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Am Eisenatod

am eisenatod

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Also known as: Beta-hch, 1,2,3,4,5,6-hexachlorocyclohexane, Gamma-hch, Alpha-hch, 58-89-9, Hexachlorane

Molecular Formula

C₆H₆Cl₆

Molecular Weight

290.8 g/mol

InChI Key

JLYXXMFPNIAWKQ-UHFFFAOYSA-N

FDA UNII

88RHN9KHN8

Lindane is the gamma-isomer of benzene hexachloride, a colorless to white colored, synthetic, crystalline solid with a slight musty odor that emits toxic fumes of hydrochloric acid and other chlorinated compounds when heated to decomposition. Lindane is used as an insecticide for hardwood logs, lumber, and crops. Lindane also has topical pediculicide and scabicide activities probably due to its neurotoxic effects. Inhalation exposure to this substance causes severe irritation of the nose and throat, causes anemia, and affects the liver, nervous, cardiovascular, and immune system. Lindane is reasonably anticipated to be a human carcinogen.

1 2D Structure

am eisenatod

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

1,2,3,4,5,6-hexachlorocyclohexane

2.1.2 InChI

InChI=1S/C6H6Cl6/c7-1-2(8)4(10)6(12)5(11)3(1)9/h1-6H

2.1.3 InChI Key

JLYXXMFPNIAWKQ-UHFFFAOYSA-N

2.1.4 Canonical SMILES

C1(C(C(C(C(C1Cl)Cl)Cl)Cl)Cl)Cl

2.2 Other Identifiers

2.2.1 UNII

88RHN9KHN8

2.3 Synonyms

2.3.1 Depositor-Supplied Synonyms

1. Beta-hch

2. 1,2,3,4,5,6-hexachlorocyclohexane

3. Gamma-hch

4. Alpha-hch

5. 58-89-9

6. Hexachlorane

7. Kwell

8. Gamma-bhc

9. Beta-bhc

10. Benzene Hexachloride

11. Epsilon-hch

12. Beta-hexachlorocyclohexane

13. Hexicide

14. Gamene

15. Scabene

16. Delta-bhc

17. Delta-hch

18. Gamma-hexachlorocyclohexane

19. Beta-lindane

20. 319-85-7

21. Aalindan

22. Aphtiria

23. Jacutin

24. Gexane

25. 319-86-8

26. 319-84-6

27. Agrocide

28. Aparasin

29. Chloresene

30. Codechine

31. Entomoxan

32. Gammalin

33. Gammaterr

34. Hexachloran

35. Hexaverm

36. Hexyclan

37. Kokotine

38. Lindafor

39. Lindosep

40. Lorexane

41. Nicochloran

42. Ovadziak

43. Owadziak

44. Pedraczak

45. Pflanzol

46. Quellada

47. Streunex

48. Aficide

49. Aplidal

50. Arbitex

51. Celanex

52. Devoran

53. Gamacid

54. Hortex

55. Lendine

56. Lentox

57. Lidenal

58. Lindex

59. Lintox

60. Linvur

61. Mszycol

62. Omnitox

63. Alpha-hexachlorocyclohexane

64. Bexol

65. Nexit

66. Viton

67. Alpha-lindane

68. Beta-1,2,3,4,5,6-hexachlorocyclohexane

69. Hcch

70. 608-73-1

71. Agrocide Wp

72. Agrocide Iii

73. Ben-hex

74. Ameisentod

75. Benhexol

76. Gammexane

77. Heclotox

78. Lasochron

79. Lindatox

80. Gammalin 20

81. Neo-scabicidol

82. Gamma-lindane

83. Nexit-stark

84. Bentox 10

85. Milbol 49

86. Nexen Fb

87. Alpha-bhc

88. Alpha-1,2,3,4,5,6-hexachlorocyclohexane

89. Nexol-e

90. Delta-hexachlorocyclohexane

91. Dol Granule

92. Gamacarbatox

93. Lindagrain

94. Lindagranox

95. Lindapoudre

96. Spruehpflanzol

97. (+)-alpha-hch

98. Agronexit

99. Esoderm

100. Gallogama

101. Gamaphex

102. Geobilan

103. Hexatox

104. Hilbeech

105. Lindagam

106. Novigam

107. Silvanol

108. Gamiso

109. Inexit

110. Isotox

111. Lindan

112. Gamma-col

113. Spritz-rapidin

114. Forst-nexen

115. Sang Gamma

116. Mglawik L

117. Agrocide 7

118. Hungaria L7

119. Ameisenmittel Merck

120. Tri-6

121. Spritzlindane

122. Lindanum

123. Delta-lindane

124. Gamma-1,2,3,4,5,6-hexachlorocyclohexane

125. Geolin G 3

126. Verindal Ultra

127. Gamma Benzene Hexachloride

128. Gamma-benzene Hexachloride

129. Tap 85

130. Detox 25

131. Alpha-hexachlorane

132. Agrocide 6g

133. Hexachlorcyclohexan

134. 6108-10-7

135. Drilltox-spezial Aglukon

136. Beta-benzene Hexachloride

137. Hexachlorocyclohexanes

138. Gammallin

139. Gammaxene

140. Gamma-hexachlorobenzene

141. .delta.-hexachlorocyclohexane

142. Delta-benzenehexachloride

143. .alpha.-lindane

144. .delta.-lindane

145. Ent 9,234

146. Alpha-benzene Hexachloride

147. Delta-benzene Hexachloride

148. .alpha.-bhc

149. .delta.-bhc

150. Epsilon-hexachlorocyclohexane

151. Bhc (mixed Isomers)

152. Ent 7,796

153. Ent 9,232

154. Latka 666

155. Gamma-hexachlorzyklohexan

156. 119911-69-2

157. Hch

158. Latka 666 [czech]

159. Benzene Hexachloride-alpha-isomer

160. Hexachlorocyclohexane, Gamma-isomer

161. Benzene Hexachloride, Gamma

162. Zeta-hch

163. .beta.-hexachlorocyclohexane

164. Hexachlorocyclohexane, Technical Grade

165. .alpha.-hexachlorocyclohexane

166. .alpha.-hexachloran

167. .alpha.-hch

168. .delta.-hch

169. .alpha.-hexachlorane

170. Bbh

171. Benzene Hexachloride (ambiguous)

172. 1a,2a,3b,4a,5b,6b-hexachlorocyclohexane

173. Benzene Hexachloride Gamma

174. (1r,2r,3r,4r,5r,6r)-1,2,3,4,5,6-hexachlorocyclohexane

175. 59nee7pcab

176. Bhc,mixtureofisomers(alpha

177. Ym80odm9pd

178. Hgi

179. Nsc-755895

180. .alpha.-hexachlorcyclohexane

181. .delta.-benzene Hexachloride

182. 88rhn9khn8

183. Ivm9a2n49k

184. (1alpha,2beta,3alpha,4beta,5alpha,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

185. Yv2d256z3n

186. Hexapoudre

187. Benzanex

188. Gamacide

189. Hexablanc

190. Hexachlor

191. Hexamul

192. Hexcidum

193. (1r,2r,3r,4r,5s,6s)-1,2,3,4,5,6-hexachlorocyclohexane

194. (1r,2r,3s,4r,5r,6s)-1,2,3,4,5,6-hexachlorocyclohexane

195. Chebi:24536

196. Chebi:28428

197. Chebi:32888

198. Chebi:39095

199. Chebi:39096

200. Dolmix

201. Gamtox

202. Isatox

203. Submar

204. Gyben

205. Beta-hexachloran

206. Arcotal S

207. Trives-t

208. Gamma Bhc

209. Hch-.delta.

210. Lacco Hi Lin

211. Nsc-11808

212. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1.alpha.,2.alpha.,3.alpha.,4.beta.,5.alpha.,6.beta.)-

213. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1.alpha.,2.alpha.,3.beta.,4.alpha.,5.alpha.,6.beta.)-

214. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1.alpha.,2.alpha.,3.beta.,4.alpha.,5.beta.,6.beta.)-

215. Bhc-.delta. Isomer

216. Gamacide 20

217. Bhc, .delta.

218. Hecoltox

219. Epsilon-hch 100 Microg/ml In Methanol

220. Ncgc00094546-04

221. Ameisenatod

222. Benhexachlor

223. Gammahexane

224. Aphtitria

225. Epsilon-hch 10 Microg/ml In Cyclohexane

226. Exagama

227. Gammahexa

228. Gammopaz

229. Lindalo

230. Lindamul

231. Lindano

232. Lindaterra

233. Novigan

234. Benzex

235. Beta-hexachlorobenzene

236. Forlin

237. Gammex

238. (1r,2r,3s,4s,5r,6s)-1,2,3,4,5,6-hexachlorocyclohexane

239. Bhc Or Hch

240. Delta-1,2,3,4,5,6-hexachlorocyclohexane

241. Detmol-extrakt

242. Epsilon-hch 100 Microg/ml In Cyclohexane

243. Fenoform Forte

244. Trans-1,2,3,4,5,6-hexachlorocyclohexane

245. Nexen-fb

246. Detmol Extract

247. Dsstox_cid_685

248. Dsstox_cid_686

249. Dsstox_cid_687

250. Borer Spray

251. .alpha.-1,2,3,4,5,6-hexachlorocyclohexane

252. .gamma.-1,2,3,4,5,6-hexachlorocyclohexane

253. Alpha-hexachloran

254. Alpha-benzenehexachloride

255. (1alpha,2alpha,3alpha,4beta,5alpha,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

256. (1alpha,2alpha,3beta,4alpha,5alpha,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

257. Agrocide 2

258. Kwell-r

259. Dsstox_rid_75733

260. Dsstox_rid_75734

261. Dsstox_rid_75735

262. Dsstox_gsid_20685

263. Dsstox_gsid_20686

264. Dsstox_gsid_20687

265. Bhc (insecticide)

266. Hch [bsi]

267. Hch [iso]

268. Cyclohexane, 1,2,3,4,5,6-hexachloro-, .alpha.-

269. Cyclohexane, 1,2,3,4,5,6-hexachloro-, .beta.-

270. Cyclohexane, 1,2,3,4,5,6-hexachloro-, .delta.-

271. Gamma-mean 400

272. Agrisol G-20

273. T-hch

274. Caswell No. 079

275. Caswell No. 527

276. Gamma-benzohexachloride

277. Cyclohexane, 1,2,3,4,5,6-hexachloro-, .gamma.-isomer

278. (1r,2c,3t,4c,5c,6t)-1,2,3,4,5,6-hexachlorocyclohexane

279. (1r,2r,3s,4r,5s,6s)-1,2,3,4,5,6-hexachlorocyclohexane

280. (1r,2t,3c,4t,5c,6t)-1,2,3,4,5,6-hexachlorocyclohexane

281. 1alpha,2alpha,3beta,4alpha,5beta,6beta-hexachlorocyclohexane

282. Scabecid

283. Gamma Hexachlor

284. Lindanum [inn-latin]

285. Pepsin

286. Gamma-benzenehexachloride

287. Gamma-hexachloro-cyclohexane

288. Atlas Steward

289. Lindano [inn-spanish]

290. Sang-gamma

291. Gamma-hch Or Gamma-bhc

292. Gamma-hexachlorcyclohexanum

293. Rcra Waste Number U129

294. Technical Hch

295. Gamma-hexachlorane

296. Theta-hch

297. Cas-58-89-9

298. Hexachlorocyclohexane, Beta-

299. Hexachlorcyclohexan [german]

300. Ent 8,601

301. Ent 9,233

302. Hexachlorocyclohexane, Alpha-

303. Hexachlorocyclohexane, Delta-

304. Hexachlorocyclohexane, Gamma-

305. 6108-11-8

306. 6108-12-9

307. Cas-319-85-7

308. Cas-608-73-1

309. Smr000857321

310. Smr000875266

311. Ccris 327

312. Ccris 328

313. Ccris 329

314. Technical Hexachlorocyclohexane

315. Trans-alpha-benzenehexachloride

316. .gamma.-bhc

317. Benzenehexachloride-alpha-isomer

318. Ccris 1449

319. Hsdb 646

320. .beta.-bhc

321. 1,2,3,4,5,6-hexachlorocyclohexane (hch)

322. D-bhc

323. .delta.,1,2,3,4,5,6-hexachlorocyclohexane

324. Lindane (gamma-hch)

325. Benzene Hexachloride-gamma Isomer

326. Cyclohexane, 1,2,3,4,5,6-hexachloro-

327. Hsdb 1606

328. Hsdb 6029

329. Hsdb 6183

330. Hsdb 6184

331. (-)-alpha-hch

332. Benzenehexachloride, Mixed Isomers

333. Gamma-bhc Benhexachlor

334. Benzene-cis-hexachloride

335. Nci-c00204

336. Eta-hexachlorocyclohexane

337. Hexachlorocyclohexane, Gamma Isomer

338. Cyclohexane, .delta.,1,2,3,4,5,6-hexachloro-

339. Hexachlorocyclohexane (all Isomers)

340. Sr-05000001837

341. Zeta-hexachlorocyclohexane

342. Drill Tox-spezial Aglukon

343. Murfume Grain Store Smoke

344. Einecs 200-401-2

345. Einecs 206-270-8

346. Einecs 206-271-3

347. Einecs 206-272-9

348. Einecs 210-168-9

349. Unii-59nee7pcab

350. Unii-ym80odm9pd

351. Epsilon-benzenehexachloride

352. Hexachlorocyclohexane (mixed Isomers)

353. Nsc 11808

354. Theta-hexachlorocyclohexane

355. .delta.-(aeeee)-1,2,3,4,5,6-hexachlorocyclohexane

356. Kwell (tn)

357. Rcra Waste No. U129

358. Unii-ivm9a2n49k

359. Cyclohexane, 1,2,3,4,5,6-hexachloro-, .delta.-isomer

360. Epa Pesticide Chemical Code 009001

361. Hexachlorocyclohexane (technical Grade)

362. Brn 1907331

363. Brn 1907334

364. Brn 1907337

365. Brn 1907338

366. Brn 3195880

367. Kanodane

368. Detmol Extrakt

369. Ai3-07796

370. Ai3-08601

371. Ai3-09232

372. Ai3-09233

373. Ai3-09234

374. H.c.h.

375. Nexit Stark

376. Lindane [hexachlorocyclohexanes]

377. 1.alpha.,2.alpha.,3.alpha.,4.beta.,5.alpha.,6.beta.-hexachlorocyclohexane

378. Benzene Hexachloride-gamma-isomer

379. Unii-5477b350ek

380. .gamma.-lindane

381. Lindane [usan:usp:inn:ban]

382. Benzene Hexachloride, All Isomers

383. Theta-bhc

384. Cyclohexane, Beta-1,2,3,4,5,6-hexachloro-

385. Cyclohexane, Delta-1,2,3,4,5,6-hexachloro-

386. Hexachlorzyklohexan

387. Beta-hch [hexachlorocyclohexanes]

388. Nexol E

389. Hch (technical)

390. Alpha-hch [hexachlorocyclohexanes]

391. D-alpha-bhc

392. Gamma-hch [hexachlorocyclohexanes]

393. Sang-.gamma.

394. Delta -bhc

395. Eta-bhc

396. Eta-hch

397. 1,2,3,4,5,6-hexachlorocyclohexane, (1.alpha.,2.alpha.,3.alpha.,4.beta.,5.alpha.,6.beta.)-

398. Cyclohexane, 1,2,3,4,5,6-hexachloro-, Alpha-

399. Cyclohexane, 1,2,3,4,5,6-hexachloro-, Gamma-

400. Lindane,(s)

401. 1,2,3,4,5,6-hexachlorocyclohexane, Gamma-isomer

402. Delta-(aeeeee)-1,2,3,4,5,6-hexachlorocyclohexane

403. Einecs 228-068-9

404. .gamma.-hexachloran

405. .gamma.-hch

406. Bhc .alpha.

407. Hch-.alpha.

408. .gamma.-hexachlorane

409. Bhc-.alpha. Isomer

410. Cyclohexane, 1,2,3,4,5,6-hexachloro-, Alpha-isomer

411. Cyclohexane, 1,2,3,4,5,6-hexachloro-, Beta-isomer

412. Cyclohexane, 1,2,3,4,5,6-hexachloro-, Delta-isomer

413. Cyclohexane, 1,2,3,4,5,6-hexachloro-, Gamma-isomer

414. Bhc(.gamma.)

415. G-bhc-.delta.

416. Hch, Technical Grade

417. Lindane (gama-hch)

418. Lindane, 97%

419. 1,2,3,4,5,6-hexachlorocyclohexane (mixture Of Isomers)

420. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (mixed Isomers)

421. Lindane (usp/inn)

422. Gammahexachlorcyclohexane

423. Spectrum_001929

424. 1a,2b,3a,4b,5a,6b-hexachlorocyclohexane

425. .beta.-lindane

426. 1alpha,2alpha,3beta,4alpha,5alpha,6beta-hexachlorocyclohexane

427. Lindane [hsdb]

428. Lindane [iarc]

429. Lindane [usan]

430. .epsilon.-bhc

431. Ai3-15109

432. Bhc, Epsilon-

433. Lindane [inn]

434. Alpha-hexachlorcyclohexane

435. Lindane [mi]

436. .gamma.-benzohexachloride

437. .gamma.-hexachlorobenzene

438. Dsstox_cid_684

439. Lindane [mart.]

440. Spectrum2_001864

441. Spectrum3_000860

442. Spectrum4_000700

443. Spectrum5_001586

444. .epsilon.-lindane

445. Bhc, Delta-

446. .beta.-hch

447. 1-alpha,2-alpha,3-alpha,4-beta,5-alpha,6-beta-hexachlorocyclohexane

448. 1-alpha,2-beta,3-alpha,4-beta,5-alpha,6-beta-hexachlorocyclohexane

449. Dsstox_cid_4134

450. Lindane [usp-rs]

451. Lindane [who-dd]

452. Lindane [who-ip]

453. .beta.-hexachloran

454. Hch, Technical Grade [hexachlorocyclohexanes]

455. Gamma Benzene Hydrochloride

456. Unii-88rhn9khn8

457. (1alpha,2alpha,3beta,4alpha,5beta,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

458. Epsilon-benzene Hexachloride

459. Bhc, .alpha.-

460. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3beta,4alpha,5alpha,6beta)-

461. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2beta,3alpha,4beta,5alpha,6beta)-

462. Dsstox_rid_75732

463. Unii-yv2d256z3n

464. .alpha.-benzene Hexachloride

465. .gamma.-benzene Hexachloride

466. 1,2,3,4,5,6-hexachlorocyclohexane Gamma Isomer

467. Benzene-1,2,3,4,5,6-hexachloride (ambiguous)

468. Bhc, .beta.-

469. Bidd:pxr0097

470. Cyclohexane, 1,2,3,4,5,6-hexachloro-, Delta-

471. Dsstox_gsid_20684

472. Dsstox_gsid_24134

473. Schembl25895

474. Schembl25896

475. Schembl75689

476. .gamma.-hexachlorocyclohexane

477. Bspbio_002479

478. Kbiogr_001199

479. Kbioss_002471

480. Spectrum330071

481. 2-05-00-00011 (beilstein Handbook Reference)

482. 4-05-00-00056 (beilstein Handbook Reference)

483. 4-05-00-00058 (beilstein Handbook Reference)

484. 4-05-00-00060 (beilstein Handbook Reference)

485. 4-05-00-00061 (beilstein Handbook Reference)

486. Mls001333088

487. Mls001335969

488. Mls001335970

489. Mls001361319

490. Beta-bhc, Analytical Standard

491. Bidd:er0090

492. Bidd:er0091

493. Bidd:er0449

494. Bidd:er0558

495. Bidd:gt0634

496. Chembl15891

497. Divk1c_000701

498. Lindane [orange Book]

499. Schembl140812

500. Schembl140813

501. Schembl472088

502. Benzene Hexachloride, .gamma.

503. Spbio_001708

504. .epsilon.-hexachlorocyclohexane

505. Delta-bhc, Analytical Standard

506. Gamma-bhc, Analytical Standard

507. Lindane [usp Impurity]

508. Chembl389022

509. Schembl7647849

510. Schembl8469477

511. Schembl9120917

512. Zinc1621

513. (+)-alpha-hexachlorocyclohexane

514. .beta.-hexachlorobenzene

515. Lindane [usp Monograph]

516. Chembl1200921

517. Chembl1714528

518. Chembl1874247

519. Chembl2272381

520. Dtxsid0024135

521. Dtxsid2020684

522. Dtxsid2020686

523. Dtxsid5024134

524. Dtxsid7020685

525. Dtxsid7020687

526. Hexachlorocyclohexane (q-isomer)

527. Hexachlorocyclohexane (z-isomer)

528. Hexachlorocyclohexane [h-isomer]

529. Lindanum [who-ip Latin]

530. Schembl10795898

531. .alpha.-666

532. .alpha.-benzohexachloride

533. .delta.-666

534. Hms502d03

535. Kbio1_000701

536. Kbio2_002464

537. Kbio2_005032

538. Kbio2_007600

539. Kbio3_001979

540. 1,2,3,4,5,6-hexachlorocyclohexane (all Stereo Isomers)

541. Nsc7909

542. Nsc8093

543. (+/-)-.alpha.-hch

544. Ninds_000701

545. (1r,2r,3s,4s,5s,6s)-1,2,3,4,5,6-hexachlorocyclohexane

546. .alpha.-benzenehexachloride

547. .beta.-666

548. Dtxsid901310407

549. Hms1923k17

550. Hms2091e05

551. Hms2230c24

552. Hms2231a06

553. Hms3369j21

554. Pharmakon1600-00330071

555. .beta.-benzene Hexachloride

556. Benzene Hexachloride-.alpha.-isomer

557. Hy-a0085

558. Nsc-7909

559. Nsc-8093

560. Nsc11807

561. Nsc11808

562. A-hexachlorocyclohexane (hch, Bhc)

563. Benzene Hexachloride (gamma-isomer)

564. Hexachlorocyclohexane,.gamma.-isomer

565. Tox21_111294

566. Tox21_200676

567. Tox21_201777

568. Tox21_202069

569. Tox21_202290

570. Tox21_300624

571. Tox21_300953

572. Tox21_302925

573. Tox21_303873

574. Bdbm50410525

575. Beta-hch 100 Microg/ml In Toluene

576. Ccg-39862

577. Nsc-11807

578. Nsc755895

579. .epsilon.-benzene Hexachloride

580. Alpha-hch 100 Microg/ml In Acetone

581. (1alpha,2alpha,3alpha,4beta,5beta,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

582. 1,2,3,4,5,6-hexachlorocyclohexane (1alpha,2alpha,3beta,4alpha,5alpha,6beta)

583. 1,2,3,4,5,6-hexachlorocyclohexane (all Stereo Isomers, Including Lindane)

584. Akos015903494

585. Akos015914103

586. Akos024390982

587. Beta-hch 1000 Microg/ml In Toluene

588. Cyclohexane,2,3,4,5,6-hexachloro-

589. Gamma-hexachlorocyclohexane [lindane And Other Hexachlorocyclohexane Isomers]

590. Zinc100068484

591. Zinc100076865

592. Zinc100076868

593. Zinc100899052

594. Zinc245204924

595. Zinc263584078

596. 1,2,3,4,5,6-hexachloro-cyclohexane

597. 5477b350ek

598. Alpha-hch 1000 Microg/ml In Toluene

599. Beta-hch 10 Microg/ml In Cyclohexane

600. Db00431

601. Delta-hch 1000 Microg/ml In Toluene

602. Gamma-hch 1000 Microg/ml In Toluene

603. Nsc 755895

604. (1alpha,2alpha,3alpha,4alpha,5alpha,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

605. Alpha-hch 10 Microg/ml In Cyclohexane

606. Beta-hch 1000 Microg/ml In N-hexane

607. Bhc (mixture Of Hexachlorocyclohexanes)

608. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3alpha,4alpha,5alpha,6beta)-

609. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3alpha,4beta,5alpha,6beta)-

610. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3alpha,4beta,5beta,6beta)-

611. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3beta,4alpha,5beta,6beta)-

612. Cyclohexane, L,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3beta,4alpha,5beta,6beta)-

613. Delta-hch 10 Microg/ml In Cyclohexane

614. G-1,2,3,4,5,6-hexachlorocyclohexane

615. Gamma-hch 10 Microg/ml In Cyclohexane

616. Gamma-hch 1000 Microg/ml In Methanol

617. Idi1_000701

618. (.+/-.)-.alpha.-hexachlorocyclohexane

619. Alpha-hch 100 Microg/ml In Cyclohexane

620. Alpha-hch 1000 Microg/ml In N-hexane

621. Beta-hexachlorocyclohexane [hsdb]

622. Cyclohexane,1,2,3,4,5,6-hexachloro-

623. Delta-hch 100 Microg/ml In Cyclohexane

624. Delta-hch 1000 Microg/ml In N-hexane

625. Gamma-hch 100 Microg/ml In Cyclohexane

626. Gamma-hch 1000 Microg/ml In N-hexane

627. Ncgc00094546-01

628. Ncgc00094546-02

629. Ncgc00094546-03

630. Ncgc00094546-05

631. Ncgc00094546-06

632. Ncgc00094546-07

633. Ncgc00094546-08

634. Ncgc00094546-09

635. Ncgc00094546-10

636. Ncgc00094546-11

637. Ncgc00159386-02

638. Ncgc00159386-03

639. Ncgc00159386-04

640. Ncgc00159386-05

641. Ncgc00163943-01

642. Ncgc00163943-02

643. Ncgc00163943-03

644. Ncgc00163943-04

645. Ncgc00163943-05

646. Ncgc00163943-06

647. Ncgc00248792-01

648. Ncgc00254541-01

649. Ncgc00254855-01

650. Ncgc00256383-01

651. Ncgc00258230-01

652. Ncgc00259326-01

653. Ncgc00259618-01

654. Ncgc00259839-01

655. Ncgc00348372-01

656. Ncgc00357135-01

657. 119911-70-5

658. 55963-79-6

659. 6108-13-0

660. Ac-11679

661. Cas-319-84-6

662. Cas-319-86-8

663. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1.alpha.,2.beta.,3.alpha.,4.beta.,5.alpha.,6.beta.)-

664. Gammahexachlorcyclohexane [who-ip]

665. Sbi-0051430.p003

666. .delta.,2,3,4,5,6-hexachlorocyclohexane

667. Gamma Benzene Hexachloride [who-ip]

668. Lindane Related Compound A [usp-rs]

669. Lindane, Pestanal(r), Analytical Standard

670. (+/-)-.alpha.-hexachlorocyclohexane

671. (+/-)-.beta.-hexachlorocyclohexane

672. .alpha.-1,2,3,4,5,6-hexachlorcyclohexane

673. Cs-0450994

674. Ft-0603490

675. Ft-0606175

676. Ft-0647466

677. H0056

678. Hch (technical) 10 Microg/ml In Isooctane

679. Hch (technical) 100 Microg/ml In N-hexane

680. Wln: L6tj Ag Bg Cg Dg Eg Fg .delta.

681. 1,2,3,4,5,6-.gamma.-hexachlorocyclohexane

682. Alpha-hch, Pestanal(r), Analytical Standard

683. Beta-hch, Pestanal(r), Analytical Standard

684. Delta-hch, Pestanal(r), Analytical Standard

685. C06988

686. C07075

687. C18738

688. D00360

689. 1,2,3,4,5,6-hexachlorocyclohexane (.gamma.)

690. 1,3,4,5,6-hexachlorcyclohexane, .beta. Isomer

691. Ab00052031_02

692. Cyclohexane,2,3,4,5,6-hexachloro-, .delta.-

693. Delta-bhc, Vial Of 100 Mg, Analytical Standard

694. 1,3,4,5,6-hexachlorocyclohexane, .gamma. Isomer

695. Alpha-1,2,3,4,5,6-hexachlorocyclohexane, 99%

696. Cyclohexane, .alpha.-1,2,3,4,5,6-hexachloro-

697. Q282003

698. .beta.-1,2,3,4,5,6-hexachlorocyclohexane

699. .delta.-(aeeee)-1,3,4,5,6-hexachlorocyclohexane

700. 1,2,3,4,5,6-hexachlorocyclohexane (gamma-isomer)

701. Cyclohexane, 1,2,3,4,5,6-hexachloro-, .gamma.-

702. J-018587

703. J-018588

704. J-018589

705. Q6445839

706. Sr-05000001837-1

707. Sr-05000001837-4

708. .delta.-1,2,3,4,5,6-hexachlorocyclohexane

709. .epsilon.-1,2,3,4,5,6-hexachlorocyclohexane

710. Alpha-hch, Certified Reference Material, Tracecert(r)

711. Cyclohexane,2,3,4,5,6-hexachloro-, .delta.-isomer

712. Q10860138

713. Q23014122

714. Cyclohexane, 1,2,3,4,5,6-hexachloro-, .alpha.-isomer

715. (1r,2c,3c,4t,5c,6t)-1,2,3,4,5,6-hexachlorocyclohexane

716. (1r,2c,3t,4t,5c,6t)-1,2,3,4,5,6-hexachlorocyclohexane

717. (1s,2r,3r,4s,5s,6s)-1,2,3,4,5,6-hexachlorocyclohexane

718. Lindane, United States Pharmacopeia (usp) Reference Standard

719. Lindane, Pharmaceutical Secondary Standard; Certified Reference Material

720. (1.alpha.,3.alpha.,4.beta.,5.alpha.,6.beta.)-1,2,3,4,5,6-hexachlorocyclohexane

721. (1.alpha.,3.beta.,4.alpha.,5.alpha.,6.beta)-1,2,3,4,5,6-hexachlorocyclohexane

722. (1alpha,2alpha,3alpha,4alpha,5alpha,6alpha)-1,2,3,4,5,6-hexachlorocyclohexane

723. (1alpha,2alpha,3alpha,4alpha,5beta,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

724. (1alpha,2alpha,3beta,4beta,5alpha,6beta)-1,2,3,4,5,6-hexachlorocyclohexane

725. 1-.alpha.,2-.alpha.,3-.beta.,4-.alpha.,5-.beta.,6-.beta.-hexachlorocyclohexane

726. 1.alpha.,2.alpha.,3.beta.,4.alpha.,5.alpha.,6.beta.-hexachlorocyclohexane

727. Beta-hch Solution, 100 Mug/ml In Methanol, Pestanal(r), Analytical Standard

728. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3alpha,4alpha,5alpha,6alpha)-

729. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3alpha,4alpha,5beta,6beta)-

730. (1.alpha.,2.alpha.,3.beta.,4.alpha.,5.alpha.,6.beta.)-1,2,3,4,5,6-hexachlorocyclohexane

731. 1,2,3,4,5,6-hexachlorocyclohexane, (1.alpha.,2.alpha.,3.beta.,4.alpha.,5.beta.,6.beta.)-

732. Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1.alpha.,2.alpha.,3.alpha.,4.beta.,5.beta.,6.beta.)-

733. Cyclohexane,2,3,4,5,6-hexachloro-, (1.alpha.,2.alpha.,3.alpha.,4.beta.,5.alpha.,6.beta.)-

734. Hch, Pestanal(r), Analytical Standard, Mixture Of Isomers (alpha:beta:gamma:delta=1:1:1:1)

2.4 Create Date

2004-09-16

3 Chemical and Physical Properties

Molecular Formula	C₆H₆Cl₆
Molecular Weight	290.8 g/mol
XLogP3	3.8
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	0
Rotatable Bond Count	0
Exact Mass	289.857116 g/mol
Monoisotopic Mass	287.860066 g/mol
Topological Polar Surface Area	0 Å²
Heavy Atom Count	12
Formal Charge	0
Complexity	104
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Information

1 of 2
Drug Name	Lindane
PubMed Health	Lindane (On the skin)
Drug Classes	Pediculicide, Scabicide
Active Ingredient	Lindane
Dosage Form	Shampoo; Lotion
Route	Topical
Strength	1%
Market Status	Prescription
Company	Wockhardt; Olta Pharms

2 of 2
Drug Name	Lindane
PubMed Health	Lindane (On the skin)
Drug Classes	Pediculicide, Scabicide
Active Ingredient	Lindane
Dosage Form	Shampoo; Lotion
Route	Topical
Strength	1%
Market Status	Prescription
Company	Wockhardt; Olta Pharms

4.2 Therapeutic Uses

Insecticides

National Library of Medicine's Medical Subject Headings. Lindane. Online file (MeSH, 2016). Available from, as of December 7, 2016: https://www.nlm.nih.gov/mesh/2016/mesh_browser/MBrowser.html

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Lindane is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of February 1, 2017: https://clinicaltrials.gov/ct2/results?term=lindane&Search=Search

Lindane is used for the topical treatment of pediculosis capitis (head lice infestation) and pediculosis pubis (pubic lice infestation) and for the topical treatment of scabies.

American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016

MEDICATION: Pediculicide, scabicide

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1023

For more Therapeutic Uses (Complete) data for Lindane (6 total), please visit the HSDB record page.

NIH/NLM; ClinicalTrials.Gov. Available from, as of February 1, 2017: https://clinicaltrials.gov/ct2/results?term=HEXACHLOROCYCLOHEXANES&Search=Search

4.3 Drug Warning

Adverse CNS effects, including dizziness and seizures, have been reported with lindane. While seizures generally have been associated with ingestion or misuse of lindane, seizures and deaths rarely have been reported following a single application of lindane shampoo or lotion used according to the manufacturers' directions. Infants, children, geriatric patients, patients weighing less than 50 kg, and patients with certain other skin conditions may be at greater risk of serious neurotoxicity than other individuals. Although the relationship to lindane is unknown, headache, pain, and paresthesia have been reported with lindane shampoo or lotion.

American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016

Alopecia, dermatitis, pruritus, and urticaria have been reported in patients using lindane shampoo or lotion.

American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016

In patients with scabies or pediculosis, pruritus (caused by an acquired sensitivity to the ectoparasites and their products) frequently persists for one to several weeks following treatment with the drug; this reaction does not indicate treatment failure and is not an indication for further treatment. Oral antihistamines and/or topical corticosteroids may be used to help relieve pruritus.

American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016

Aplastic anemia has been reported with prolonged administration of lindane lotion. Inhalation of lindane vapors may produce headache, nausea, vomiting, and irritation of eyes, nose, and throat.

American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016

For more Drug Warnings (Complete) data for Lindane (17 total), please visit the HSDB record page.

4.4 Minimum/Potential Fatal Human Dose

Fatal oral dose: Adults: 28 g

Lelkin, J.B., Paloucek, F.P., Poisoning & Toxicology Compendium. LEXI-COMP Inc. & American Pharmaceutical Association, Hudson, OH 1998., p. 354

4.5 Drug Indication

For the treatment of patients infested with Sarcoptes scabiei or pediculosis capitis who have either failed to respond to adequate doses, or are intolerant of other approved therapies.

Used as a pancreatic enzyme replacement in pancreatic insufficiency. It is intended to mimic naturally produced human pepsin. Pepsin powder is prepared from the gastric mucosa of pigs, cattle or sheep. In the laboratory, it is primarily used for the unspecific hydrolysis of proteins and peptides in acidic media. In addition, it provides limited hydrolysis of native immunoglobulins, yielding biologically active fragments. In certain supplements, pepsin may be combined with betaine and HCl (hydrochloric acid) to aid in digestion in various gastrointestinal conditions,.

5 Pharmacology and Biochemistry

5.1 Pharmacology

Scabies is a common, highly pruritic infestation of the skin caused by Sarcoptes scabiei (lice). It is a very contagious condition with specific lesions, such as burrows, and nonspecific lesions, such as papules, vesicles and excoriations. The typical areas of the body it affects are finger webs, scalp (hair), wrists, axillary folds, abdomen, buttocks, inframammary folds and genitalia (males). It is characterized by intense night-time itching. Scabies is spread through close personal contact (relatives, sexual partners, schoolchildren, chronically ill patients and crowded communities). Scabies infestations and the corresponding symptoms can be eliminated by killing the scabies with topical insecticides or scabicides. Lindane is a scabicide that is essentially an organochloride insecticide.

Pepsin digests protein. It classified by the FDA that is characterizing enzyme activity is that of a peptide _hydrolase_.

5.2 ATC Code

A - Alimentary tract and metabolism

A09 - Digestives, incl. enzymes

A09A - Digestives, incl. enzymes

A09AA - Enzyme preparations

A09AA03 - Pepsin

P - Antiparasitic products, insecticides and repellents

P03 - Ectoparasiticides, incl. scabicides, insecticides and repellents

P03A - Ectoparasiticides, incl. scabicides

P03AB - Chlorine containing products

P03AB02 - Lindane

5.3 Absorption, Distribution and Excretion

Absorption

Lindane is absorbed significantly through the skin. A mean peak blood concentration of 28 nanograms per mL occurred in infants and children 6 hours after total body application of lindane lotion for scabies.

/MILK/ The present study was conducted to highlight the existing level of organochlorine-pesticides (OCPs) from human milk (n=45) and blood serum (n=40) of female workers who pick cotton in Khanewal District, southern Punjab, Pakistan. Source apportionment, congener-specific analysis, and risk surveillance of OCPs are reported from human milk and blood samples. Levels of OCPs in milk and blood serum samples ranged from 15.7 ppb to 538.3 ppb and from 16.4 ppb to 747.1 ppb, respectively, and were lower than previously published reports from other regions of the globe. Congener-specific analysis revealed that DDTs were predominant, followed by hexachlorocyclohexane, chlordane, and hexachlorobenzene. Calculated results for source apportionment analysis suggested that contamination load was a new input of DDTs as well as the historic use of lindane in the study area. Levels of OCPs in milk and blood serum were significantly (p<0.05) correlated with age, time period of picking cotton, and number of children. Health risk revealed that female workers had risk of cancer among 1 per million; however, noncarcinogenic risks were not considerable.

PMID:27684504 Yasmeen H et al; Environ Toxicol Chem doi: 10.1002/etc.3633 (Epub ahead of print) (2016)

A 1% lindane cream (Kwell) was applied to skin of 9 voluteers, left on for 12 hours and washed off with soap and water. Plasma concentratioin increased to 10.3 ng/mL (range 2-24 ng/mL).

PMID:6153210 Hosler J et al; J Invest Dermatol 74 (1): 51-3 (1980)

... Serum concentrations of lindane were determined in infants and children with and without scabies infection following application of 1% lindane lotion to the body surface area /for 24 hours instead of the maximum of 12 hours/ prescribed by the label. Studies were performed on 20 infected and noninfected patients who averaged 33 to 64 months of age ... Specimens of blood for determination of lindane concentrations were obtained at 0, 2, 4, 6, 8, 12, 24, and 48 hours after topical application of 1% lotion. The highest measured blood concentration from the clinical study was 0.064 ug/mL /at 6 hours/.

USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Lindane. p.19 September 25, 2002. Available from, as of December 8, 2016: https://www.epa.gov/pesticides/reregistration/status.htm

... Transplacental passage ... has been established ...

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V20 220 (1979)

For more Absorption, Distribution and Excretion (Complete) data for Lindane (22 total), please visit the HSDB record page.

Chronically, lindane is the least likely to bioaccumulate ... The alpha, beta, and delta isomers have a low degree of acute toxicity, but are retained in body tissues for a longer period than lindane.

Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 667

BHC is absorbed through all portals including the intact skin. ... In rats given BHC by mouth ... 80% /was/ absorbed when given as a solution in olive oil but only 6% absorbed when given as aqueous suspension. Highest concn were found in adipose tissue and lowest in blood and muscle. Peak values were reached in 2-5 days. By 2 wk after ip admin, 34% of dose was recovered in feces mostly unchanged and only 5% in urine.

Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-240

Trace amt of HCH have been detected in human milk and blood, and transplacental passage of HCH has been established.

/MILK/ Concentrations of < / = 4 ppm of BHC have been found in the milk of ewes after they were dipped with Entomoxan (0.5% BHC).

Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 668

For more Absorption, Distribution and Excretion (Complete) data for Hexachlorocyclohexanes (14 total), please visit the HSDB record page.

When single doses of (36)Cl-labelled alpha-HCH ... were given ip to rats at level of 200 mg/kg body weight ... approx 80% of total radioactivity was excreted in urine and 20% in feces. ... Pretreatment of rats with phenobarbital accelerated rate of excretion ...

In rats fed 800 mg/kg diet ... for 20 months, 3.5 mg/g ...were found in adipose tissue; levels in other tissues were lower by factor of 5-10. ... Upon cessation of dietary exposure ... /alpha isomer/ disappeared from fat depots within 3 wk. ... /It is/ stored in adipose tissue of dogs ... to lesser degree in liver.

ln feeding experiments with broiler breeder hens, the ratio of the level of HCH in the animal fat to the level in the feed was 1.8 for alpha-HCH ... . The ratio of the level of HCH in eggs to the level in the feed was 0.10 for alpha-HCH ... on a whole egg basis

In rats, 65% of ip dose of (14)C-alpha-HCH was excreted in urine and 16% in feces within 4 wk. ... Chlorothiophenols were also detected in urine, and proportion incr when animals were pretreatd with alpha-HCH.

For more Absorption, Distribution and Excretion (Complete) data for alpha-Hexachlorocyclohexane (15 total), please visit the HSDB record page.

When labelled beta-hexachlorocyclohexane was administered orally to female Sprague-Dawley rats, 80% was ... absorbed. ... Beta-HCH fed at 100 mg/kg diet for 20 months was stored to greater extent /than alpha- or delta-HCH/, the concentration in adipose tissue being 1.9 mg/g; brain contained 130 ug/g and liver only 20 ug/g. Upon cessation of dietary exposure ... it persisted in adipose tissue in small amt after 14 wk. ... It is stored to lesser degree in ... kidneys and adrenals ... .

In rats preadapted by feeding ... beta-hexachlorocyclohexane at dietary level of 10 ppm for 10 days and then given single oral dose of radioactive beta-BHC, total of 12.2 to 13.0% of radioactive material was recovered in urine and 5.4 to 5.8% in feces during 1st 10 days after ingestion.

Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 216

Experiments with alpha-, beta-, and gamma-hexachlorocyclohexane showed that the absorption rates of the isomers were approx equal. In 30-day feeding studies with rats, adipose tissue took up the alpha-HCH faster than beta-HCH, and much faster than gamma-HCH. Accumulation of beta-HCH in mammals is related to its low rate of metabolism and transport.

Macholz R; Nahrung 26 (9): 747-57 (1982)

The time at which beta-hexachlorocyclohexane reaches storage equilibrium in fat /of rats/ is not less than 8 weeks. In mice it reaches a constant level after 12 weeks of feeding at dietary levels less than 50 ppm. ... BHC is transferred by way of the placenta, but the rate is negligible. ... Only 1.6 to 2.2% of carbon-14 beta-BHC admin to pregnant mice was retained by the fetuses, while the dams retained 33.2 to 53.7%. ... /However,/ a high proportion of (carbon-14 beta-BHC admin to dams during lactation was secreted in ... milk so that at end of lactation the young retained 60.0 to 63.8% of total dose, while very little remained in the mothers.

Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 214

For more Absorption, Distribution and Excretion (Complete) data for beta-Hexachlorocyclohexane (19 total), please visit the HSDB record page.

In rats fed 800 mg/kg diet ... delta-HCH ... for 20 months ... 0.55 mg/kg ... was found in adipose tissue; levels in other tissues were lower by factor of 5-10. ... Upon cessation of dietary exposure ... it disappeared from fat depots within 3 weeks ...

Umbilical cord and venous blood samples were collected at the time of delivery from 52 mothers living in urban and rural areas of the Atoya River basin, Nicaragua ... /and/ analyzed for 13 organochlorine pesticides: 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (pp'-DDT); 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (pp'-DDE); pp'-dichlorophenyldichlorodiene (pp'-DDD); alpha-hexachlorocyclohexane (alpha-HCH); beta-hexachlorocyclohexane (beta-HCH); gamma-hexachlorocyclohexane (gamma-HCH); delta-hexachlorocyclohexane (delta-HCH); toxaphene; dieldrin; endrin; aldrin; heptachlor; and heptachlor epoxide. In venous blood only pp'-DDE (100% of samples), pp'-DDT (1.92%), dieldrin (15.38%), heptachlor (15.38%), gamma-HCH (7.69%), beta-HCH (11.53%), and delta-HCH (1.92%) were found, whereas in cord blood only pp'-DDE (100%), pp'-DDT (3.84%), dieldrin (19.23%), and heptachlor (9.16%), were found.

PMID:11453673 Dorea JG et al; Environ Res 86 (3): 229-37 (2001)

The accumulation of hexachlorocyclohexane, one of the most commonly used chlorinated insecticides, was studied in a high-risk group of people who are exposed during its manufacturing process. The serum HCH concentration was estimated by quantitating its alpha, beta, gamma, and delta-isomers with the help of GLC analysis. Exposed workers involved in maintenance work were found to have 3 times higher HCH residues than the controls, while in the plant operators and supervisors the levels were 5 times higher. The most severely exposed were the handlers who are in direct contact with the insecticide. The level of serum HCH residues in them was found to be about 12 times higher than those in the controls. The percentage composition of the insecticide, with respect to the different isomers, varied up to 20% for the gamma-isomer, up to 30% for alpha-isomer and had between 60%-100% of the beta-isomer in the samples. The serum levels of the insecticides were clearly related to the workers' job-related close contact, intensity, frequency, and the duration of their exposure. The total of HCH residues in the sera studied were in the range of 0.143-1.152 ppm. ...

PMID:2423460 Nigam SK et al; Int Arch Occup Environ Health 57: 315-20 (1986)

The chronic toxicity for isomers of BHC decreases in the order beta > alpha > gamma > delta and is directly related to their tissue retention, and inversely to rates of metabolism. This contrasts with the order of acute toxicities, which are in the decreasing order of gamma > alpha > delta > beta.

Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 668

... Chronically, lindane is the least likely to bioaccumulate ... The alpha, beta, and delta isomers have a low degree of acute toxicity, but are retained in body tissues for a longer period than lindane.

Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 667

5.4 Metabolism/Metabolites

Primarily hepatic through dechlorination leading to 2-chlorophenol, 0-chlorophenol, chlorocyclohexane, chlorocyclohexanol.

Pepsin is the first of several enzymes that digest proteins. In the stomach, polypeptide chains bind in the deep active site groove of pepsin, and are then digested into smaller pieces. Following this, a variety of proteases and peptidases in the intestine complete the process. The small fragments, which are amino acids and dipeptides, are then absorbed by cells for use as metabolic energy or construction of new proteins.

Metabolism of gamma-Hexachlorocyclohexane (HCH) was studied examining 21 workers producing this insecticide. Using gas chromatography in combination with ECD and mass spectrometry 14 mono-, di-, tri- and tetrachlorophenols were identified in the urine samples of the workers. Seven dihydroxychlorobenzenes of still unknown configuration were detected by mass spectrometry. Ten of the more abundant metabolites, di-, tri- and tetrachlorophenols were determined quantitatively in all urine samples. 2,4,6-; 2,3,5- and 2,4,5-trichlorophenol turned out to be the main metabolites of gamma-HCH. They were excreted in nearly equal quantities. ...

PMID:6192092 Angerer J et al; Int Arch Occup Environ Health 52 (1): 59-68 (1983)

The primary metabolites of lindane are chlorophenols and chlorobenzenes. Chlorinated metabolites in the urine have been found in lindane production workers. The major metabolite is trichlorophenol, which accounted for approximately 58% of lindane metabolites identified in the urine. Other metabolites are dichlorophenols, tetrachlorophenols, hexachlorobenzene, tetrachlorocyclohexanol, and pentachlorocyclohexene. Pentachlorophenol has also been identified as a urinary metabolite in humans after occupational exposure.

Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1065

Human liver microsomes metabolized lindane to 4 primary metabolites, gamma-1,2,3,4,5,6-hexachlorocyclohex-1-ene; gamma-1,3,4,5,6-pentachlorocyclohex-1-ene; beta-1,3,4,5,6-pentachlorocyclohex-1-ene; and 2,4,6-trichlorophenol. The secondary metabolites, 2,3,4,6-tetrachlorophenol and pentachlorobenzene were also formed.

PMID:6180560 Fitzloff JF et al; Xenobiotica 12 (3): 197-202 (1982)

In mice, urinary metabolites of single ip injection ... accounted for 57% of dose ... and consisted mostly of glucuronide and sulfate conjugates of 2,4,6-trichlorophenol and 2,4-dichlorophenol. No mercapturic acid conjugates were detected. When ... administered ip to rats, 2,3,5- and 2,4,5-trichlorophenol were identified in urine ... free or as conjugates with glucuronic and/or sulfuric acid. When weanling Sprague-Dawley rats were fed 400 mg/kg diet lindane, 3,4-dichlorophenol, 2,4,6-trichlorophenol, 2,3,4,5- and 2,3,4,6-tetrachlorophenol and 2,3,4,5,6-pentachloro-2-cyclohexene-1-ol were identified in urine. Pentachlorobenzene, 2,3,4,6- and 2,3,5,6-tetrachlorophenol and 2,4,6-trichlorophenol were excreted in urine of rats given oral doses ... pretreatment of rats with other organochlorine pesticides modified lindane metabolism.

For more Metabolism/Metabolites (Complete) data for Lindane (12 total), please visit the HSDB record page.

Mammalian biotransformation of BHC isomers involves formation of chlorophenols (trichlorophenol, tetrachlorophenol and pentachlorophenol), which are excreted free and as conjugates of sulfuric and glucuronic acids.

National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 585

The primary urinary metabolites are chlorophenols and 1,1,4-trichlorocyclohexane-4,5-epoxide. The conversion occurs mainly by the action of hepatic enzymes.

DHHS/ATSDR; Toxicological Profile for alpha-, beta-, gamma-, and delta-Hexachlorocyclohexane p. 115 PB2006-100003 (August 2005). Available from, as of December 8, 2016: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=754&tid=138

...The urine of occupationally exposed workers (apparently to technical-grade HCH in manufacturing processes), /was analyzed and found to contain/, apart from alpha-, beta-, gamma-, and delta-HCH, traces of hexa- and pentachlorobenzene, gamma- and delta-pentachlorocyclohexane, pentachlorophenol, 2,3,4,5-, 2,3,4,6-, and 2,3,5,6-tetrachlorophenol, and several trichlorophenols, as well as the glucuronides of several of these metabolites. The pentachlorocyclohexenes, tetrachlorophenol, hexachlorobenzene, and pentachlorophenol were also identified in the blood.

WHO; Environ Health Criteria 123: alpha and beta-Hexachlorocyclohexanes (1991). Available from, as of March 28, 2017: https://www.inchem.org/documents/ehc/ehc/ehc123.htm

Conjugated 2,4,6-trichlorophenol was major urinary metabolite /of alpha-HCH/ ...

Sphingomonas paucimobilis B90A is able to degrade the alpha-, beta-, gamma-, and delta-isomers of hexachlorocyclohexane (HCH). It contains the genes linA, linB, linC, linD, linE, and linR, which have been implicated in HCH degradation. In this study, dynamic expression of the lin genes was measured in chemostat-grown S. paucimobilis B90A by RNA dot blot hybridization and real-time reverse transcriptase PCR upon exposure to a pulse of different HCH isomers. Irrespective of the addition of HCH, linA, linB, and linC were all expressed constitutively. In contrast, linD and linE were induced with alpha-HCH (2 mg/liter) and gamma-HCH (7 mg/liter). A sharp increase in mRNA levels for linD and linE was observed from 10 to 45 min after the addition of alpha- or gamma-HCH. Induction of linD and linE was not detectable upon the addition of 0.7 mg of gamma-HCH per liter, although the compound was degraded by the cells. The addition of beta-HCH (5 mg/liter) or delta-HCH (20 mg/liter) did not lead to linE and linD induction, despite the fact that 50% of the compounds were degraded. This suggests that degradation of beta- and delta-HCH proceeds by a different pathway than that of alpha- and gamma-HCH.

PMID:15528530 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC525160 Suar M et al; Appl Environ Microbiol 70 (11): 6650-6 (2004)

Perdeuterated analogs were used in the study of the in vivo and in vitro metabolism of ... alpha-hexachlorocyclohexane ... In vivo, the rate of disappearance from depot fat, the major body store of HCH, was markedly slowed by perdeuteration in the case of alpha-HCH (H/D 6.3).

Portig J; Pestic Chem: Hum Welfare Environ, Proc Int Congr Pestic Chem, 5th 3: 401-405 (1983)

When alpha-hexachlorocyclohexane was applied to plants, the level of beta-HCH on the plants was shown to increase, showing transformation of alpha-HCH to beta-HCH.

Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 77

For more Metabolism/Metabolites (Complete) data for alpha-Hexachlorocyclohexane (6 total), please visit the HSDB record page.

... /In rats/ 2,4,6-trichlorophenol is a ... metabolite ... of ... beta-hexachlorocyclohexane. Pathway favored ... is by way of hydroxylation of 1,3,5-trichlorobenzene, one of products of dehydrochlorination ... an alternative pathway /is proposed/ involving direct hydroxylation ... to alpha-chlorohydrins, which, following rapid, spontaneous loss of HCL yielded one of the isomers of pentachlorocyclohexanone; loss therefrom of two molecules of HCL led directly to 2,4,6-trichlorophenol. ... /Also it is an/ in vitro metabolite of ... beta-HCH in rat-liver microsomes ... the reaction is oxidative and catalyzed by cytochrome p450.

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979., p. 463

In rats fed 600-3000 mg/kg beta hexachlorocyclohexane the following metabolites were identified in urine, liver, and kidney: 2,3,5-trichloroanisole, 2,3,6-trichloroanisole, 3,4,5-trichloroanisole, 2,3,4,6-tetrachloroanisole, 2,3,4,5-tetrachloroanisole, 2,4,6-trichlorophenol, 2,3,5-trichlorophenol, 2,3,6-trichlorophenol, 2,4,5-trichlorophenol, 3,4,5-trichlorophenol, & 2,3,4-trichlorophenol.

PMID:6180701 Macholz RM et al; Arch Toxicol 50 (1): 85-8 (1982)

... /In rats/ 2,4,6-trichlorophenol is ... metabolite ... of ... delta-hexachlorocyclohexane. Pathway favored ... for formation ... /is/ by way of hydroxylation of 1,3,5-trichlorobenzene, one of products of dehydrochlorination ... an alternative pathway /is proposed/ involving direct hydroxylation ... to alpha-chlorohydrins, which, following rapid, spontaneous loss of HCl yielded one of the isomers of pentachlorocyclohexanone; loss therefrom of two mols of HCl led directly to 2,4,6-trichlorophenol.

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979., p. 463

... 2,4,6-Trichlorophenol is /an/ ... in vitro metabolite of ... delta-HCH in rat-liver microsomes ... the reaction is oxidative and catalyzed by cytochrome p450. ...Purification of ... /glutathione-dependent/ dechlorinating enzyme from rat-liver cytosol has been achieved.

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979., p. 463

d-Hexachlorocyclohexane (d-HCH), one of the prevalent isomers of technical HCH, was enantioselectively dehydrochlorinated by the dehydrochlorinases LinA1 and LinA2 from Sphingobium indicum B90A to the very same d-pentachlorocyclohexene enantiomer. Racemic d-pentachlorocyclohexene, however, was transformed with opposite enantioselectivities by the two enzymes. A transformation pathway based on an anti-1,2-elimination, followed by a syn-1,4-elimination and a subsequent syn-1,2-elimination is postulated.

PMID:23872559 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811360 Geueke B et al; Appl Environ Microbiol 79 (19): 6180-3 (2013)

5.5 Biological Half-Life

18 hours

Gamma-HCH (Lindane) is rapidly metabolized; beta-HCH has been detected in serum 10-15 years after exposure; [TDR, p. 753]

TDR - Ryan RP, Terry CE, Leffingwell SS (eds). Toxicology Desk Reference: The Toxic Exposure and Medical Monitoring Index, 5th Ed. Washington DC: Taylor & Francis, 1999., p. 753

Half-life: Children: 17-22 hours

Lelkin, J.B., Paloucek, F.P., Poisoning & Toxicology Compendium. LEXI-COMP Inc. & American Pharmaceutical Association, Hudson, OH 1998., p. 353

The elimination half-life of lindane is 21 hours in adults.

Goldfrank, L.R., Goldfrank's Toxicologic Emergencies 9th Ed. 2011., McGraw-Hill, New York, N.Y., p. 1479

The half-life of lindane in blood is approximately 18 hours.

American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016

... We present a case of a massive suicidal ingestion of lindane in which the patient survived the ingestion, though he did expire shortly thereafter from an unrelated cause pre-discharge. Pharmacokinetic analysis of serum lindane concentrations was performed with Phoenix WinNONLIN. The estimated distribution half-life for lindane was 10.3 hr, and the terminal half-life was 162.9 hr ... .

PMID:24805102 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371023 Wiles DA et al; J Med Toxicol 11 (1): 106-9 (2015)

For more Biological Half-Life (Complete) data for Lindane (6 total), please visit the HSDB record page.

The half-life for the clearance of alpha-HCH from depot fat was found to be 6.9 days in female rats and 1.6 days in male rats. ...After a single oral dose of 200 mg/kg body weight /to Wistar rats/, the approximate half-life in females for the elimination from brain was 6 days.

WHO; Environ Health Criteria 123: alpha and beta-Hexachlorocyclohexanes p.46 (1991). Available from, as of June 8, 2006: https://www.inchem.org/documents/ehc/ehc/ehc123.htm

... After administration of a single oral dose of 200 mg/kg bw /beta-HCH to Wistar rats/; the approximate half-life for elimination from the brain was 20 days in females.

WHO; Environ Health Criteria 123: alpha and beta-Hexachlorocyclohexanes p. 109 (1991). Available from, as of March 30, 2017: https://www.inchem.org/documents/ehc/ehc/ehc123.htm

...The absorption of beta-HCH from the gastrointestinal tract in mice was 80-95%, most of this being accumulated in adipose tissue. The elimination followed a 2-stage mechanism, the half-life for the first stage being 2.5 days and that for the second stage being 18 days. The half-life for clearance from blood in rats (sex not specified) was 1 month, and the half-life for clearance from fat was 14 days in male rats and 28 days in female rats. ...A half-life for clearance from "internal organs" of 22 days in female rats /was reported/. A half-life of 20 days for the clearance from the brain of female rats was reported. In cows the half-life for clearance from fat was 4.2-22.0 weeks. The elimination in humans was slow after continuous exposure ceased, the concentration in fatty tissues decreasing only slightly over several years.

WHO; Environ Health Criteria 123: alpha and beta-Hexachlorocyclohexanes p. 97 (1991). Available from, as of March 30, 2017: https://www.inchem.org/documents/ehc/ehc/ehc123.htm

5.6 Mechanism of Action

Lindane is an organochloride insecticide that has similar neurotoxic protperties to DDT. It exerts its parasiticidal action by being directly absorbed through the parasite's exoskeleton (primarily lice, or scabies) and their ova. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for lindane, and other insecticides such as endosulfan, and fipronil. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system. This results in paralysis, convulsions, and death. Lindane has very low ovicidal activity.

Glands present in the mucous membrane lining of the stomach produce and store an inactive protein named _pepsinogen_. Impulses from the vagus nerve and the hormonal secretions of the hormones _gastrin_ and _secretin_ promote the release of pepsinogen into the stomach, where it is mixed with hydrochloric acid and quickly converted to the active enzyme _pepsin_. The digestive potency of pepsin is highest at the acidic pH of normal gastric juice. In the intestine, the gastric acids are then neutralized, and pepsin is no longer effective. Pepsin, the proteolytic enzyme of the stomach is normally responsible for less than 20% of the protein digestion occuring the gastrointestinal tract. It is an endopeptidase enzyme that metabolizes proteins to peptides. It preferentially hydrolyzes peptide linkages where one of the amino acids is aromatic. Pepsin, like other protease enzymes, is produced from an inactive precursor, _pepsinogen_, which is stored in granule form in the chief cells of the stomach and are released by a process called _exocytosis_. In the digestive tract, pepsin activity only contributes to the partial breakdown of proteins into smaller units called peptides, which then either are absorbed from the intestine into the bloodstream or are broken down further by pancreatic enzymes.

gamma-HCH interacts with cellular membranes and may produce several generalized cytotoxic effects associated with impaired membrane function. In rat renal cortical tubules, glucose uptake and cyclic AMP accumulation were altered by gamma-HCH treatment. Transport of D-galactose and L-leucine across enterocytes was decreased in chickens injected daily with gamma-HCH for 7 days. Rats exposed orally to 5 mg/kg/day technical-grade HCH 5 days/week, for 3-6 months, exhibited significantly decreased levels of phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate in the erythrocyte membrane and cerebrum. An in vitro study showed that gamma-HCH altered the action potential and transmembrane currents in frog heart (atrial) myocytes. gamma-HCH also has been shown to block gap junctional intercellular communication in Sertoli cells by inducing the aberrant endocytosis of Connexin 43 and zonula occludens-1 within Rab5 positive endosomes via the activation of the extracellular signal-regulated kinases. Inhibition of intercellular communication could potentially lead to uncontrolled cell growth and tumor promotion. gamma-HCH inhibited gap junction and intercellular communication in myometrial cell cultures isolated from rats on gestation day 10 by creating an oxidative stress environment. gamma-HCH also inhibited spontaneous phasic contractions in late gestation rat uterus.

DHHS/ATSDR; Toxicological Profile for alpha-, beta-, gamma-, and delta-Hexachlorocyclohexane p.136 PB2006-100003 (August 2005). Available from, as of December 8, 2016: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=754&tid=138

Oxidative stress in the liver has been suggested as a mechanism of gamma-HCH-induced hepatotoxicity. This condition is characterized in the rat liver by a reduction in hepatic glutathione content, lipid peroxidation, the microsomal generation of superoxide radical coupled to cytochrome P-450 induction, and a decrement in superoxide dismutase and catalase activity. Dose-dependent inhibition of intercellular communication in cultured rat hepatocytes, with subsequent reversal by addition of vitamin E or superoxide dismutase, indicates oxidative stress as a hepatotoxic mechanism. Species differences exist in the activities of hepatic metabolizing enzymes, and it has been demonstrated that gamma-HCH at a dose of 10 mg/kg/day for 6 days increased the hepatic cytochrome P-450 as well as glutathione-S-transferase in the rat, but not in the rabbit or monkey. Thus, oxidative stress and hepatotoxicity are produced with gamma-HCH treatment in rats, but not in the rabbit and monkey. Inhibition of Mg2+-ATPase activity has also been observed in rat liver tissue, suggesting an ATPase enzyme sensitivity to the action of gamma-HCH. The researchers suggested that some toxic effects appearing in mammals as a result of gamma-HCH exposure may arise from its influence on this ATPase activity. An in vitro study in mammalian CHO-K1 cells indicated that both gamma-HCH and an unspecified HCH isomer mixture induced glutathione peroxidase and glutathione reductase activities as a defense mechanism against oxidative stress.

DHHS/ATSDR; Toxicological Profile for alpha-, beta-, gamma-, and delta-Hexachlorocyclohexane p.137 PB2006-100003 (August 2005). Available from, as of December 8, 2016: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=754&tid=138

In rat cortical neurons, expression of the protooncogene c-fos, which is associated with seizure activity and is induced by elevated intracellular calcium levels, was increased by gamma-HCH treatment but decreased by delta-HCH treatment. Treatment-related changes in c-fos expression suggested that gamma-HCH induces seizures through the activation of calcium channels, while inhibition of calcium channels by delta-HCH results in anticonvulsant effects. ...In a study on the cytotoxic action of delta-HCH and gamma-HCH in cultured rat cerebellar granule neurons, both isomers were found to induce an increase in the free intracellular Ca2+ concentration. ...delta-HCH may exert its action by stimulating a large influx of Ca2+. delta-HCH was found to be more potent and active as a cytotoxic agent then gamma-HCH, and the differences in cytotoxicity and neurotoxic action may be related to their action on the different Ca2+ pools. Other suggestive data concerning mechanisms by which HCH causes neurological effects in animals include enhanced synaptic activity, altered GABA functional activity, and inhibition of, or oxidative damage to Na+- K+-ATPase activity. In general, the mechanism of toxicity of HCH on the nervous system appears to be similar to those of other neurotoxic organochlorine insecticides.

Several isomers of hexachlorocyclohexanes (HCHs) have been shown to be toxic to mammals. Previous studies have revealed that the delta isomer (delta-HCH) was particularly potent toward disrupting Ca2+ homeostasis in a variety of excitable and nonexcitable cells and altering contractility of cardiac muscle. The effects of the delta and gamma isomers of HCH were further investigated on isolated ventricular myocytes from guinea pig and on single cardiac ryanodine receptor (RyR2) Ca2+-release channels from cardiac SR vesicles. Intracellular Ca2+ transients were examined in electrically stimulated cells using the fluorescent dye indo-1, and twitch contractions of myocytes were analyzed using a video-based edge motion detection system. Exposure of myocytes to delta- but not gamma-HCH depressed the peak of intracellular Ca2+ transients and prolonged recovery time. These effects were correlated with the ability of delta-HCH to inhibit the binding of [3H]ryanodine, a conformationally sensitive probe for RyR2 function, to SR preparations (IC50 = 2 and 18 uM for high- and low-affinity interactions, respectively). Measurements of single-channel gating kinetics under voltage-clamp provided direct evidence of a potent isoform-selective activation of RyR2 by delta-HCH. Results from these studies revealed that delta-HCH alters Ca2+ homeostasis and contractility in cardiac myocytes and that the mechanism can be ascribed, at least in part, to a direct interaction with the RyR2 channel complex.

PMID:10087040 Buck ED et al; J Pharmacol Exp Ther 289 (1): 477-85 (1999)

Patch clamp experiments using rat dorsal root ganglia (DRG) neurons showed differential actions of the 4 HCH isomers. Gamma-HCH had a weak potentiating action and a strong inhibitory action on gamma-aminobutyric acid (GABA)-induced currents. Delta-HCH had a strong potentiating action and an inhibitory action. Alpha-HCH and Beta-HCH had little or no effect on GABA-induced currents. The differential modulation of GABA response by HCH isomers accounts for variable symptoms of poisoning in insects and mammals. However, somewhat different results were obtained for the effects of HCH isomers on the alpha 1-beta 3-gamma 2S (short splice variants of the gamma 2 subunit) and alpha 6-beta 3-gamma 2S subunit combinations of GABA-A receptors expressed in Xenopus oocytes. GABA responses were inhibited by gamma-HCH, potentiated by alpha- and delta-HCH, and not affected by beta-HCH. Furthermore, the alpha subunit composition had no influence on these effects of HCH isomers. These differences in the responses to chemicals represent an example of the dissimilarity between native receptors and receptors expressed in xenopus oocytes which is often encountered.

Krieger, R. (ed.). Handbook of Pesticide Toxicology. Volume 1, 2nd ed. 2001. Academic Press, San Diego, California., p. 343

Gamma-aminobutyric acid-induced (36)Cl(-) flux /into membrane microsacs/ was inhibited by several cyclodienes and gamma-BHC with the following order of decreasing potency: endosulfan I > endrin I > endosulfan II > dieldrin > heptachlor epoxide > gamma-BHC > heptachlor. The non-insecticidal beta-BHC had no effect, while the IC50 (concn of insecticide that inhibits 50% of the binding of 2 nM (35)S-tert-butylbicyclophosphorothionate to rat brain membranes) values for gamma-BHC and alpha-BHC were 1 and 0.2 uM, respectively.

PMID:3009836 Abalis IM et al; J Toxicol Environ Health 18 (1): 13-23 (1986)

Alpha-hexachlorocyclohexane (alpha-HCH) is one of eight structural isomers that have been used worldwide as insecticides. Although no longer produced or used agriculturally in the United States, exposure to HCH isomers is of continuing concern due to legacy usage and persistence in the environment. The U.S. Environmental Protection Agency (EPA) classifies alpha-HCH as a probable human carcinogen and provides a slope factor of 6.3 (mg/kg-day)(-1) for the compound, based on hepatic nodules and hepatocellular carcinomas observed in male mice and derived using a default linear approach for modeling carcinogens. EPA's evaluation, last updated in 1993, does not consider more recently available guidance that allows for the incorporation of mode of action (MOA) for determining a compound's dose-response. Contrary to the linear approach assumed by EPA, the available data indicate that alpha-HCH exhibits carcinogenicity via an MOA that yields a nonlinear, threshold dose-response. In our analysis, we conducted an MOA evaluation and dose-response analysis for alpha-HCH-induced liver carcinogenesis. We concluded that alpha-HCH causes liver tumors in rats and mice through an MOA involving increased promotion of cell growth, or mitogenesis.

PMID:26713892 Bradley AE et al; Regul Toxicol Pharmacol 76: 152-73 (2016)

The mechanisms of tumor promotion in liver by various xenobiotics of diverse structure are not well understood. However, these tumor promoters share the ability to exert growth-stimulatory effects on hepatocytes. Our laboratory has been utilizing normal rat hepatocytes under defined conditions of primary cultures, to investigate growth-stimulatory actions of liver tumor promoters. We have shown that most, if not all, of the liver tumor promoters tested stimulate hepatocyte DNA synthesis when added in combination with epidermal growth factor (EGF), insulin, and glucocorticoids. In the present study, /the authors/ sought evidence for the role of the Na(+)/H(+) antiporter and cytoplasmic alkalinization in the direct growth-stimulatory actions of tumor promoters on hepatocytes. Hepatocytes cultured under conditions (bicarbonate-buffered medium) where intracellular pH (pH(i)) was independent of extracellular pH (pH(e)), EGF- and insulin-stimulated rates of DNA synthesis were unaffected by modest changes in pH(e). However, under conditions (HEPES-buffered medium) where pH(i) varied in a linear fashion with pH(e), rates of EGF- and insulin-stimulated DNA synthesis were highly dependent on pH(e). Similarly, 12-O-tetradecanoylphorbol-13-acetate (TPA) and alpha-hexachlorocyclohexane (HCH)-stimulated DNA synthesis were pH(e)-dependent but were stimulatory over different pH(e) ranges, suggesting that these promoters may act by distinct mechanisms. Chemicals that are capable of inducing rapid cytoplasmic alkalinization, ammonium chloride (1 and 15 mM) and monensin (0.5 microM), were found to stimulate hepatocyte DNA synthesis. The role of the Na(+)/H(+) antiport in controlling pH(i) of hepatocytes was demonstrated by artificially acidifying 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl (BCECF)-loaded isolated hepatocytes with 20 mM sodium acetate and the use of specific inhibitors. Amiloride and its analogues inhibited pH(i) recovery from the acid load in a dose dependent manner and the relative potency of these inhibitors paralleled their K(i) values for the Na(+)/H(+) antiport. At concentrations that stimulate hepatocyte DNA synthesis, some liver tumor promoters phenobarbital (PB) and HCH, were found to cause a rapid rise pH(i) in isolated hepatocytes which was sensitive to amiloride and its analogues. Taken together, our data suggest that activation of Na(+)/H(+) antiport activity may be one mechanism whereby some liver tumor promoters stimulate hepatocytes DNA synthesis.

PMID:12599209 Lee CH et al; J Cell Physiol 195 (1): 61-9 (2003)

Krieger, R. (ed.). Handbook of Pesticide Toxicology. Volume 1, 2nd ed. 2001. Academic Press, San Diego, California., p. 343

/Delta-HCH causes/ sustained elevation of cytosolic Ca+2 /by acting as a/ ryanodine receptor activator /and/ inducing Ca+2 influx into cytoplasm from the endoplasmic reticulum. /From table/

Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 60

Delta-HCH altered calcium homeostasis and contractility of cardiac myocytes through interaction with ryanodine receptors. Delta-HCH also induced a profound increase in ionic permeability in lipid bilayers, and the calcium-dependent current produced by delta-HCH was selective for mono-valent cations (K+ >> Cs+ > Na+).

Krieger, R. (ed.). Handbook of Pesticide Toxicology. Volume 1, 2nd ed. 2001. Academic Press, San Diego, California., p. 344

Krieger, R. (ed.). Handbook of Pesticide Toxicology. Volume 1, 2nd ed. 2001. Academic Press, San Diego, California., p. 343

delta-Hexachlorocyclohexane (delta-HCH) interacts with cardiac ryanodine-sensitive Ca2+ channels (RyR2), accounting in part for altered Ca2+ transients and contractility. Analysis of channel gating kinetics in the presence of delta-HCH also revealed a nonfluctuating membrane current that remained even after RyR2 channels were blocked. /The authors/ further elucidated the nature of a direct interaction between delta-HCH and biological membranes by measuring ionic currents across planar lipid bilayers made from defined lipids lacking cellular protein using voltage-clamp. Dimethyl sulfoxide, in the presence or absence of 50 uM ... delta-HCH, produced negligible steady-state current with symmetric 100 mM CsCl in the range of +/-50 mV. However, the addition of 50 uM Ca2+ to the bilayer chamber in the presence of delta-HCH induced a profound increase in ionic permeability ... . Significantly, the permeability increase 1) was proportional with increasing Ca2+ to approximately 600 uM and saturated between 1 and 2 mM Ca2+ regardless of holding potential, 2) occurred only when delta-HCH and Ca2+ were added to the same side of the membrane, and 3) was independent of the order of addition or of the side of the membrane to which delta-HCH and Ca2+ was added. The Ca2+-dependent current produced by delta-HCH was highly selective for monovalent cations (K+ >> Cs+ > Na+), with negligible conductance for Ca2+ or Cl-. In symmetric 100 mM K+, the conductance induced with 50 uM concentration each of delta-HCH and Ca2+ was 4.25 pA/mV. The results show that delta-HCH increases the ionic permeability of phospholipid membranes by two distinct Ca2+-dependent mechanisms: one mediated through RyR and the other mediated by a unique ionophore activity.

PMID:10087041 Buck ED, Pessah IN; J Pharmacol Exp Ther 289 (1): 486-93 (1999)

PMID:10087040 Buck ED et al; J Pharmacol Exp Ther 289 (1): 477-85 (1999)