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443 Williams, S.C., Marco, G.J., Simoneaux, B.J. & Ballantine, L. (1984) Percutaneous absorption of 14 C-profenofos in rats. Unpublished report No. ABR-84023 from Ciba-Geigy Corporation, Greensboro, North C arolina, USA. Submitted to WHO by Syngenta Crop Protection, Greensboro, North Carolina, USA. Wing, K.D., Glickman, A.H. & Casida, J.E. (1983) Oxidative bioactivation of S-alkyl phosphorothiolate p esticides: stereospecificity of profenofos insecticide activation. Science, 219, 63–65. Winkler, G. (1996) CGA 15’324 tech. - skin sensitization test in the guinea-pig - maximization test. Unpublished report No. 962054 from Ciba-Geigy Ltd, Basel, Switzerland. Submitted to WHO by Syngenta Crop Protection, Greensboro, North Carolina, USA. PROFENOFOS 403–443 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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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
Page 184 and 185:
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
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175 Figure 1. Chemical structures o
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177 In a comparative study, the abs
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179 Figure 2. Main pathways of biot
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181 (iv) Dermal sensitization In a
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183 observed in rats at the highest
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185 Mortality was not affected by t
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187 the group at 100 ppm, reduction
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189 and five females per group were
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191 10-12%) than those of controls
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193 Comments Biochemical aspects Or
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195 Toxicological evaluation Althou
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197 Metabolism in animals Toxicolog
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199 Harrison, M.P. (1984a) Cyhaloth
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DIFENOCONAZOLE First draft prepared
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203 a sex difference nor any marked
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205 demonstrated that the highest t
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207 Figure 3. Proposed metabolic pa
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209 of the study were unremarkable.
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211 Table 3. Results of studies of
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213 The no-observed-adverse-effect
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215 lower than those of rats in the
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217 hepatocellular enlargement. In
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219 i.e. males lost 15.4% and femal
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221 and 357. This reduced food cons
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223 There was very high mortality a
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225 Table 6. Treatment-related hist
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227 Rats Groups of 80 CRL:CD(SD)®
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229 Table 7. Histopathology finding
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231 D. Temporal association. The fe
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233 2.5 Reproductive toxicity (a) M
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235 t estes weights in the males at
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237 continued to be lower than thos
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239 Corpora lutea in each ovary wer
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241 S1 + S2, not ossified — —
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243 in the control group and in the
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245 physically examined for changes
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249 can occur in untreated mice, in
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251 Study of reproductive toxicity
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257 of the test article on microsom
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259 Ophthalmoscopic examinations pe
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261 the radioactivity was re-elimin
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263 In a single-dose study of neuro
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265 Estimate of acceptable daily in
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267 Clapp, M.J.L., Killick, M.E., H
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269 Herbold, B. (1983c) THS 2212 tr
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271 Pinto, P. (2006b) Difenoconazol
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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
Page 408 and 409: 393 The Meeting concluded that the
Page 410 and 411: 395 Toxicologically significant com
Page 412 and 413: 397 Harada, T. (1983) A review on m
Page 414 and 415: 399 Murakami, M., Yoshitake, A. & H
Page 416: 401 Tarui, H. (2005b) In vitro meta
Page 419 and 420: 404 Explanation Profenofos is the I
Page 421 and 422: 406 The metabolism of ring-labelled
Page 423 and 424: 408 2. Toxicological studies 2.1 Ac
Page 425 and 426: 410 Rabbits Groups of two male and
Page 427 and 428: 412 Groups of five male and five fe
Page 429 and 430: 414 control group and in the test g
Page 431 and 432: 416 of the rabbits at the highest d
Page 433 and 434: 418 The NOAEL for brain acetylcholi
Page 435 and 436: 420 Table 2. Histopathological find
Page 437 and 438: 422 1 out of 70; lowest dose, 3 out
Page 439 and 440: 424 body‐weight gains (3-10% decr
Page 441 and 442: 426 treated groups for body-weight
Page 443 and 444: 428 (b) Short-term studies of neuro
Page 445 and 446: 430 represented as equally as possi
Page 447 and 448: 432 pound and the equitoxic mixture
Page 449 and 450: 434 Inhibition of brain acetylcholi
Page 451 and 452: 436 Toxicological evaluation Erythr
Page 453 and 454: 438 Neurotoxicity/delayed neurotoxi
Page 455 and 456: 440 Harris, S.B. (1982) A teratolog
Page 457: 442 Puri, E. (1982a) Autoradiograph
Page 461 and 462: 446 Evaluation for acceptable daily
Page 463 and 464: 448 Table 2. Calculated pharmacokin
Page 465 and 466: 450 time, while the concentration i
Page 467 and 468: 452 Sum 91.5 — — — — —
Page 469 and 470: 454 Mice In a study of absorption,
Page 471 and 472: 456 findings were observed on necro
Page 473 and 474: 458 was observed (relative to contr
Page 475 and 476: 460 The deaths were considered to b
Page 477 and 478: 462 The LOAEL was 8000 ppm (529.1 a
Page 479 and 480: 464 e xamination was performed befo
Page 481 and 482: 466 43%, 71% and 59% (control, lowe
Page 483 and 484: 468 At interim kill, no significant
Page 485 and 486: 470 2.5 Reproductive toxicity (a) M
Page 487 and 488: 472 necropsy. The uterus and ovarie
Page 489 and 490: 474 (b) Short-term studies of neuro
Page 491 and 492: 476 were noted at day 4. Liver weig
Page 493 and 494: 478 In a 90-day dietary study of to
Page 495 and 496: 480 Levels relevant to risk assessm
Page 497 and 498: 482 Beyrouty, P. (2001b) A time of
Page 499 and 500: 484 Hemmings, P.A. (1991a) Residue
Page 501 and 502: 486 Simpson, E. (2003) Historical c
Page 503 and 504: 488 All the pivotal studies met the
Page 505 and 506: 490 or distribution of [ 14 C]zoxam
Page 507 and 508: 492 indicated that zoxamide is very
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494 Metabolite RH141,452 (3,5-dichl
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496 2.2 Short-term studies of toxic
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498 The only findings of note were
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500 canine juvenile polyarteritis s
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502 Table 10. Organ weight and hist
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504 Week 52 3 167 2 795 2 538 2 052
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506 weights were increased in a dos
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508 The zoxamide metabolites, RH 14
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510 Table 15 Pup body weights durin
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512 consumption were monitored thro
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514 anti-tubulin compounds at 37 °
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516 were higher than those of the c
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518 Acute neurotoxicity b 2000 mg/k
Page 535 and 536:
520 Ferguson, J.S., Morrison, R.D.
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522 Snyder, P.W., Kazacos, E.A., Sc
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524 14. Pesticide residues in food.
Page 541 and 542:
526 50. Pesticide residues in food
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528 84. Pesticide residues in food
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