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131 men was exposed for 1 h to actual concentrations of cyfluthrin of about 0.75 μg/l. Vital signs were recorded before, immediately after and 1.5, 2 and 3 h after the start of the exposure. In addition, in the first experiment vital signs were also recorded at 12 and 24 h after the start of the exposure, and in the second group 10 h after the start of the exposure. Electrocardiograms (ECGs) were recorded immediately before and after exposure and at 24 h (first experiment) or at 10 h (second experiment) after the start of exposure. The mucous membranes of the nose, oropharynx and eyes were examined immediately before and after exposure. For haematology and clinical chemistry, blood was sampled just before the start and 24 h (first experiment) or 10 h (second experiment) after the start of the exposure. Urine analysis was performed before and 24 h (first experiment) and 10 h (second experiment) after the start of the experiment. Statements of adherence to GLP and QA were included. There were no clinically significant or drug-related abnormalities in vital signs, ECGs or clinical laboratory tests after either exposure session. In the first experiment, only two of the subjects tolerated exposure for the defined period of l h, mild to moderate irritation of the mucous membranes of the nose, upper respiratory tract, throat and eyes and mild hyperaemia of the nasal mucosa being observed. The effects resolved within l h after treatment. In the second experiment, all subjects tolerated exposure for the defined period of l h. Mild irritation of the mucous membranes of the nose and throat and mild hyperaemia of the nasal mucosa were reported. The effects resolved within l h after treatment (Ruddy et al., 1998). Cyfluthrin caused a topical skin effect, characterized by a stinging sensation in the affected areas in laboratory workers. Areas most commonly affected were the face, and mucosal tissues (e.g. prepuce). Since this chemical adheres strongly to skin and is not washed off by soap and water, it is possible to contaminate various parts of the body with cyfluthrin present on the hands (Flucke & Lorke, 1979; Miksche, 1979; Faul, 1984; Faul & Krauthausen, 1995). Yearly medical examinations of factory workers revealed no effects on body weights, haematological and urine analysis parameters, ALT and gamma glutamyl transferase (GGT) activities and thoracic organs, as examined by X-rays (Faul, 1988; Kollert, 1988; Faul & Krauthausen, 1995). Beta-cyfluthrin 4. Toxicological studies 4.1 Acute toxicity The results of studies of acute toxicity with beta-cyfluthrin are summarized in Table 4. The observed clinical signs (increased salivation, uncoordinated movements, increased activity and vocalization, and reduced, laboured breathing, apathy, straddle-legged gait (mostly in the rear legs), and reduced sensitivity to external stimuli) were typical of this class of pyrethroids. Table 4. Results of studies of acute toxicity with beta-cyfluthrin Species Strain Sex Route Formulation LD 50 (mg/kg bw;) Mouse NMRI Male Oral PEG 400 91 a Female LC 50 (μg/l) Purity (%) Reference 165 a (1987b) b — 99.1 Heimann CYFLUTHRIN AND BETA-CYFLUTHRIN X-X JMPR 2006
132 Rat Wistar Male Female Male Female Rat Wistar Male Female Male Female Rat Wistar Male Female Male Female Rat ?? Male Male Rat ?? Male Male Dog Beagle Male Female Hen White Leghorn Rat Wistar Male Female Rat Wistar Male Female Rat Wistar Male Female Rat Wistar Male Female Rat Wistar Male Female Rat Wistar Male/ Female Dog Beagle Male Female Oral PEG 400 380 a 651 a 655 1369 Oral Xylene 211 a 336 a 307 343 Oral Acetone/oil 1 : 10 84 a Oral Oral Water/Cremophor EL Water/Cremophor EL 77 a 141 108 — 99.1 Heimann (1987c) b — 99.1 Heimann (1987d) b — 99.1 Heimann (1987e) b 16 a — NS Heimann (1984c) 11 a — NS Heimann (1986a) Oral Tylose > 5000 (emesis) c > 5000 — 98.5 Von Keutz (1985) > 5000 — 98.5 Flucke (1985a) b Dermal PEG400 > 5000 — 98.7–99.1 Heimann > 5000 (1987f) b Dermal Xylene > 5000 — 98.7–99.1 Heimann > 5000 (1987g) b Inhalation (4 h) Ethanol/PEG 400 — 90 98.5 Pauluhn 100 (1985a) Inhalation (4 h) Ethanol/PEG 400 — 82 97.9 Pauluhn 81 (1988a) b Inhalation (4 h) Dust — 967 98.5 Pauluhn 695 (1985a) Female Oral Water/Cremophor EL Inhalation (4 h) Dust — 532 97.9 Pauluhn (1988a) b Intravenous Tylose 5 — 98.5 Von Keutz (1985) Mouse NMRI Male Intraperitoneal PEG400 18 — 98.0 Krötlinger (1988) b Rat Wistar Male Female Intraperitoneal PEG400 917 — 99.1 Heimann (1987h) b NS, not stated. a Fasted animals. b Statements of adherence to QA and GLP were included. c In the study in dogs, vomiting occurred at both doses (2500 and 5000 mg/kg bw) shortly after administration. (a) Dermal absorption The rate and extent of dermal absorption of radioactivity was investigated after topical application of [ 14 C]beta-cyfluthrin (radiochemical purity, > 99%) at a concentration of 125 g/l or CYFLUTHRIN AND BETA-CYFLUTHRIN 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
Page 63 and 64:
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
Page 91 and 92:
78 concentrations were increased at
Page 93 and 94: 80 times were slightly, but signifi
Page 95 and 96: 82 in males and females rats at 250
Page 97 and 98: 84 End-point Test object Dose a (LE
Page 99 and 100: 86 parental rats was not markedly a
Page 101 and 102: 88 groups in conception frequencies
Page 103 and 104: 90 0.7 ± 3.5%, 1.8 ± 4.2%, 2.9 ±
Page 105 and 106: 92 In this study of developmental n
Page 107 and 108: 94 3. Observations in humans In the
Page 109 and 110: 96 was 100 ppm, equal to 10 mg/kg b
Page 111 and 112: 98 Acute toxicity Rat, LD 50 , oral
Page 113 and 114: 100 Mellert, W., Kaufmann, W. & Hil
Page 116 and 117: CYFLUTHRIN AND BETA-CYFLUTHRIN Firs
Page 118 and 119: 105 Table 1. Diastereoisomer pairs
Page 120 and 121: 107 (i) In vivo Rats Four groups of
Page 122 and 123: 109 2. Toxicological studies 2.1 Ac
Page 124 and 125: 111 Species Strain Sex Route Formul
Page 126 and 127: 113 Rat Groups of 20 male and 20 fe
Page 128 and 129: 115 group and in the groups at the
Page 130 and 131: 117 cyfluthrin (purity, 95.5-95.9%)
Page 132 and 133: 119 In a short-term study of exposu
Page 134 and 135: 121 and dissection. At termination,
Page 136 and 137: 123 2.5 Reproductive toxicity (a) M
Page 138 and 139: 125 gestation. The vehicle was 1% C
Page 140 and 141: 127 females was exposed during days
Page 142 and 143: 129 were not seen in rats in the co
Page 146 and 147: 133 40 g/l, in a flowable concentra
Page 148 and 149: 135 were removed from five males an
Page 150 and 151: 137 weights and food consumption we
Page 152 and 153: 139 In females at the highest dose,
Page 154 and 155: 141 The dermal toxicity of cyfluthr
Page 156 and 157: 143 The Meeting concluded that the
Page 158 and 159: 145 Estimate of acute reference dos
Page 160 and 161: 147 Cage, S. (2004) [ 14 C]-beta-cy
Page 162 and 163: 149 Heimann, K.G. (1984c) FCR 4545
Page 164 and 165: 151 Jones, R.D. & Hastings, T.F. (1
Page 166 and 167: 153 Pauluhn, J. & Mohr, U. (1984).
Page 168: 155 Von Keutz, E. (1987) FCR 4545 -
Page 171 and 172: 158 Zeta-cypermethrin .............
Page 173 and 174: 160 Evaluation for acceptable daily
Page 175 and 176: 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
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182 for premature deaths, 10 male a
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184 by gavage for days 7 to 19 of g
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186 observed at the intermediate an
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188 The females recovered from this
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190 tibial nerve (SPTN), trigeminal
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192 4. Toxicological studies 4.1 Ac
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194 for 5 weeks. Observations inclu
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196 caused obvious irritation and r
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198 days 6-15 of gestation. After m
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200 was observed in two males at 72
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202 control and other treated group
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204 Table 14. Results of studies of
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206 (b) Developmental toxicity Rats
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208 mild and temporary paraesthesia
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210 range appeared to exist for the
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212 for which the LD 50 was > 2000
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214 substances. Since conventional
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216 Critical end-points relevant fo
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218 Butterworth, S.T.G. & Clark, D.
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220 East Millstone, New Jersey, USA
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222 Jersey, USA. Submitted to WHO b
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224 Toxicology Laboratory (Tunstall
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226 Ullrich, B. (2003) Report on a
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228 Cyromazine was first evaluated
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230 were taken for the measurement
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232 highest dose, rather than indic
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234 Tissue residues: Tissues a < 0.
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236 Because of the low total recove
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238 Name Description Compound found
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240 After each dose of [U- 14 C tri
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242 In male and female monkeys give
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244 stress and discomfort during th
Page 259 and 260:
246 Table 18. Dermal absorption of
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248 rate under steady-state conditi
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Page 265 and 266:
252 the test substance. The method
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254 taken for haematological and bi
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256 not differ appreciably from pre
Page 271 and 272:
258 Analysis of the diets showed th
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260 considered to be biologically s
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262 observed incidence probably rel
Page 277 and 278:
264 c Cyromazine was assayed twice
Page 279 and 280:
266 2.5 Reproductive toxicity (a) M
Page 281 and 282:
268 either sporadic or as a consequ
Page 283 and 284:
270 fetuses were removed, weighed a
Page 285 and 286:
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.
Page 291 and 292:
278 of melamine powder into the rab
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280 reduction in the survival of ma
Page 295 and 296:
282 There is significantly less ris
Page 297 and 298:
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
Page 325 and 326:
312 Human a Dietary administration
Page 327 and 328:
314 Piccirillo, V.J. (1978) Acute o
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316 Haloxyfop (racemic), its sodium
Page 331 and 332:
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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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
Page 363 and 364:
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
Page 375 and 376:
362 Groups of 17 male and 17 female
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364 No compound-related effects wer
Page 379 and 380:
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
Page 393 and 394:
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
Page 403 and 404:
390 marked inanition, decreased fae
Page 405 and 406:
392 Females Relative liver weightt
Page 407 and 408:
394 were patch-tested specifically
Page 409 and 410:
396 In studies of developmental tox
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398 Rat, LC 50 , inhalation Rabbit,
Page 413 and 414:
400 Gollapudi, B.B. & Lick, S.J. (1
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TEMEPHOS First draft prepared by De
Page 418 and 419:
405 by thin-layer chromatography (T
Page 420 and 421:
407 In a special study to investiga
Page 422 and 423:
409 concluded that temephos was of
Page 424 and 425:
411 Table 3. Effects on mean erythr
Page 426 and 427:
413 Females 0 1.091 1.224 1.324 1.3
Page 428 and 429:
415 of up to 18 ppm. In the group a
Page 430 and 431:
417 Chromosomal aberration DNA repa
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419 of the birds treated with temep
Page 434 and 435:
421 concentration of 1 ppm. Only on
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423 being appreciably less than thi
Page 438 and 439:
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
Page 449 and 450:
436 At 100 mg/kg bw, slightly decre
Page 451 and 452:
438 There were no treatment-related
Page 453 and 454:
440 Table 6. Incidence of malformat
Page 455 and 456:
442 Dose (mg/kg bw) (grouped by exp
Page 457 and 458:
444 1157 12/21 (57.1)*** 27.2 ± 33
Page 459 and 460:
446 versus placebo): increased appe
Page 461 and 462:
448 activity, tiptoe gait, landing
Page 463 and 464:
450 Noakes, J.P. (2005a) Thianendaz
Page 465 and 466:
452 tests normally performed and th
Page 467 and 468:
454 Radiolabel was excreted primari
Page 469 and 470:
456 the excretory organs, was the r
Page 471 and 472:
458 Table 6. Excretion of radioacti
Page 473 and 474:
460 of unchanged parent compound we
Page 475 and 476:
462 M10 (KNO 1891) + M11 (KNO 1893)
Page 477 and 478:
464 on body weights. Exposure at 15
Page 479 and 480:
466 The no-observed-adverse-effect
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468 Hepatocytes, hypertrophy 0 2 6
Page 483 and 484:
470 they may also be related to var
Page 485 and 486:
472 weights of males were approxima
Page 487 and 488:
474 Thyroid weight (mg): Week 12 6
Page 489 and 490:
476 Table 17. Relevant findings in
Page 491 and 492:
478 Dogs In a dose range-finding st
Page 493 and 494:
480 Prostate / uterine weight (g) 2
Page 495 and 496:
482 the treatment groups receiving
Page 497 and 498:
484 No gross findings were observed
Page 499 and 500:
486 received a macroscopic examinat
Page 501 and 502:
488 Although decreased concentratio
Page 503 and 504:
490 Sciatic nerve; No. examined 50
Page 505 and 506:
492 are caused by the higher incide
Page 507 and 508:
494 2.5 Reproductive toxicity (a) M
Page 509 and 510:
496 In a two-generation study of re
Page 511 and 512:
498 In dams that died or were sacri
Page 513 and 514:
500 No clinical signs or increased
Page 515 and 516:
502 Table 33. Selected variations a
Page 517 and 518:
504 Days 16-21 73.3 78.7 62.5 44.3*
Page 519 and 520:
506 Thiacloprid was not teratogenic
Page 521 and 522:
508 Table 37. Motor and locomotor a
Page 523 and 524:
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,
Page 529 and 530:
516 (iv) Comparative study on liver
Page 531 and 532:
518 and relative liver weight in an
Page 533 and 534:
520 at 2500 ppm. The administration
Page 535 and 536:
522 No macroscopic changes were det
Page 537 and 538:
524 The following procedures were p
Page 539 and 540:
526 litter for the group at 1000 pp
Page 541 and 542:
528 Hepatic enzyme activities in th
Page 543 and 544:
530 subtypes 1A1, 2B1, 2D1 and othe
Page 545 and 546:
532 Long-term studies of toxicity a
Page 547 and 548:
534 The Meeting concluded that ther
Page 549 and 550:
536 Estimate of acceptable daily in
Page 551 and 552:
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
Page 563 and 564:
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
Page 571 and 572:
558 Evaluation for acute reference
Page 573 and 574:
560 increased thyroid weights in th
Page 575 and 576:
562 Table 4. Results of bone-marrow
Page 577 and 578:
564 malformations between the contr
Page 579 and 580:
566 In a study of prenatal developm
Page 581 and 582:
568 combination of heparin and an a
Page 583 and 584:
570 Table 10. Selected findings fro
Page 585 and 586:
572 In a short-term study of neurot
Page 588 and 589:
ANNEX 1 Reports and other documents
Page 590 and 591:
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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