animals in Experiment 11, a second experiment was initiated . Animals in groups 1 (control), 3 (0.4%) and 4 (0 .6%) were used in the second experiment . The control group was continued as previously described . Biuret was added to the basal diet at the rate of 5.0% and 10.0% and fed to groups 3 and 4, respectively. This feeding experiment was continued for 140 days to observe any long range effects of a high Biuret diet . On the 35th and 98th days, one randomly selected animal from each of the three groups was killed and subjected to gross necropsy. There were no significant differences in growth rates among the six groups fed for only 30 days or the three test groups that were fed for 140 days . The appetites were normal, all animals appeared thrifty throughout the duration of the experiment, and no illnesses or deaths occurred. All specimens submitted for histological examination were found to be normal . Slight changes which occurred could not be attributed to Biuret toxicity. Since Biuret is chemically related to urea it might be expected that the reaction of the rat body to Biuret would be similar to its reaction to urea. Observation of a higher water intake among the Biuret-fed groups with no evident histological changes was noted . Effects of Various Levels of Biuret in the Diet on Laboratory Rats : Exp . Days on Biuret (N) Average Gain Test (%) (gm) 1 30 0.0 6 139.6

0.2 6 135 .0 0.4 6 130.3 0.6 6 141 .0 0.8 6 142.4 1 .0 6 137.0 11 140 0

.0 4 206.8 5.0 4 203.1 10.0 4 198.2 99.1 %purity (2) valid with restrictions Provides basic data Sub-acute other : steer male other: Angus and Hereford oral feed 84 days daily none see Method (3)

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## 5. Toxicity

Control group Method Year GLP Test substance Method Id 108-19-0 Date 03.07 .2007 yes other 1956 no other TS : Forty-five yearling steers, 25 Angus and 20 Herefords, ranging in weight from 450 to 650 pounds were randomly sorted into five groups according to weight and breed. The five groups were fed a high-roughage, lowconcentrate wintering ration in dry lot for 84 days. The basal ration was made up of 36.5%Atlas silage (hay basis), 24% cottonseed hulls, 6% alfalfa leaf meal, 11%blackstrap molasses, and from 13%to 20%milo grain and 1 %minerals (bonemeal and salt) . The crude protein supplements used were 7.5% cottonseed meal (Group 1), 1 % feed-urea (Group 2), 1 %crude Biuret (Group 3), 1 .5% a mixture of crude Biuret and feed-urea (Group 4), and 1 .25%of a urea-fatty acid complex (Group 5) . The total intake of each group was adjusted to that of the lowest consuming group. This was accomplished by hand feeding. Each ration was calculated to supply equal amounts of dry matter, total digestible nutrients, and except for Group 4, protein equivalent . Group 4 was 1 .4% higher in crude protein equivalent . The urea-fatty acid complex was 75% urea and 25%cottonseed foots . Animals were observed for signs of toxicity and average weight gain was calculated at study termination . Result : As shown in the table below, the average gains made by the control group and the urea group (Group 2) were not significantly different . However, when the urea was replaced with the crude Biuret (Group 3), a significantly lower gain resulted (p<0.01) . This group also consumed the least feed and therefore, restricted the intake of the other groups. When additional urea (42 gm) was included with the crude Biuret (Group 4), the average gain was increased 0.50 pounds, a difference highly significant statistically (p<0.01) . Thus, simply adding urea overcame the adverse effects of Biuret . Although Group 4 gained slightly more than the group fed urea alone (Group 2), the difference was not significant . The increase of 0.18 pounds in daily gain may suggest that contrary to the results obtained with Group 3, the Biuret nitrogen was utilized to some extent by the ruman bacteria . The group fed urea-fatty acid complex (Group 5) gained essentially the same as the urea fed group (Group 2) . Based on this single study it appears that urea fed as a urea-fatty acid complex is efficiently utilized.

Test substance Reliability Group Av. Gain Av. Daily Gain (Ib) (Ib) 1 (control) 94.7 1 .13** 2 (urea) 88.4 1 .05** 3 (crude Biuret) 60.5 0 .72 4 (crude Biuret-urea) 102.9 1 .23** 5 (urea-fatty acid) 91 .5 1 .09* *Values significantly (p<0.05) greater than for the group fed crude Biuret alone. **Value highly significantly (p<0.01) greater than for group fed crude Biuret atone. crude Biuret (60%Biuret and 40%urea) Diets containing crude Biuret (60%Biuret and 40%urea) (2) valid with restrictions

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## 5. Toxicity

27.06.2007 Provides basic data Id 108-19-0 Date 03.07 .2007 (3) Type . Species : other : pullets (New Hampshire poultry) Sex : no data Strain : no data Route of admin. : oral feed Exposure period ; not specified Frequency of treatm

. : daily Post exposure period : none Doses . 1 % Control group : yes, concurrent no treatment Method : other Year . 1956 GLP : no Test substance : other TS Method

Remark Result

Test substance Conclusion Reliability 27.06.2007 Type : Sub-acute Species : other : lamb Sex . no data Strain : no data Route of admin. : oral feed Exposure period : 84 days Frequency of treatm

. : daily Post exposure period : none Doses , Control group : yes, concurrent no treatment Method : other Year : 1956 Eighty New

Hampshire pullets, 8weeks of age, were randomly selected and divided into eight groups of 10 each according to weight . Four dietary treatments (basal, urea, Biuret, and soybean) allowed two groups of 10 within each treatment . Group 1 (control) was fed a milo-soybean meal basal ration calculated to contain 14.5% crude protein. It consisted of 83.5%milo grain, 12.0%soybean oil meal, 0 .5% vitamin mixture, and 4.0% of a mineral mixture. Groups 2 and 3 were fed the same basal diet except 1 % of the milo of each ration was replaced with 1 % % feed urea or 1 % purified Biuret, respectively, which raised the calculated crude protein equivalents to 17 .3% . Group 4was fed the basal diet with enough milo replaced by soybean oil meal to raise the calculated crude protein value to 17 .3% . Duration of the study was not reported . Feed consumption was about 5% lower for the Biuret and urea supplemented groups than for the control and soybean oil meal supplemented groups. The body weight gain of the birds receiving the added soybean oil meal (Group 4: 458.0 gm) was significantly higher than that of the basal (399.8 gm), urea (393.5 gm) and Biuret (359.0 gm) groups. The inclusion of Biuret or urea had no statistically significant effect on body weight gain . 99.1 %purity Neither urea nor Biuret is toxic to 8-week old pullets when added to the ration at this level . (2) valid with restrictions Provides basic data (3)

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## 5. Toxicity GLP Test substance Method

Result

Test substance Conclusion Reliability 25 .06 .2007 Type : Sub-chronic Species : cattle Sex : female Strain : other : Ayrshire Route of admin. : oral feed Exposure period : 15 weeks Frequency of treatm

. : daily Post exposure period : 3 week period for subgroup of 3 animals Doses : 2.6% Control group : yes, concurrent no treatment Method : other Year : 1968 GLP : no Test substance : other TS (3)

Method : Experiment 2: A continuous-type design was used to examine the effect of more prolonged treatment and in order to minimize the effects of individual animal variation with the small number of cows (21), a preliminary feeding period of 4 weeks was given during which all cows received a high-quality commercial concentrate and the same hay that was to be fed during the experimental period . The results obtained in the preliminary period was later used to adjust the results fromthe experimental period by covariance analysis. Twendy-one Ayrshire cows, 30 to 80 days old, were used for this 15-week feeding study. Groups of 3 were organized based on stage of lactation, no other TS Id 108-19-0 Date 03.07 .2007 Twenty-seven fine wool lambs, weighing 50-70 pounds, were divided into three groups of nine each and for 84 days fed rations consisting of 42.5% cottonseed hulls, 10%blackstrap molasses, and 40-45%ground milo . The various crude protein supplements were 7.5%cottonseed meal (Group 1), 1 % cottonseed meal plus 1 % urea feed-urea (Group 2), and 1 % cottonseed plus 1 %

crude Biuret (Group 3) . All three rations were calculated to supply equal levels of dry matter, total digestible nutrients and crude protein. In order to prevent differences related to palatability of the rations, the total intake of each was adjusted to that of the lowest consuming group. This was accomplished by hand feeding twice daily. Daily observations of water intake and urination were monitored. Average weight gain was calculated at study termination. One lamb fromeach test group was killed and a gross necropsy conducted. The Biuret group was the slowest, the urea group intermediate and the control group the fastest in cleaning up the rations. Therefore, feed consumption of the Biuret-fed group controlled the feed intake of the other groups. Daily observations indicated greater water intake and urination for the NPN-fed groups, these conditions being more apparent for the Biuret group than for the urea group. An examination of the internal organs showed no changes among the lambs from the three treatment groups. Diets containing crude Biuret (60% Biuret and 40%urea) It was apparent that the consumption of the crude Biuret-urea mixture or of urea along did not cause toxic symptoms, unless the depression of appetite is considered a symptom . (2) valid with restrictions Provides basic data

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## 5. Toxicity Id 108-19-0 Date 03.07 .2007 number of lactations and milk production in earlier lactations . The experimental feeding treatments (control, biuret, urea) were randomly allocated to the 3 cows in each group. The average number of lactations/cow

was 3. In order to make the total amount of N supplied in the diets more critical in this experiment, the concentration of urea was reduced from2.9% to 2.1 % and of biuret from 3.9%to 2.6% . This change lowered the contribution of the 2 NPN sources to 43% from 52%in Exp 1 . The total N content of the concentrates in Exp 2 was about 80%of that fed in Exp 1 . The formulation of the 3 concentrate mixtures used in Exp 2 is provided below . The changes compared to Exp 1 were made to provide a control concentrate with a less soluble formof protein and one which was less dependent on the N content of a single cereal .

Composition %on air-dry basis Ingredient Control Biuret Urea Biuret* - 2.6 - Urea" - - 2.1 Soybean meal 2.5 Decorticated Groundnut cake 5.8 - - Decorticated Cotton cake 2 .5 - - Linseed cake 3 .5 - - Copra cake 10.7 - - Barley 33.0 43.7 44.0 Maize 33 .0 43.7 43.9 Starch - 2.0 2 .0 Minerals" 3.0 3.0 3.0 Molasses 5.0 5.0 5.0 "Biuret : 7%

moisture, 39%N in D.M . Urea : 0 .7% moisture, 46% N in D.M . Supplements of vitamins A and D3, trace minerals and spices were added to all concentrates, and in addition elemental suphur (520 g/ton) was added to the biuret and urea concentrates. Milk samples fromthe whole udder were taken at 4 consecutive milkings once a week and the 4 samples pooled in proportion to yield for chemical analysis. Cell count was measured weekly on the pooled sample and monthly on quarter samples for each cow . At the end of Exp 2, 3 cows continued on the same biuret treatment diet for a further 3 weeks to allow a measurement of the nitrogen balance of each cow to be made. Feces (8-hr intervals), urine (24-hr intervals), and milk (collected every milking period; averaged each 48 h) were analyzed for nitrogen content Result : The estimated energy intake in Exp 2 was 108-109% using the Woodman standard calculation. The milk production was about 10%less on the biuret diet compared to control . The percentages of fat and protein in the milk from the biuret treatment was higher than from the control treatment, but the weights of the milk constituents was slightly lower in the biurettreated group than from the control treatment . Liveweight changes and water consumption were not affected by experimental treatment . The three cows that had received biuret concentrated continued to do so during a nitrogen balance trial that lasted 3 weeks . Each cow was slightly in 34/64p. 35



## 5. Toxicity Id 108-19-0 Date 03 .07 .2007 negative balance, the average being - 4 g N/cow/day. Reliability : (2) valid with restrictions Provides basic data 27.06 .2007 Type Species Sex Strain Route of admin . Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method (48)

. Sub-acute : cattle

. female : other : Ayrshire : oral feed

. 7 weeks : daily

. none : 3.9% : yes, concurrent no treatment

. other : 1968

. no : other TS Experiment 1 : The design of Exp 1 was of the balanced change-over type with 18 Ayrshire cows . The animals were divided into 6 groups with the cows in each group as similar as possible in milk yield and stage of lactation. They were then allotted at randomto the treatment sequences in2 orthogonal 3 x 3 Latin squares . The average lactation number of the cows was 3, with only 4 of themhave had more than 3 lactations . Each cowhad been milking for 60-70 days before the experiment started. Each diet consisted of good quality hay with one of the 3 concentrate mixtures and was fed for periods of 7 weeks. The formulation of the 3 concentrate mixtures is provided below : Composition %

on air-dry basis Ingredient Control Biuret Urea Biuret* - 3.9 - Urea* - - 2,9 Decorticated Groundnut cake 23.3 - - Barley 66.6 81 .9 85.7 Starch - 7.0 4.2 Oat husks 2 .9 - - Minerals* 2.4 2.4 2.4 Molasses 4.8 4.8 4.8 *Biuret : 7%moisture, 39% N in D.M . Urea: 0.7% moisture, 46% N in D.M . Supplements of vitamins A and D3, trace minerals and spices were added to all concentrates, and in addition elemental suphur (520 g/ton) was added to the biuret and urea concentrates . It can be seen that the biuret and urea N replaced that derived from the groundnut cake in the control concentrate. The biuret and the urea both supplied 52%of the total N in these concentrates . On 2 separate days each week in the final 2 weeks of each feeding period the cows were milked with a quarter milking bucket . Samples of milk from each quarter were taken for chemical analysis and for cell count . In each

35/64

## 5. Toxicity

Result

Reliability Id 108-19-0 Date 03.07 .2007 of the other weeks one 24-h whole-udder sample was taken for analysis. The cows were weighed at the same time on 2 consecutive mornings of each week. Experiment 1 : The estimated energy intake in Exp 1 was 102-104% using the Woodman standard calculation. The milk production was about 10% less on the biuret diet compared to control . The percentages of fat and protein in the milk fromthe biuret treatment was higher than fromthe control treatment, but the weights of the milk constituents was slightly lower in the biuret-treated group than fromthe control treatment . Liver weight changes and water consumption were not affected by experimental treatment . (3) invalid Does not provide useful hazard information 27.06.2007 (48) Remark

Reliability 27.06.2007 Type : Sub-acute Species : other : lamb Sex . no data Strain : no data Route of admin. : oral feed Exposure period : 72 days Frequency of treatm

. : daily Post exposure period . none Doses : 3% Control group : yes, concurrent no treatment Biuret is an FDA-approved (Federal Register . Rules and Regulations . 21 CFR Part 573. Federal Register 68(99) :27904. 2003) nonprotein nutrient (NPN) supplement for ruminants and a good deal of data exists for toxicity and nutritive dosages of urea/Biuret combinations for these animals . Generally, plant proteins stimulate the most efficient animal growth and milk production. Animal response is satisfactory, however, when biuret and other NPN products provide part of the nitrogen requirements . When low quality forage diets deficient in nitrogen were fed to ruminants, response to feed grade biuret was very good . Supplementation with biuret stimulated good response fromanimals receiving mediumand high energy diets. Biuret is an ideal supplement because ruminant animals may be fed more biuret than urea. The low solubility of biuret allows it to remain longer in the rumen. Biuret is hydrolyzed more slowly to ammonia and carbon dioxide in the rumen than urea and thereby eliminates toxic accumulation of ammonia in blood plasma. This is cited as the primary reason biuret is readily consumed by animals at high levels. Biuret is comparatively non-toxic even when supplying nitrogrn at levels several times the requirements of the animal . This enlarges the margin of safety permitting feeding of higher concentrations of biuret in the diet than of other commercial NPN products. Biuret exhibits no undesireable palatability characteristics . Its low solubility and slow

degradation rate reduces the hazard of self-feeding on a continuing or intermittent basis. Additional studies to support the low toxicity of biuret to animals are summarized in this article. (2) valid with restrictions Provides basic data (9)

36/64p. 37



## 5. Toxicity Method : other Year . 1956 GLP : no Test substance : other TS Method

Result

Test substance Reliability 27.06.2007 Type : Sub-acute Species : cattle Sex : female Strain : no data Route of admin. : oral feed Exposure period : 7 to 10 days Frequency of treatm

. : daily Post exposure period : none Doses : see Method Control group : no data specified Method : other Year : 1959 GLP : no Test substance : other TS Method Result Id 108-19-0 Date 03.07 .2007

Two lambs were individually penned and for 72 days fed twice daily the same ration fed the control group in the 84 day lamb feeding study. Crude Biuret was added to the ration of one of the lambs to provide a level of 3% Biuret and 2%urea. Animals were observed for signs of toxicity, food consumption was monitored, and average weight gain was calculated. This addition of crude Biuret to a cottonseed meal supplemented ration did not appear to reduce the rate of feed consumption. Gains were essentially the same, 25.5 pound and 25.0 pounds for the control and treated lamb, respectively. Although only two lambs were involved the limited data indicated that Biuret added in excess to a diet already adequate in protein was relatively inert . Even at this high level, approximately 68 gm/day, no toxic symptoms or depression of appetite occurred . Diets containing crude Biuret (60% Biuret and 40%urea) (3) invalid Insufficient number of animals

: 20 g 80%biuret was added to a regular diet and fed to dairy cows for a period of 7 to 10 days. Animals were observed for signs of toxicity. Milk yield and the content of fat/nonprotein nitrogen in the milk and nonprotein nitrogen content of the blood were measured. : There were no effects on their health, yield of milk or contents of fat and nonprotein nitrogen in the milk, nor on the nonprotein nitrogen content of the blood. Reliability : (3) invalid 27.06.2007 Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Does not provide useful hazard information : Sub-acute : other : horses, rabbits and sows

. no data

. no data : oral feed : see Method : daily : see Method (3)

(9) (16)

37/64p. 38



## 5. Toxicity Control group Method Year GLP Test substance no data specified other 1959 no other TS Id 108-19-0 Date 03.07 .2007

Method : Horses were fed 10 g 80%biuret daily (duration not specified) ; 15 g 80%biuret was given to sows daily for 8 days; 3 g pure biuret was given to adult rabbits daily for 7 days. All animals were observed for signs of toxicity. Result : There were no apparent effects on the health of any species. Reliability : (3) invalid Does not provide useful hazard information 27.06.2007 Type : Sub-chronic Species : sheep Sex : no data Strain : no data Route of admin. : oral feed Exposure period : 593 days Frequency of treatm

. : daily Post exposure period . Doses : 3.78 g/kg bw Control group : no data specified NOAEL

. = 3780 - mg/kg bw Method : other Year : 1959 GLP : no Test substance : other TS Method Result Test substance Reliability 27.06.2007 (9) (17)

Sheep were fed diets containing Biuret in amounts equal to 75%of the daily nitrogen intake for 593 days. Growth, reproduction and wool production were not adversely affected. Feed grade Biuret (3) invalid Does not provide useful hazard information Type : Sub-acute Species : cattle Sex : female Strain : no data Route of admin. : oral feed Exposure period : 84 days Frequency of treatm

. : daily Post exposure period . none Doses , Control group . Method : other Year , 1972 GLP : no Test substance : other TS Method Comparison of feed grade biuret with other nitrogen supplements for maintenance of cattle grazing or being fed protein deficient forage. (12)

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## 5. Toxicity

Result

Reliability 27.06.2007 Type Species Sex Strain Route of admin . Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method

Result Id 108-19-0 Date 03 .07 .2007 Average initial weight (kg) and average daily weight gain (kg) were reported . Basal Diet : Dormant range grass (winter) Source Animal No . Days Wt (kg) Daily gain (kg) 57%SM PG 10 84 487 - .66 17%SM Cows 10 84 469 - .96 5 .3% urea Cows 9 84 465 - .84 5 .5% biuret Cows 9 84 477 - .95 where SM

= soybean meal ; PG = pregnant Pregnant cows maintained their weight as well on a dry biuret supplement as on a liquid urea supplement or soybean meal supplement, when fed (or grazing on) low

protein forage or roughages. (3) invalid Does not provide useful hazard information

. Sub-acute

. cattle

. female

. no data : oral feed : 107 to 113 days : daily

. none other 1971 no other TS Comparison of feed grade biuret with other nitrogen supplements for maintenance of cattle grazing or being fed protein deficient forage. Average initial weight (kg) and average daily weight gain (kg) were reported . (9) (32)

Basal Diet : Grass hay, straw and supplement Pregnant cows maintained their weight as well on a dry biuret supplement as on a liquid urea supplement or soybean meal supplement, when fed (or grazing on) low

protein forage or roughages. Source Animal No. Days Wt (kg) Daily gain (kg) Biuret PG 42 107 493 .10 Biuret Beef 40 113 488 .15 SM Cows 44 107 474 .16 SM Cows 42 113 483 .16 where SM

= soybean meal ; PG = pregnant Reliability : (3) invalid 27.06.2007 Does not provide useful hazard information Type : Sub-acute Species : cattle Sex : female (1) (9)

39/64p. 40



## 5. Toxicity Strain . no data Route of admin. : oral feed Exposure period . Frequency of treatm

. . Post exposure period . Doses . Control group . Method : other Year : 1971 GLP : no Test substance : other TS Method

Result Id 108-19-0 Date 03.07 .2007

Comparison of feed grade biuret with other nitrogen supplements for maintenance of cattle grazing or being fed protein deficient forage . Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet : Corn stalk pasture Source Animal No. Days Wt (kg) Daily gain (kg) None Beef 51 84 435 - .42 Biuret Cows 64 84 452 .08 Pregnant cows grazing corn stalks maintained their weight when supplemented with nitrogen from biuret, but lost considerable weight without a nitrogen supplement . Reliability : (4) not assignable 27.06 .2007 Original reference not reveiwed (9) (13) Type : Sub-chronic Species : cattle Sex . male Strain : no data Route of admin . : oral feed Exposure period : 91 days Frequency of treatm

. : daily Post exposure period . Doses Control group . Method : other Year : 1969 GLP : no Test substance : other TS Method Comparison of feed grade biuret with other nitrogen supplements for maintenance of cattle grazing or being fed protein deficient forage . Average initial weight (kg) and average daily weight gain (kg) were reported . Basal Diet : Grass pasture (winter) and pelleted supplement Result : Source Animal No. Days Wt (kg) Daily gain (kg) None Beef 8 91 218 .08 50%Biuret Steers 8 91 218 .25 75%Biuret Steers 8 91 218 .17 50% Urea Steers 8 91 218 .17

40/64p. 41



## 5. Toxicity

Reliability 27.06.2007 Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method

Result

Reliability Id 108-19-0 Date 03 .07 .2007 33%Urea Steers 8 91 218 .09 CM Steers 8 91 218 .28 where CM

= cottonseed meal On winter range biuret was as effective as cottonseed meal and better than urea for wintering beef calves. (4) not assignable Original reference not reveiwed (9) (41)

. Sub-acute

. cattle

. male : oral feed : 84 days : daily

. none other 1970 no other TS Comparison of feed grade biuret with other nitrogen supplements for maintenance of cattle grazing or being fed protein deficient forage. Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet : Grass pasture plus liquid supplement (winter) Source Animal No. Days Wt (kg) Daily gain (kg) None Beef 12 84 204 - .14 Molasses Calves 12 84 202 - .05 Biuret Calves 12 84 205 .07 Biuret+salt Calves 12 84 213 .02 Urea Calves 12 84 204 - .11 On winter range biuret was better than urea for wintering beef calves. (3) invalid Does not provide useful hazard information 27.06.2007 (9) (34) Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year : Sub-acute

. cattle

. male

. no data : oral feed : 84 days : daily

. none

. other : 1964 41/64p. 42



## 5. Toxicity GLP Test substance Method

Result

Reliability 27 .06 .2007 no other TS Id 108-19-0 Date 03.07 .2007 Comparison of feed grade biuret with other nitrogen supplements for maintenance of cattle grazing or being fed protein deficient forage. Average initial weight (kg) and average daily weight gain (kg) were reported . Basal Diet : Veld hay (4.2% protein) Source Animal No. Days Wt (kg) Daily gain (kg) None Beef 15 84 371 - .24 Biuret Steers 15 84 381 .07 Urea Steers 15 84 382 .06 70%Biuret, Steers 15 84 380 .06 30%Urea Cattle would maintain weight on low quality hay (4.2% protein) supplemented with biuret or urea, while control animals not receiving either biuret lost weight . (3) invalid Does not provide useful hazard information (9) (21) Type : Sub-acute Species : sheep Sex . female Strain . no data Route of admin. : oral feed Exposure period : 63 days Frequency of treatm

. : daily Post exposure period . none Doses . Control group . Method : other Year : 1964 GLP : no Test substance : other TS Method : Comparison of feed grade biuret with other nitrogen supplements for maintenance of mature ewes. Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet : Veld hay (3.0% protein) Animal type and sex: Wintering ewes Result : Source No. Days Wt (kg) Daily gain (kg) None 10 63 34 .6 -78 Biuret 10 63 34.5 -13 Reliability 27.06.2007 21 g of biuret in a supplement would maintain ewes on veld hay contaiing less than 3%crude protein. The ewes cupplemented with biuret consumed about 12%more hay. (3) invalid Does not provide useful hazard information (9) (22)

42/64p. 43



## 5. Toxicity Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method

Result

Reliability 27.06.2007 Sub-chronic sheep female no data oral feed 93 days daily none other 1969 no other TS Id 108-19-0 Date 03.07.2007

Comparison of feed grade biuret with other nitrogen supplements for maintenance of mature ewes. Average initial weight (kg), average daily weight gain (kg), and average weight of lamb weaned per ewe were reported . Basal Diet : Winter range plants plus supplements (1967) Animal type and sex: Pregnant range ewes No. of animals / group: 30 Days on test : 93 Source Wt (kg) Daily gain (kg) Avg . lamb wt (kg) SM 65.5 48 19.8 12.5% B 65.0 34 15.8 25%B 65.9 48 18.6 50%B 65.5 38 18.2 SM 66.4 39 14.9 12.5% urea 66.4 39 16.0 25%urea 65.0 44 16.2 50%urea 64.5 44 16.1 Where B = biuret ; SM

= soybean meal There were no significant differences in weight gains among the ewes nor in kilograms of lamb weaned per ewe among the supplement treatments . (3) invalid Does not provide useful hazard information (9) (47) Type : Sub-chronic Species : sheep Sex : female Strain : no data Route of admin. : oral feed Exposure period : 93 days Frequency of treatm . . daily Post exposure period . none Doses . Control group . Method : other Year : 1969 GLP : no Test substance : other TS 43/64p. 44



## 5. Toxicity

Method Id 108-19-0 Date 03.07.2007 Comparison of feed grade biuret with other nitrogen supplements for maintenance of mature ewes . Average initial weight (kg), average daily weight gain (kg), and average weight of lamb weaned per ewe were reported. Basal Diet : Winter range plants plus supplements (1968) Animal type and sex: Pregnant range ewes No. of animals / group: 30 Days on test : 93 Result : Source Wt (kg) Daily gain (kg) Avg. lamb wt (kg) SM 64.1 28 17.0 12.5% B 63 .9 28 18 .5 25% B 63.5 30 16.3 50% B 64 .8 28 17.9 SM 63 .9 41 18.6 12.5% urea 63 .9 32 18.2 25%urea 64.5 31 18.1 50%urea 64.5 28 17.0 Reliability 27.06.2007 Type : Sub-chronic Species : sheep Sex : female Strain . no data Route of admin . : oral feed Exposure period : 112 days Frequency of treatm

. : daily Post exposure period : none Doses , Control group . Method : other Year . 1964 GLP : no Test substance : other TS Method

Result Where B = biuret; SM = soybean meal There were no significant differences in weight gains among the ewes nor in kilograms of lamb weaned per ewe among the supplement treatments . (3) invalid Does not provide useful hazard information (9) (47)

Comparison of feed grade biuret with other nitrogen supplements for maintenance of mature ewes. Only the average daily weight gain (kg) was reported. Basal Diet : Veld grass hay (4.2%crude protein) Animal type and sex: Maiden ewes No. of animals/ group: 10 Days on test : 112 Source Avg. daily gain (kg) None -70 Cornmeal + phosphate -41 Biuret 10

44/64p. 45



## 5. Toxicity

Reliability 27.06.2007 Type : Sub-acute Species : sheep Sex : female Strain : no data Route of admin . : oral feed Exposure period : 42 days Frequency of treatm

. : daily Post exposure period : none Doses . Control group . Method : other Year : 1964 GLP : no Test substance : other TS Id 108-19-0 Date 03.07.2007

(9) (21)

Method : Comparison of feed grade biuret with other nitrogen supplements for maintenance of mature ewes. Only the average daily weight gain (kg) was reported . Basal Diet : Telf hay (7.9% crude protein) Animal type and sex: Maiden ewes No. of animals / group: 10 Days on test : 42 Result : Source Avg . daily gain (kg) None 17 Cornmeal + phosphate 77 Biuret 64 Urea 40 30%biuret; 70%urea 89 40%biuret; 60%urea 65 50%biuret; 50%urea 69 60%biuret ; 40%urea 90 70%biuret ; 30%urea 72 Reliability 27 .06 .2007 Type Species Sex Strain Route of admin . Exposure period Urea 14 30%biuret ; 70%urea 1 40%biuret ; 60%urea 1 50%biuret ; 50%urea 11 60%biuret ; 40%urea -3 70%biuret ; 30%urea 10 (3) invalid Does not provide useful hazard information

All supplements containing either biuret or urea produced substantial ewe growth (40 to 90 g per day) . (3) invalid Does not provide useful hazard information Sub-acute cattle male no data oral feed 70 days (9) (21)

45/64

## 5. Toxicity

Frequency of treatm

. : daily Post exposure period : none Doses . Control group . Method : other Year : 1964 GLP : no Test substance : other TS Method

Result Reliability 27.06.2007 Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method

Result Id 108-19-0 Date 03.07.2007

Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed low protein forage. Average initial weight (kg) and the average daily weight gain (kg) was reported . Basal Diet : Telf hay (7 .9%crude protein) No. of animals / group: 15 Days on test : 70 Source Animal type Avg . initial wt (kg) Avg. daily gain (kg) None Beef 344 .43 Biuret Steers 342 .56 Urea Steers 343 .56 70%B,30%U Steers 343 .54 (3) invalid Does not provide useful hazard information Sub-acute cattle male no data oral feed 84 days daily none other 1969 no other TS (9) (21)

Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed low protein forage. Average initial weight (kg), average daily weight gain (kg), and Feed/kg gain (air dry basis) were reported . Basal Diet : Bermuda grass hay (6.25%crude protein) and supplement No. of animals / group: 32 Days on test: 84 Source Animal type Avg. initial wt (kg) Avg. daily gain (kg) Feed/kg gain 33% B mix Beef 203 .42 10.2 67% B mix Steers 202 .39 11 .6 33% U mix Steers 202 .33 12 .9 CM Steers 202 .37 10.9p. 47



## 5. Toxicity

Reliability 27 .06.2007 Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method

Result

Reliability 27.06.2007 Where B = biuret ; U = urea; CM = cottonseed meal Id 108-19-0

Date 03.07 .2007

Cattle receiving biuret supplements gained faster than cattle receiving urea or cottonseed meal . (3) invalid Does not provide useful hazard information Sub-chronic cattle male no data oral feed 120 days daily none other 1971 no other TS (9) (41)

Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed low protein forage. Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet : Elephant grass, fresh chopped (6.7%crude protein) dry basis No. of animals / group: 8 Days on test : 120 Source Animal type Avg. initial wt (kg) Avg . daily gain (kg) ControlBeef 256 .24 Biuret Bulls 256 .33 Urea Bulls 256 .28 Cattle receiving biuret supplements gained faster than cattle receiving no supplements or urea. (3) invalid Does not provide useful hazard information (4) (9) Type : Sub-acute Species : cattle Sex . male Strain . no data Route of admin. : oral feed Exposure period : 84 days Frequency of treatm

. : daily Post exposure period . none Doses . Control group . Method : other Year : 1971 GLP : no Test substance : other TSp. 48



## 5. Toxicity Method

Result Id 108-19-0 Date 03.07.2007 Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed lowprotein forage. Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet : Oat hay (4.5% crude protein) No. of animals / group: 8 Days on test : 84 Source Animal type Avg . initial wt (kg) Avg. daily gain (kg) None Beef 253 .14 Biuret Steers 255 .31 Urea Steers 259 .47 Molasses plus urea Steers 251 .49 Cottonseed meal Steers 25 .06 Cattle supplemented with urea grew faster than control cattle, or those receiving supplements of biuret or cottonseed meal . Another group, receiving a urea-molasses liquid supplement had higher gains, but this was attributed to an increase in consumption of energy and nitrogen. The energy and nitrogen contents of all the diets were much below the requirement for efficient gains. Reliability : (3) invalid Does not provide useful hazard information 27 .06.2007 Type : Sub-acute Species : cattle Sex . male Strain , no data Route of admin. : oral feed Exposure period : 66 days Frequency of treatm

. : daily Post exposure period : none Doses . Control group . Method : other Year : 1972 GLP : no Test substance : other TS Method

Result

Reliability 27 .06.2007 (9) (14)

Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed low protein forage . Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet : Sagebrush-bunch grass range - summer Days on test : 66 Source Animal type No. Avg. initial wt (kg) Avg. daily gain (kg) None Beef 42 234 .44 Biuret Steers 49 237 .53 Cattle receiving biuret supplements gained faster than cattle receiving no supplements . (3) invalid Does not provide useful hazard information (9) (29)

48/64p. 49



## 5. Toxicity Type : Sub-chronic Species : cattle Sex : female Strain : no data Route of admin. : oral feed Exposure period : 100 days Frequency of treatm

. : daily Post exposure period : none Doses Control group . Method : other Year : 1968 GLP : no Test substance : other TS Method

Result

Reliability 27.06.2007 Type : Sub-chronic Species : cattle Sex . male Id 108-19-0 Date 03.07 .2007

Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed lowprotein forage with added energy feeds . Average initial weight (kg) and average daily weight gain (kg) were reported . Basal Diet : Range forage (summer) No. of animals per group: 5 Days on test : 100 Source Animal type Avg. initial wt (kg) Avg. daily gain (kg) No additional supplement : None Beef 253 .35 Biuret Heifers 253 .68 Urea Heifers 253 .57 Cottonseed meal Heifers 253 .58 Plus barley supplement : None Beef 253 .58 Biuret Heifers 253 .77 Urea Heifers 253 .68 Cottonseed meal Heifers 253 .77 Cattle grazing crested wheatgrass grew faster with the nitrogen frombiuret supplements than that from urea or cottonseed meal . In a second study, each animal received 300 g barley grain daily as a carrier for the NPN supplements . The authors postulated that feed grade biuret may stimulate a greater intake of forage than cottonseed meal while cattle fed urea often refuse to consume their entire supplement . Other groups of cattle on the same range pastures and nitrogen supplements were also supplemented with energy (barley grain) to provide for .9 kg daily gain. Barley feeding was increased as the range forage matured in order to compensate for its declining quality. The animal response to biuret was equivalent to that with cottonseed meal and better than with urea. The most economical gains were by cattle receiving biuret and the higher level of energy. (3) invalid Does not provide useful hazard information (9) (31)

49/64p. 50



## 5. Toxicity Strain . no data Route of admin. : oral feed Exposure period . 112-113 days Frequency of treatm

. : daily Post exposure period : none Doses . Control group . Method : other Year . 1969 GLP : no Test substance : other TS Id 108-19-0 Date 03.07 .2007

Method : Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed low protein forage with added energy feeds. Average initial weight (kg) and average daily weight gain (kg) were reported . Basal Diet : Meadow

hay plus barley Days on test : 112-113 Result : Source Animal type No. Avg. initial wt (kg) Avg. daily gain (kg) Feed/kg gain Biuret Beef 12 212 .55 10.7 CM Steers 12 218 .58 10.3 B & CM Steers 12 214 .61 9.8

Reliability Biuret Beef 18 184 .48 10.8 Urea Steers 18 194 .47 11 .7 CM Steers 18 189 .55 10.2 Biuret Beef 12 177 .43 13.4 CM Steers 12 180 .45 12.9 B & CM Steers 12 178 .48 12.2 Where B = Biuret, CM = Cottonseed meal Growing cattle fed native meadowhay plus barley grain gained almost as well on a biuret supplement as on cottonseed meal, but a combination of biuret and cottonseed meal produced the most efficient gains. (3) invalid Does not provide useful hazard information 27.06.2007 (9) (42) Type : Sub-acute Species : cattle Sex : female Strain : no data Route of admin. : oral feed Exposure period : 81 days Frequency of treatm

. : daily Post exposure period . none Doses . Control group . Method : other Year . 1972 UP : no Test substance : other TS 50/64p. 51



## 5. Toxicity

Method

Result Id 108-19-0 Date 03.07 .2007 Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed low protein forage with added energy feeds. Average initial weight (kg) and average daily weight gain (kg) were reported . Basal Diet: Grass hay and grain Days on test: 173 No . of animals per group : 81 Source Animal type Avg. initial wt (kg) Avg. daily gain (kg) Alfalfa hay Beef 199 .47 Biuret Heifers 210 .35 Alfalfa hay replacing one-half of the grass hay (12.8% crude protein) produced more rapid gains than grass hay plus a biuret supplement (11 .5% crude protein) . Reliability : (3) invalid Does not provide useful hazard information 27.06.2007 Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method (9) (25) Sub-chronic cattle male no data oral feed 112 days daily none other 1968 no other TS Comparison of feed grade biuret with other nitrogen supplements for growth of cattle grazing or being fed low protein forage with added energy feeds. Average daily weight gain (kg) was reported. Basal Diet : Wheat strawplus energy feed in supplement (about 7%crude protein) Days on test : 112 No. of animals per group: 10 Result : Source Animal type Avg. daily gain (kg) ControlBeef .17 Biuret Steers .34 Urea Steers .37 Soybean meal Steers .46 Cattle fed wheat strawplus corn grain supplemented with biuret or urea gave improved growth over non-nitrogen supplemented controls, but they did not gain as rapidly as cattle fed soybean meal supplements . Reliability : (3) invalid Does not provide useful hazard information 27.06.2007 (9) (39) 51/64

## 5. Toxicity

Type Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Post exposure period Doses Control group Method Year GLP Test substance Method

Result

Test substance Conclusion Reliability Sub-acute rat male no data i .p. 21 days daily 7 days 150 mg yes, concurrent no treatment other 1956 no other TS Id 108-19-0 Date 03.07 .2007

Eight 300- to 400-gmmale rats were divided into a control and treatment group. All rats had been treated alike fromweaning time. The four rats of each group were individually housed and continued to be fed a basal diet . Biuret of C

.P. quality (150 mg) was dissolved in a minimumvolume of physiological saline solution and administered by a single daily intraperitoneal injection for a period of 21 days to the treated group. After the 21-day injection period, both groups of animals were held for an additional 7 days prior to study termination. All animals were weighed at study initiation and termination, observed for signs of toxicity, and subjected to gross necropsy. Average daily body weight gains of 2.38 and 2.05 grams were reported for the control and Biuret-treated groups, respectively. The difference in weight gain was not statistically significant and was likely due to the daily use of the needle (the control group did not receive shaminjections) . All animals maintained normal appetites, appeared thrifty, and no mortality occurred . After termination of injections, the treated group made slightly higher gains that the control group during the next seven-day period. On gross examination of the body cavity and organs of the control and injected animals, the peritoneumof the injected animals showed slightly greater vascularity. 99.1 %purity The authors concluded that evidently the Biuret was absorbed and eliminated without serious toxic effects . (3) invalid Route not relevant 27.06.2007 (3) 5.5 GENETIC TOXICITY `IN VITRO` 5.6 GENETIC TOXICITY `IN VIVO` 5.7 CARCINOGENICITY

## 5. Toxicity

5.8.1 TOXICITY TO FERTILITY 5.8.2 DEVELOPMENTAL TOXICITY/TERATOGENICITY 5.8 .3 TOXICITY TO REPRODUCTION, OTHER STUDIES Type In vitro/in vivo Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Duration of test Doses Control group Method Year GLP Test substance Method

Result

Reliability 27.06.2007 Type : other In vitro/in vivo . In vivo Species . cattle Sex : female Strain : no data Route of admin. : oral feed Exposure period : during lactation Frequency of treatm . : daily Duration of test . 105-115 days other In vivo cattle female no data oral feed during lactation daily 114 days other 1969 no other TS Id 108-19-0 Date 03 .07 .2007

Comparison of feed grade biuret with other nitrogen supplements for cows nursing calves and lactating dairy cows. Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet : Meadow

hay, barley plus fat (fed to cows) No. of animals per group: 26-28 Days on test : 114 Source Animal type Avg . initial wt (kg) Avg. daily gain (kg) Biuret Nursing61 .62 Urea Beef 63 .60 CM Calves 64 .65 Where CM

= cottonseed meal Beef calves grew

as well when the lactating cows were fed meadowhay supplemented with biuret compared to calves nursing cows supplemented with cottonseed meal or urea . (4) not assignable Original reference not reveiwed (9) (30)

53/64

## 5. Toxicity

Doses Control group Method Year GLP Test substance Method

Result

Reliability 27.06.2007 Type In vitro/in vivo Species Sex Strain Route of admin. Exposure period Frequency of treatm

. Duration of test Doses Control group Method Year GLP Test substance Method Id 108-19-0 Date 03.07 .2007

other 1971 no other TS Comparison of feed grade biuret with other nitrogen supplements for cows nursing calves and lactating dairy cows. Average initial weight (kg) and average daily weight gain (kg) were reported. Basal Diet: Mountain meadow pasture No. of animals per group: 46-52 Days on test: 105-115 Source Animal type Days Avg . initial wt (kg) Avg. daily gain (kg) None Nursing 105 -- .97 Biuret Beef calves 105 -- .95 None Lactating 115 424 .26 Biuret Cows 115 414 .30 There was no difference in weight gains of cows or nursing calves when supplemented with biuret while grazing mountain meadowpasture. The author speculated that perhaps nitrogen was not deficient in the diet . (4) not assignable Original reference not reveiwed

. other

. In vivo : cattle no data oral feed see results see results other 1971 no other TS (2) (9)

Comparison of feed grade biuret with other nitrogen supplements for cows nursing calves and lactating dairy cows . Average daily weight gain (kg) was reported . Basal Diet : Native salt grass pasture Result : Source Animal type No . Days Avg. daily gain (kg) None Nursing 11 132 .71 Biuret Beef calves 21 132 .72

born before 54/64p. 55 

# 5. Toxicity test

25 .06.2007 Type : other In vitro/in vivo . In vivo Species : cattle Sex : female Strain . no data Route of admin. . Exposure period . Frequency of treatm

. . Duration of test . Doses . Control group . Method : other Year . 1956 GLP : no Test substance : other TS (2) (9)

Result : When cows were fed 20 g biuret and 20 g urea, there was no difference in milk production, milk composition or health of the cows when compared to control animals. 27.06.2007 (9)(19) Type : other In vitro/in vivo : In vivo Species : other : cattle, goat, sheep Sex : female Strain , no data Route of admin . . Exposure period . Frequency of treatm

. . Duration of test . Doses . Control group . Method : other Year . 1959 GLP : no Test substance : other TS Result None Nursing beef 14 132 .68 Biuret calves born 14 132 .80

after test Id 108-19-0 Date 03.07 .2007

None Weaned beef 35 54 .68 Biuret calves 38 54 1 .03 None Lactating 83 132 - .06 Biuret Cows 79 132 .02 Both nursing calves and lactating cows on salt grass pasture gained faster when fed a biuret supplement .

Concentrate mixtures containing 2 to 3% urea and 25 to 40%molasses, replacing soybean meal in diets for milking cows, left milk yields unaffected. Biuret or crude biuret was given to daily cows, goats, and sheep without affecting their health, milk production, quality of milk, or

55/64p. 56



## 5. Toxicity blood composition. Id 108-19-0 Date 03.07 .2007 25.06.2007 (9) (18) 5.9 SPECIFIC INVESTIGATIONS 5.10 EXPOSURE EXPERIENCE 5.11 ADDITIONAL REMARKS

56/64

## 6. Analyt . Meth . for Detection and Identification

6 .1 ANALYTICAL METHODS Id 108-19-0 Date 03 .07.2007

6.2 DETECTION AND IDENTIFICATION

## 7. Eff. Against Target Org. and Intended Uses

7.1 FUNCTION 7.2 EFFECTS ON ORGANISMS TO BE CONTROLLED 7.3 ORGANISMS TO BE PROTECTED 7.4 USER Id 108-19-0 Date 03 .07.2007

7 .5 RESISTANCE

## 8

. Meas. Nec. to Prot . Man, Animals, Environment

8.1 METHODS HANDLING AND STORING 8.2 FIRE GUIDANCE 8.3 EMERGENCY MEASURES 8.4 POSSIB. OF RENDERING SUBST. HARMLESS 8.5 WASTE MANAGEMENT 8.6 SIDE-EFFECTS DETECTION 8.7 SUBSTANCE REGISTERED AS DANGEROUS FOR GROUND WATER Id 108-19-0 Date 03.07 .2007

8.8 REACTIVITY TOWARDS CONTAINER MATERIAL

## 9. References

(1) Id 108-19-0 Date 03.07 .2007 Anonymous (1971) Kedlor or soybean oil meal as a protein source for cows wintered on hay and straw

. Annual Livestock Roundup 22:17. Dickinson Exp. St . N . Dakota State Univ., Dlckinson (as cited in Fonnesbeck et al ., 1975) (2) Behrens, W .C. (1971) Protein-mineral supplements for ruminants grazing notive forage . Anim . Nutr . and Health July, p. 12 (as cited in Fonnesbeck et al ., 1975) (3) Berry, W .T ., Riggs, J .K ., and Kunkel, H.O . (1956) The lack of toxicity of biuret to animals . Journal of Animal Sciences 15:225. (4) Chicco, C.F., T.A. Schultz, A .A. Carnerali, L. Oropeza and C .B. Ammerman (1971) Biuret and urea in supplements for bovines fed green chop elephant grass. J . Anim . Sci . 33:133 (as cited in Fonnesbeck et al ., 1975) (5) Clark, R., Barrett, E.L., and J .H. Kellerman (1965) A comparison between nitrogen

retention from urea, buiret, triuret and cyanuric acid by sheep on a lowprotein roughage diet . J . S. African Vet. Med . Ass. 36 : 79 (6) Clark, R., E.L. Barrett and J .H. Kellerman (1963) A comparison between nitrogen retention

from biuret and urea by sheep on a low protein roughage diet . J .S. African Vet . Med. Ass. 34 :419 (as cited in Fonnesbeck et al ., 1975) (7) Epiwin, v3.20 (8) Farlin et al ., (1968) Cited in Fonnesbeck et al ., 1975 (9) Fonnesbeck, P.V., Kearl, L .C. and Harris, L .E. (1975) Feed Grade Biuret as a Protein

Replacement for Ruminants . Journal of Animal Science, vol 40, no. 6, pp. 1150-1184. (10) Gadet, R. Soubies, L. and Fourcassie, F. (1959) Investigations on the toxic effects and

evolution of biuret in soil . Ann Agron Paris 10:609-660. (11) Handbook of Chemistry and Physics (1979) 60th ed . Weast, R .C. (ed.) Boca Raton, FL: CRC Press Inc., p. C-214. (cited in BibIioLine(c) 1997-2006, NISC International, Inc. All Rights Reserved . www .nisc .com) (12) Hatfield, E .E., Garrigus, U .S., Forbes, R.M ., Neumann, A.L. and Gaither, W . (1959) J . Animal Sci . 18: 1208. (as cited in Fonnesbeck et al ., 1975) (13) Heath, M .E. and M

.P. Plumlee (1971) Using cornstalks for pasture. Purdue Agronomy Field Day Rep. Purdue Univ., Lafayette, Indiana (as cited in Fonnesbeck et al ., 1975) (14) Hull, J .L., W .N. Garrett and J .G. Morris (1971) Wintering beef steers on low quality roughages with nitrogen supplements . Calif. Agr. 25(3) :10 (as cited in Fonnesbeck et al ., 1975) (15) Iwata et al ., (1958; 1961) cited in Fonnesbeck et al ., 1975 (16) Iwata, H . (1959) Effects of urea and its derivatives on milk production and quality. Inter . Dairy Cong. Proc. 15th Cong. London, 1 :54 . (17) Iwata, H ., K. Kobayashi, Y. Sato and Y . Watanabe. (1959) Effects of biret and heated urea on farmanimals. Kyushu Univ. Fac. Ast . Sci . Bull . 17 :69.p. 61



## 9 . References Id 108-19-0 Date 03.07 .2007 (18) Iwata, H., K. Kobayashi, Y . Sato and Y. Watanabe. (1959) Effects of biret and heated urea on farmanimals. Kyushu Univ. Fac. Ast . Sci . Bull . 17:69. (as cited in Fonnesbeck et al ., 1975) (19) Iwata, H., Y. Sato and K. Arima (1956) The effect of biuret on domestic animals in relation

to the utilization of urea. Chikusan No. Kenkyu. 10:31 (as cited in Fonnesbeck et al ., 1975) (20) Jensen, H.L. (1966) Transformation of biuret by microorganisms. Tidsskr . Planteavi .

70:160-170. (21) MacKenzie, H .I . and R.E. Altona (1964) Biuret as a supplement to roughage rations for sheep and cattle. J . S. African Vet . Med. Ass. 35:301 (as cited in Fonnesbeck et al ., 1975) (22) MacKenzie, H .I . and R.E . Altona (1964) Observations on a biuret-containing lick as a nitrogen supplement to low-quality roughage. J .S. African Vet . Med . Ass. 35:309 (as cited in Fonnesbeck et al ., 1975) (23) Mieske, J .C., W .J . Van Arsdell, R.W

. Luecke and J .A. Hoefer (1955) The utilization of urea and biuret as sources of nitrogen for growing-fattening lambs . J . Anim . Sci . 14:941 (as cited in Fonnesbeck et al ., 1975) (24) Mithyantha, M .S., Kulkarni, D.S., Tripathi, S.C., and Agnihothrudu, V . (1977) Biuret and Crop Production . Fertilizer News, 23(3) : 13-18. (25) Nichols, N.E., A.L. Lesperance and W .C. Behrens (1972) Performance of beef cows fed biuret or alfalfa . Proc. Western Sect. Amer . Soc. Anim . Sci . 23:582 (as cited in Fonnesbeck et al ., 1975) (26) Nishihara, H ., Shoji, K., and Hori, M . (1965) Studies on the biuret hydrolyzing enzyme from Mycobacterium ranae. Biken Journal 8(1) :23-34. (27) Nishihara, H., Shoji, K., and Hori, M . (1965) Studies on the biuret hydrolyzing enzyme from Mycobacterium ranae. Binen's Journal 8(1) :23. (28) Orgata, T. (year not specified) The injurious effect of biuret on plant growth . MemEhime

Univ. 8 :449-564. (29) Probert, C .L. and A.L. Lesperance (1972) A biuret supplement for steers on summer range . Proc . Western Sect . Amer . Soc. Anim . Sci . 23 :176 (as cited in Fonnesbeck et al ., 1975) (30) Raleigh, R.J . (1969) Biuret, urea, and cottonseed meal as nitrogen supplements for range

livestock production. Proc. Mont . Nutr. COnf . Mont . State Univ. Bozeman. 20:39 (as cited in Fonnesbeck et al ., 1975) (31) Raleigh, R.J . and H.A. Turner (1968) Biuret and urea in cattle supplements . Proc. Western

Sect . Amer . Soc. Anim . Sci . 19:301 (as cited in Fonnesbeck et al ., 1975) (32) Rush, I ., W .E. Sharp and R

. Totusek (1972) Self fed dry and liquid supplements containing natural protein and non-protein nitrogen for wintering range cows . Okla. Agr . Exp. Sta. Range Sci . Res. 43 (as cited in Fonnesbeck et al ., 1975) (33) Swart, R.W . and W .M . Lynch (1972) The lowtoxicity of feed grade biuret to cattle and sheep. Practicing Nutr . 6:6 (as cited in Fonnesbeck et al ., 1975)p. 62



## 9. References Id 108-19-0 Date 03.07 .2007 (34) Templeton, J .A., R.W . Swart and O.C. Bucek (1970) Use of biuret in liquid supplements for ruminants . Proc. Western Sect . Amer . Soc. Anim . Sci . 21 :183 (as cited in Fonnesbeck et al ., 1975) (35) The 1977-78 Aldrich Catalog/Handbook of Organic and Biochemicals . (1978) No. 18.

Aldrich Chemical Co., Milwaukee, WI . (cited in BibIioLine(c) 1997-2006, NISC International, Inc. All Rights Reserved. www .nisc .com) (36) The 2000-2001 Aldrich Handbook of Fine Chemicals and Laboratory Equipment (2000)

Aldrich Chemical Co., Milwaukee, WI . (cited in BibIioLine(c) 1997-2006, NISC International, Inc. All Rights Reserved. www .nisc .com) (37) The Fertilizer Institute (2007) Personal Communication with William Herz, VP, Scientific

Affairs, TFI, Washington, DC (38) The Merck Index (1976) 9th Edition. Windholz, M . (ed .) Merck and Company, Inc., Rahway, NJ ., pg 170

. (cited in BibIioLine(c) 1997-2006, NISC International, Inc. All Rights Reserved . www .nisc .com) (39) Thomas, O .O ., J .L. Van Horn and R.L. Blackwell (1968) Biuret and urea in supplements fed cattle grazed on native range. Feeders Day, Rep. PR-53 (as cited in Fonnesbeck et al ., 1975) (40) Tiwari, A.D. (1972) Metabolismof biuret by rumiinants : In vitro and in vivo studies . Ph.D.

Theses. Univ. of Illinois, Urbana-Champaign . (as cited in Fonnesbeck et al ., 1975) (41) Tollett, J .T., R.W . Swart, R.M

. loset and J .A. Templeton (1969) Biuret as a nitrogen source for wintering steers. Proc. Western Sect . Amer . Soc. Anim . Sci . 20:325 (as cited in Fonnesbeck et al ., 1975) (42) Turner, H.A. and R.J . Raleigh (1969) Biuret and urea for growing cattle. Proc. Western

Sect . Amer . Soc. Anim . Sci . 20:331 (as cited in Fonnesbeck et al ., 1975) (43) USEPA (1983) 21 C .F .R. § 184.1923 Urea. Title 21 - Food and Drugs (44) USEPA (2002) http ://www .epa .gov/fedrgstr (45) USEPA (2002) http://www .epa .gov/oppsrrd1/REDs/urea tred .htm ; http://216.239.51 .104/search?q=cache :p1264Z8FFIJ :www

.fda .gov/cder/ogd/rld/12154s24.pdf+FDA+category+C+urea&hl=en&ct=cln k&cd=1 &gl=us (46) USEPA (2003) [Federal Register : May 22, 2003 (Volume 68, Number 99)] [Rules and

Regulations] [Page 27904] Fromthe Federal Register Online via GPO Access [wais .access .gpo.gov] [DOCID:fr22my03-5] (47) Van Horn, J .L., 0 .0. Thomas, J . Drummond and R.L. Blackwell (1969) Biuret and urea supplements for range ewes . Proc. Western Sect . Amer. Soc. Anim . Sci . 20:319 (as cited in Fonnesbeck et al ., 1975) (48) Waite, R., Castle, M .E., Watson, J .N. and Drysdale, A.D. (1968) Biuret and urea in concentrates for milking cows. J . Dairy Res. 35: 191 . 62/64p. 63



## 9. References Id 108-19-0 Date 03.07.2007 (49) YALKOWSKY, SH and DANNENFELSER, RM (1992), as cited in EPIWIN v.3 .20 Database

63/64p. 64



## 10. Summary and Evaluation

10.1 END POINT SUMMARY 10.2 HAZARD SUMMARY 10.3 RISK ASSESSMENT Id 108-19-0 Date 03.07 .2007

Memo . Pesticide Tolerance Reassessmet Risk Assessment Remark . Fromthe available animal studies and other data, EPA has concluded that urea exhibits a low

toxicity and exposures to urea used either as an active or inert pesticide ingredient present a reasonable certainty of no harmto human health. The Agency's analysis of extensive toxicological data in numerous species supports the 1995 decision to grant permanent exemptions from the requirement of a tolerance for residues of the frost protectant when used before harvest in the production of raw agricultural commodities . Source : http ://www .epa .gov/oppsrrdl/REDs/urea tred .htm 03.07 .2007 Memo : Estimating Risk FromContaminants Contained in Agricultural Fertilizers Remark : " . . .(M)ost fertilizers do not pose harmto human health or the environment . Risks of concern fromfertilizer products can be attributed to arsenic, and dioxins found in select liming agents and micronutrients." Biuret is not found in liming agent sor micronutrients . Source : http ://www .epa .gov/epaoswer/hazwaste/recycle/fertiliz/risk/ 03 .07 .2007