chemical Class
Nitro- and polycylic- musks
Chemicals in the class:
Cashmeran, Celestolide, Galaxolide, Musk ambrette, Musk ketone, Musk moskene, Musk tibetene, Musk xylene, Phantolide, Tonalide, Traseolide
Summary
Nitro- and polycyclic musks are synthetic fragrance ingredients typically used in cosmetics, perfume, air fresheners, cleansing agents, detergents, and soap. Musks are also used as food additives, and in cigarettes and fish baits. Commonly used musks contaminate lakes and fish in the United States and Europe (Fromme 2001; Peck 2004, 2006; Duedahl-Olesen 2005; Kannan 2005). Nitro- and polycyclic musks tend to accumulate in the fatty tissues of our bodies, and are often detected in breast milk as well as blood (Rimkus 1996; Liebl 2000; TNO 2004, 2005; Hutter 2005).
In laboratory studies, some nitromusks have been linked to cancer (Maekawa 1990; Apostolidis 2002). Studies of nitromusks in people suggest that high levels of some of these chemicals are associated with reproductive and fertility problems in women (Eisenhardt 2001). Some also produce skin irritation and sensitization (Parker 1986; Hayakawa 1991).
Growing concerns about the health effects of nitromusks have led the European Union to ban the use of some of these chemicals in cosmetics and personal care products. As a result, the use of polycyclic musks has increased. However, laboratory studies suggest that polycyclic musks, like nitromusks, may also affect hormone systems (Seinen 1999; Chou 1999a; Bitsch 2002; Gomez 2005; Schreurs 2004, 2005a, b). Two particular musk chemicals, a nitromusk (musk ambrette) and a polycyclic musk that both produced neurotoxic effects in laboratory animals, have been removed from the market voluntarily. In the United States, all musk chemicals are unregulated, and safe levels of exposure have not yet been set.
Nitro- and polycylic- musks
Fragrance ingredients. Build up in human tissues. May harm hormone system.
Top health concerns for Nitro- and polycylic- musks (References)
| health concern or target organ | weight of evidence |
| Cancer | limited |
| Endocrine system | unknown |
Other health concerns for Nitro- and polycylic- musks (References)
| health concern or target organ | weight of evidence |
| Persistent, accumulates in wildlife and/or people | probable |
| Skin | unknown |
| Immune system (including sensitization and allergies) | possible |
| Brain and nervous system | unknown |
| Reproduction and fertility | unknown |
| Gastrointestinal (including liver) | unknown |
| Chronic effects, general | unknown |
Violations, restrictions, and warnings for Nitro- and polycylic- musks (References)
Fragrance with restrictions on use/concentration.
Unsafe for use in cosmetics, Canada.
Unsafe according to International Fragrance Association.
Other relevant risk considerations for Nitro- and polycylic- musks (References)
Wildlife and environmental toxicity.
Toxicity Classifications (References)
| classification | governing entity/references |
| Cancer - limited evidence of carcinogenicity | Apostolidis, S., T. Chandra, et al. (2002). "Evaluation of carcinogenic potential of two nitro-musk derivatives, musk xylene and musk tibetene in a host-mediated in vivo/in vitro assay system." Anticancer Res 22(5): 2657-62., Maekawa, A., Y. Matsushima, et al. (1990). "Long-term toxicity/carcinogenicity of musk xylol in B6C3F1 mice." Food Chem Toxicol 28(8): 581-6. |
| Chronic effects, general - weight of evidence unknown/unassessed | Luckenbach, T. and D. Epel (2005). "Nitromusk and polycyclic musk compounds as long-term inhibitors of cellular xenobiotic defense systems mediated by multidrug transporters." Environ Health Perspect 113(1): 17-24. |
| Endocrine disruptor - suspected or limited evidence | Seinen, W., J. G. Lemmen, et al. (1999). "AHTN and HHCB show weak estrogenic--but no uterotrophic activity." Toxicol Lett 111(1-2): 161-8., Schreurs, R. H., E. Sonneveld, et al. (2005b). "Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays." Toxicol Sci 83(2): 264-72., Schreurs, R. H., E. Sonneveld, et al. (2005a). "Examination of the in vitro (anti)estrogenic, (anti)androgenic and (anti)dioxin-like activities of tetralin, indane and isochroman derivatives using receptor-specific bioassays." Toxicol Lett 156(2): 261-75., Bitsch, N., C. Dudas, et al. (2002). "Estrogenic activity of musk fragrances detected by the E-screen assay using human mcf-7 cells." Arch Environ Contam Toxicol 43(3): 257-64., Chou, Y. J. and D. R. Dietrich (1999). "Interactions of nitromusk parent compounds and their amino-metabolites with the estrogen receptors of rainbow trout (Oncorhynchus mykiss) and the South African clawed frog (Xenopus laevis)." Toxicol Lett 111(1-2): 27-36., Gomez, E., A. Pillon, et al. (2005). "Estrogenic activity of cosmetic components in reporter cell lines: parabens, UV screens, and musks." J Toxicol Environ Health A 68(4): 239-51. |
| Endocrine system toxicity - weight of evidence unknown/unassessed | Bitsch N, Dudas C, Korner W, Failing K, Biselli S, Rimkus G, et al. 2002. Estrogenic activity of musk fragrances detected by the E-screen assay using human mcf-7 cells. Arch Environ Contam Toxicol 43(3): 257-264. |
| Fragrance subject to restrictions: safe only within recommended use or concentration limits, according to industry safety panel (International Fragrance Association) | International Fragrance Association Codes & Standards |
| Fragrance unsafe for use in cosmetics according to industry safety panel (International Fragrance Association) | International Fragrance Association Codes & Standards |
| Gastrointestinal system toxicity - weight of evidence unknown/unassessed | Steinberg, P., T. Fischer, et al. (1999). "Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtaline (AHTN)." Toxicol Lett 111(1-2): 151-60. |
| IARC 3: mixed or limited evidence on human cancer potential (International Agency for Research on Carcinogens) | Inter'l Agency for Research on Cancer (IARC) Carcinogens |
| Limited evidence in humans - endocrine system toxicity | Eisenhardt, S., B. Runnebaum, et al. (2001). "Nitromusk compounds in women with gynecological and endocrine dysfunction." Environ Res 87(3): 123-30. |
| Limited evidence in humans - skin toxicity | Parker, R. D., E. V. Buehler, et al. (1986). "Phototoxicity, photoallergy, and contact sensitization of nitro musk perfume raw materials." Contact Dermatitis 14(2): 103-9. |
| Limited evidence of a carcinogenic effect (European Union classification); Limited evidence of a carcinogenic effect; Explosive; Risk of explosion by shock, friction, fire or other sources of ignition; Dangerous for the environment; Very toxic to aquatic organisms | European Union - Classification & Labelling |
| Nervous system toxicity - weight of evidence unknown/unassessed | Spencer PS, Bischoff-Fenton MC, Moreno OM, Opdyke DL, Ford RA. 1984. Neurotoxic properties of musk ambrette. Toxicology and applied pharmacology 75(3): 571-575. Rimkus G, Butte W, Geyer H. 1997. Critical conciderations on the analysis and bioaccumulation of Musk Xylene and other synthetic nitro musks in fish. Chemosphere 35(7): 1497-1507. Ford RA, Api AM, Newberne PM. 1990. 90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat. Food Chem Toxicol 28(1): 55-61. |
| Persistent, bioaccumulative toxicant - Limited or emerging evidence in open scientific literature | Emerging PBTs from peer-reviewed literature |
| Persistent, bioaccumulative toxicant - Oslo-Paris (OSPAR) Convention for the Protection of the Marine Environment of the North-East Atlantic, chemical of concern | OSPAR (2002). OSPAR List of Substances of Possible Concern. Secondary OSPAR List of Substances of Possible Concern. Secondary OSPAR. Place Published, OSPAR Convention for the Protection of the Marine Environement of North-East Atlanic. |
| Potential breast cancer risks | Bitsch N, Dudas C, Korner W, Failing K, Biselli S, Rimkus G, et al. 2002. Estrogenic activity of musk fragrances detected by the E-screen assay using human mcf-7 cells. Arch Environ Contam Toxicol 43(3): 257-264. |
| Prohibited from use in Canadian cosmetics | Canada's Cosmetic Ingredient Hotlist |
| Reproductive effects - weight of evidence unknown/unassessed | Rimkus GG, Wolf M. 1996. Polycyclic musk fragrances in human adipose tissue and human milk. Chemosphere 33(10): 2033-2043. Rimkus G, Butte W, Geyer H. 1997. Critical conciderations on the analysis and bioaccumulation of Musk Xylene and other synthetic nitro musks in fish. Chemosphere 35(7): 1497-1507. Ford RA, Api AM, Newberne PM. 1990. 90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat. Food Chem Toxicol 28(1): 55-61., Eisenhardt S, Runnebaum B, Bauer K, Gerhard I. 2001. Nitromusk compounds in women with gynecological and endocrine dysfunction. Environ Res 87(3): 123-130. |
| Reproductive toxicant - limited evidence | Eisenhardt, S., B. Runnebaum, et al. (2001). "Nitromusk compounds in women with gynecological and endocrine dysfunction." Environ Res 87(3): 123-30. |
| Skin sensitizer | Cronin E. 1984. Photosensitivity to musk ambrette. Contact dermatitis 11(2): 88-92. Parker RD, Buehler EV, Newmann EA. 1986. Phototoxicity, photoallergy, and contact sensitization of nitro musk perfume raw materials. Contact dermatitis 14(2): 103-109. Menz J, Muller SA, Connolly SM. 1988. Photopatch testing: a six-year experience. Journal of the American Academy of Dermatology 18(5 Pt 1): 1044-1047. Thune P, Jansen C, Wennersten G, Rystedt I, Brodthagen H, McFadden N. 1988. The Scandinavian multicenter photopatch study 1980-1985: final report. Photo-dermatology 5(6): 261-269. DeLeo VA, Suarez SM, Maso MJ. 1992. Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990. Archives of dermatology 128(11): 1513-1518. FDA (Food and Drug Administration). 1992. Cosmetic Handbook. Center for Food Safety and Applied Nutrition: FDA/Industry Activities Staff Booklet: 1992., Parker, R. D., E. V. Buehler, et al. (1986). "Phototoxicity, photoallergy, and contact sensitization of nitro musk perfume raw materials." Contact Dermatitis 14(2): 103-9. |
| Skin toxicity - weight of evidence unknown/unassessed | Hayakawa R, Matsunaga K, Arima Y. 1987. Depigmented contact dermatitis due to incense. Contact dermatitis 16(5): 272-274., Parker RD, Buehler EV, Newmann EA. 1986. Phototoxicity, photoallergy, and contact sensitization of nitro musk perfume raw materials. Contact dermatitis 14(2): 103-109. |
| Strong evidence in humans - skin toxicity | Cronin E. 1984. Photosensitivity to musk ambrette. Contact dermatitis 11(2): 88-92. Parker RD, Buehler EV, Newmann EA. 1986. Phototoxicity, photoallergy, and contact sensitization of nitro musk perfume raw materials. Contact dermatitis 14(2): 103-109. Menz J, Muller SA, Connolly SM. 1988. Photopatch testing: a six-year experience. Journal of the American Academy of Dermatology 18(5 Pt 1): 1044-1047. Thune P, Jansen C, Wennersten G, Rystedt I, Brodthagen H, McFadden N. 1988. The Scandinavian multicenter photopatch study 1980-1985: final report. Photo-dermatology 5(6): 261-269. DeLeo VA, Suarez SM, Maso MJ. 1992. Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990. Archives of dermatology 128(11): 1513-1518. FDA (Food and Drug Administration). 1992. Cosmetic Handbook. Center for Food Safety and Applied Nutrition: FDA/Industry Activities Staff Booklet: 1992. |
| Suspected persistent, bioaccumulative toxicant - Environment Canada, July 2006 chemical inventory review | EC (Environment Canada). 1994. Accelerated Reduction/Elimination of Toxics (ARET). ARET substance list of persistent, bioaccumulative and toxic chemicals. |
| Wildlife and environmental toxicity | Balk F, Ford RA. 1999. Environmental risk assessment for the polycyclic musks AHTN and HHCB in the EU. I. Fate and exposure assessment. Toxicology letters 111(1-2): 57-79. Wollenberger L, Breitholtz M, Ole Kusk K, Bengtsson BE. 2003. Inhibition of larval development of the marine copepod Acartia tonsa by four synthetic musk substances. Sci Total Environ 305(1-3): 53-64. Carlsson G, Norrgren L. 2004. Synthetic musk toxicity to early life stages of zebrafish (Danio rerio). Arch Environ Contam Toxicol 46(1): 102-105., Breitholtz M, Wollenberger L, Dinan L. 2003. Effects of four synthetic musks on the life cycle of the harpacticoid copepod Nitocra spinipes. Aquat Toxicol 63(2): 103-118. Wollenberger L, Breitholtz M, Ole Kusk K, Bengtsson BE. 2003. Inhibition of larval development of the marine copepod Acartia tonsa by four synthetic musk substances. Sci Total Environ 305(1-3): 53-64., Chou YJ, Dietrich DR. 1999. Interactions of nitromusk parent compounds and their amino-metabolites with the estrogen receptors of rainbow trout (Oncorhynchus mykiss) and the South African clawed frog (Xenopus laevis). Toxicology letters 111(1-2): 27-36. Breitholtz M, Wollenberger L, Dinan L. 2003. Effects of four synthetic musks on the life cycle of the harpacticoid copepod Nitocra spinipes. Aquat Toxicol 63(2): 103-118. Wollenberger L, Breitholtz M, Ole Kusk K, Bengtsson BE. 2003. Inhibition of larval development of the marine copepod Acartia tonsa by four synthetic musk substances. Sci Total Environ 305(1-3): 53-64. Carlsson G, Norrgren L. 2004. Synthetic musk toxicity to early life stages of zebrafish (Danio rerio). Arch Environ Contam Toxicol 46(1): 102-105. |
