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215 (b) Alpha-Cypermethrin Species Study Effect NOAEL LOAEL Mouse Three-month study Toxicity 50 ppm, equal to 250 ppm, equal to of toxicity a 6.3 mg/kg bw per day 33 mg/kg bw per day Rat Rabbit Eighteen-month Toxicity 30 ppm, equal to c arcinogenicity a study of toxicity and 3 mg/kg bw per day Carcinogenicity 300 ppm, equal to 35 mg/kg bw per day d — Three-month study Toxicity 180 ppm, equivalent to of toxicity a 18 mg/kg bw per day 100 ppm, equal to 10.6 mg/kg bw per day 540 ppm, equivalent to 54 mg/kg bw per day Developmental Maternal toxicity 9 mg/kg bw per day 18 mg/kg bw per day toxicity c Embryo/fetotoxicity 9 mg/kg bw per day 18 mg/kg bw per day Acute neurotoxicity c Neurotoxicity 4 mg/kg bw 20 mg/kg bw Developmental Maternal toxicity 15 mg/kg bw per day 30 mg/kg bw per day toxicity c Embryo/fetotoxicity 30 mg/kg bw per day d — Toxicity 90 ppm, equivalent to Dog Three-month study of toxicity a 2.2 mg/kg bw per day One-year study of Toxicity 60 ppm, equivalent to toxicity a 1.5 mg/kg bw per day a Dietary administration. b Two or more studies combined. c Gavage administration. d Highest dose tested. 270 ppm, equivalent to 6.7 mg/kg bw per day 120 ppm, equivalent to 3 mg/kg bw per day (c) Zeta-Cypermethrin Species Study Effect NOAEL LOAEL Rat Three-month study of Toxicity 250 ppm, equal to 500 ppm, equal to toxicity a 17 mg/kg bw per day 34 mg/kg bw per day Multigeneration r eproductive toxicity a Parental and offspring toxicity 100 ppm, equal to 6 mg/kg bw per day 375 ppm, equal to 22 mg/kg bw per day Developmental Maternal toxicity 12.5 mg/kg bw per day 25 mg/kg bw per day t oxicity c Embryo/fetotoxicity 35 mg/kg bw per day d — Acute neurotoxicity c Neurotoxicity 10 mg/kg bw 50 mg/kg bw Three-month study of Neurotoxicity 75 ppm, equal to neurotoxicity a 5 mg/kg bw per day a Dietary administration. b Two or more studies combined. c Gavage administration. d Highest dose tested. Estimate of acceptable daily intake for humans 0–0.02 mg/kg bw Estimate of acute reference dose 0.04 mg/kg bw Information that would be useful for continued evaluation of the compound 400 ppm, equal to 26 mg/kg bw per day Results from epidemiological, occupational health and other such observational studies of h uman exposures CYPERMETHRINS X-X JMPR 2006
216 Critical end-points relevant for setting guidance values for exposure to cypermethrins Absorption, distribution, excretion and metabolism in mammals Rate and extent of oral absorption T max , approximately 3 h; approximately 50–70% absorbed Dermal absorption Approximately 1% in humans Distribution Throughout the body; highest levels in fat, present mainly as cisisomers Potential for accumulation The elimination half-life in fat was 10–25 days after a single oral dose; radioactivity accumulated in fat and skin after repeated oral dosing Rate and extent of excretion Rapid; > 95% excreted in 48 h Metabolism in animals Extensive, no unchanged cypermethrin excreted in the urine Toxicologically significant compounds (animals, Parent plants, environment) Acute toxicity (cypermethrin) Rat, LD 50 , oral 200 to > 3000 mg/kg bw Rat, LD 50 , dermal > 1600 mg/kg bw (xylene vehicle); > 4800 mg/kg bw undiluted Rat, LC 50 , inhalation 1.260 mg/l air Guinea-pigs, skin sensitization (test method used) Sensitizer (maximization); non-sensitizer (Buehler) Acute toxicity (alpha-cypermethrin) Rat, LD 50 , oral 64 to > 5000 mg/kg bw, depending on vehicle Rat, LC 50 , inhalation 1.590 mg/l air Acute toxicity (zeta-cypermethrin) Rat, LD 50 , oral 86–367 mg/kg bw (corn oil vehicle) Short-term studies of toxicity Target/critical effect Clinical signs of neurotoxicity Lowest relevant oral NOAEL 2.2 mg/kg bw per day (90-day study in dogs) Lowest relevant dermal NOAEL 20 mg/kg bw per day (21-day study in rabbits) Lowest relevant inhalation NOAEL 0.050 mg/l (21-day study in rats) Genotoxicity No genotoxic potential Long-term studies of toxicity and carcinogenicity Target/critical effect Reduced body-weight gain and food consumption Lowest relevant NOAEL 7.5 mg/kg bw per day (2-year dietary study in rats) Carcinogenicity Not carcinogenic in rats and mice Reproductive toxicity Reproduction target/critical effect No reproductive effects; decreased pup body weight Lowest relevant reproductive NOAEL 6 mg/kg bw per day (rats) Developmental target/critical effect Decreased fetal weights (rats) Lowest relevant developmental NOAEL 9 mg/kg bw per day Neurotoxicity Target/critical effect Clinical signs, changes in FOB tests and degenerative changes to the sciatic nerve Lowest relevant NOAEL 4 mg/kg bw per day (single-dose study in rats) Delayed neurotoxicity Target/critical effect No delayed effect Lowest relevant NOAEL > 1000 mg/kg bw per day (hens) Medical data Paraesthesia after dermal exposure CYPERMETHRINS X-X JMPR 2006
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Pesticide residues in food — 2006
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TABLE OF CONTENTS Page List of part
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Dr Helen Hakansson, Institute of En
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Abbreviations used ADI ALT APDM ARf
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Introduction The toxicological mono
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BIFENAZATE First draft prepared by
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5 In a series of experiments, group
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7 In a study of the time-course of
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9 the administered dose in males an
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11 limited absorption of parent com
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13 NAME/No. STRUCTURE D1989 OCH 3 D
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15 2.1 Acute toxicity Results of st
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17 (f) Sensitization In a study of
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19 Table 9. Clinical chemistry effe
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21 The degree of this finding was m
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23 On histopathological examination
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25 (equal to 0, 0.9, 10.4 or 25 mg/
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27 Haemoglobin (g/dl): Before treat
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29 weekly. Blood and urine samples
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31 (females) (equal to 0, 1.0, 3.9,
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33 Cytogenetic test Chinese hamster
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35 groups of 30 males and 30 female
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37 and placed in 10% ammonium sulfi
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39 was > 5000 mg/kg bw. The LC 50 i
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41 Multigeneration study of reprodu
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43 Medical data No significant adve
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45 Trutter, J.A. (1997a) 28-Day die
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48 Evaluation for acceptable daily
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50 Table 2. Radioactivity in blood
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52 10 10 0.42 0.0462 0.63 0.0080 8.
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54 Figure 2. Transfer of radioactiv
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56 Skin 33.07 61.59 0.5 17.94 17.29
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58 Table 10. Summary of metabolites
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60 Table 14. Summary of identified
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62 Table 18. Summary of metabolites
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64 Table 19. Structures of identifi
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66 Metabolite Structure O M510F14 N
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68 Metabolite Structure M510F39 N O
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70 2. Toxicological studies 2.1 Acu
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72 1% Tylose CB 30.000. The injecti
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74 the end of dosing. Blood samples
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76 examinations were carried out 8
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78 concentrations were increased at
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80 times were slightly, but signifi
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82 in males and females rats at 250
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84 End-point Test object Dose a (LE
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86 parental rats was not markedly a
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88 groups in conception frequencies
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90 0.7 ± 3.5%, 1.8 ± 4.2%, 2.9 ±
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92 In this study of developmental n
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94 3. Observations in humans In the
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96 was 100 ppm, equal to 10 mg/kg b
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98 Acute toxicity Rat, LD 50 , oral
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100 Mellert, W., Kaufmann, W. & Hil
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CYFLUTHRIN AND BETA-CYFLUTHRIN Firs
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105 Table 1. Diastereoisomer pairs
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107 (i) In vivo Rats Four groups of
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109 2. Toxicological studies 2.1 Ac
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111 Species Strain Sex Route Formul
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113 Rat Groups of 20 male and 20 fe
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115 group and in the groups at the
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117 cyfluthrin (purity, 95.5-95.9%)
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119 In a short-term study of exposu
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121 and dissection. At termination,
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123 2.5 Reproductive toxicity (a) M
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125 gestation. The vehicle was 1% C
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127 females was exposed during days
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129 were not seen in rats in the co
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131 men was exposed for 1 h to actu
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133 40 g/l, in a flowable concentra
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135 were removed from five males an
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137 weights and food consumption we
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139 In females at the highest dose,
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141 The dermal toxicity of cyfluthr
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143 The Meeting concluded that the
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145 Estimate of acute reference dos
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147 Cage, S. (2004) [ 14 C]-beta-cy
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149 Heimann, K.G. (1984c) FCR 4545
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151 Jones, R.D. & Hastings, T.F. (1
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153 Pauluhn, J. & Mohr, U. (1984).
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155 Von Keutz, E. (1987) FCR 4545 -
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158 Zeta-cypermethrin .............
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160 Evaluation for acceptable daily
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162 polar metabolites, which are fu
Page 177 and 178: 164 for up to 70 days. Signs typica
Page 179 and 180: 166 rapidly metabolized by cleavage
Page 181 and 182: 168 2. Toxicological studies 2.1 Ac
Page 183 and 184: 170 Table 2. Effect of cis : trans
Page 185 and 186: 172 Table 3. Significant haematolog
Page 187 and 188: 174 Rabbits Occluded dermal applica
Page 189 and 190: 176 1100 ppm in weeks 1-6, with inc
Page 191 and 192: 178 Wistar-derived (Alderley Park)
Page 193 and 194: 180 At 1500 ppm, liver APDM activit
Page 195 and 196: 182 for premature deaths, 10 male a
Page 197 and 198: 184 by gavage for days 7 to 19 of g
Page 199 and 200: 186 observed at the intermediate an
Page 201 and 202: 188 The females recovered from this
Page 203 and 204: 190 tibial nerve (SPTN), trigeminal
Page 207 and 208: 194 for 5 weeks. Observations inclu
Page 209 and 210: 196 caused obvious irritation and r
Page 211 and 212: 198 days 6-15 of gestation. After m
Page 213 and 214: 200 was observed in two males at 72
Page 215 and 216: 202 control and other treated group
Page 217 and 218: 204 Table 14. Results of studies of
Page 219 and 220: 206 (b) Developmental toxicity Rats
Page 221 and 222: 208 mild and temporary paraesthesia
Page 223 and 224: 210 range appeared to exist for the
Page 225 and 226: 212 for which the LD 50 was > 2000
Page 227: 214 substances. Since conventional
Page 231 and 232: 218 Butterworth, S.T.G. & Clark, D.
Page 233 and 234: 220 East Millstone, New Jersey, USA
Page 235 and 236: 222 Jersey, USA. Submitted to WHO b
Page 237 and 238: 224 Toxicology Laboratory (Tunstall
Page 239 and 240: 226 Ullrich, B. (2003) Report on a
Page 241 and 242: 228 Cyromazine was first evaluated
Page 243 and 244: 230 were taken for the measurement
Page 245 and 246: 232 highest dose, rather than indic
Page 247 and 248: 234 Tissue residues: Tissues a < 0.
Page 249 and 250: 236 Because of the low total recove
Page 251 and 252: 238 Name Description Compound found
Page 253 and 254: 240 After each dose of [U- 14 C tri
Page 255 and 256: 242 In male and female monkeys give
Page 257 and 258: 244 stress and discomfort during th
Page 259 and 260: 246 Table 18. Dermal absorption of
Page 261 and 262: 248 rate under steady-state conditi
Page 265 and 266: 252 the test substance. The method
Page 267 and 268: 254 taken for haematological and bi
Page 269 and 270: 256 not differ appreciably from pre
Page 271 and 272: 258 Analysis of the diets showed th
Page 273 and 274: 260 considered to be biologically s
Page 275 and 276: 262 observed incidence probably rel
Page 277 and 278: 264 c Cyromazine was assayed twice
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268 either sporadic or as a consequ
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270 fetuses were removed, weighed a
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272 The NOAEL for maternal toxicity
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274 In New Zealand White rabbits, c
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276 and litters with malformations.
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278 of melamine powder into the rab
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280 reduction in the survival of ma
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282 There is significantly less ris
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284 Toxicological data Cyromazine h
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286 Toxicological evaluation The Me
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288 Other toxicological studies Tox
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290 IARC (1999a) Some chemicals tha
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292 Simoneaux, B. & Marco, G. (1984
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294 Declaration of Helsinki (Cristi
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296 lowered arousal level at doses
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298 Cerebellum 3 1 51** 76** 80** 7
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300 Table 4. Maximum inhibition of
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302 auditory/physical examination w
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304 • • • • • Home-cage o
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306 Dogs Groups of four male and fo
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308 capsules. Some volunteers recei
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310 Blood was taken for measurement
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312 Human a Dietary administration
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314 Piccirillo, V.J. (1978) Acute o
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316 Haloxyfop (racemic), its sodium
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318 Recovery of radioactivity in ur
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320 skin of nine male and nine fema
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322 1.2 Biotransformation Mice In a
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324 2. Toxicological studies 2.1 Ac
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326 96%) at a concentration designe
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328 was centrilobular hepatocellula
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330 The treatment had no effect on
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332 All dogs were killed for autops
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334 with that of controls (but no s
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336 Table 4. Results of studies of
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338 doses of up to 1.0 mg/kg bw per
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340 delayed ossification in the hyo
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342 Mice In a GLP-compliant study,
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344 and in females at the highest d
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346 Between January 1999 and Januar
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348 The Meeting concluded that halo
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350 Critical end-points for setting
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352 Elcombe, B.M. (2002a) Effects o
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354 Scortichini, B.H., Bohl, R.W. &
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356 Economic Co-operation and Devel
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358 There were no treatment-related
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360 comparable to control levels. A
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362 Groups of 17 male and 17 female
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364 No compound-related effects wer
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366 Berry, D. & Gore, C.W. (1975) P
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368 Quinoxyfen has not been evaluat
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370 In the main study, which compli
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372 Concentrations of total radioac
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374 several hydroxy-quinoxyfen meta
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376 There were no mortalities or ad
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378 at doses of ≥ 100 mg/kg bw pe
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380 In a GLP-compliant study to det
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382 control group. This was observe
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384 The homogeneity and stability o
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386 Testes weight (g) at 24 months
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388 slight (3 out of 30) hepatocell
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390 marked inanition, decreased fae
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392 Females Relative liver weightt
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394 were patch-tested specifically
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396 In studies of developmental tox
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398 Rat, LC 50 , inhalation Rabbit,
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400 Gollapudi, B.B. & Lick, S.J. (1
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TEMEPHOS First draft prepared by De
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405 by thin-layer chromatography (T
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407 In a special study to investiga
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409 concluded that temephos was of
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411 Table 3. Effects on mean erythr
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413 Females 0 1.091 1.224 1.324 1.3
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415 of up to 18 ppm. In the group a
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417 Chromosomal aberration DNA repa
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419 of the birds treated with temep
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421 concentration of 1 ppm. Only on
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423 being appreciably less than thi
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425 Lowest relevant developmental N
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427 WHO (1991) Safe use of pesticid
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430 All new studies with thiabendaz
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432 use of this dose form was consi
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434 At 1000 mg/kg bw, qualitative e
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436 At 100 mg/kg bw, slightly decre
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438 There were no treatment-related
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440 Table 6. Incidence of malformat
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442 Dose (mg/kg bw) (grouped by exp
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444 1157 12/21 (57.1)*** 27.2 ± 33
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446 versus placebo): increased appe
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448 activity, tiptoe gait, landing
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450 Noakes, J.P. (2005a) Thianendaz
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452 tests normally performed and th
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454 Radiolabel was excreted primari
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456 the excretory organs, was the r
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458 Table 6. Excretion of radioacti
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460 of unchanged parent compound we
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462 M10 (KNO 1891) + M11 (KNO 1893)
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464 on body weights. Exposure at 15
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466 The no-observed-adverse-effect
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468 Hepatocytes, hypertrophy 0 2 6
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470 they may also be related to var
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472 weights of males were approxima
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474 Thyroid weight (mg): Week 12 6
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476 Table 17. Relevant findings in
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478 Dogs In a dose range-finding st
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480 Prostate / uterine weight (g) 2
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482 the treatment groups receiving
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484 No gross findings were observed
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486 received a macroscopic examinat
Page 501 and 502:
488 Although decreased concentratio
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490 Sciatic nerve; No. examined 50
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492 are caused by the higher incide
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496 In a two-generation study of re
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498 In dams that died or were sacri
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500 No clinical signs or increased
Page 515 and 516:
502 Table 33. Selected variations a
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504 Days 16-21 73.3 78.7 62.5 44.3*
Page 519 and 520:
506 Thiacloprid was not teratogenic
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508 Table 37. Motor and locomotor a
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510 Day 91 19.78 20.00 19.58 18.22*
Page 525 and 526:
512 Table 40. Selected findings in
Page 527 and 528:
514 plate incorporation procedure,
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516 (iv) Comparative study on liver
Page 531 and 532:
518 and relative liver weight in an
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520 at 2500 ppm. The administration
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522 No macroscopic changes were det
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524 The following procedures were p
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526 litter for the group at 1000 pp
Page 541 and 542:
528 Hepatic enzyme activities in th
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530 subtypes 1A1, 2B1, 2D1 and othe
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532 Long-term studies of toxicity a
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534 The Meeting concluded that ther
Page 549 and 550:
536 Estimate of acceptable daily in
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538 dated 27 July, from Bayer AG, W
Page 553 and 554:
540 Kroetlinger, F. (1995a) YRC 289
Page 555 and 556:
542 Wetzig, H. & Geiss, V. (1998b)
Page 557 and 558:
544 Table A1. NOAELs and LOAELs for
Page 559 and 560:
546 2.2 Postulated mode of action (
Page 561 and 562:
548 • • • Chromosomal aberrat
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550 Table A3. NOAELs and LOAELs for
Page 565 and 566:
552 Appendix 2 Table B1. List of an
Page 567 and 568:
554 Metabolite Structure / trivial
Page 569 and 570:
556 Metabolite Structure / trivial
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558 Evaluation for acute reference
Page 573 and 574:
560 increased thyroid weights in th
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562 Table 4. Results of bone-marrow
Page 577 and 578:
564 malformations between the contr
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566 In a study of prenatal developm
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568 combination of heparin and an a
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570 Table 10. Selected findings fro
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572 In a short-term study of neurot
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ANNEX 1 Reports and other documents
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577 31. Pesticide residues in food:
Page 592 and 593:
579 66. Pesticide residues in food
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581 100. Pesticide residues in food
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