Toxicity Testing Strategies to Determine Needs and Priorities (1984) / Chapter Skim
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APPENDIXES
APPENDIXES
Pages 129-198
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From page 129... ...
Sodium decyldiphenyletherdisulfonate Trichlorobenzyl chloride Benzenecarbothioamide, 2,5-dichloro Citric acid, trisodium salt Benzenamine, compound with 1,3,5-trinitro benzene (1:1) Ethylene thiourea Acetic acid, (2,4-dichlorophenoxy)
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From page 130... ...
-, trisodium salt 2-Propanamine, sulfate * p-Nitrophenyldimethylthionophosphate 2,4-Dichlorophenoxyacetic acid, alkylamine salt *
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From page 131... ...
* Calcium acetate Sucrose benzoate Laureth-3 Potassium oleate PEG-100 stearate Cocamine oxide Sodium myristyl sulfate Tetrasodium EDTA Cetearyl alcohol Dimethyl cocamine p-Cresol DM Hydantoin Isosteareth-6 carboxylic acid Dehydroacetic acid Spinach extract Benzophenone-11 PEG-200 Guanidine carbonate PPG-2 methyl ether D & C Orange No.
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From page 132... ...
Zinc carbonate , Glyceryl tri-C10_lg acids Potassium iodide Benzophenone-7 Ethylene brassylate Sodium monodiethylaminopropyl cocoaspartate Nonoxyno1-4 Ceteareth-17 Ammonium myreth sulfate Poloxamine 908 Isostearamidopropyl dimethylamine lactate Ditridecyl sodium sulfosuccinate Styrene/maleic anhydride copolymer ~ e Grape Julce FD & C Green No. 3 Corn poppy extract PEG-8 oleate Unavailable 977066-07-1 150-38-9 9004-99-3 977063-59-4 977058-53-9 3486-35-9 Unavailable 7681-11-0 85-19-8 105-95-3 977068-51-1 7311-27-5 977063-70-9 27731-61-9 11111-34-5 55852-15-8 2673-22-5 9011-13-6 977064-74-6 2353-45-9 Unavailable 9004-96-0 977055-26-7 101-54-2 39464-69-2 8014-29-7 977064-18-8 104-98-3 68439-53-2 75-31-0 68989-01-5 61788-85-0 8016-70-4 977068-15-7 557-04-0 31692-79-2 9087-53-0 633-96-5 75-57-0 144-55-8 977067-59-6 ~5322-68-3 28474-90-0 1643-20-5 Unavailable N-Phenyl-~-phenylenediamine Oleth-4-phosphate Rue oil Decyl mercaptomethylimidazole Urocanic acid PPG-20 lanolin ether Isopropylamine Quaternium-3 PEG-7 hydrogenated castor oil Hydrogenated soybean oil Cll_l3 isoparaffin Magnesium stearate Dimethiconol PPG-4-ceteth-5 D & C Orange No.
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From page 133... ...
~: r . ~: CAS Number d PEG-7 glyceryl cocoate Cocamidopropylamine oxide TEA-oleamido PEG-2 sulfosuccinate Pareth-45-11 Nonyl nonoxynol-10 phosphate Stearoxytrimethylsilane Solvent yellow 44 Alginic acid DRUGS AND EXCIPIENTS IN DRUG FORMULATIONS 977064-68-8 68155-09-9 Unavailable Unavailable Unavailable Unavailable 0478-20-8 9005-3~-7 *
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From page 134... ...
Norharman Ionone, gamma Triethylamine hydrochloride Cupric sulfate, anhydrous Ammonium thiocyanate Yeast extract, Baker's Dimethylphenylpiperazinium iodide Sulfide ion Allyl nonanoate Geranium oil Benzyl thiocyanate Polyvinyl ethyl ether Elemene, alphaMethyl isobutyrate Jasmine absolute 134 50-01-1 341-69-5 70-51-9 124-29-8 1622-61-3 58-22-0 51-43-4 Unavailable 9002-7-5 Unavailable 1221-56-3 1338-54-1 Unavailable 8006-40-4 8012-89-3 9004-64-2 64-55-1 7558-80-7 31103-86-3 533-74-4 556-08-1 7632-51-1 5405-41-4 977014-63-3 977001-13-0 244-63-3 79-76-5 554-68-7 7758-98-7 1762-95-4 8013-01-2 54-77-3 18496-25-8 7493-72-3 8000-46-2 3012-37-1 25104-37-4 5951-67-7 547-63-7 8031-01-4
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From page 135... ...
Hydrazine hydrate 7803-57-8 DI-Dodecyl tin oxide 22 73-48-5 Molybdic acid 11099-00-6 Celery seed extract Unavailable Diethylene glycol dibenzoate 120-55-8 ~-Menth- 1-en-9-o 1 184 7 9-68-0 * Sodium lauryl sulfate 151-21-3 Guanidoethyl cellulose 9069-21-0 Lipase, animal 977033-78-5 S i 1 icon 7440-21-3 2-Ethylhexyl 9,10-epoxystearate 141-38-8 1,4-Dihydroxy-9,10-anthraquinone 81-64-1 Phytoene 540-04-5 Isoamyl isobutyrate 2050-01-3 2-Tridecanone 593-08-8 _-tert-Butylacrylamide 107-58-4 *
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From page 136... ...
Disperse Orange #3 1,4-Dianilinoanthraquinone Dimethylol melamine Tetrakisthydroxymethyl~phosphonium chloride 2-Ethylhexyl mercaptoacetate Pentaerythritol monostearate Itaconic acid-methyl methacrylate copolymer 2,6,6-Trimethyl-2-cyclohexen-1-one Geranial 3,4,5,6-Dibenzacridine Ion-exchange membrane Methyl hydrogen siloxane Valproic acid 13150-00-0 7631-86-9 112-79-8 96-70-8 2835-39-4 109-01-3 6381-91-5 9002-86-2 7779-65-9 102-16-9 [515-64-0] 51022-98-1 500-40-3 977032-85-1 54~-40-5 5224-23-7 31019-46-2 977001-58-3 574-93-6 20427-59-2 68608-32-2 730-40-5 2944-12-9 5001-80-9 124-64-1 7659-86-1 78-23-9 27155-24-4 20013-73-4 141-27-5 ~24-53-3 Unavailable 63148-57-2 99-66-1 CHEMICALS IN COMMERCE Product~on at Least 1 Million Pounds/Year Chemical CAS Number ~ 1 .
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From page 137... ...
trimethoxy) Benzenesulfonic acid, 3-~(ethoxycarbonyl~aminol-, monosodium salt Hexanedioic acid, polymer with methyloxirane polymer with oxirane ether with oxybis= [propanol ]
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From page 138... ...
-2-methylphenyl~azol-, disodium salt Hexanedioic acid, dimethyl ester, polymer with N,N'-bis(2-aminoethyl) -1,2-ethanediamine and dimethyl pentanedioate Bicycloi3.1.0]
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From page 139... ...
~) tetrakis-, hexammonium disodium salt Vanadic acid (H4V2O7)
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From page 140... ...
-1,2-ethanediamine and (chloromethyl) oxtrane, nonylphenol-modified Naphthalenesulfonic acid, dibutyl-, ammonium salt 1,4-Benzenedicarboxylic acid, dimethyl ester, polymer with dimethyl pentanedioate, I,6-hexanediol, and 2,2'-oxybisiethanol]
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From page 141... ...
Hexanoyl chloride Benzeneethanol, alpha-butyl-, acetate Cyclotrisiloxane, hexamethyl-, polymer with (l,l-dimethylethyl~ethenylbenzene and (l-methyl= ethenyl~benzene 1,2-Benzenedicarboxylic acid, compound with benzenamine (1:1) Imidodisulfuric acid, ammonium salt Benzenamine, _,N-dimethyl-4-~4-(methylamino)
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From page 142... ...
, tetraphenyl ester Benzemide, 4-methoxy-3-nitro-N-phenyl Indol-3-ol, dihydrogen phosphate (ester) , disodium salt *
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From page 143... ...
Benzemide, N-hydroxy-N-phenyl Phosphonic acid, dodecyl-, diethyl ester Iridium oxide 9-Octadecenoic acid (Z.) -, methyl ester, sulfurized, copper-treated 2-Propenoic acid, ethyl ester, polymer with ethenylbenzene, formaldehyde, and 2-propenamide lH-3a,7-Methanoazulene, octahydro-3,8,8-trimethyl 6-methylene-, [3R-~3alpha,3abeta,7beta,= 8aalpha)
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From page 144... ...
-lH-pyrazol-l-yl] -, sodium salt Benzoic acid, 2-hydroxy-, methyl ester 1-Octen-3-ol 2-Naphthalenesulfonic acid, 8-hydroxy-5,7-dinitro 1,8-Naphthalenedicarboxylic acid, dipotassium salt Barium peroxide 2-Propenoic acid, octadecyl ester 9,10-Anthracenedione, 1,4-diamino 2-Propenoic acid, homopolymer, sodium salt Chromate(3-)
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From page 145... ...
-, disodium salt 1,3-Propanediol, 2-~(benzoyloxy~methyl] 2-methyl-, dibenzoate Octadecanoic acid, 12-hydroxy-, methyl ester CHEMICALS IN COMMERCE Production Unknown or Inaccessible , - , , , 2-Propanone, 1-(2-furanyl)
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From page 146... ...
-, monosodium salt Safflower oil, polymer with conjugated safflower oil, glycerol, methyl methacrylate, pen ta= erythritol, phthalic anhydride, and styrene Propanoic acid, 3,3'-thiobis-, diethyl ester Distillates (petroleum) , solvent-dewaxed light paraffinic Poly~oxy-1,2-ethanedlyl)
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From page 147... ...
tert-Dodecanethiol 2-Anthracenesulfonic acid, 1-amino-9,10-dihydro 4-~4-~(methylamino~methyl~phenyl~amino] 9,10-dioxo-, monosodium salt Benzenemethanol, alpha-ethynyl-alpha-methyl Fatty acids, tall-oil, polymers with dipropylene glycol, maleic anhydride, and pitch *
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From page 148... ...
= azo] -, disodium salt Hexanoic acid, 2-ethyl-, cobalt(2+)
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From page 149... ...
-1,3-propanediyl ester Benzenesulfonic acid, dodecyl-, sodium salt Soybean oil, polymer with benzoic acid, isophthalic acid, and phthalic anhydride Safflower oil, polymer with E~tert-butylbenzoic acid, glycerol, lauric acid, and phthalic anhydride Acetic acid, (3-methylbutoxy) -, 2-propenyl ester Fatty acids, coca, polymers with isophthalic acid neopentyl glycol, and trimellitic anhydride 1,4-Diisocyanatobenzene *
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From page 150... ...
ester, monosodium salt Fatty acids, tallow, lithium salts 64755-02-8 Amines, C10_16-alkyldimethyl 6 7700-98-5 1,3,5-Triazine-2,4,6-triamine, polymer with 62412-64-0 formaldehyde, hydrochloride Octanoic acid, 2-butyl Cyclopentanone, 2-hexylidene Fatty acids, tall-oil, reaction products with 2-~2-aminoethyl~aminoJethanol, quaternized with sulfate diethyl Benzenediazonium, 4-(diethylamino) -, chloride, compound with zinc chloride Titanium nitride Quaternary ammonium compounds, bisthydrogenated tallow alkyl~dimethyl, chlorides 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, isobutylated Hexanedioic acid, polymer with 1,6-hexanediol Naphtho[1,2-d~thiazol-2-amine Formaldehyde, polymer with oxybistpropanol]
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From page 152... ...
:, Q lc at .4 .1 _ ~ .~ ~ § :n X A; C O 4 JO · - C C ~ O U · O ~ C: _ ~ O C)
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From page 153... ...
cn X t,3 §c ,, E In ~ ~ o So ;,3 ~ 0 ~ o o ~ 8~ C~ P: ~4 o ~ o ,~ 4U Z ~ ~ ° , En En 03 0 ~ En En Z O U]
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From page 157... ...
up 0 a: En ~ ~ c)
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From page 163... ...
Additional studies appropriate to duration and route of intended use; some studies required in target species; if target species is food-producing animal, see direct food additives in Appendix B Or perform test 24.
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From page 165... ...
APPENDIX H REFERENCE PROTOCOLS FOR TOXICITY TESTING Test Reference Sourcea 1. Acute oral toxicity -- rodent IRLG, 1981c 2.
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From page 166... ...
Test 13. Subchronic oral toxicity -- nonrodent: 6- to 12-mo study 14.
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From page 167... ...
29. Acute delayed neurotoxicity 30.
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From page 168... ...
Marzulli, F
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From page 169... ...
APPENDIX I REFERENCE PROTOCOL GUIDELINES FOR NEUROBE~VTORAL-TOX ICITY TESTS Neurobehavioral-toxicity testing requires both morphologic and behavioral assessment. With current methods, the effects of some chemicals are most reliably detected by measuring morphologic changes, whereas other chemicals produce behavioral changes without, as yet, the identification of any morphologic basis.
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From page 170... ...
of SMA and schedule-controlled behavior are two of the most sensitive tests for determining the behavioral effects of pesticides. A battery of sophisticated techniques for more detailed evaluation of substances for neurobehavioral effects is gradually being developed (Geller et al., 1979~.
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From page 171... ...
Specificity of neurobehavioral toxicity may be expressed as the ratio of the LDso to the neurobehaviorally toxic dose. Neurobehavioral-toxicity evaluation and its relative importance should include a comparison with other toxicity data on the substance.
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From page 172... ...
DETERMINATION OF ADEQUACY OF NEUROBE~VIO=L-TOXIC I TY TESTI Because no reference protocol guidelines for neurobehavioral-toxicity testing have been established and because much evidence of neurobehavioral toxicity exists in qualitative descriptions of the adverse effects of substances, the Committee on Toxicity Data Elements has established a series of criteria for judging the adequacy of neurobehavioral-toxicity testing, including observations of effects. The neurobehavioral-toxicity data base (see Figure I-1)
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From page 173... ...
/ Review of the Toxicity Data Bases of Chemicals in the Sample Neurobehavioral toxicity / \ Functional Morphologic (behavioral) (neuropathologic)
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From page 174... ...
REFERENCES Ferster, C
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From page 175... ...
Government agencies in the United States are attempting to make their approaches compatible with those guidelines, and the Committee on Toxicity Data Elements accepted the guidelines as the standard against which genetic-toxicity studies were to be measured. The OECD testing strategy has two stages.
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From page 176... ...
· A substance studied for each Stage 1 end point in tests not conducted according to the OECD protocol guidelines, but nevertheless regarded by the committee as adequate, was considered to have met the committee's standard for an adequate (A) study of genetic toxicity.
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From page 177... ...
APPENDIX K CONCEPTUAL ISSUES CONCERNING THE INTERPRETATION OF RESULTS OF STUDIES OF REPRODUCTIVE AND DEVELOPMENTAL TOXICITY Interpretation of studies of reproductive and developmental toxicity required an awareness of potential confounding factors, such as interspecies differences in toxicokinetics and developmental biology. These factors notwithstanding, tests for adverse effects on reproduction are not the same as tests for adverse effects on development (e.g., in utero growth retardation, functional decrements evident after birth, death of the conceptus, and production of live or dead terata)
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From page 179... ...
For required tests For tests not required Roadblocks to getting toxicity information Adequacy of the data base Analysis of individual toxicity studies Analysis of the complete toxicity data base Analysis of the complete data base 179
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From page 180... ...
Adequacy Ratings of Required Toxicity Tests That Were_Performed for a Pesticide or Inert Ingredient of Pesticide Formulationa Necessary Toxicit Testsb ~.
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Summary Ratings for the Quality of All Information in a Dossier 1. Breadth of known exposure a.
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6. Evidence of inaccessible toxicity data a.
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From page 183... ...
Starting materials 2. Manufacturing processes B
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From page 184... ...
Occupational exposure 1. Number of people exposed: a.
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From page 185... ...
. ~ Manufacturing processes, including pathways of chemical synthesis, and production volumes.
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From page 186... ...
· Manufacturers, trade associations, and large industrial consumers of the substances in the sample. ACCESS TO DATA The Committee on Toxicity Data Elements encountered several roadblocks when searching for data.
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From page 187... ...
Negative results (findings of no toxic effects) often are not reported art all.
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From page 191... ...
Helpful information was also obtained from the files of the Registry of Toxic Effects of Chemical Substances and from the Toxicology Data Bank. Six reference books were consulted for information on each chemical (Doull et al., 1980; Hawley, 1977; Physicians Desk Reference, 1981; Sollmann, 1957; Weast and Astle, 1979; Windholz et al., 1976~.
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From page 192... ...
The 26-yr-old collection of toxicologic information in the TIC includes data produced before the collection began and acquired through retrospective literature searches, in addition to data generated from the establishment of the collection to the present. The TIC is also a repository of reprints gathered for reports of NaC committees, as well as of some private reprint collections donated by toxicologists.
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From page 193... ...
However, these documents contained only a few of the substances of interest to the committee. Toxicity data on several chemicals were found in unclassified documents maintained by NIOSH (National Institute for Occupational Safety and Health, 1982~.
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From page 194... ...
A followup letter -- which included a complete description of the project, an alphabetized list of the 100 substances, a request for unpublished toxicity data, and a questionnaire -- was sent to each company. The questionnaire contained the following questions: · Is the material that is produced in your work environment regulated by FDA, OSHA [the Occupational Safety and Health Administration]
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From page 195... ...
It is very difficult -- often impossible -- to locate and contact all the current manufacturers of a given substance. AVAILABILITY AND ROLE OF INFORMATION OTHER THAN TOXICITY DATA Information on intended uses was readily available from the reference textbooks for most cosmetic ingredients, drugs and excipients in drug formulations, and food additives.
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From page 196... ...
The lack of suitable exposure data places an even more severe limitation on the application of inferences drawn from analyses of the chemicals in the final sample to the larger "select universe" and on the development of quantitative dose-response models for chemicals in the environment. The assembled toxicity data on the 100 substances provide a good base for examining the predictive nature of toxicity-testing models; however, the absence of exposure data prevents a similar examination of exposure models.
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From page 197... ...
1982. Subfile excerpted from the NIOSH Registry of Toxic Effects of Chemical Substances.
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