41Sunderman, F.W., Jr, Maenza, R.M., Hopfer, S.M., Mitchell, J.M., Allpass, P.R. & Darnjanov, 1.
(1979) Induction of renal cancers in rats by intrarenal injection of nickel subsulfide. J. environ.
Pathol. Toxicol.,21, 1511-1527
42Damjanov, 1., Sunderman, F.W., Jr, Mitchell, J.M. & Allpass, P.R. (1978) Induction oftesticular
sarcomas in Fischer rats by intratesticular injection of nickel subsulfide. Cancer Res., 38,
43Albert, D.M., Gonder, J.R., Papale, J., Craft, J.L., Dohlman, H.G., Reid, M.C. & Sunderman,
F.W., Jr (1980) Induction of ocular neoplasms in Fischer rats by intraocular injection o/nickel
subsulfde. ln: Brown, S.S. & Sunderman, F.W., Jr, eds, Nickel Toxicology, New York,
Academic Press, pp. 55-58
44Yarita, T. & Nettesheim, P. (1978) Carcinogenicity of nickel subsulfide for respiratory tract rnucosa.
Cancer Res., 38,3140-3145
45Hildebrand, H.F. & Biserte, G. (1979) Cylindricallaminated bodies in nickel-subsulphide-induced
rhabdornyosarcoma in rabbits. Eur. J. Cel! BioL., 19, 276-280
46Hildebrand, H.F. & Biserte, G. (1979) Nickel sub-sulphide-induced leiomyosarcoma in rabbit white
skeletal muscle. A light microscopical and ultrastructural study. Cancer,
43, 1358-1374
47Hildebrand, H.F. & Tetaert, D. (1981) Ni3S2-induced leiomyosarcomas in rabbit skeletal muscle:
analysis of the tumoral myosin and its significance in the retrodifferentiation concept. Oncodev.
Biol. Med., 2, 101-108
48Kasprzak, K.S., Gabryel, P. & Jarczewska, K. (1983) Carcinogenicity of nickel(II)hydroxides and
nickel(II)sulfate in Wistar rats and its relation to the in vitro dissolution rates. Carcinogenesis,4,
49Stoner, G.D., Shimkin, M.B., Troxell, M.C., Thompson, T.L. & Terry, L.S. (1976) Test for
carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice.
Cancer Res., 36, 1744-1747
50Sunderman, F.W., Jr, McCully, K.S. & Hopfer, S.M. (1984) Association between erythrocytosis
and renal cancers in rats following intrarenal injection of nickel compounds. Carcinogenesis,5,
51Torjussen, W. (1979) Nickel as carcinogenic factor in nasal carcinoma. Acta otolaryngol., Suppl.
360, 125
52Barton, R.T. & HØgetveit, A.C. (1980) Nickel-related cancers of
the respiratory tract. Cancer,
3061 -3064
53Torjussen, W. (1985) Occupational nasal cancer caused by nickel and nickel cornpounds.
Rhinology,23, 101-105
54IARC Monographs, Suppl. 6,417-420, 1987
TARD (Group 2A)
A. Evidence for carcinogenicity to humans (limited)
No epidemiological study of nitrogen mustard as a single agent was available to the
Working. Group. However, it is the principal alkylating agent in leukaemogenic combination chemotherapy given for Hodgkin's disease, and other alkylating agents are clearly
leukaemogenic (see p. 254). The many case reports of cancer following topical application of
nitrogen mustard cannot be interpreted with certainty because concurrent treatment with
radiation and other potent drugs has been the rule rather than the exception, and
occasionally such associations would be expected by chance.
Squamous-cell carcinomas of the skin following long-term topical application of
nitrogen mustard alone or in combination with systemic therapy for mycosis fungoidesl-4
and psoriasiss-7 have been observed to appear on skin surfaces not exposed to the sun.
B. Evidence for carcinogenicity to animaIs (sufficíent)
Nitrogen mustard, administered mainly as the hydrochloride, has been tested for carcinogenicity in mice and rats by subcutaneous, intravenous and intraperitoneal administration
ce after
and by skin painting. It produced mainly lung tumours and lymphomas in mi
subcutaneous, intravenous and intraperitoneal administration. Intravenous injection of
nitrogen mustard to rats induced tumours in different organs8. Application by skin painting
produced local tumours in mice in a dose-dependent manner9,lO.
C. Other relevant data
Nitrogen mustard is a bifunctional alkylating agent. ln one study, it induced chromosomal aberrations in lymphocytes of treated patients!!.
Nitrogen mustard induced dominant lethal mutations and induced micronuclei in
bone-marrow cells of mice exposed in vivo and alkylated DNA of ascites cells in experomal aberrations, sister chromatid
exchanges and unscheduled DNA synthesis in human cells in vitro. ln rodent cells in vitro, it
imental animaIs treated in vivo. It induced chromos
induced sister chromatid exchanges, chromos
omal aberrations and DN A damage; studies
on the induction of mutation were inconclusive. It transformed mouse C3H lOTlj2 cells.
Nitrogen mustard induced aneuploidy and somatic mutation and recombination in
Drosophila, chromosomal aberrations in plants, mitotic recombination and mutation in
fungi, and mutation and DNA damage in bacterialI.
IDu Vivier, A., Vonderheid, E.C., Van Scott, E.J. & Urbach, F. (1978) Mycosis fungoides, nitrogen
mustard and skin cancer. Br. J. Dermatol., 99, 61-63
2Kravitz, P.H. & McDonald, C.J. (1978) Topical nitrogen mustard induced carcinogenesis. Acta
dermatol. venereol., 58, 421-425
3Lee, L.A., Fritz, K.A., Golitz, L., Fritz, T.J. & Weston, W.L. (1982) Second cutaneous malignancies
in patients with mycosis fungoides treated with topical nitrogen mustard. J. Am. Acad.
Dermatol., 7,590-598
4Abel, E.A., Sendagorta, E. & Hoppe, R.T. (1986) Cutaneous malignancies and metastaticsquamous
cell carcinoma following topical therapies for mycosis fungoides. J. Am. Acad. Dermatol., 14,
5Halprin, K.M., Comerford, M. & Taylor, J.R. (1982) Cancer in patients with psoriasis. J. Am. Acad.
Dermatol, 7, 633-638
6Ganor, S. (1983) Skin cancer in psoriatics treated with nitrogen mustard. J. Am. Acad. Dermatol., 9,
7Halprin, K.M., Comerford, M. & Taylor, J.R. (1982) Skin cancer in psoriatics treated with nitrogen
mustard. J. Am. Acad. Dermatol., 8, 164-165
8/ARC Monographs, 9, 193-207, 1975
9Zackheim, H.S. & Smuckler, E.A. (1980) Tumorigenic effect oftopical mechlorethamine, BCNU and
CCNU in mice. Experientia,36, 1211-1212
Epstein, J.H. (1984) Nitrogen mustard (mechlorethamine) and UVB photocarcinogenesis: a dose
response effect. J. invest. Dermatol., 83, 320-322
II/ARC Monographs, Suppl. 6,421-424, 1987
oeHRATOXIN A (Group 3)
A. Evidence for carcinogenicity to humans (inadequate)
Incidence of and mortality from urothelial urinary-tract tumours have been correlated
with the geographical distribution of Balkan endemic nephropathy in Bulgaria and
Yugoslavia. A relatively high frequency of contamination of cereals and bread with
ochratoxin A has been reported in an area of Yugoslavia where Balkan endemic
nephropathy is present. No report of a direct association between ochratoxin A and human
cancer is availablel.
B. Evidence for carcinogenicity to animais (limited)
When ochratoxin A was administered in the diet of mice for 24 months, renal adenornas
and carcinomas were observed in males and sorne hepatocellular carcinomas were observed
in females in one study2 andhepatomas and renal-cell tumours in male miee in another
study3. Other studies by oral administration and studies by subcutaneous injection to mice
and rats were inadequate in terms ofthe numbers of animaIs used and survival rates!.
C. Other relevant data
No data were available on the genetic and related effects of ochratoxin A in humans.
Ochratoxin A did not induce sister chromatid exchanges in bone-marrow cells of
Chinese hamsters treated in vivo or mutation in rodent cells treated in vitro; conflcting
results were obtained for induction of unscheduled DNA synthesis in rodent hepatocytes.
Ochratoxin A did not induce mutation in yeast or bacteria4.
I/ARC Monographs, 31, 191-206, 1983
2Bendele, A.M., Carlton, W.W., Krogh, P.A. & Lilehoj, E.B. (1985) Ochratoxin A carcinogenesis in
the (C57BL/6J x C3H)F1 mouse. J. natl Cancer /nst., 75, 733-742