Application for the Reassessment of a Hazardous Substance under ...

More documents

Recommendations

Info

25.1 Key Study:KEY STUDY: Oral• Type of study:• Species:• Strain:• Sex/Numbers:• Test material:• Dose levels:Minimal incipient toxicity, human;Human;Not applicable;4 or 5 males/test group; 2 male controls;Dichlorvos (unspecified source, Batch/Lot No. & purity);1.0, 1.5, 2.0 or 2.5 mg/day by capsule for 28 days (for70kg adult, equivalent to 0.014, 0.021, 0.029 and 0.036mg/kg b.w./day);• Endpoint: Symptoms; plasma and RBC ChE activities(potentiometric method of Michel (1949), which estimatesthe cholinesterase activity based on the change in pH withtime, ΔpH/hour); clinical chemistry, haematology andurinary parameters;• Remarks: No treatment-related symptoms or effect on anyhaematology, clinical chemistry or urinary parameter were reported. RBC ChEactivity was unaffected by treatment.No effect on plasma ChE activity at 1 or 1.5 mg/day was reported following 4weeks of dosing, however, no data were provided to substantiate this finding.At 2.0 mg/day, mean plasma ChE activity was depressed by >20% relative topretreatment activity from the second week of administration, reaching amaximum of 29% 3 days after treatment ended. When the data were correctedto account for this reduction in activity in the controls (up to 12%), the level ofinhibition in the dichlorvos group was approximately 20% from the secondweek of dosing (maximum of 25% at day 19). This was considered atoxicologically significant level of inhibition despite the absence of statisticalanalysis to support the finding. Three days after the cessation of dosing, plasmaChE activity remained depressed by 22%.At 2.5 mg/day, toxicologically-significant inhibition (>20% relative topretreatment activity) of plasma ChE activity occurred after 2 weeks of dosing.Treatment was stopped after 20 days because the level of inhibition hadreached 30%. Following a 15-day washout period, plasma ChE activityreturned to pretreatment levels.A supplementary group of subjects was treated with 1.5 mg/g dichlorvos.Progressive inhibition of plasma ChE activity occurred from the second week,reaching a maximum of 41% at the end of the 60-day treatment period (relativeDichlorvos reassessment – application Page 254 of 436
to pretreatment activity). When the data were corrected to account for thedeclining activity in the control group (up to 24%), inhibition of plasma ChEactivity in the dichlorvos subjects was 27% after 16 days and continued to bedepressed by 13-21% for the remainder of the dosing period. During the 74-day post-treatment period, plasma ChE activity recovered to control levelswithin 2 weeks. The author indicated that over a period of approximately 3weeks (corresponding to post-treatment days 31-48), there was a generaldecrease in plasma ChE activity in the performing laboratory due to a technicalproblem.• NOAEL =• LOAEL =• GLP:• Test Guideline:1.0 mg/day (0.014 mg/kg b.w./day for 70kg adult);1.5 mg/day (based on toxicologically-significant inhibition(>20% of pretreatment levels) of plasma ChE activity).No information;No information;• Reference source: Rider JA (1967) ―Determination of the minimal incipienttoxicity of dichlorvos in humans.‖ Report and Study no.unspecified. Lab: Gastrointestinal Research Laboratory,Franklin Hospital, San Francisco, CA, USA. Sponsor:Shell Chemical Company, Agricultural ChemicalsDivision, New York, New York, USA. Report date:October 1967. Unpublished. (Original not sighted;APVMA, 2008a);• Reliability:Klimisch score 2 = reliable with restrictions;Justification for Key Study status: Rider (1967) was not conducted to GLP or TestGuideline. However, the APVMA considered the study robust enough to use theNOAEL as basis of their occupational and residential risk assessments.Note: The APVMA (2008a) concluded that:“The NOEL was 1.0 mg/d[ay], based on toxicologically-significant inhibitionof plasma ChE activity at and above 1.5 mg/d[ay]. In the absence ofbodyweight data for the test subjects it is assumed that the average bodyweightfor young healthy men is 70 kg. Therefore the NOEL, using this figure, is0.014 mg/kg bw/d[ay].‖[See Appendix 1: APVMA - Summary of benchmarks used in occupational riskassessments, for fuller details.]KEY STUDY: Oral• Type of study:21-day capsule study in humans;Dichlorvos reassessment – application Page 255 of 436
Page 1 and 2:
Application for the Reassessment of
Page 3 and 4:
6.1 Evaluation of options to streng
Page 5 and 6:
EXECUTIVE SUMMARYIn briefERMA New Z
Page 7 and 8:
Aerosol containing 50 g/kgdichlorvo
Page 9 and 10:
ERMA New Zealand‘s recommendation
Page 11 and 12:
26 - 29Outdoor public space usage30
Page 13 and 14:
Substance details1-8,11-16,20-25,30
Page 15 and 16:
1.2.3 In 2008, the Environmental Ri
Page 17 and 18:
Table 1. Dichlorvos-containing subs
Page 19 and 20:
public environments and use for bio
Page 21 and 22:
available to it. In preparing this
Page 23 and 24:
3.3 International regulatory positi
Page 25 and 26:
3.6 Classification3.6.1 The HSNO cl
Page 27 and 28:
Hazard Class /SubclassClassificatio
Page 29 and 30:
Hazard Class /SubclassClassificatio
Page 31 and 32:
Rates:Fogging: 13 ml / litre (water
Page 33 and 34:
BV2 SurfaceInsecticideBV2 SurfaceIn
Page 35 and 36:
Table 7.Dichlorvos outdoor and indo
Page 37 and 38:
Scenario Crop/Use Method Rate Appli
Page 39 and 40:
humidity conditions. The higher res
Page 41 and 42:
4.3 EnvironmentIdentification of ad
Page 43 and 44:
4.3.9.3 Aquatic environment - Groun
Page 45 and 46:
is considered to be highly improbab
Page 47 and 48:
RiskGroupRQ range Level of risk Use
Page 49 and 50:
RiskGroupRQ range Level of risk Use
Page 51 and 52:
assessment, as the Use Scenario inc
Page 53 and 54:
Nonnegligible1 < RQ < 10Nonnegligib
Page 55 and 56:
Table 12.LifecycleStageImport,manuf
Page 57 and 58:
LifecycleStageUse -bystanderUseScen
Page 59 and 60:
Table 13.Identification of benefici
Page 61 and 62:
value that can be attributed to dic
Page 63 and 64:
outbreak, MAF‘s ability to demons
Page 65 and 66:
the duty of the Crown is not merely
Page 67 and 68:
5.1.7.1 J. Hicking stated that dich
Page 70 and 71:
Table 14. Comparative of hazard cla
Page 72 and 73:
Crop Pest Active ingredient Preharv
Page 74 and 75:
Crop Pest Active ingredient Preharv
Page 76 and 77:
SECTION 6- PROPOSALS TO MANAGE RISK
Page 78 and 79:
Assessment was carried out with spe
Page 80 and 81:
6.1.11 Controls to protect bystande
Page 82 and 83:
Table 16Effect of additional contro
Page 84 and 85:
Use Scenario Receptor Level of Risk
Page 86 and 87:
Page 88 and 89:
Page 90 and 91:
Page 92 and 93:
Page 94 and 95:
Page 96 and 97:
Page 98 and 99:
Page 100 and 101:
Page 102 and 103:
Page 104 and 105:
Page 106 and 107:
have, and notes the following as ar
Page 108 and 109:
Table 18Summary of benefits associa
Page 110 and 111:
UseScenariosAssessment ofEffectOutc
Page 112 and 113:
Substance detailsHSR000126DDVPInsec
Page 114 and 115:
Table 22.there are no practicable r
Page 116:
7.4 Preliminary Recommendations7.4.
Page 119 and 120:
method and LOQ)Water (principle ofm
Page 121 and 122:
Appendix B: Environmental Fate of d
Page 123 and 124:
Bioconcentration factor Gnathopogon
Page 125 and 126:
Table C.2:Scenarios used in exposur
Page 127 and 128:
Scenario 3: Vegetables - 1 applicat
Page 129 and 130:
FIELD AND STANDARD POND HALFLIFE VA
Page 131 and 132:
insectivorous bird7 Passionfruit Sm
Page 133 and 134:
4 Leafyvegetables(BBCH ≥50)4 Leaf
Page 135 and 136:
summer)7 passionfruit(BBCH 10-19)7
Page 137 and 138:
Ground (lowboom)0.03 0.03 1.07 1.07
Page 139 and 140:
Appendix D: Ecotoxicity of dichlorv
Page 141 and 142:
ioaccumulationClearance timeLevel o
Page 143 and 144:
Table D.5:Toxicity to terrestrial i
Page 145 and 146:
Appendix E: Risk Assessment: Enviro
Page 147 and 148:
Aquatic organsimsTable E.3:Environm
Page 149 and 150:
12345Crop type Table I.1 (Annex 1)
Page 151 and 152:
7 passionfruit(BBCH 20-39)7 passion
Page 153 and 154:
Fruit (tree) 2052 70759 >50Passionf
Page 155 and 156:
Appendix F: Human Toxicity of dichl
Page 157 and 158:
CONTENTS:Title Page 11 Purpose 2Con
Page 159 and 160:
2 SUBSTANCE IDENTIFICATIONIUPAC nam
Page 161 and 162:
However, dichlorvos has genotoxic p
Page 163 and 164:
4 ABSORPTION, DISTRIBUTION, METABOL
Page 165 and 166:
aerosol cans (230-330 g dichlorvos)
Page 167 and 168:
4.3 Metabolism:found in tissues of
Page 169 and 170:
dose of 1.0 mg/kg bw, a single gava
Page 171 and 172:
eports. LD 50 = 46.4 mg/kg b.w. is
Page 173 and 174:
6 ACUTE DERMAL 6.1HSNO Classificati
Page 175 and 176:
7 ACUTE INHALATION 6.1HSNO Classifi
Page 177 and 178:
measured and it was not possible to
Page 179 and 180:
8 SKIN IRRITATION 6.3 & CORROSION 8
Page 181 and 182:
9 EYE IRRITATION 6.4 & CORROSION 8.
Page 183 and 184:
10 RESPIRATORY SENSITISATION 6.5AHS
Page 185 and 186:
Justification for Classification: U
Page 187 and 188:
12 MUTAGENICITY 6.6HSNO Classificat
Page 189 and 190:
ERMA New Zealand CONFIDENTIAL Repor
Page 191 and 192:
The ATSDR (1997) reported:“Dichlo
Page 193 and 194:
•ATSDR (1997): http://www.atsdr.c
Page 195 and 196:
13 CARCINOGENICITY 6.7HSNO Classifi
Page 197 and 198:
fibroadenomas were observed in 6 (1
Page 199 and 200:
• Sex/Numbers:• Test material:
Page 201 and 202:
The NTP Peer Review concluded that:
Page 203 and 204: concurrent studies for comparison w
Page 205 and 206: The APVMA (2008a) reported a chroni
Page 207 and 208: was exposed. The estimated daily in
Page 209 and 210: 14 REPRODUCTIVE TOXICITY 6.8HSNO Cl
Page 211 and 212: ppm during premating days, signific
Page 213 and 214: Toxicology, Chemistry and Life Scie
Page 215 and 216: addition, there was an increase in
Page 217 and 218: • Maternal toxicity NOAEL =• Ma
Page 219 and 220: Research Triangle Park, North Carol
Page 221 and 222: 16 REPRODUCTIVE OR DEVELOPMENTAL TO
Page 223 and 224: 17 SPECIFIC TARGET ORGAN TOXICITY 6
Page 225 and 226: There was a significant dose-relate
Page 233 and 234: KEY STUDY:• Type of study:• Spe
Page 235 and 236: BACKGROUND:The APVMA (2008a) also r
Page 237 and 238: cholinesterases can only be estimat
Page 241 and 242: Ltd, Sittingbourne Research Center,
Page 243 and 244: 23 OTHER POTENTIAL TOXIC ENDPOINTS2
Page 245 and 246: ―Results“Mortalities and clinic
Page 247 and 248: 1984). QA study. Study conducted ac
Page 249 and 250: “No information was located on im
Page 251 and 252: “Comment: These incidents clearly
Page 253: 25 ACCEPTABLE OPERATOR EXPOSURE LEV
Page 257 and 258: cholinesterase inhibition in health
Page 259 and 260: protect agricultural workers who ha
Page 261 and 262: Wash: refers to skin washes; Dressi
Page 263 and 264: Hazard Class/SubclassHazardclassifi
Page 265 and 266: Hazard Class/SubclassHazardclassifi
Page 267 and 268: REFERENCES:APVMA, 2008a. ―DICHLOR
Page 269 and 270: Appendix 1:APVMA - Summary of bench
Page 271 and 272: “Inhalational NOEL for Occupation
Page 273 and 274: activity). In fact, treatment was s
Page 275 and 276: LAST PAGEDichlorvos reassessment -
Page 277 and 278: Dichlorvos:Occupational, Bystander,
Page 279 and 280: CONTENTS:Title Page 11 Purpose 2Con
Page 281 and 282: 3ACTIVITY SCENARIOS3.1 Table (I) su
Page 283 and 284: access of bystanders to treated are
Page 285 and 286: can reduce dermal exposures to mixe
Page 287 and 288: contaminated with, respectively 0.0
Page 289 and 290: The modelling is based upon dischar
Page 291 and 292: Table II: Occupational Exposure Est
Page 293 and 294: Table III: Occupational Exposure Es
Page 295 and 296: Operation / RPE / PPETable IV: Occu
Page 297 and 298: 1.25L product/ha; work rate, 1.25 h
Page 299 and 300: Application: Air-hose RPE + chem. r
Page 301 and 302: Application: Half-face RPE + overal
Page 303 and 304: P for RPE (% penetration): none, 1
Page 305 and 306:
Table X: Occupational Exposure Esti
Page 307 and 308:
provided: work day exposure is limi
Page 309 and 310:
5POST-APPLICATION OR RE-ENTRY WORKE
Page 311 and 312:
D = DFR x TC x DA x WR x AR x P / B
Page 313 and 314:
Re-entry into out-door crops (Scena
Page 315 and 316:
Re-entry into treated glasshouses d
Page 317 and 318:
acceptable 240 minutes after applic
Page 319 and 320:
Re-entry into treated glasshouses u
Page 321 and 322:
Table XVII: Re-entry into glasshous
Page 323 and 324:
lowest use rate (52 mg/m 3 ; 1300g
Page 325 and 326:
DA = percentage dermal absorption [
Page 327 and 328:
Re-entry into treated enclosed indu
Page 329 and 330:
nature of the building itself, not
Page 331 and 332:
Conclusions on re-entry worker expo
Page 333 and 334:
6BYSTANDER & RESIDENT EXPOSURE & RI
Page 335 and 336:
Children’s incidental ingestion o
Page 337 and 338:
Table XX: Spray driftExposure throu
Page 339 and 340:
Exposure through contactwithcontami
Page 341 and 342:
Conclusions on bystander and reside
Page 343 and 344:
Table XXIII: Dichlorvos Use Scenari
Page 345 and 346:
mixing/loading. Mixing/loading fogg
Page 347 and 348:
7.23 Re-entry for ventilation of in
Page 349 and 350:
REFERENCES:APVMA, 2008a. ―DICHLOR
Page 351 and 352:
Appendix 1:Occupational Exposure Es
Page 353 and 354:
FactorExposure (μg/kg a.i. handled
Page 355 and 356:
Inhalation exposure from cylinder c
Page 357 and 358:
[0.01875 x {(0.018 x 0.05) + (2.68
Page 359 and 360:
With half-face respirator (protecti
Page 361 and 362:
With full-body chemical resistant c
Page 363 and 364:
Appendix 4:Occupational Exposure Es
Page 365 and 366:
With overalls and gloves (protectio
Page 367 and 368:
The Dermal Exposure (D) is 2.06 μg
Page 369 and 370:
TTR = turf transferable residues -
Page 371 and 372:
F = fraction of residue retained on
Page 373 and 374:
TTR = transferable residues - the E
Page 375 and 376:
Public Space ApplicationsScenario (
Page 377 and 378:
ERMA New Zealand‟s comment on the
Page 379 and 380:
Enclosed SpaceAgricultural UseOutdo
Page 381 and 382:
Appendix H: Qualitative Descriptors
Page 383 and 384:
1.3. The likelihood applies to the
Page 385 and 386:
Appendix I: Data from which classif
Page 387 and 388:
Endpoint Units * Dichlorvos Propoxu
Page 389 and 390:
Toxicity mixture calculationsSubcla
Page 391 and 392:
Subclass 9.3 -Ecotoxicity to terres
Page 393 and 394:
Table J.1:Existing controls for dic
Page 395 and 396:
TrackingcontrolsIdentification cont
Page 397 and 398:
Table J.2:Summary of default contro
Page 399 and 400:
Hazardous Substances (Classes 1 to
Page 401 and 402:
Hazardous Substances (Classes 6, 8,
Page 403 and 404:
Hazardous Substances (Classes 6, 8,
Page 405 and 406:
(a) means piping that—(i) is conn
Page 407 and 408:
Code I29 Regs 51, 52 Signage requir
Page 409 and 410:
Non-HSNO Act controlsAgricultural C
Page 411 and 412:
Appendix K: Overseas regulatory act
Page 413 and 414:
Product Use Further details ofuseSu
Page 415 and 416:
Risk assessment identified concerns
Page 417 and 418:
Current usesFormulations:Methods of
Page 419 and 420:
CanadaStatusPMRA are undertaking a
Page 421 and 422:
Appendix L: Parties consulted durin
Page 423 and 424:
Animal Products Act 19995. The purp
Page 425 and 426:
14. Regulatory control of these pro
Page 427 and 428:
Zealand‘s trade in primary produc
Page 429 and 430:
processed and stored. It employs ve
Page 431 and 432:
may be taken to risk management in
Page 433 and 434:
Appendix A• Agricultural Compound
Page 435 and 436:
Appendix O: ReferencesACVM (2010) h
show all

Application for the Reassessment of a Hazardous Substance under ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?