Benzene-induced cancers: abridged history and occupational health impact.
Benzene-induced cancer in humans was first reported in the late 1920s. Carcinogenesis findings in animals were not reported conclusively until 1979. Industry exploited this "discrepancy" to discredit the use of animal bioassays as surrogates for human exposure experience. The cardinal reason for the delay between first recognizing leukemia in humans and sought-after neoplasia in animals centers on poor design and conduct of experimental studies. The first evidence of carcinogenicity in animals manifested as malignant tumors of the zymbal glands (sebaceous glands in the ear canal) of rats, and industry attempted to discount this as being irrelevant to humans, as this organ is vestigial and not present per se in humans. Nonetheless, shortly thereafter benzene was shown to be carcinogenic to multiple organ sites in both sexes of multiple strains and multiple species of laboratory animals exposed via various routes. This paper presents a condensed history of the benzene bioassay story with mention of benzene-associated human cancers.
Huff
James
J
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27514, USA. huff1@niehs.nih.gov
D000818:Animals; D001554:Benzene / Q000266:history* / Q000633:toxicity; D001555:Benzene Derivatives / Q000266:history* / Q000633:toxicity; D001681:Biological Assay; D002274:Carcinogens, Environmental / Q000266:history* / Q000633:toxicity; D049673:History, 20th Century; D006801:Humans; D007221:Industry / Q000266:history; D009369:Neoplasms / Q000139:chemically induced / Q000266:history*; D009784:Occupational Diseases / Q000453:epidemiology / Q000266:history; D016273:Occupational Exposure / Q000009:adverse effects / Q000266:history; D016272:Occupational Health / Q000266:history*
D001555:Benzene Derivatives; D002274:Carcinogens, Environmental; D001554:Benzene
Am J Ind Med. 1985;7(5-6):403-13
3890530
Jpn J Cancer Res. 1990 Mar;81(3):207-12
2112522
Ann N Y Acad Sci. 1988;534:1-30
3291703
Prog Clin Biol Res. 1996;394:77-102
8778812
Food Chem Toxicol. 1992 Sep;30(9):737-47
1365401
Med Lav. 1982 Jul-Aug;73(4):446-50
7177032
Scand J Work Environ Health. 1992;18 Suppl 1:31-7
1411375
Ann N Y Acad Sci. 2002 Dec;982:198-207
12562638
IARC Monogr Eval Carcinog Risks Hum. 1999;71 Pt 2:433-51
10476456
Mutat Res. 1997 Jan 3;373(1):113-23
9015160
Scand J Work Environ Health. 1992;18 Suppl 1:74-82
1411383
Environ Health Perspect. 1979 Oct;32:297-300
120250
IARC Sci Publ. 1979;(25):179-89
457152
Scand J Work Environ Health. 1992;18 Suppl 1:83-9
1411384
Environ Health Perspect. 1995 Jul-Aug;103(7-8):680-3
7588478
IARC Sci Publ. 1990;(104):233-9
2228121
Prog Clin Biol Res. 1984;141:347-63
6326159
Environ Health Perspect. 1996 Dec;104(12):1264-1267
10736606
EMBO Rep. 2007 Apr;8(4):309-15
17401403
Am J Ind Med. 2004 Feb;45(2):222-3; author reply 224-5
14748054
Am J Ind Med. 1985;7(5-6):415-46
4003403
Ann Epidemiol. 2003 Aug;13(7):485-94
12932623
Cancer. 1988 Aug 1;62(3):635-44
3164642
Toxicol Ind Health. 1989 Oct;5(5):699-730
2815102
IARC Monogr Eval Carcinog Risks Hum. 1999;71 Pt 2:749-68
10476471
Annu Rev Pharmacol Toxicol. 1991;31:621-52
2064387
Ren Fail. 1991;13(4):211-25
1780490
Toxicol Ind Health. 1995 Mar-Apr;11(2):119-49
7491630
Toxicol Appl Pharmacol. 2003 Jan 1;186(1):7-17
12583988
Environ Health Perspect. 1995 Sep;103 Suppl 6:173-5
8549469
Annu Rev Pharmacol Toxicol. 1979;19:511-30
378109
Int J Occup Environ Health. 2006 Jul-Sep;12(3):268-72
16967835
Environ Health Perspect. 1996 Oct;104 Suppl 5:1105-12
8933061
Int J Occup Environ Health. 2002 Jul-Sep;8(3):284-6
12358086
Natl Toxicol Program Tech Rep Ser. 1980 Aug;203:1-123
12778176
Natl Toxicol Program Tech Rep Ser. 1986 Apr;289:1-277
12748714
Am J Ind Med. 1995 Feb;27(2):293-300
7755018
Cancer Metastasis Rev. 1989 Jun;8(1):1-22
2667783
Environ Health Perspect. 1987 Oct;74:229-35
3691430
IARC Monogr Eval Carcinog Risks Hum. 2006;88:1-478
17366697
Environ Health Perspect. 1993 Apr;100:201-10
8354167
Environ Health Perspect. 2002 Dec;110(12):A736-7; author reply A737-9
12460809
Mutat Res. 2004 Mar;566(2):99-130
15164977
Toxicology. 2004 Apr 15;197(2):185-7
15003328
Am J Ind Med. 1996 Mar;29(3):227-35
8833775
Science. 1985 Feb 1;227(4686):548-9
3966163
Environ Health Perspect. 1996 Dec;104 Suppl 6:1339-41
9118917
Occup Environ Med. 1998 Oct;55(10):705-11
9930093
Environ Health Perspect. 1989 Jul;82:125-63
2676495
Ann N Y Acad Sci. 2006 Sep;1076:80-9
17119194
Ann N Y Acad Sci. 1997 Dec 26;837:15-52
9472329
Carcinogenesis. 1993 Mar;14(3):525-9
8453730
Am J Public Health. 2005;95 Suppl 1:S30-4
16030335
Ann N Y Acad Sci. 1997 Dec 26;837:77-95
9472331
Toxicol Pathol. 2001 Mar-Apr;29(2):180-6
11421485
Ann N Y Acad Sci. 1976;271:49-57
1069539
Environ Health Perspect. 2005 Mar;113(3):A152
15743701
IARC Sci Publ. 1992;(116):437-75
1428093
Mutat Res. 2000 Apr;462(2-3):407-21
11523541
Chem Res Toxicol. 2001 Jan;14(1):25-33
11170505
Drug Metab Rev. 2000 May;32(2):129-37
10774769
Environ Health Perspect. 2003 Apr;111(4):A203-4
12676636
Environ Health Perspect. 1993 Dec;101 Suppl 5:149-51
8013403
Public Health Rep. 2002 Nov-Dec;117(6):493-7
12576528
Toxicol Ind Health. 1993 May-Jun;9(3):415-38
8367884
Chem Biol Interact. 2005 May 30;153-154:129-35
15935809
Annu Rev Public Health. 1987;8:355-85
3555527
Int J Occup Med Environ Health. 2004;17(1):35-41
15212204
Natl Toxicol Program Tech Rep Ser. 1989 Oct;366:1-248
12692638
IARC Monogr Eval Carcinog Risks Hum. 1999;71 Pt 2:691-719
10476468
J Natl Cancer Inst. 1997 Jul 16;89(14):1065-71
9230889
Mol Carcinog. 1993;7(3):135-8
8489710
FASEB J. 2001 Jan;15(1):195-203
11149907
Mod Pathol. 1996 Jun;9(6):606
8782195
Med Lav. 1979 Sep-Oct;70(5):352-7
554913
IARC Sci Publ. 1999;(150):75-88
10626210
Environ Health Perspect. 1989 Jul;82:109-24
2792037
Epidemiology. 2003 Sep;14(5):569-77
14501272
Environ Health Perspect. 2006 Nov;114(11):A632-3
17107829
Int J Occup Environ Health. 2007 Jan-Mar;13(1):107-17
17427355
Toxicol Sci. 2000 May;55(1):17-23
10788555
IARC Monogr Eval Carcinog Risk Chem Hum. 1982 May;29:93-148
6957390
Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12233-7
7991611
Cancer Res. 1990 Oct 15;50(20):6592-9
2208121
FASEB J. 1992 Jun;6(9):2698-706
1612294
Fundam Appl Toxicol. 1993 May;20(4):413-36
8314458
Scand J Work Environ Health. 2005 Jun;31(3):227-32
15999576
Ann N Y Acad Sci. 2002 Dec;982:26-45
12562627
Cancer Res. 1995 Sep 1;55(17):3759-62
7641190
Toxicology. 2004 May 20;198(1-3):31-8
15138027
Am J Ind Med. 1980;1(2):233-43
7044110
Ann N Y Acad Sci. 2006 Sep;1076:1-14
17119190
Ann N Y Acad Sci. 2002 Dec;982:208-30
12562639
Lancet. 1977 Jul 9;2(8028):76-8
69157
Ann N Y Acad Sci. 1988;534:78-83
3291727
Carcinogenesis. 2004 Jan;25(1):133-41
14514661
Ann N Y Acad Sci. 1988;534:427-40
3389672
Environ Health Perspect. 1993 Dec;101 Suppl 5:45-53
8013424
Ann N Y Acad Sci. 1999;895:56-79
10676409
Ann N Y Acad Sci. 2002 Dec;982:46-69
12562628
Jpn J Cancer Res. 1989 Sep;80(9):795-807
2513295
Prog Clin Biol Res. 1996;394:3-23
8778803
Environ Health Perspect. 2005 Oct;113(10):1271-6
16203233
Regul Toxicol Pharmacol. 1992 Oct;16(2):111-25
1279759
Environ Health Perspect. 2004 Jun;112(8):A459-61
15175190
Toxicol Pathol. 2003 Sep-Oct;31(5):468-70
14692613
Toxicol Pathol. 1999 Jul-Aug;27(4):448-55
10485826
Ann N Y Acad Sci. 1997 Dec 26;837:1-14
9472328
Mt Sinai J Med. 1994 Nov;61(6):504-8
7838166
Environ Health Perspect. 1993 Dec;101 Suppl 5:125-35
8013399
Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):385-91
17337645
Environ Health Perspect. 1982 Nov;45:185-98
7140693
Food Chem Toxicol. 2001 Jul;39(7):739-44
11397520
Prog Clin Biol Res. 1984;141:43-64
6718388
Environ Health Perspect. 1975 Jun;11:251-319
1100368
Environ Health Perspect. 1999 Jul;107(7):A341-2
10405250
Ann N Y Acad Sci. 2002 Dec;982:190-7
12562637
Ann N Y Acad Sci. 2002 Dec;982:177-89
12562636
Environ Health Perspect. 2001 Oct;109(10):A458-60
11675275
Chem Biol Interact. 2005 May 30;153-154:23-32
15935797
Toxicol Pathol. 2004 Mar-Apr;32 Suppl 1:40-8
15209402
Boll Soc Ital Biol Sper. 1957 May;33(5):506-7
13479566
Environ Health Perspect. 1997 Sep;105(9):904-6
9341100
Environ Health Perspect. 1996 Dec;104 Suppl 6:1349-52
9118919
Environ Health Perspect. 1996 Mar;104 Suppl 1:123-34
8722116
Carcinogenesis. 1997 Jan;18(1):97-105
9054595
Am J Ind Med. 2004 Apr;45(4):382-5
15029572
Ann N Y Acad Sci. 2006 Sep;1076:800-9
17119257
Environ Health Perspect. 1991 Dec;96:23-31
1820269
Environ Health Perspect. 1990 Jun;86:313-21
2205492
Ann N Y Acad Sci. 2002 Dec;982:137-48
12562633
Int J Occup Environ Health. 2005 Apr-Jun;11(2):217-20
15875903
Ann Ist Super Sanita. 2006;42(2):113-7
17033130
Arch Toxicol Suppl. 1987;10:10-26
3555413
Environ Health Perspect. 1998 Dec;106(12):A582-A583
10207116
Ann N Y Acad Sci. 1988;534:412-26
3389671
Ann N Y Acad Sci. 2006 Sep;1076:90-109
17119195
Am J Ind Med. 1996 Mar;29(3):225-6
8833774
Am J Ind Med. 1983;4(5):589-630
6353911
Am J Ind Med. 2001 Aug;40(2):117-26
11494338
Carcinogenesis. 1988 Nov;9(11):2045-52
3052903
Drug Metab Rev. 2000 May;32(2):119-28
10774768
Boll Soc Ital Biol Sper. 1957 May;33(5):496-9
13479563
Prog Clin Biol Res. 1996;394:xiii-xix, 1-479
8778791
Jpn J Cancer Res. 1991 Nov;82(11):1211-9
1752780
Regul Toxicol Pharmacol. 1993 Oct;18(2):365-8
7506437
Ann N Y Acad Sci. 1999;895:10-26
10676406
Environ Health Perspect. 2001 May;109(5):437-42
11401753
Med Lav. 1982 Jul-Aug;73(4):441-5
7177031
Am J Ind Med. 1982;3(1):11-6
7124739
Pharmacol Toxicol. 1993;72 Suppl 1:12-27
8474975
Int J Occup Environ Health. 2002 Jul-Sep;8(3):249-70
12358081