Musk xylene
Encyclopedia
Musk xylene was the most widely used of the "nitro-musks", a type of synthetic musk fragrance
, which mimic natural musk
. It has been used as a perfume
fixative
in a wide variety of consumer products, and is still used in some cosmetics
and fragrances.
Use of musk xylene has declined sharply since the mid-1980s due to safety and environmental concerns. Its explosive and carcinogen
ic hazards are recognized to be borderline, and musk xylene is a useful example of the lowest level of such risks which need to be taken into account. However, it is a very persistent
and very bioaccumulative
polluant in the aquatic environment (vPvB substance), and is the first substance to be proposed as a "substance of very high concern
" (SVHC) for these reasons alone under the European Union
REACH Regulation.
(1,3-dimethylbenzene), by a Friedel–Crafts alkylation with tert-butyl chloride
and aluminium chloride
followed by nitration
with fuming nitric acid
or with a 70:30 mixture of nitric acid and sulfuric acid
. The crude product is recrystallized from 95% ethanol
.
Musk xylene has been used in a wide variety of consumer products since the early 1900s, usually in very small quantities. World production of nitro musks in 1987 was about 2500 tonnes, but had fallen to about 1000 tonnes by the early 1990s: musk xylene made up roughly two-thirds of the production of nitro musks during this period. Production was concentrated in Western Europe, with the United Kingdom
alone accounting for 28% of world production of nitro musks.
Use of musk xylene continued to decline through the 1990s, as fragrance manufacturers voluntarily switched to alternative fragrance compounds. For example, musk xylene has not been used in Japanese products (on a voluntary basis) since 1982, and the Association of the German Toiletries and Detergents Industry (IKW) recommended the replacement of musk xylene by another compound in 1993. Production of musk xylene in the European Union
came to a halt and, by 2000 (the last year for which full data are available), imports to Europe were only 67 tonnes, with China
as the most important source. The estimated 2008 usage of musk xylene in the European Union was 25 tonnes.
Musk xylene is still permitted for use in cosmetics products (except oral care products) in the European Union under the Cosmetics Directive
. The permitted quantities are: up to 1% in fine fragrances; up to 0.4% in eau de toilette; up to 0.03% in other products. European Union suppliers must inform their customers on request if a product contains more than 0.1% by weight of musk xylene.
has listed musk xylene as a "substance of very high concern
" (SVHC) under the REACH Regulation, judging it to be "very persistent and very bioaccumulative" (vPvB) but not meeting the criteria for human or environmental toxicity to be of concern.
Manual of Test Methods and Criteria as a substance which shows some explosive properties but which does not have to be transported as Class 1 dangerous goods
under the Model Regulations. It is transported as small flakes in plastic bags (maximum 50 kg net mass), which are themselves within cardboard drums to avoid tearing. This does not count as "confinement" in the meaning of explosives tests: indeed, the special packing is intended to prevent over-confinement during transport.
It will explode when detonated under confinement (UN gap test) or when heated under confinement (Koenen test), but does not explode under the BAM fallhammer test (limiting impact energy 25 J) or the BAM friction test (limiting load >360 N). There is no ignition, explosion, self-heating or visible decomposition when musk xylene is heated (without confinement) to 75 °C for 48 hours.
Nevertheless, musk xylene is classified in the European Union as an explosive under the Dangerous Substances Directive and as a category 1.1 explosive under the CLP Regulation. The European Union classification reflects the fact that hazardous heating under confinement cannot be excluded in the industrial use of musk xylene, as opposed to its transport, and so it is necessary to warn potential users of the risk.
s. It has been placed into Group 3 ("not classifiable as to their carcinogenicity to humans") by the International Agency for Research on Cancer
(IARC),, and is classified in the European Union
as category 3 carcinogen ("cause concern for man owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment") under the Dangerous Substances Directive and a category 2 carcinogen ("suspected human carcinogen") under the CLP Regulation.
These classifications are based mainly on a single study of oral exposure to musk xylene in B6C3F1-strain mice
. The mice showed a highly significant increase in liver
adenoma
s and carcinoma
s at median dietary intakes of 170 mg/kg body weight (males) and 192 mg/kg body weight (females), as well as significant increases in adenomas in the Harderian gland
(male mice only) and in the liver at median dietary intakes of 91 mg/kg body weight (males) and 101 mg/kg body weight (females).
The European Union Risk Assessment Report makes a number of observations about this study:
Musk xylene is not genotoxic. It has significant effects on liver function which are similar to those shown by phenobarbital
, for example, induction of CYP2B6
and other cytochrome P450 enzymes. The human carcinogenicity of phenobarbital has been the subject of debate, but it is currently classified in group 2B by the IARC and this appears to have been an important consideration in the classification of musk xylene as a category 3 carcinogen under the Dangerous Substances Directive. Nevertheless, the European Union Risk Assessment Report admits that musk xylene is a "borderline case".
A further complication is the metabolism
of musk xylene. One route of metabolism is through reduction of one or more nitro groups by the intestinal microflora (gut bacteria) to produce aromatic amine
s such as p-NH2-musk xylene. This metabolite has a different liver toxicity: in particular, it inhibits the CYP1B enzymes by covalent binding.
It should be noted that the induction of cytochrome P450 enzymes, the most likely cause of rodent carcinogenicity, is a threshold phenomenon, with a no observed effect level (NOEL) of 10 mg/kg/day in mice and a lowest observed effect level (LOEL) of 10 mg/kg/day in rats. The lowest oral dose which caused cancer (LOAEL) in B6C3F1-mice was 70 mg/kg/day. These are 1–3 orders of magnitude higher than human exposure, which is principally dermal rather than oral.
near Tokyo
, and subsequently in the river water itself, especially at the outlets of sewage treatment
plants. This led to a voluntary moratorium on the use of musk xylene in Japan from 1982. Similar residues were subsequently found in European waters such as the Elbe
, Stör
and Ruhr rivers in Germany
, the German Bight
area of the North Sea
and sewage treatment plant outlets in Sweden
. Typical concentrations were >0.001 µg/l in sea water, 0.001–0.01 µg/l in river water and 0.01–0.1 µg/l (sometimes higher) in the effluent from sewage treatment plants.
These findings indicate that musk xylene is not completely removed from wastewater
by the sewage treatment process. Two studies in Germany found compared musk xylene concentrations in incoming wastewater and sewage treatment plant effluent, and found removal rates of 82% and 58%. However, they are not concentrations which are expected to be toxic to aquatic life. The European Union Risk Assessment Report reviewed more than a dozen studies of the toxicity of musk xylene to algae and to aquatic vertebrates and invertebrates, and all found no observed effect concentrations greater than 10 µg/l, the chronic aquatic toxicity threshold in the EU REACH Regulation.
The biodegradation of musk xylene in sea water and in mixed sea water/sediment systems was studied in laboratory simulations using carbon-14
labelled musk xylene, and the results discussed in an addendum to the European Union Risk Assessment Report. The half-life in marine sediment was esimated to be 60 days or less, with biodegradation occurring by anaerobic reduction of the nitro groups. The half-life in sediment-free sea water was estimated to be more than 150 days, far above the "very persistent" threshold of 60 days. The 2008 addendum also discussed the photolysis of musk xylene in water and in air, which are rapid: however, photolysis was not considered to be relevant in the persistence of musk xylene in the environment, and was not taken into account in classifying it as a "very persistent" substance.
Several different primary bioaccumulation studies were reviewed in the European Union Risk Assessment Report, with bioaccumulation factors varying between 640 l/kg and 6740 l/kg. Given that musk xylene has a very high octanol
–water partition coefficient
(log Kow = 4.9), the higher bioaccumulation factors were considered to be the more significant. The 2008 addendum considered a further laboratory study from the Japanese Ministry of International Trade and Industry
which was not available to the authors of the original Risk Assessment Report and which also showed bioaccumulation factors in fish (Cyprinus carpio) that were higher than the REACH threshold of 5000 l/kg for "very bioaccumulative" substances. Bioaccumulation factors of more than 5000 l/kg (wet weight basis) have also been found in carp (Carassius carassius) and eels (Anguilla anguilla) from a sewage treatment pond.
Synthetic musk
Synthetic musks, known as white musks in the perfume industry, are a class of synthetic aromachemicals created by chemist and fragrance companies to emulate the scent of deer musk or other natural musk...
, which mimic natural musk
Musk
Musk is a class of aromatic substances commonly used as base notes in perfumery. They include glandular secretions from animals such as the musk deer, numerous plants emitting similar fragrances, and artificial substances with similar odors. Musk was a name originally given to a substance with a...
. It has been used as a perfume
Perfume
Perfume is a mixture of fragrant essential oils and/or aroma compounds, fixatives, and solvents used to give the human body, animals, objects, and living spaces "a pleasant scent"...
fixative
Fixative (perfumery)
In perfumery, a fixative is a natural or synthetic substance used to reduce the evaporation rate and improve stability when added to more volatile components. This allows the final product to last longer while keeping its original fragrance. Fixatives are indispensable commodities to the perfume...
in a wide variety of consumer products, and is still used in some cosmetics
Cosmetics
Cosmetics are substances used to enhance the appearance or odor of the human body. Cosmetics include skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and...
and fragrances.
Use of musk xylene has declined sharply since the mid-1980s due to safety and environmental concerns. Its explosive and carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
ic hazards are recognized to be borderline, and musk xylene is a useful example of the lowest level of such risks which need to be taken into account. However, it is a very persistent
Persistent organic pollutant
thumb|right|275px|State parties to the Stockholm Convention on Persistent Organic PollutantsPersistent organic pollutants are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes...
and very bioaccumulative
Bioaccumulation
Bioaccumulation refers to the accumulation of substances, such as pesticides, or other organic chemicals in an organism. Bioaccumulation occurs when an organism absorbs a toxic substance at a rate greater than that at which the substance is lost...
polluant in the aquatic environment (vPvB substance), and is the first substance to be proposed as a "substance of very high concern
Substance of very high concern
A substance of very high concern is a chemical substance for which it has been proposed that the use within the European Union be subject to authorisation under the REACH Regulation...
" (SVHC) for these reasons alone under the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
REACH Regulation.
Production and use
Musk xylene is produced from meta-xyleneM-Xylene
m-Xylene is an aromatic hydrocarbon, based on benzene with two methyl substituents.It is an isomer of o-xylene and p-xylene. The m stands for meta, meaning the two methyl substituents are at locants 1 and 3 on the aromatic ring....
(1,3-dimethylbenzene), by a Friedel–Crafts alkylation with tert-butyl chloride
Tert-Butyl chloride
tert-Butyl chloride is a colorless, liquid organic compound at room temperature. It is sparingly soluble in water, with a tendency to undergo spontaneous solvolysis when dissolved into it...
and aluminium chloride
Aluminium chloride
Aluminium chloride is the main compound of aluminium and chlorine. It is white, but samples are often contaminated with iron trichloride, giving it a yellow colour. The solid has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large...
followed by nitration
Nitration
Nitration is a general chemical process for the introduction of a nitro group into a chemical compound. The dominant application of nitration is for the production of nitrobenzene, the precursor to methylene diphenyl diisocyanate...
with fuming nitric acid
Nitric acid
Nitric acid , also known as aqua fortis and spirit of nitre, is a highly corrosive and toxic strong acid.Colorless when pure, older samples tend to acquire a yellow cast due to the accumulation of oxides of nitrogen. If the solution contains more than 86% nitric acid, it is referred to as fuming...
or with a 70:30 mixture of nitric acid and sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
. The crude product is recrystallized from 95% ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
.
| Product | Mass fraction (%) |
|---|---|
| Skin cream Moisturizer Moisturizers or emollients are complex mixtures of chemical agents specially designed to make the external layers of the skin softer and more pliable, by increasing its hydration by reducing evaporation. Naturally occurring skin lipids and sterols as well as artificial or natural oils,... |
0.0075 |
| Deodorant Deodorant Deodorants are substances applied to the body to affect body odor caused by bacterial growth and the smell associated with bacterial breakdown of perspiration in armpits, feet and other areas of the body. A subgroup of deodorants, antiperspirants, affect odor as well as prevent sweating by... |
0.0075 |
| Shampoo Shampoo Shampoo is a hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair... |
0.01 |
| Household detergent Detergent A detergent is a surfactant or a mixture of surfactants with "cleaning properties in dilute solutions." In common usage, "detergent" refers to alkylbenzenesulfonates, a family of compounds that are similar to soap but are less affected by hard water... s |
0.02 |
| Aftershave Aftershave Aftershave describes a lotion, gel, balm, powder, or liquid used mainly by men after they have finished shaving. It may contain an antiseptic agent such as denatured alcohol or stearate citrate to prevent infection of cuts... |
0.03 |
| Toilet soap Soap In chemistry, soap is a salt of a fatty acid.IUPAC. "" Compendium of Chemical Terminology, 2nd ed. . Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford . XML on-line corrected version: created by M. Nic, J. Jirat, B. Kosata; updates compiled by A. Jenkins. ISBN... |
0.04 |
| Air freshener Air freshener Air fresheners are consumer products used in homes or commercial products used in restrooms that typically emit fragrance. There are two broad air freshener categories: continuous action and instant action... |
0.07 |
| Cologne Eau de Cologne Eau de Cologne or simply Cologne is a toiletry, a perfume in a style that originated from Cologne, Germany. It is nowadays a generic term for scented formulations in typical concentration of 2-5% essential oils. However as of today cologne is a blend of extracts, alcohol, and water... /eau de toilette |
0.075 |
| Fine fragrance Perfume Perfume is a mixture of fragrant essential oils and/or aroma compounds, fixatives, and solvents used to give the human body, animals, objects, and living spaces "a pleasant scent"... |
0.05–0.1 |
| Sources: International Agency for Research on Cancer (1996); European Union Risk Assessment Report (2005). | |
| NOTE: Use of musk xylene varies widely between different countries and manufacturers; these figures should be regarded as indicative maxima for the period 1990–present. | |
Musk xylene has been used in a wide variety of consumer products since the early 1900s, usually in very small quantities. World production of nitro musks in 1987 was about 2500 tonnes, but had fallen to about 1000 tonnes by the early 1990s: musk xylene made up roughly two-thirds of the production of nitro musks during this period. Production was concentrated in Western Europe, with the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
alone accounting for 28% of world production of nitro musks.
Use of musk xylene continued to decline through the 1990s, as fragrance manufacturers voluntarily switched to alternative fragrance compounds. For example, musk xylene has not been used in Japanese products (on a voluntary basis) since 1982, and the Association of the German Toiletries and Detergents Industry (IKW) recommended the replacement of musk xylene by another compound in 1993. Production of musk xylene in the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
came to a halt and, by 2000 (the last year for which full data are available), imports to Europe were only 67 tonnes, with China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
as the most important source. The estimated 2008 usage of musk xylene in the European Union was 25 tonnes.
Musk xylene is still permitted for use in cosmetics products (except oral care products) in the European Union under the Cosmetics Directive
Cosmetics Directive
Council Directive 76/768/EEC of 1976-07-27 on the approximation of the laws of the Member States relating to cosmetic products is the main European Union law on the safety of cosmetics. It was made under Art. 100 of the Treaty of Rome...
. The permitted quantities are: up to 1% in fine fragrances; up to 0.4% in eau de toilette; up to 0.03% in other products. European Union suppliers must inform their customers on request if a product contains more than 0.1% by weight of musk xylene.
Safety
Musk xylene is an analogue of the explosive trinitrotoluene (TNT), so it is unsurprising that its safety characteristics have been studied in some detail. Indeed, the nitro musks were first discovered in an attempt to produce new high explosives. It has also been used – albeit in very small amounts – in mass-market consumer products for the last hundred years. The discovery of musk xylene residues in the environment prompted new concerns about its possible long-term toxicity, and led to the sharp decline in its use from the mid to late 1980s. The European Chemicals AgencyEuropean Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical, scientific and administrative aspects of the Registration, Evaluation, Authorisation and Restriction of Chemicals system...
has listed musk xylene as a "substance of very high concern
Substance of very high concern
A substance of very high concern is a chemical substance for which it has been proposed that the use within the European Union be subject to authorisation under the REACH Regulation...
" (SVHC) under the REACH Regulation, judging it to be "very persistent and very bioaccumulative" (vPvB) but not meeting the criteria for human or environmental toxicity to be of concern.
Explosive properties
Musk xylene is used as an example case in the United NationsUnited Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...
Manual of Test Methods and Criteria as a substance which shows some explosive properties but which does not have to be transported as Class 1 dangerous goods
Dangerous goods
Dangerous goods are solids, liquids, or gases that can harm people, other living organisms, property, or the environment. They are often subject to chemical regulations. "HazMat teams" are personnel specially trained to handle dangerous goods...
under the Model Regulations. It is transported as small flakes in plastic bags (maximum 50 kg net mass), which are themselves within cardboard drums to avoid tearing. This does not count as "confinement" in the meaning of explosives tests: indeed, the special packing is intended to prevent over-confinement during transport.
It will explode when detonated under confinement (UN gap test) or when heated under confinement (Koenen test), but does not explode under the BAM fallhammer test (limiting impact energy 25 J) or the BAM friction test (limiting load >360 N). There is no ignition, explosion, self-heating or visible decomposition when musk xylene is heated (without confinement) to 75 °C for 48 hours.
Nevertheless, musk xylene is classified in the European Union as an explosive under the Dangerous Substances Directive and as a category 1.1 explosive under the CLP Regulation. The European Union classification reflects the fact that hazardous heating under confinement cannot be excluded in the industrial use of musk xylene, as opposed to its transport, and so it is necessary to warn potential users of the risk.
Carcinogenicity
Musk xylene also demonstrates some of the problems of classifying substances as carcinogenCarcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s. It has been placed into Group 3 ("not classifiable as to their carcinogenicity to humans") by the International Agency for Research on Cancer
International Agency for Research on Cancer
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations....
(IARC),, and is classified in the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
as category 3 carcinogen ("cause concern for man owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment") under the Dangerous Substances Directive and a category 2 carcinogen ("suspected human carcinogen") under the CLP Regulation.
These classifications are based mainly on a single study of oral exposure to musk xylene in B6C3F1-strain mice
House mouse
The house mouse is a small rodent, a mouse, one of the most numerous species of the genus Mus.As a wild animal the house mouse mainly lives associated with humans, causing damage to crops and stored food....
. The mice showed a highly significant increase in liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...
s and carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
s at median dietary intakes of 170 mg/kg body weight (males) and 192 mg/kg body weight (females), as well as significant increases in adenomas in the Harderian gland
Harderian gland
Harderian gland is a gland found within the eye's orbit which occurs in vertebrates that possess a nictitating membrane....
(male mice only) and in the liver at median dietary intakes of 91 mg/kg body weight (males) and 101 mg/kg body weight (females).
The European Union Risk Assessment Report makes a number of observations about this study:
- it was conducted on a single species; no studies are available on, for example, rats;
- B6C3F1-strain mice are known to be particularly prone to liver cancers;
- the doses were high, and toxic effects (especially on the liver) were observed in the test animals;
- the mechanism of tumour development is unclear.
Musk xylene is not genotoxic. It has significant effects on liver function which are similar to those shown by phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
, for example, induction of CYP2B6
CYP2B6
Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene. CYP2B6 is a member of the Cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances.- Function :...
and other cytochrome P450 enzymes. The human carcinogenicity of phenobarbital has been the subject of debate, but it is currently classified in group 2B by the IARC and this appears to have been an important consideration in the classification of musk xylene as a category 3 carcinogen under the Dangerous Substances Directive. Nevertheless, the European Union Risk Assessment Report admits that musk xylene is a "borderline case".
A further complication is the metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
of musk xylene. One route of metabolism is through reduction of one or more nitro groups by the intestinal microflora (gut bacteria) to produce aromatic amine
Aromatic amine
An aromatic amine is an amine with an aromatic substituent - that is -NH2, -NH- or nitrogen group attached to an aromatic hydrocarbon, whose structure usually contains one or more benzene rings. Aniline is the simplest example....
s such as p-NH2-musk xylene. This metabolite has a different liver toxicity: in particular, it inhibits the CYP1B enzymes by covalent binding.
It should be noted that the induction of cytochrome P450 enzymes, the most likely cause of rodent carcinogenicity, is a threshold phenomenon, with a no observed effect level (NOEL) of 10 mg/kg/day in mice and a lowest observed effect level (LOEL) of 10 mg/kg/day in rats. The lowest oral dose which caused cancer (LOAEL) in B6C3F1-mice was 70 mg/kg/day. These are 1–3 orders of magnitude higher than human exposure, which is principally dermal rather than oral.
Environmental concerns
The first concerns about musk xylene arose in the early 1980s, with the detection of musk xylene residues in fish from the Tama RiverTama River
The is a major river in Yamanashi, Kanagawa and Tokyo Prefectures on Honshū, Japan. It is officially classified as a Class 1 river by the Japanese government....
near Tokyo
Tokyo
, ; officially , is one of the 47 prefectures of Japan. Tokyo is the capital of Japan, the center of the Greater Tokyo Area, and the largest metropolitan area of Japan. It is the seat of the Japanese government and the Imperial Palace, and the home of the Japanese Imperial Family...
, and subsequently in the river water itself, especially at the outlets of sewage treatment
Sewage treatment
Sewage treatment, or domestic wastewater treatment, is the process of removing contaminants from wastewater and household sewage, both runoff and domestic. It includes physical, chemical, and biological processes to remove physical, chemical and biological contaminants...
plants. This led to a voluntary moratorium on the use of musk xylene in Japan from 1982. Similar residues were subsequently found in European waters such as the Elbe
Elbe
The Elbe is one of the major rivers of Central Europe. It rises in the Krkonoše Mountains of the northwestern Czech Republic before traversing much of Bohemia , then Germany and flowing into the North Sea at Cuxhaven, 110 km northwest of Hamburg...
, Stör
Stör
The Stör is a river in Schleswig-Holstein, Germany, right tributary of the Elbe. Its total length is 87 km. The Stör rises east of Neumünster, and flows west through Neumünster, Kellinghusen, and Itzehoe. The Stör joins the Elbe near Glückstadt....
and Ruhr rivers in Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
, the German Bight
German Bight
German Bight is the southeastern bight of the North Sea bounded by the Netherlands and Germany to the south, and Denmark and Germany to the east . To the north and west it is limited by the Dogger Bank. The Bight contains the Frisian and Danish Islands. The Wadden Sea is approximately ten to...
area of the North Sea
North Sea
In the southwest, beyond the Straits of Dover, the North Sea becomes the English Channel connecting to the Atlantic Ocean. In the east, it connects to the Baltic Sea via the Skagerrak and Kattegat, narrow straits that separate Denmark from Norway and Sweden respectively...
and sewage treatment plant outlets in Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
. Typical concentrations were >0.001 µg/l in sea water, 0.001–0.01 µg/l in river water and 0.01–0.1 µg/l (sometimes higher) in the effluent from sewage treatment plants.
These findings indicate that musk xylene is not completely removed from wastewater
Wastewater
Wastewater is any water that has been adversely affected in quality by anthropogenic influence. It comprises liquid waste discharged by domestic residences, commercial properties, industry, and/or agriculture and can encompass a wide range of potential contaminants and concentrations...
by the sewage treatment process. Two studies in Germany found compared musk xylene concentrations in incoming wastewater and sewage treatment plant effluent, and found removal rates of 82% and 58%. However, they are not concentrations which are expected to be toxic to aquatic life. The European Union Risk Assessment Report reviewed more than a dozen studies of the toxicity of musk xylene to algae and to aquatic vertebrates and invertebrates, and all found no observed effect concentrations greater than 10 µg/l, the chronic aquatic toxicity threshold in the EU REACH Regulation.
The biodegradation of musk xylene in sea water and in mixed sea water/sediment systems was studied in laboratory simulations using carbon-14
Carbon-14
Carbon-14, 14C, or radiocarbon, is a radioactive isotope of carbon with a nucleus containing 6 protons and 8 neutrons. Its presence in organic materials is the basis of the radiocarbon dating method pioneered by Willard Libby and colleagues , to date archaeological, geological, and hydrogeological...
labelled musk xylene, and the results discussed in an addendum to the European Union Risk Assessment Report. The half-life in marine sediment was esimated to be 60 days or less, with biodegradation occurring by anaerobic reduction of the nitro groups. The half-life in sediment-free sea water was estimated to be more than 150 days, far above the "very persistent" threshold of 60 days. The 2008 addendum also discussed the photolysis of musk xylene in water and in air, which are rapid: however, photolysis was not considered to be relevant in the persistence of musk xylene in the environment, and was not taken into account in classifying it as a "very persistent" substance.
Several different primary bioaccumulation studies were reviewed in the European Union Risk Assessment Report, with bioaccumulation factors varying between 640 l/kg and 6740 l/kg. Given that musk xylene has a very high octanol
Octanol
Octanol is a straight chain fatty alcohol with eight carbon atoms and the molecular formula CH37OH. Although the term octanol usually refers exclusively to the primary alcohol 1-octanol, there are other less common isomers of octanol such as the secondary alcohols 2-octanol, 3-octanol and...
–water partition coefficient
Partition coefficient
In chemistry and the pharmaceutical sciences, a partition- or distribution coefficient is the ratio of concentrations of a compound in the two phases of a mixture of two immiscible solvents at equilibrium. The terms "gas/liquid partition coefficient" and "air/water partition coefficient" are...
(log Kow = 4.9), the higher bioaccumulation factors were considered to be the more significant. The 2008 addendum considered a further laboratory study from the Japanese Ministry of International Trade and Industry
Ministry of International Trade and Industry
The Ministry of International Trade and Industry was one of the most powerful agencies of the Government of Japan. At the height of its influence, it effectively ran much of Japanese industrial policy, funding research and directing investment...
which was not available to the authors of the original Risk Assessment Report and which also showed bioaccumulation factors in fish (Cyprinus carpio) that were higher than the REACH threshold of 5000 l/kg for "very bioaccumulative" substances. Bioaccumulation factors of more than 5000 l/kg (wet weight basis) have also been found in carp (Carassius carassius) and eels (Anguilla anguilla) from a sewage treatment pond.
Further reading
- "ATP (2004) to the Cosmetics Directive": Commission Directive 2004/88/EC of 7 September 2004 amending Council Directive 76/768/EEC concerning cosmetic products for the purpose of adapting Annex III thereto to technical progress. OJEC L287, 8.9.2004, pp. 5–6.
- "ATP (2004) to the Dangerous Substances Directive": Commission Directive 2004/73/EC of 29 August 2004 adapting to technical progress for the 29th time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. OJEC L152, 30.04.2004, pp. 1–311.
- "CLP Regulation": Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. OJEC L353, 31.12.2008, pp. 1–1355.. .
- European Union Risk Assessment Report (2005). "5-tert-butyl-2,4,6-trinitro-m-xylene (musk xylene)". 3rd Priority List, Volume 55..
- "GHS": . ..... OSPAR background document.
- Position document prepared for the European Chemicals Bureau (9 December 2002). Classification and labelling of musk-xylene.
- "REACH Regulation": Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency. OJEUOfficial Journal of the European UnionThe Official Journal of the European Union is the official gazette of record for the European Union . It is published every working day in all of the official languages of the member states. Only legal acts published in the Official Journal are binding.It was first published on 30 December 1952 as...
L396, 30.12.2006, pp. 1–849.. Technical report for the European Chemicals AgencyEuropean Chemicals AgencyThe European Chemicals Agency is an agency of the European Union which manages the technical, scientific and administrative aspects of the Registration, Evaluation, Authorisation and Restriction of Chemicals system...
. - "UN Manual of Tests and Criteria":
- "UN Model Regulations": .. . Monograph 121. , 14 January 2009., 14 January 2009..