Pesticide residues in food â 2007: Toxicological ... - ipcs inchem

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225 Table 6. Treatment-related histopathology findings in a study of carinogenicity in mice fed diets containing difenoconazole Dietary concentration (ppm) Males Females 0 10 30 300 2500 a 4500 0 10 30 300 2500 a N E N E N E N E N E N E N E N E N E N E N E Liver Hepatocellular adenoma Hepatocellular carcinoma Single-cell necrosis Finding Death/ scheduled termination Focal/multifocal necrosis Early b 0 2 0 2 0 2 0 4 0 0 0 14 0 3 0 3 0 4 0 4 0 11 g Interim c 0 10 1 10 2 10 0 10 1 10 2 10 0 10 0 10 0 10 0 10 1 10 Recovery d 0 9 — — — — — — 0 10 3 10 — — — — — — — — 0 10 Late e 0 18 3 16 1 21 2 22 9 16 6 20 0 26 0 14 0 21 0 15 5 10 Terminal f 4 31 6 32 5 27 7 24 3 34 9 16 0 24 0 35 0 29 1 35 10 29 Early 0 2 0 2 0 2 0 4 0 0 0 14 0 3 0 3 0 4 0 4 0 11 Interim 0 10 0 10 0 10 0 10 0 10 2 10 0 10 0 10 0 10 0 10 0 10 Recovery 0 9 — — — — — — 1 10 1 10 — — — — — — — — 0 10 Late 0 18 0 16 1 21 0 22 1 16 4 20 0 26 0 14 0 21 0 15 2 10 Terminal 1 31 0 32 0 27 0 24 3 34 6 16 0 24 0 35 1 29 0 35 2 29 Early 0 2 0 2 0 2 1 4 0 0 14 14 0 3 0 3 0 4 0 4 9 11 Interim 0 10 1 10 1 10 3 10 10 10 10 10 0 10 0 10 0 10 3 10 10 10 Recovery 1 9 — — — — — — 6 10 3 10 — — — — — — — — 0 10 Late 0 18 1 16 0 21 2 22 11 16 17 20 0 26 0 14 0 21 1 15 0 10 Terminal 4 31 3 32 1 27 7 24 25 34 9 16 3 24 0 35 0 29 2 35 8 29 Early 0 2 0 2 1 2 1 4 0 0 6 14 0 3 0 3 0 4 0 4 1 11 Interim 0 10 0 10 0 10 2 10 1 10 0 10 0 10 0 10 0 10 1 10 0 10 Recovery 0 9 — — — — — — 0 10 0 10 — — — — — — — — 0 10 Late 1 18 1 16 3 21 2 22 5 16 5 20 1 26 1 14 0 21 0 15 2 10 Terminal 3 31 1 32 0 27 1 24 5 34 5 16 3 24 1 35 0 29 6 35 3 29 DIFENOCONAZOLE 201–272 JMPR 2007
226 Hepatocellular Early 0 2 0 2 0 2 1 4 0 0 14 14 0 3 0 3 0 4 0 4 6 11 hypertrophy Interim 0 10 1 10 0 10 1 10 10 10 10 10 0 10 0 10 0 10 0 10 10 10 Recovery 1 9 — — — — — — 4 10 2 10 — — — — — — — — 1 10 Late 4 18 9 16 7 21 13 22 15 16 6 34 1 26 1 14 1 21 3 15 8 10 Terminal 12 31 6 32 8 27 11 24 32 34 11 16 1 24 6 35 1 29 4 35 28 29 Fatty change Early 0 2 0 2 0 2 1 4 0 0 2 14 0 3 0 3 0 4 0 4 1 11 Interim 2 10 1 10 0 10 2 10 5 10 9 10 0 10 0 10 2 10 1 10 4 10 Recovery 0 9 — — — — — — 0 10 1 10 — — — — — — — — 0 10 Late 0 18 0 16 0 21 0 22 1 16 13 20 0 26 0 14 0 21 0 15 0 10 Terminal 0 31 0 32 0 27 1 24 7 34 7 16 0 24 1 35 0 29 3 35 4 29 Biliary stasis Early 0 2 0 2 0 2 0 4 0 0 1 14 0 3 0 3 0 4 0 4 0 11 Interim 0 10 0 10 0 10 0 10 3 10 10 10 0 10 0 10 0 10 0 10 6 10 Recovery 0 9 — — — — — — 9 10 6 10 — — — — — — — — 9 10 Late 0 18 0 16 0 21 0 22 12 16 20 20 0 26 0 14 0 21 3 15 6 10 Terminal 1 31 0 32 0 27 3 24 32 34 13 16 0 24 0 35 0 29 0 35 29 29 From Cox et al. (1989a) N, No. of mice with finding; E, No. of mice examined. a Fed diet containing difenoconazole at 3000 ppm until day 21. b Early unscheduled deaths in weeks 1–52. c Interim kill in week 53. d Recovery group, killed in week 57. e Late unscheduled deaths in weeks 53–79. f Terminal kill in weeks 79–80. g No histopathology on 10 early deaths (mice ‘replaced’ by mice from control group). DIFENOCONAZOLE 201–272 JMPR 2007
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Pesticide residues in food — 2007
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TABLE OF CONTENTS Page List of part
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Dr Vicki L. Dellarco, Office of Pes
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Abbreviations used 3-MC ACTH ADI ai
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MRL MS MS/MS MTD NMR NOAEC NOAEL NO
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Introduction The toxicological mono
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AMINOPYRALID First draft prepared b
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5 higher renal excretion in the gro
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7 Table 4. Recovery of radioactivit
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9 Table 7. Pharmacokinetic paramete
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11 (c) Exposure by inhalation Five
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13 Table 9. Acute toxicity of amino
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15 The data from urine analysis rev
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17 18, monthly for palpable masses.
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19 Table 12. Body weights of rats f
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21 Table 15. Results of assays for
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23 in both groups, feed consumption
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25 neurotoxicity after 12 months. B
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27 The same five time-mated NZW rab
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29 Mortality was increased in all g
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31 Levels relevant to risk assessme
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33 References Brooks, K.J. (2001a)
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35 Consulting, The Dow Chemical Com
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ATRAZINE First draft prepared by Ru
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39 in the early 1990s; this reflect
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41 Maximum concentrations in the bl
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43 In a study on comparative metabo
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45 Table 1. Metabolism of atrazine
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47 Figure 2. Proposed metabolic pat
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49 to intact skin; and that no read
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51 the highest dose, and food consu
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53 mice (evaluated as roughly equiv
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55 Table 5. Incidence of mammary tu
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57 Table 6. Selected findings from
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59 was decreased when compared with
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61 Table 9. Selected findings of a
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63 proestrus at the expense of days
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65 Table 10. Selected studies of ge
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67 End-point Test object Concentrat
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69 Table 12. Relevant findings in a
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73 respectively) and in males at th
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77 All dams survived until the end
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79 250 and 500 ppm. Body-weight gai
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81 In an assay for reverse mutation
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83 on pubertal development in femal
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85 parameters (decreased pH, specif
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Page 104 and 105:
89 0, 75, 150 or 300 mg/kg bw per d
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91 The NOAEL was 25 ppm, equal to 1
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93 In a study on the effect of atra
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95 Delayed parturition was seen at
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97 observed in the pair-fed group.
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99 examined, offspring in the atraz
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101 antagonize E2-induced luciferas
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103 increase in steroidogenesis is
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105 The immune system of adult mice
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107 In a later review of cancer epi
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109 In a 25-day study in rabbits tr
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111 developmental toxicity were 10
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113 regulation in male offspring in
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115 (d) Diaminochlorotriazine (DACT
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117 Developmental target/critical e
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119 • The failure to ovulate resu
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121 The relationship between increa
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123 Table A2. Comparison of paramet
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125 Ballantine, L., Murphy, T. G. &
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127 Dunkelberg, H., Fuchs, J., Heng
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129 Heneweer, M., van den Berg, M.
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131 Lindsay, L.A., Wimbert, K.V., G
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133 Morseth, S.L. (1996d) Chronic (
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135 Rudzki, M.W., Batastina, G., &
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137 Tennant, A.H., Peng, B. & Klige
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AZINPHOS-METHYL First draft prepare
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141 methylation and oxidation of me
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143 Table 1. Acute oral toxicity of
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145 Table 2. Cholinesterase activit
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147 at the highest dose. In both sp
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149 Table 6. Cholinesterase activit
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151 Table 8. Fertility of F 0 and F
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153 Table 10. Fertility parameters
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155 Groups of 22 mated Sprague-Dawl
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157 after completion of the feeding
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159 reduced motor activity in males
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161 sensitivity with that of labora
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163 measures to prevent worker expo
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165 when brain cholinesterase activ
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167 Critical end-points for setting
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169 Eiben, R., Schmidt, W., & Loese
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171 Myhr, B.C. (1983) Evaluation of
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LAMBDA-CYHALOTHRIN First draft prep
Page 190 and 191: 175 Figure 1. Chemical structures o
Page 192 and 193: 177 In a comparative study, the abs
Page 194 and 195: 179 Figure 2. Main pathways of biot
Page 196 and 197: 181 (iv) Dermal sensitization In a
Page 198 and 199: 183 observed in rats at the highest
Page 200 and 201: 185 Mortality was not affected by t
Page 202 and 203: 187 the group at 100 ppm, reduction
Page 204 and 205: 189 and five females per group were
Page 206 and 207: 191 10-12%) than those of controls
Page 208 and 209: 193 Comments Biochemical aspects Or
Page 210 and 211: 195 Toxicological evaluation Althou
Page 212 and 213: 197 Metabolism in animals Toxicolog
Page 214 and 215: 199 Harrison, M.P. (1984a) Cyhaloth
Page 216 and 217: DIFENOCONAZOLE First draft prepared
Page 218 and 219: 203 a sex difference nor any marked
Page 220 and 221: 205 demonstrated that the highest t
Page 222 and 223: 207 Figure 3. Proposed metabolic pa
Page 224 and 225: 209 of the study were unremarkable.
Page 226 and 227: 211 Table 3. Results of studies of
Page 228 and 229: 213 The no-observed-adverse-effect
Page 230 and 231: 215 lower than those of rats in the
Page 232 and 233: 217 hepatocellular enlargement. In
Page 234 and 235: 219 i.e. males lost 15.4% and femal
Page 236 and 237: 221 and 357. This reduced food cons
Page 238 and 239: 223 There was very high mortality a
Page 242 and 243: 227 Rats Groups of 80 CRL:CD(SD)®
Page 244 and 245: 229 Table 7. Histopathology finding
Page 246 and 247: 231 D. Temporal association. The fe
Page 248 and 249: 233 2.5 Reproductive toxicity (a) M
Page 250 and 251: 235 t estes weights in the males at
Page 252 and 253: 237 continued to be lower than thos
Page 254 and 255: 239 Corpora lutea in each ovary wer
Page 256 and 257: 241 S1 + S2, not ossified — —
Page 258 and 259: 243 in the control group and in the
Page 260 and 261: 245 physically examined for changes
Page 264 and 265: 249 can occur in untreated mice, in
Page 266 and 267: 251 Study of reproductive toxicity
Page 272 and 273: 257 of the test article on microsom
Page 274 and 275: 259 Ophthalmoscopic examinations pe
Page 276 and 277: 261 the radioactivity was re-elimin
Page 278 and 279: 263 In a single-dose study of neuro
Page 280 and 281: 265 Estimate of acceptable daily in
Page 282 and 283: 267 Clapp, M.J.L., Killick, M.E., H
Page 284 and 285: 269 Herbold, B. (1983c) THS 2212 tr
Page 286 and 287: 271 Pinto, P. (2006b) Difenoconazol
Page 288 and 289: DIMETHOMORPH First draft prepared b
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275 Five different treatment groups
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277 To investigate the significance
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279 and the E : Z isomer ratio was
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281 Table 10. Tissue distribution o
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283 (e) Dermal sensitization The de
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285 females at the highest dose, to
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287 The NOAEL was 10 mg/kg bw per d
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289 concentrations in females were
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291 health, moribundity and mortali
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293 0-9%, mean, 3.5%; only one out
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Table 26. Organ weights adjusted to
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297 cell hyperplasia. The testes tu
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299 unscheduled DNA synthesis, the
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301 Figure 3. Cumulative percentage
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303 Rabbits In a dose-range finding
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305 (b) Potentiation of hexobarbito
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307 0.2% or less of the administere
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309 eye-opening, pinna unfolding or
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311 Lowest relevant inhalation NOAE
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313 Gardner, J.R. (1989) CME 151 te
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315 van de Waart, E.J. (1991b) Eval
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318 Committee on Pesticide residues
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320 (a) Ocular irritation Rabbits T
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322 weights were decreased in males
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324 toxicity was 5 mg/kg bw per day
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326 respectively; range for histori
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328 Table 4. Incidence of Leydig-ce
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330 and/or bilateral) was noted in
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332 No treatment-related signs of m
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334 Table 6. Incidence of selected
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336 or teratogenic potential at the
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338 and progesterone. The concentra
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340 the doses used in the 1-year st
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342 No neurotoxic effects were seen
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344 Lowest relevant reproductive NO
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346 Keller, D.A. (1992c) Oncogenici
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PROCYMIDONE First draft prepared by
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351 Rats Groups of five male and fe
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353 Table 1. Pharmacokinetic parame
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355 Seven doses C max (µg equivale
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357 Three groups of five male and f
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359 The excretion of radioactivity
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361 Figure 1. Proposed metabolic pa
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363 water consumption were determin
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365 finding. Histopathology reveale
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367 The NOAEL was 500 ppm, equivale
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369 The NOAEL was 100 mg/kg bw per
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371 at 2000 ppm. Histopathology rev
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373 b Each test was conducted in tr
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375 experimental period. Rats were
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377 hypospadias, testicular atrophy
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379 a single dose, which produced o
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381 The anti-androgenic activities
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383 but only at 6000 ppm after 13 w
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385 The results are summarized in T
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387 males (all litters) in the grou
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389 procymidone (18-27% of the admi
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391 Procymidone induced liver tumou
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393 The Meeting concluded that the
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395 Toxicologically significant com
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397 Harada, T. (1983) A review on m
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399 Murakami, M., Yoshitake, A. & H
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401 Tarui, H. (2005b) In vitro meta
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404 Explanation Profenofos is the I
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406 The metabolism of ring-labelled
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408 2. Toxicological studies 2.1 Ac
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410 Rabbits Groups of two male and
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412 Groups of five male and five fe
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414 control group and in the test g
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416 of the rabbits at the highest d
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418 The NOAEL for brain acetylcholi
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420 Table 2. Histopathological find
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422 1 out of 70; lowest dose, 3 out
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424 body‐weight gains (3-10% decr
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426 treated groups for body-weight
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428 (b) Short-term studies of neuro
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430 represented as equally as possi
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432 pound and the equitoxic mixture
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434 Inhibition of brain acetylcholi
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436 Toxicological evaluation Erythr
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438 Neurotoxicity/delayed neurotoxi
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440 Harris, S.B. (1982) A teratolog
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442 Puri, E. (1982a) Autoradiograph
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PYRIMETHANIL First draft prepared b
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447 Table 1. Excretion profile in r
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449 Table 3. Half-life of pyrimetha
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451 Table 4. Identification of meta
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453 SN 614 277. The presence of the
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455 2. Toxicological studies 2.1 Ac
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457 treated rabbits showed slight e
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459 still evident in the liver; how
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461 In a 90-day feeding study, grou
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463 per day or 800 mg/kg bw per day
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465 The dosing solutions were prepa
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467 mortality and morbidity. Change
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469 2.4 Genotoxicity Pyrimethanil w
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471 mean body‐weight gains. After
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473 Analysis of dosing solutions in
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475 In a 7-day feeding study, group
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477 at 200 mg/kg bw. These clinical
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479 s ystemic toxicity was 400 ppm
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481 Acute toxicity Rat, LD 50 , ora
Page 498 and 499:
483 Grosshans, F. (2003) Pyrimethan
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485 Markham, L.P. (1989d) Technical
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ZOXAMIDE First draft prepared by I.
Page 504 and 505:
489 The excretion of radioactivity
Page 506 and 507:
491 Table 3. Mean concentration of
Page 508 and 509:
493 Table 4. Distribution of metabo
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495 were also found in the urine, a
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497 owing to the absence of a dose-
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499 The NOAEL was 30 000 ppm, equiv
Page 516 and 517:
501 Table 9. Haematological finding
Page 518 and 519:
503 Table 11. Body weight, food con
Page 520 and 521:
505 daily for signs of moribundity,
Page 522 and 523:
507 Table 14 Results of studies of
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509 phase. The study was certified
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511 Table 16. Spleen weights and hi
Page 528 and 529:
513 FOB/motor activity assessment,
Page 530 and 531:
515 Excretion was primarily in the
Page 532 and 533:
517 days 14 to 21. Increased relati
Page 534 and 535:
519 Lowest relevant inhalation NOAE
Page 536 and 537:
521 Morrison, R.D. & Gillette, D.M.
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ANNEX 1 Reports and other documents
Page 540 and 541:
525 31. Pesticide residues in food:
Page 542 and 543:
527 67. Pesticide residues in food
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529 101. Pesticide residues in food
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