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47 Figure 2. Proposed metabolic pathway for atrazine in primates and humans N SCH 2 CHCOOH NHCOCH 3 N N H N N H CGA-359008 N SCH 2 CHCOOH NH 2 N N H N N H Cl N N Cl N H N Atrazine Cl N H Cl H 2 N N N N N H N N H 2 N N NH 2 G-30033 G-28273 G-28279 H N N N N NH 2 N SCH 2 CHCOOH NH 2 N N SCH 2 CHCOOH NH 2 N N SCH 2 CHCOOH NH 2 N H 2 N N N H H 2 N N NH 2 N H N NH 2 N SCH 2 CHCOOH NHCOCH 3 N N SCH 2 CHCOOH NHCOCH 3 N H 2 N N N H 2 N N NH 2 H N NH 2 H N CGA-246059 CGA-10582 CGA-30379 N SCH 2 CHCOOH NHCOCH 3 N and greater, also showed chromodacryorrhoea and salivation. No treatment-related gross changes in organs were seen at necropsy. The LD 50 was 235 mg/kg bw (Sachsse and Bathe, 1975a). (b) Dermal irritation In a study on skin irritation potential, atrazine powder (0.5 g) was applied to intact and abraded skin of three male and three female Himalayan rabbits. The treated area was occluded for 24 h. A very slight erythema was observed in three rabbits (abraded) at 24 h after application and in one rabbit at 72 h. The study differed from present OECD test guidelines in that the test material was not moistened, the exposure period was for 244 h not 4 h; that abraded skin sites were used in addition ATRAZINE 37–138 JMPR 2007
48 Figure 3. Primary metabolic pathway for hydroxyatrazine in the rat OH N N (H 3 C) 2 HCHN N NHCH 2 CH 3 ( 14 C)-hydroxyatrazine (G-34048) OH OH N N N N (H 3 C) 2 HCHN N NH 2 H 2 N N NHCH 2 CH 3 [ 14 C]-GS-17794 [ 14 C]-GS-17792 Table 2. Results of studies of acute toxicity with atrazine Species Strain Sex Route Rat Rat Mouse Mouse Rat Rat Rat Rat Rat Tif:RAI HSD:(SD) Tif:MAG HSD:(ICR) Tif:RAIf Tif:RAIf Tif:RAIf HSD:(SD) Tif:RAI Males & females Males & females Males & females Males & females Males & females Males & females Males & females Males & females Males & females Purity (%) LD 50 (mg/kg) LC 50 (mg/l air) Oral (in 2% CMC) NR 1869 — Oral (40% w/v in water) Reference Sachsse & Bathe (1975b) 97.7 3090 — Kuhn (1991a) Oral (in 2% CMC) NR 3992 — Sachsse & Bathe (1975c) Oral (in 0.5% CMC) 97.7 > 1332 — Kuhn (1988) Dermal (in 2% CMC) NR > 3100 — Dermal (in 0.5% CMC) CMC, carboxymethyl cellulose; NR, not reported. Sachsse & Bathe (1976) 97.1 > 2000 — Hartmann (1993) Inhalation 96.7 — > 5.15 Hartmann (1989) Inhalation 97.4 — > 5.82 Holbert (1991) Intraperitoneal (in 2% CMC) NR 235 — Sachsse & Bathe (1975a) ATRAZINE 37–138 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
Page 12 and 13: MRL MS MS/MS MTD NMR NOAEC NOAEL NO
Page 14: Introduction The toxicological mono
Page 18 and 19: AMINOPYRALID First draft prepared b
Page 20 and 21: 5 higher renal excretion in the gro
Page 22 and 23: 7 Table 4. Recovery of radioactivit
Page 24 and 25: 9 Table 7. Pharmacokinetic paramete
Page 26 and 27: 11 (c) Exposure by inhalation Five
Page 28 and 29: 13 Table 9. Acute toxicity of amino
Page 30 and 31: 15 The data from urine analysis rev
Page 32 and 33: 17 18, monthly for palpable masses.
Page 34 and 35: 19 Table 12. Body weights of rats f
Page 36 and 37: 21 Table 15. Results of assays for
Page 38 and 39: 23 in both groups, feed consumption
Page 40 and 41: 25 neurotoxicity after 12 months. B
Page 42 and 43: 27 The same five time-mated NZW rab
Page 44 and 45: 29 Mortality was increased in all g
Page 46 and 47: 31 Levels relevant to risk assessme
Page 48 and 49: 33 References Brooks, K.J. (2001a)
Page 50 and 51: 35 Consulting, The Dow Chemical Com
Page 52 and 53: ATRAZINE First draft prepared by Ru
Page 54 and 55: 39 in the early 1990s; this reflect
Page 56 and 57: 41 Maximum concentrations in the bl
Page 58 and 59: 43 In a study on comparative metabo
Page 60 and 61: 45 Table 1. Metabolism of atrazine
Page 64 and 65: 49 to intact skin; and that no read
Page 66 and 67: 51 the highest dose, and food consu
Page 68 and 69: 53 mice (evaluated as roughly equiv
Page 70 and 71: 55 Table 5. Incidence of mammary tu
Page 72 and 73: 57 Table 6. Selected findings from
Page 74 and 75: 59 was decreased when compared with
Page 76 and 77: 61 Table 9. Selected findings of a
Page 78 and 79: 63 proestrus at the expense of days
Page 80 and 81: 65 Table 10. Selected studies of ge
Page 82 and 83: 67 End-point Test object Concentrat
Page 84 and 85: 69 Table 12. Relevant findings in a
Page 88 and 89: 73 respectively) and in males at th
Page 92 and 93: 77 All dams survived until the end
Page 94 and 95: 79 250 and 500 ppm. Body-weight gai
Page 96 and 97: 81 In an assay for reverse mutation
Page 98 and 99: 83 on pubertal development in femal
Page 100 and 101: 85 parameters (decreased pH, specif
Page 104 and 105: 89 0, 75, 150 or 300 mg/kg bw per d
Page 106 and 107: 91 The NOAEL was 25 ppm, equal to 1
Page 108 and 109: 93 In a study on the effect of atra
Page 110 and 111: 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
Page 140 and 141:
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
Page 170 and 171:
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
Page 190 and 191:
175 Figure 1. Chemical structures o
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177 In a comparative study, the abs
Page 194 and 195:
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
Page 248 and 249:
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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Page 264 and 265:
249 can occur in untreated mice, in
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251 Study of reproductive toxicity
Page 268 and 269:
Page 270 and 271:
Page 272 and 273:
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
Page 282 and 283:
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
Page 292 and 293:
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
Page 318 and 319:
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
Page 328 and 329:
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
Page 366 and 367:
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
Page 451 and 452:
436 Toxicological evaluation Erythr
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438 Neurotoxicity/delayed neurotoxi
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440 Harris, S.B. (1982) A teratolog
Page 457 and 458:
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
Page 464 and 465:
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
Page 488 and 489:
473 Analysis of dosing solutions in
Page 490 and 491:
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
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
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503 Table 11. Body weight, food con
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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
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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
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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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