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

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361 Figure 1. Proposed metabolic pathways of procymidone Cl O Cl O Cl O NH HO N N HO 2 C Cl Cl O Cl O PCM-NH-COOH PCM-4'-OH PROCYMIDONE COOH Cl O Cl O O COOH CH 2 O OH N N CH 2 OH HO OH Cl O Cl O PCM-CH 2 OH-COOH PCM-CH 2 OH-Glucuronide Cl O Cl O CH 2 OH COOH N N Cl O PCM-CH 2 OH Cl O PCM-COOH Cl O Cl O CH 2 OH COOH NH HOOC Cl PA-1'-CH 2 OH Cl NH HOOC PA-1'-COOH Cl HOOC NH CH 2 OH Cl HOOC NH COOH Cl O PA-2'-CH 2 OH Cl O PA-2'-COOH Cl Cl O COOH NH 2 Cl N H HO DCA-glucuronide OH OH Cl DCA DCA, 3,5-dichloroaniline; PA, procymidone acid; PA-CH 2 OH, hydroxyprocymidone acid; PA-COOH, carboxyprocymidone acid; PCM, procymidone; PCM-CH 2 OH, hydroxyprocymidone; PCM-NH-COOH, carboxyprocymidone. PROCYMIDONE 349–401 JMPR 2007
362 Table 9. Results of studies of acute toxicity with procymidone Species Strain Sex Route Vehicle LD 50 (mg/kg bw) LC 50 (mg/l air) Rat SD M & F Oral Corn oil > 5 000 — 92.3 96.5 Mouse dd M & F Oral Corn oil > 5 000 — 92.3 96.5 Rat SD M & F Dermal Corn oil > 2 500 — 92.3 96.5 Purity (%) Reference Kadota et al. (1976a) Segawa (1977) Kadota et al. (1976a) Segawa (1977) Kadota et al. (1976a) Segawa (1977) Mouse dd M & F Dermal Corn oil > 2 500 — 92.3 96.5 Kadota et al. (1976a) Segawa (1977) Rat SD M & F SC Corn oil > 10 000 — 92.3 96.5 Kadota et al. (1976a) Segawa (1977) Mouse dd M & F SC Corn oil > 10 000 — 92.3 96.5 Kadota et al. (1976a) Segawa (1977) Rat SD M & F IP Corn oil 850 (M) — 92.3 Kadota et al. (1976a) 730 (F) Rat SD M & F IP Corn oil 1 440 (M) — 96.5 Segawa (1977) 1 450 (F) Mouse dd M & F IP Corn oil 1 560 (M) — 92.3 Kadota et al. (1976a) 1 900 (F) Mouse dd M & F IP. Corn oil 2 030 (M) 2 050 (F) — 96.5 Kadota et al. (1976a); Segawa (1977) Rat SD M & F Inhalation Fine dust — > 1.5 mg/l MMAD < 2.4 μm 99.5 Suzuki & Kato (1988); Tsuji (1994) IP, intraperitoneal; F, female; M, male; MMAD, mass median aerodynamic diameter; SC; subcutaneous; SD, Sprague-Dawley. (b) Dermal and ocular irritation and dermal sensitization Procymidone was a slight transient irritant to rabbit skin (all signs had disappeared by 24 h; Kadota & Miyamoto, 1976), but produced no irritation to the rabbit eye (Kadota & Miyamoto, 1976). Procymidone was not a skin sensitizer in guinea-pigs in a repeated injection (10 + 1 doses) protocol using 1% or 5% w/v preparations in corn oil (Okuno, 1975), nor in a GLP-compliant Magnusson & Kligman maximization study using concentrations of 1% w/v for intradermal induction, 25% w/v for topical induction and 25% w/v for challenge application (Nakanishi et al., 1991). 2.2 Short-term studies of toxicity (a) Mice Oral route Groups of 15 male and 15 female ICR mice received diets containing procymidone (purity, 96.9%) at a concentration of 0, 50, 150 or 500 ppm for 13 weeks. The mice were observed twice per day for clinical signs of toxicity and mortality and body weights were determined weekly. Food and PROCYMIDONE 349–401 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
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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
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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
Page 326 and 327: 311 Lowest relevant inhalation NOAE
Page 328 and 329: 313 Gardner, J.R. (1989) CME 151 te
Page 330: 315 van de Waart, E.J. (1991b) Eval
Page 333 and 334: 318 Committee on Pesticide residues
Page 335 and 336: 320 (a) Ocular irritation Rabbits T
Page 337 and 338: 322 weights were decreased in males
Page 339 and 340: 324 toxicity was 5 mg/kg bw per day
Page 341 and 342: 326 respectively; range for histori
Page 343 and 344: 328 Table 4. Incidence of Leydig-ce
Page 345 and 346: 330 and/or bilateral) was noted in
Page 347 and 348: 332 No treatment-related signs of m
Page 349 and 350: 334 Table 6. Incidence of selected
Page 351 and 352: 336 or teratogenic potential at the
Page 353 and 354: 338 and progesterone. The concentra
Page 355 and 356: 340 the doses used in the 1-year st
Page 357 and 358: 342 No neurotoxic effects were seen
Page 359 and 360: 344 Lowest relevant reproductive NO
Page 361 and 362: 346 Keller, D.A. (1992c) Oncogenici
Page 364 and 365: PROCYMIDONE First draft prepared by
Page 366 and 367: 351 Rats Groups of five male and fe
Page 368 and 369: 353 Table 1. Pharmacokinetic parame
Page 370 and 371: 355 Seven doses C max (µg equivale
Page 372 and 373: 357 Three groups of five male and f
Page 374 and 375: 359 The excretion of radioactivity
Page 378 and 379: 363 water consumption were determin
Page 380 and 381: 365 finding. Histopathology reveale
Page 382 and 383: 367 The NOAEL was 500 ppm, equivale
Page 384 and 385: 369 The NOAEL was 100 mg/kg bw per
Page 386 and 387: 371 at 2000 ppm. Histopathology rev
Page 388 and 389: 373 b Each test was conducted in tr
Page 390 and 391: 375 experimental period. Rats were
Page 392 and 393: 377 hypospadias, testicular atrophy
Page 394 and 395: 379 a single dose, which produced o
Page 396 and 397: 381 The anti-androgenic activities
Page 398 and 399: 383 but only at 6000 ppm after 13 w
Page 400 and 401: 385 The results are summarized in T
Page 402 and 403: 387 males (all litters) in the grou
Page 404 and 405: 389 procymidone (18-27% of the admi
Page 406 and 407: 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
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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.
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489 The excretion of radioactivity
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491 Table 3. Mean concentration of
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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
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501 Table 9. Haematological finding
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503 Table 11. Body weight, food con
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505 daily for signs of moribundity,
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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
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513 FOB/motor activity assessment,
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515 Excretion was primarily in the
Page 532 and 533:
517 days 14 to 21. Increased relati
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519 Lowest relevant inhalation NOAE
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521 Morrison, R.D. & Gillette, D.M.
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ANNEX 1 Reports and other documents
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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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