Several wild type plant species of the spurge (Euphorbiaceae) family are currently under investigation worldwide as renewable sources of industrial raw materials. In particular, the innovative non-food crops Euphorbia lathyris and Jatropha curcas are being considered for the production of certain industrial chemicals and of biodiesel. However, owing to their content of irritant and hyperplasiogenic toxins of the diterpene ester type, the plants involved as well as their products and waste materials are known to be more or less poisonous to animals and humans (‘predictive toxicology’). More specifically, long term chronic exposure to wild type species of spurge, their products and waste materials, may impose upon human organs and tissues a risk of carcinogenesis. Consequently, for safe handling of the new crop, appropriate measures of occupational protection are required (‘preventive toxicology’). Corresponding precautions have been taken in several places in Germany in raising crops of E. lathyris at annual yields of more than 100 ha over a period of 10 years. As a result, no serious ailments have occurred so far in workers involved in the harvest, in the processing of seeds, or in the handling of waste materials. Similar measures of protection may be used in the case of other wild type species of spurge. Hence, if they are handled properly, there is no need to incriminate collectively wild type species of Euphorbiaceae as sources of hazard of occupational cancer. In the long run, for mass cultivation of species of spurge valued as innovative non-food crops, plant varieties may be developed, by classical breeding and/or by gene technological means, which are low in or free from DTE toxins yet high in the product(s) sought. Before a vision of this kind becomes reality, a considerable input of interdisciplinary basic and agricultural research guided by toxicological and analytical knowhow must be invested.
Get full access to this article
View all access options for this article.
References
1.
HeckerE. and SosathS.: ‘Green plants for industrial oleochemicals’, Interdisc. Sci. Rev., 1989, 14, 241–247.
2.
HeckerE. and SosathS.: ‘Wolfsmilchgewächse (Euphorbiaceen) als nachwachsende Resourcen der Oleochemie – Aktuelle bioorganische Analytik und Präventivtoxikologie’, Fat Sci. Technol., 1989, 91, 468–478.
3.
HeckerE. and SosathS.: Chem. Labor Tech., 1991, 42, 121–129.
4.
ZoebeleinH.(ed.): ‘Dictionary of renewable resources’; 1997, Weinheim, VCH Verlagsgesellschaft mbH.
5.
HeckerE., GläserS., GminskiR., KraussR., KrauterG., KretschmerH., WinterA., SchlattererK., SteebL., and ZahnP.: ‘Monographies on 34 genera of Euphorbiaceae and Thymelaeaceae used as phyto-medicinal drugs’, in ‘Hagers Handbuch der Pharmazeutischen Praxis’, 5th edn, Vols. 2 and 3, (ed. BlaschekW., HänselR., KellerK., ReichlingJ., RimplerH., and SchneiderG.); 1998, Berlin and Heidelberg, Springer-Verlag.
6.
HondelmannW.: ‘Domestication of Euphorbia lathyris as a potential new oil crop’, in ‘New crops for temperate regions’, (ed. AnthonyK. R. M.et al.), 206–221; 1993, London, Chapman and Hall.
7.
CalvinM.: ‘Hydrocarbons from plants’, Naturwissenschaften, 1980, 67, 523–533.
8.
CalvinM., NemethyE. K., RedenbaughK., and OtvosJ. W.: ‘Plants as a direct source of fuel’, Experientia, 1982, 38, 18–22.
9.
CalvinM.: ‘Fuel oils from euphorbs and other plants’, Bot. J. Linn. Soc., 1987, 94, 97–110.
10.
KleimannR., SmithC. R., and YatesS. G.: ‘Search for new industrial oils. XII. Fifty-eight Euphorbiaceae oils including one rich in vernolic acid’, J. Am. Oil Chem. Soc., 1965, 42, 169–172.
11.
HirsingerF.: ‘New annual oil crops’, in ‘Oil crops of the world’, (ed. RöbbelenG., DowneyR. K., and A. Ashri;519–532; 1989, New York, NY, McGraw-Hill.
12.
VogelR.: ‘Ansätze zur züchterischen Bearbeitung der Platzfestigkeit bei Euphorbia lagascae Spring., einer möglichen Rohstoffquelle für oleochemische Verwendungen’, Dissertation, Universität Göttingen, Germany, 1990.
13.
Proc. Jatropha 97: Int. Symp. on ‘Biofuel and industrial products from Jatropha curcas and other tropical oil seed plants’, Managua, Nicaragua, February1997.
14.
SeipE. H., OttH. H., and HeckerE.: ‘Skin irritant and tumor promoting diterpene esters of the tigliane type from Chinese tallow tree (Sapium sebiferum)’, Plant. Med., 1983, 49, 199–203.
15.
LiuS. Q., PezzuzutoJ. M., KinghornA. D., and ScheldH. W.: ‘Additional biologically active constituents of the Chinese tallow tree (Sapium sebiferum)’, J. Nat. Prod., 1988, 51, 619–620.
16.
JeffreyB. S. J. and PadleyF. B.: ‘Chinese vegetable tallow characterization and contamination by Stillingia oil’, J. Am. Oil Chem. Soc., 1991, 68, 123–127.
17.
FrankeW.: ‘Nutzpflanzenkunde’, 168; 1981, Stuttgart and New York, NY, Thieme-Verlag.
18.
AlfaroM. De J. and De PadillaF. C.: ‘Physico-chemical characteristics of the Barinas nut (Caryodendron orinocense Karst. Euphorbiaceae) crude oil’, Arch. Latinoam. Nutr., 1994, 44, 172–175.
19.
HeckerE.: ‘Structure-activity relationships in diter-pene esters irritant and cocarcinogenic in mouse skin’, in ‘Carcinogenesis – a comprehensive survey: mechanisms of tumor promotion and cocarcinogenesis’, (ed. SlagaT. J., SivakA., and BoutwellR. K.), Vol. 2, 11–48; 1978, New York, NY, Raven.
HeckerE.: ‘Tumor promoters of the irritant diterpene ester type as risk factors of cancer in man’, Bot. J. Linn. Soc., 1987, 94, 197–219.
22.
HeckerE.: ‘Cocarcinogens of the diterpene ester type as principal risk factors of cancer in Curacao and possibly in South China. Identification of second order risk factors of cancer in multifactorial carcinogenesis’, in ‘Cancer of the liver, esophagus and nasopharynx’ (ed. WagnerG. and ZhangY.-H.), 101–114; 1987, Berlin and Heidelberg, Springer-Verlag.
23.
SchultesR. R.: ‘Members of the Euphorbiaceae in primitive and advanced societies’, in ‘The Euphor-biales, chemistry, taxonomy and economic botany. Proceedings in celebration of the Linnean Society Bicentenary’, (ed. JuryS. L.et al.), 79–95; 1987, London, Academic Press.
24.
HeckerE.: Guest Editorial on ‘Tumorpromotoren als Krebsrisikofaktoren – eine neuartige Kategorie definierter Kanzerogene in der Umwelt’Arch. Geschwulstforsch., 1990, 60, 409–421.
25.
AppelK. E., FürstenbergerG., HapkeH. J., HeckerE., HildebrandtA. G., KoranskyW., MarksF., NeumannH. G., OhnesorgeandF. K., and Schulte-HermannR.: Guest Editorial on ‘Chemical carcinogenesis: definitions of frequently used terms’, J. Cancer Res. Clin. Oncol., 1990, 116, 232–236.
26.
ArcosJ. C., ArgusM. F., and WooY. T.(ed.): ‘Chemical induction of cancer: modulation and combination effects. An inventory of many factors which influence carcinogenesis’, 227–233; 1995, Berlin, BirkhäuserVerlag.
27.
GminskiR., KrauterG., and HeckerE.: ‘Biological assays for irritant, tumor-initiating and tumor-promoting activities. II. Classification of environmental materials polluted by toxins of the TPA-activity type by their irritant and tumor-promoting activities in mouse skin’, J. Cancer Res. Clin. Oncol., 1998, to be published.
28.
AdolfW., OpferkuchH. J., and HeckerE.: ‘Irritant phorbol derivatives from four Jatropha species’, Phytochemistry, 1984, 23, 129–132.
29.
BiehlJ. and HeckerE.: ‘Irritant and antineoplastic principles of some species of the genus Jatropha (Euphorbiaceae)’, Plant. Med., 1986, 50, 430. See also J. Biehl: ‘Über irritierende Diterpene der Pflanzenfamilie der Euphorbiaceae, insbesondere des Genus Jatropha, deren ko-und antikarzinogene Wirkung’, Dissertation, UniversitätHeidelberg, Germany, 1987.
30.
MarksF. and FürstenbergerG.: ‘Tumor promotion in skin’, in ‘Chemical induction of cancer: modulation and combination effects. An inventory of the many factors which influence carcinogenesis’, (ed. ArcosJ. C.), 125–160; 1995, Berlin, Birkhäuser.
31.
MarksF.: ‘Hyperplastic transformation, the response of the skin to irritation and injury’, in ‘Skin pharmacology and toxicology’ (ed. GalliC. L., MarinovichD. M., and HensbyC. N.), 121; 1990, New York, NY, Plenum.
32.
DigiovanniJ.: ‘Modification of multistage carcinogenesis in mice’, Prog. Exp. Tumor Res., 1991, 33, 192–229.
AldazC. M., ContiC. J., GimenzJ. B., SlagaT. J., and Klein-SzantoA. J. P.: ‘Cutaneous changes during prolonged application of 12-O-tetradecanoylphorbol-13-acetate on mouse skin and residual effects after cessation of treatment’, Cancer Res., 1985, 45, 2753–2759.
35.
Meighan-ManthaR. L., WellsteinA., and RiegelA. T.: ‘Differential regulation of extracellular signalregulated kinase 1 and 2 activity during 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of HL-60 cells’, Exp. Cell Res., 1997, 234, 321–328.
36.
UmezawaK., WeinsteinI. B., HorowitzA., FujikiH., MatsushimaT., and SugimuraT.: ‘Similarity of teleocidin B and phorbol ester tumor promoters in effects on membrane receptors’, Nature, 1991, 290, 411–413.
37.
Klein-SzantoA. J. and SlagaT. J.: ‘Numerical variation of dark cells in normal and chemically induced hyperplastic epidermis with age of animal and efficiency of tumor promoter’, Cancer Res., 1981, 41, 4437–4440.
38.
GlasoM. and WettelandP.: ‘Morphometric evaluation of dark and clear basal cells during early 2-stage chemical skin carcinogenesis in the hairless mouse using two different fixation methods’, APMIS, 1990, 98, 695–712.
39.
petrusevskaR. T., FürstenbergerG., MarksF, and FusenigN. E.: ‘Cytogenetics effects caused by phorbol ester tumor promoters in primary mouse keratinocyte cultures: correlation with the convertogenic activity of TPA in multistage carcinogenesis’, Carcinogenesis, 1988, 9, 1207–1215.
40.
Schulte-HermannR., BurschW., Grasl-KrauppB., TorokL., EllingerA., and MullauerL.: ‘Role of active cell death (apoptosis) in multi-stage carcinogenesis’, Toxicol. Lett., 1995, 82/83, 143–148.
41.
AyaT., KinoshitaT., ImaiS., OsatoT., OhigashiH., and KoshimizuK.: ‘Comment on ‘Chromosome translocation and c-MYC activation by Epstein–Barr virus and Euphorbia tirucalli in B lymphocytes’, Lancet, 1991, 337, 1190.
42.
Zur HausenH., BornkammG. W., SchmidtR., and HeckerE.: ‘Tumor initiators and promoters in the induction of Epstein–Barr-Virus’, Proc. Natl. Acad. Sci. (USA), 1979, 76, 782–785.
43.
ItoY., YanaseS., TokudaH., KrishishitaM., OhigashiH., HirataM., and KoshimizuK.: ‘Epstein Barr virus activation by tung oil, extracts of Aleurites fordii and its diterpene ester 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate’, Cancer Lett., 1983, 18, 87–95.
44.
KlozU., HergenhahnM., FellhauerM., and HeckerE.: ‘Induction of Epstein-Barr virus early antigens by tumor promoters of the diterpene ester type in Raji cells and specific (receptor) binding as compared to irritant and promoting activities’, J. Cancer Res. Clin. Oncol., 1989; 115, 148–156.
JungC., MohrH., and HeckerE.: ‘Stimulation of functions of immunocompetence in human lymphocytes by antineoplastic polyfunctional diterpene esters (DTE) in vitro’, Proc. 45th Annual Cong, of the Society for Medical Plant Research, Regensburg, September1997, G10.
47.
FischerS. M., CameronG. S., BaldwinJ. K., JashewayD. W., PatrickK. E., and BeluryM. A.: ‘The arachidonic cascade and multistage carcinogenesis in mouse skin’, in ‘Skin carcinogenesis mechanisms and human relevance’, (ed. SlagaT. J., Klein-SzantoA. J. P., BoutwellR. K., StevensonD. E., SpitzerH. L., and D'MottoB.), 249–264; 1989, New York, NY, AlanR. Liss.
48.
FürstenbergerG., HagedornH., JacobiT., BesemfelderE., StephanM., LehmannW. D., and MarksF.: ‘Characterization of an 8-lipoxygenase activity induced by the phorbol ester tumor promoter 12–0-tetradecanoylphorbol-13-acetate in mouse skin in vivo’, J. Biol. Chem., 1991, 266, 15738–15745.
49.
KriegP., KinzigA., Ress-LoschkeM., VogelS., VanlandinghamB., StephanM., LehmannW. D., MarksF., and FürstenbergerG.: ‘12-lipoxygenase isoenzymes in mouse skin tumor development’, Mol. Carcinog., 1995, 14, 118–129.
50.
TakigawaM., BoutwellR. K., and VermaA. K.: ‘Evidence that an elevated level of ornithine decarboxylase may be essential to tumor promotion by phorbol esters’, in ‘Polyamines: basic and clinical aspects’, (ed. ImahoriK., SuzukiF., SuzukiO., and BachrachU.), 1–8; 1985, Utrecht, VNU Science Press.
51.
ImamotoA., BeltranL. M., FujikiH., ChenicekK. J., and DigiovanniJ.: ‘Enhanced induction of epidermal ornithine decarboxylase activity in C57BL/6 compared to DBA/2 mice by protein kinase C-activating skin tumor promoters: relevance to genetically mediated differences in promotion susceptibility’, Carcinogenesis, 1992, 13, 177–182.
52.
PerchelettJ. P. and PerchelettE. M.: ‘Antioxidants and multistage carcinogenesis in mouse skin’, Free Radic. Biol. Med., 1989, 7, 377–408.
53.
WeiH. and FrenkelK.: ‘In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin’, Cancer Res., 1991, 51, 4443–4449.
54.
YamasakiH.: ‘Short-term assays to detect tumor-promoting activity of environmental chemicals’, in ‘Skin carcinogenesis: mechanisms and human relevance’, (ed. SlagaT. J., Klein-SzantoA. J. P., BoutwellR. K., StevensonD. E., SpitzerH. L., and D'MottoB.), 265–279; 1989, New York, NY, AlanR. Liss.
55.
BakerT. K., BachowskiS., StevensonD. E., WalborgE. F., and KlauningJ. E.: ‘Modulation of gap junctional intercellular communication in rodent, monkey and human hepatocyte by nongenotoxic compounds’, in ‘Growth factors and tumor promotion: implication for risk assessment’, (ed. McClainR. M., SlagaT. J., LeBoeufR., and PitotH.), 71–80; 1997, New York, NY, Wiley-Liss.
56.
HeckerE.: ‘Cell membrane associated protein kinase C as receptor of diterpene ester co-carcinogens of the tumor promoter type and phenotypic expression of tumors’, Drug Res., 1985, 35, 1890–1903.
57.
KrauterG., et al.: ‘Structure/activity relationships of polyfunctional diterpenes of the tigliane type, VIII A pharmacophore model for protein kinase C activators based on structure/activity studies and molecular modeling of the tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate and 3-O-tetradecanoylingenol. Eur. J. Biochem., 1996, 242, 417–427.
58.
NishizukaY.: ‘The role of protein kinase C in cell surface signal transduction and tumor promotion’, Nature, 1985, 308, 693–698.
59.
BlumbergP. M.: ‘Protein kinase C as the receptor for the phorbol ester tumor promoters’, Cancer Res., 1988, 48, 1–8.
60.
WeinsteinI. B.: ‘Nonmutagenic mechanisms in carcinogenesis: role of protein kinase C in signal transduction and growth control’, Environ. Health Per sped., 1991, 93, 175–179.
61.
BasuA.: ‘The potential of protein kinase C as a target for anticancer treatment’, Pharmacol. Ther., 1993, 59, 257–280.
62.
MagnelliL. and ChiarugiV.: ‘Regulation of p53 by protein kinase C during multistage carcinogenesis’, J. Cancer Res. Clin. Oncol., 1997, 123, 365–374.
63.
MizunoF., OsatoT., ImaiS., KoizumiS., AyaT., KinoshitaT., HiraiN., HirotaM., OhigashiH., and KoshimizuK.: ‘Epstein-Barr virus enhancing plant promoters in east Africa’, AIDS Res., 1991, 2, Suppl. 1, 151–155.
64.
HeckerE., GläserS., and GminskiR.: ‘Konditionalkanzerogene als eine neuartige Kategorie von Krebsrisikofaktoren am Beispiel der Tumorpromotoren des Diterpenestertyps – Wissenschaftliche Grundlagen für die Abschätzung und Bewertung eines möglichen iatrogenen Krebsrisikos durch Inhaltsstoffe bestimmter pflanzlicher Arzneimittel’, Pharm. Ztg Wiss., 1991, 136, 251–264.
65.
PolackA., LauxG., HergenhahnM., KlozU., RoeserH., HeckerE., and BornkammG.: ‘Short term assays for detection of conditional carcinogens I. Construction of DR–CAT Raji cells and some of their characteristics as tester cells’, Int. J. Cancer, 1992, 50, 611–616.
66.
HeckerE.: ‘Wirkungs/Dosis-Beziehungen im Mäusehautmodell der Solitärkanzerogenese mit dem Tumorinitiator 7, 12-Dimethylbenz [a] anthracen als Umweltrisikofaktor – Hypothesen und praktische Konsequenzen’, in ‘Chemische Krebsrisikofaktoren der Umwelt’, (ed. SchlattererB.), 1–19; 1991, Berlin,Erich Schmidt Verlag.
67.
HeckerE.: ‘Wirkungs/Dosis-Beziehungen im Mäusehautmodell der Konditionalkanzerogenese mit dem Tumorpromotor 3-O-Tetradecanoylingenol als Umweltrisikofaktor – Hypothesen und praktische Konsequenzen’, in ‘Chemische Krebsrisikofaktoren der Umwelt’, (ed. SchlattererB.), 177–196; 1991, Berlin, Erich Schmidt Verlag.
68.
YuspaS. H.: ‘The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis’, Cancer Res., 1994, 54, 1178–1189.
69.
HeckerE. and RippmannF.: ‘Outline of a descriptive general theory of environmental chemical carcinogenesis – experimental threshold doses for tumor promoters’, in ‘Mechanisms of environmental mutagenesis – Carcinogenesis’, (ed. KappasA.), 167–173; 1990, New York, NY, Plenum.
70.
EdlerL., SchmidtR., WeberE., RippmannF., and HeckerE.: ‘Biological assays for irritant, tumor-initiating and promoting activities. III. Computer-assisted management and validation of biodata generated by standardized initiation/promotion protocols in skin of mice’, J. Cancer Res. Clin. Oncol, 1991, 117, 205–216.
71.
HeckerE., LutzD., WeberJ., GoerttlerK., and MortonJ. F.: ‘Multistage tumor development in the human esophagus – the first identification of cocarcinogenes of the tumor promoter type as principal carcinogenic risk factors in a local life style cancer’, Prog. Clin. Biol. Res., 1983, 132B, 219–238.
72.
ZayedS. M. A. D., FarghalyM., TahaH., GottaH., and HeckerE.: ‘Dietary cancer risk from conditional carcinogens in produce of livestock fed on species of spurge (Euphorbiaceae). I. Skin irritant and tumor promoting ingenane type diterpene esters in Euphorbia peplus, one of several herbaceous Euphorbia species contaminating fodder of livestock’, J. Cancer Res. Clin. Oncol., 1998, 124, 131–140.
73.
NawitoM., AhmedY. F., ZayedS. M. A. D., and HeckerE.: ‘Dietary cancer risk from conditional carcinogens in produce of livestock fed on species of spurge (Euphorbiaceae). II. Pathophysiological investigations in lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk-raised kids’, J. Cancer Res. Clin. Oncol., 1998, 124, 179–185.
74.
ZayedS. M. A. D., FarghalyM., TahaH., GminskiR., and HeckerE.: Dietary cancer risk from conditional carcinogens in produce of livestock fed on species of spurge (Euphorbiaceae). III. Milk of lactating goats fed on Euphorbia peplus is polluted by tumor promoters of the ingenane diterpene ester type’, J. Cancer Res. Clin. Oncol., 1998, to be published.
75.
OhigashiH., KoshimizuK., TokudaH., HiramatsuS., JatoJ., and ItoY.: ‘Epstein-Barr virus inducing activity of Euphorbiaceae plants commonly grown in Cameroon’, Cancer Lett., 1985, 28, 135–141.
76.
Van Den BoschC., GriffinB. E., KazembeP., DziweniC., and KadzamiraL.: ‘Are plant factors a missing link in the evolution of endemic Burkitt lymphoma?’, Br. J. Cancer, 1993, 68, 1232–1235.
77.
KokwaroJ. O.: ‘Euphorbiaceae’, in ‘Medicinal plants of East Africa’, (ed. KokwaroJ. O.), 85–100; 1979, Nairobi, East Africa Literature Bureau.
78.
OsatoT., MizunoF., ImaiS., AyaT., KinoshitaT., KizumiS., SugimuraM., TokudaH., ItoY., HiraiN., HirotaM., OhigashiH., KoshimizuK., MurataG., Kofi-TsekpoW., WereJ. B. O., and MugambiM.: ‘Euphorbia tirucalli in high risk areas of Burkitt's lymphoma in Africa’, in ‘Epidemiology and prevention of cancer’, (ed. SasakiR. and AokiK.), 17–21; 1990, Nagoya, University of Nagoya.
79.
HirayamaT. and ItoY.: ‘A new view of the etiology of nasopharyngeal carcinoma’, Prev. Med., 1981, 10, 614–622.
80.
ZengY., ZhongJ. M., MoY. K., and MiaoX. C.: ‘Epstein-Barr virus early antigen induction in Raji cells by Chinese medicinal herbs’, Intervirology, 1983, 19, 201–204.
81.
NorhanonA. W. and YadavM.: ‘Tumor promoter activity in Malaysian Euphorbiaceae’, Br. J. Cancer, 1995, 71, 776–779.
82.
HormozdiariH., DayN. E., ArameshB., and MahboubiE.: ‘Dietary factors and esophageal cancer in the Caspian littoral of Iran’, Cancer Res., 1975, 35, 3493–3498.
83.
FürstenbergerG. and HeckerE.: ‘On the active principles of the spurge family (Euphorbiaceae), XI. The skin irritant and tumor promoting diterpene esters of Euphorbia tirucalli L. Originating from South Africa’, Z. Naturforsch. C, 1985, 40, 631–646.
84.
FürstenbergerG. and HeckerE.: ‘On the active principles of the spurge family (Euphorbiaceae), XII. Highly unsaturated irritant diterpene esters from Euphorbia tirucalli L. Originating from Madagascar’, J. Nat. Prod., 1986, 49, 386–397.
85.
ClaysonD. B., MunroI. C., ShubikP., and SwenbergJ. A.(ed.): ‘Progress in predictive toxicology’, 1990, Amsterdam, Elsevier.
86.
GmiznskiR. and HeckerE.: ‘General strategy for estimation and assessment of a possible risk of cancer by diterpene ester type conditional carcinogens of plant origin’, Plant. Med., 1993, 59Suppl. 7, A685–A686.
87.
HeckerE., GläserS., GminskiR., KrauterG., WinterA., and ZahnP.: ‘Tumorpromotoren als neuartige Risikofaktoren iatrogener Krebsauslösung – Zur Abschätzung und Bewertung von Gesundheitsrisiken durch bestimmte pflanzliche Arzneimittel’, Biol. Med., 1997, to be published.
88.
EULA: ‘Untersuchungen möglicher gesundheitlicher Risikofaktoren bei der Produktion und Verarbeitung von Wolfsmilchgewächsen (Euphorbiaceen) in der Landwirtschaft, Modellvorhaben 1987–1991 des Bundesministerium für Ernährung, Landwirtschaft und Forsten (BMELF), Bonn, Germany’; 1991, Heidelberg, Deutsches Krebsforschungzentrum Heidelberg.
89.
EULA: ‘Entwicklung von Kurzzeittesten auf Gehalt an hautreizenden Diterpenen/Ölsäuregehalt für pflanzenzüchterische Belange bei Samen von Euphorbia lathyris sowie toxikologische Begleitung des Großanbaus von Euphorbia lathyris 1993–1995. Forschungsprojekt 92PV030 Fachagentur “Nachwachsende Rohstoffe”, Quedlinburg, Germany’; 1996, Heidelberg, Deutsches Krebsforschungzentrum Heidelberg.
90.
GminskiR., KretschmerH., and HeckerE.: ‘Monographie Euphorbia’, in ‘Hagers Handbuch der Pharmazeutischen Praxis’, 5th edn, Vol. 2, (ed. BlaschekW., HänselR., KellerK., ReichlingJ., RimplerH. and SchneiderG.), 619–666; 1998, Berlin and Heidelberg, Springer-Verlag.
91.
AdolfW. and HeckerE.: ‘On the active principle of the spurge family. III. Skin irritants and cocarcinogenic factors from the caper spurge’, Z. Krebsforsch., 1975, 84, 325–344.
92.
HirotaM., SuttajitM., SuguriH., EndoY., ShudoK., WongchaiV., and HeckerE.: ‘A new tumor promoter from the seed oil of Jatropha cur cas L., an intramolecular diester of 12-desoxy-16-hydroxyphorbol’, Cancer Res., 1988, 48, 5800–5804.
93.
GandhiV. M., CherianK. M., and MulkyM. J.: ‘Toxicological studies on ratanjyot oil’, Food Chem. Toxicol., 1995, 33, 39–42.
94.
GläserS. and HeckerE.: ‘Monographie Jatropha’, in ‘Hagers Handbuch der Pharmazeutischen Praxis’, 5th edn, Vol. 2, (ed. BlaschekW., HänselR., KellerK., ReichlingJ., RimplerH., and SchneiderG.), 887–900; 1998, Berlin and Heidelberg, Springer-Verlag.
95.
SauerweinM., SporerF., and WinkM.: ‘Insect-toxicity of phorbol esters from Jatropha curcas seed oil’, Plant. Med., 1993, 59, A686.
96.
LiuS. Y., SporerF., WinkM., JourdaneJ., HenningR., LiY. L., and RuppelA.: ‘Anthraquinones in Rheum palmatum and Rumex dentatus (Polygonaceae), and phorbol esters in Jatropha cur cas (Euphorbiaceae) with molluscicidal activity against the schistosome vector snails Oncomelania, Biomphalaria and Bulinus’, Trop. Med. Int. Health, 1997, 2, 179–188.
97.
StaubmannR., FoidlG., FoidlN., GuebitzG. M., LaffertyR. M., Valencia-ArbizuV. M., and SteinerW.: ‘Biogas production from Jatropha curcas press-cake’, Appl. Biochem. Biotechnol., 1997, 63–65, 457–467.
98.
SchmidtR. and HeckerE.: ‘Biological assays for irritant, tumor-initiating and tumor-promoting activities, II. Standardized initiation/promotion protocol and semiquantitative estimation of promoting (or initiating) potencies in skin of NMRI mice’, J. Cancer Res. Clin. Oncol., 1989, 115, 516–524.
99.
HoriuchiT., FujikiH., HirotaM., SuttajitM., SuganumaM., YoshiokaA., WongchaiV., HeckerE., and SugimuraT.: ‘Presence of tumor promoters in the seed oil of Jatropha curcas L. From Thailand’, Jpn. J. Cancer Res. (Gann.), 1987, 78, 223–226.
100.
SuttajitM., WongchaiV., HirotaM., and FujikiH.: ‘New tumor promoter of Jatropha curcas L. In Thailand’, in ‘Epidemiology and prevention of cancer’, (ed. SasakiR. and AokiK.), 22–27; 1990, Nagoya, University of Nagoya Press.
101.
BeckerN. and WahrendorfJ.: ‘Krebsatlas der Bundesrepublik Deutschland (1981–1990)’, 3rd edn; 1997, Berlin, Springer-Verlag.
102.
GminskiR. and HeckerE.: ‘Neue Ölsaaten aus der Familie der Wolfsmilchgewächse als nachwachsende Resourcen der Oleochemie – Erfassung und Verhütung von Berufs-und Umweltrisiken’, in Proc. Conf. Gesellschaft Deutscher Chemiker, Wege und Beiträge zur Chemie zum Sustainable-Development: Stoffe und Umwelt, Heidelberg, Germany, Nov. 1997, to be published.
103.
GminskiR. and HeckerE.: ‘Toxicology of some species of the Euphorbiacene family considered as innovative sources of industrial seed oils’, in Proc. Jatropha 97: Int. Symp. on ‘Biofuel and industrial products from Jatropha curcas and other tropical oil seed plants’, Managua, Nicaragua, Feb. 1997, 58.
