Pharmaceuticals and Care Products in the ... - ACS Publications

Chapter 10

Environmental Risks of Musk Fragrance Ingredients 1

1

2

Froukje Balk , Han Blok , and Daniel Salvito 1

Haskoning Consulting Engineers and Architects, P.O. Box 151, 6500 AD Nijmegen, The Netherlands Research Institute of Fragrance Materials, Two University Plaza, Suite 406, Hackensack, NJ 07601

Downloaded by UNIV OF ARIZONA on July 28, 2012 | http://pubs.acs.org Publication Date: July 30, 2001 | doi: 10.1021/bk-2001-0791.ch010

2

Synthetic musk fragrance ingredients are used in many personal care products and in household cleaning products. Representatives are the polycyclic musks ( A H T N and H H C B ) and the nitromusks (musk ketone and musk xylene). The environmental fate and behavior of these substances are reviewed. Comparison of environmental concentrations with toxicity data shows that the risks of these substances for aquatic and terrestrial organisms, as well as for the aquatic food chain, are low.

Introduction Personal care products are marketed for direct use by the consumer and have intended end uses primarily on the human body, according to the definition of Daughton and Ternes ( i ) . This category includes cosmetics, toiletries, and fragrances. The odor of these products is a highly important element and often a key factor for the consumer. Fragrance ingredients are used not only in personal

168

© 2001 American Chemical Society

In Pharmaceuticals and Care Products in the Environment; Daughton, C., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2001.

169 care products but also in many consumer and household products such as detergents and cleaning products. In fact, their use in the categories of soaps, fabric softeners, detergents, and cleaners accounts for more than half of the total use, and less than 40% is used in personal care products. The concentration of fragrances varies strongly per product type or category. In colognes and eau de toilette, the concentration may be between 5 and 8%, whereas in perfume extracts it may be up to 20%. Approximate concentrations in cosmetics like skin and hair care products and bath/shower products are 0.5%, and in products where they are intended to mask product odors, it is less than 0.1%. For detergents, the concentrations range from 0.1% to 5% (2 3). Synthetic musks are important ingredients in fragrances because of their typical musky scent and their fixative properties. Synthetic musks comprise a series of chemicals that emulate the odor of the musk deer and musk rats, but have different chemical structures: nitromusks (NMs) and polycyclic musks (PCMs). The most important are the polycyclic musks with 6-acetyl-1,1,2,4,4,7hexamethyltetraline (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-y-2-benzopyran (HHCB) as the major products. Together they represent about 95% of the E U market and 90% of the U S market for all polycyclic musks. Other members of this group are A D B I , A H M I , and A I T L Chemical names, structures, and characteristics are given in Table I. The nitromusks make less than 8% of the synthetic musks volume in the E U and less than 6% of the U S volume. The main representatives of this group are musk ketone and musk xylene. Fragrance ingredients have attracted attention in the past decade following the detection of certain N M s and the PCMs in samples of surface water, fish and human adipose tissue, and milk in Germany (4,5,6,7,8,9). These findings prompted more environmental sampling and analysis in other countries and initiated a series of discussions on the environmental safety of these substances. In the O S P A R (Oslo and Paris Commissions for the Prevention of Marine Pollution) Action Plan of 1998, musk compounds were included in the category of 'diffuse sources and groups of substances' to be considered for action. In the Netherlands, on behalf of the Ministry of the Environment ( V R O M ) an environmental risk assessment was carried out on the N M s (musk ketone and musk xylene) by the Dutch National Institute of Public Health and the Environment R I V M (10,11). A t the same time, human health effects of the N M s and PCMs were evaluated by the E U Scientific Committee on Cosmetics. In the meantime, the N M s were also included on the EU's Third Priority List related to the E U Existing Chemicals Regulation (EEC 793/93). With The Netherlands as the rapporteur, R I V M will proceed with a risk assessment for the environment, for the consumer, and for occupational health. Simultaneously with these events, the Research Institute of Fragrance Materials (RIFM) initiated a risk assessment for the two most important PCMs. The reports have been adopted by the Dutch


s


170 authorities (3) and published (12,13). Both A H T N and H H C B are on the EU's Fourth Priority List for the Existing Chemicals Regulation. During the process, more physico-chemical and ecotoxicity data are being generated to refine the risk assessment results. The environmental risks of musk ketone and musk xylene and for A H T N and H H C B will be reviewed here.

Emission


Use Volume The use volumes for Europe have been surveyed by R I F M (Research Institute of Fragrance Materials) and by IFRA (International Fragrance Association) since 1992. There has clearly been a general downward trend in the use of the four major musks, as in 1998 the use volume for each was reduced roughly by a factor of 2 or more as compared with 1992 (Table I).

Table I: Use volume [metric tons] of Nitromusks and Polyeyelie Musks in Europe

1992

Europe 1995

1998

Nitromusks Musk ketone Musk xylene Moskene Musk tibetene

124 174 17 3

61 110 5 0.8

40 86

885 2400

585 1482 34 3 40

385 1473 18 19 2

Polycyclic musks AHTN HHCB ADBI AHMI AITI

Release to the environment Due to their application in detergents, household cleaning products, and bath and hair care products, most of the production volume of the N M s and the PCMs is released to the sewer after use. The share of the fragrance ingredients used in these categories is estimated at 75% of the total use volume in the E U


171


(Fig. 1). For practical reasons, it is assumed for the environmental risk assessment that the remaining 25% (personal care, toiletries, perfumes) will be washed off after use and also be released to the sewer as well.

Figure 1. The use offragrance oil in the European Union.

Environmental fate and behavior Identification and physico-chemical characteristics Nitromusks are nitrated aromatics and polycyclic musks are substituted indanes and tetralins. The characteristics of representatives of both groups of synthetic musks is given in Table II. Common physico-chemical characteristics are their hydrophobic behavior (log K o w > 4.5) and poor solubility in water, at a level of 0.1 to 2 mg/L. Based on the lipophilicity of the substances, they are expected to adsorb strongly to organic materials such as sewage sludge, sediments, and lipid tissue.


172

Table II. Characteristics of musk fragrance ingredients. a

Identification and characteristics

Structure

Nitromusks Musk ketone C A S : 81-14-1 3,5-dinitro-2,6-dimethyl-4t-butyl-acetofenone

C H N 0 M W 294.3 S 1.9 mg/L log K o w 4.3 Vp 0.04 χ 1 0 Pa 1 4

I 8

2

5

b


3

Musk xylene C A S : 81-15-2 2,4,6-trinitro-1,3-dimethyl5-t-butylbenzene

C H N 0 M W 297.3 S 0.49 mg/L log Kow 4.9 Vp 0.03 χ 10' Pa 1 2

1 5

3

6

b

3

Moskene C A S : 116-66-5 1,1,3,3,5-pentamethyl-4,6dinitroindane

b

b

NCL

C H N 0 M W 278.3 S 0.17 mg/L log K o w 5.39 * Vp 0.00023 Pa 1 4

1 8

2

4

b

h

Musk tibetene C A S : 145-39-1 1 -ter-butyl-3,4,5-trimethyl2,6- dinitrobenzene

C H N 0 M W 266.3 S 0.29 mg/L log Kow 5.18 Vp 0.00058 Pa 1 3

1 8

2

4

b

b

b

Polycyclic mush AHTN

Ci H 0 M W 258.4 S 1.25 mg/L log K o w 5.7 Vp 0.0608 Pa 8

C A S : 21145-77-7 and 1506-02-1 Tonalid®, Fixolide® 7-acetyl-1,1,3,4,4,6hexamethyl-1,2,3,4tetrahydronaphtalene

2 6


173

Table II. Continued


HHCB C A S : 1222-05-5 Galaxolide 50®, Abbalide® 1,3,4,6,7,8-hexahydro4,6,6,7,8,8-hexamethylcyclopenta[gamma]2-benzopyran

ABDI

C H 0 M W 258.4 S 1.75 mg/L log Kow 5.9 V p 0.0727 Pa 1 8

2 6

C H 0 M W 244.4 S 0.22 mg/L log Kow 5.93 Vp 0.0192 Pa 1 7

C A S : 13171-00-1 Celestolide®, Crysolide® 4-aeetyl-6-tert-butyl-1,1dimethylindan

AITI

C H 0 M W 258.4 S 0.09 mg/L log K o w 6.31 Vp 0.0091 Pa 1 8

C A S : 68140-48-7 Traseolide® 5-acetyl-l,l,2,6tetramethyl-3-isopropylindan

AHMI

b

b

b

2 6

C, H 0 M W 244.4 S 0.25 mg/L log Kow 5.85 Vp 0.0196 Pa 7

C A S : 15323-35-0 Phantolid® 5 -acetyl-1,1,2,3,3,6hexamethylindan

2 4

b

b

b

2 4

b

b

b

" MW: molecular weight; S: water solubility, Vp: vapor pressure b

estimated value (14); log Kow tends to be overestimated for these substances


174


Bioaccumulation The synthetic musks have attracted attention because they were detected in fish samples. With log K o w between 4.3 and 5.9, a high bioaccumulation potential is expected. However, most experiments with fish show bioaccumulation factors (fresh weight), between 500 and 1500. Bioconcentration factors (BCFs ) are summarized in Table III. Field-derived BCFs have been included for comparison. These values tend to be lower than the ones determined in the laboratory. However, it is always difficult to determine the exposure conditions for fish caught in surface waters (varying water concentrations, exposure to both dissolved and sorbed contaminants, presence of other substances, history, etc.). The test design of the bioaccumulation experiments with musk ketone, A H T N , and H H C B included the measurement of metabolites. For these three substances, it could be established that they are transformed to more polar metabolites in a relatively short time and that these metabolites are rapidly excreted by the fish. Elimination half-lives were estimated at 2.5 days for musk ketone, 1 to 2 days for A H T N , and 2 to 3 days for H H C B . This indicates that the accumulation of these substances is highly reversible (11,12). Degradability The biodegradability of musk ketone, musk xylene, A H T N , and H H C B has been investigated in standard tests. These tests follow the oxygen consumption or carbon dioxide production over time. Under the conditions of these standard tests (OECD T G 301 or 302 for ready or inherent biodégradation), the mineralization of these substances is slow. In the two-phase closed bottle test (ISO 10708), A H T N and A H M I showed a low level of mineralization (12-21%) (12,13). The PCMs, however, are not persistent and they are biotransformed. A H T N , H H C B , and A H M I were shown to degrade in certain soil samples and in cultures inoculated with soil microorganisms to various more polar metabolites within a few days to a week. In another study with an air-borne fungus, later on amended with a soil slurry, H H C B was transformed to its lactone and to more polar structures and some C 0 . In a microcosm study with four soil types, an average of 14% H H C B remained after one year, showing that H H C B was disappearing with a half-life of approximately 4 months (12). When added to activated sludge, H H C B was transformed to its lactone (log K o w 4.0) and HHCB-hydroxy acid (log Kow 0.5). After 24 h, the overall metabolite pattern 2


175

Table III. Substance

Bioaccumulation of musk fragrance ingredients. log Source BCF [method]

Nitromusks musk 4.3 ketone

Rainbow trout (8+21 ) d - B C F = 1380 [ C] Xenopus l l d - B C F = 3 [GC] environmental samples B C F = 1100 Bluegill sunfish (16+12)d-BCF = 1600 [ C] Rainbow trout (190+250)d-BCF = 4400 [GC/MS] Zebrafish 4à-BŒ^ = An [ C ] Xenopus 4 d - B C F = 47 [ C] lld-BCF =12[GC] Rainbow trout 2 l d - B C F 10 to 60 [GC/MS] ww

14


w w

musk xylene

4.9

ww

14

ww

! 4

14

(U) (15) (16) (U) (17) (15) (15)

a

a

ww

(18)

ww

w w

moskene

5.4

Polycyclic musks AHTN

5.7

environmental samples B C F = 4100 Xenopus l l d - B C F = 12 [GC] w w

Zebrafish (14+26)d-BCF = 600 [GC/MS] Bluegill sunfish (28+28)d-BCF = 597 [ C, L C / H P L C ] ww

ww

(16)

(15)

(19) (12)

14

environmental samples: Eel B C F ^ = 200 to 650 non-eel B C F = 50 to 145

{12)

environmental samples: E e l B C F = 410 R u d d B C F = 460 Tench B C F = 280 * Mussel B C F = 560

(20)

W W

6

w w

b

ww

W W

b

W W

Continued on next page.


176 Table III. Continued HHCB

5.9

Zebrafish (14+26)d-BCF = 624 [GC/MS] Bluegill sunfish (2%+2%)â-BŒ^ = 1584 [ C, T L C / H P L C ]

(19) (12)

environmental samples: Eel B C F = 150to600 non-eel B C F = 49 to 188

(12)

environmental samples: E e l B C F = 290 R u d d B C F = 230 Tench B C F = 620 Mussel B C F = 500

(20)

ww

14

w w

W W

b


w w

b

ww

6

W W

b

W W

a

The different values may be explained by the transformation into metabolites that are included in detection by C and not by GC. Recalculated from B C F with fraction lipids (data for a sewage pond in SH, Germany) 1 4

b

Lipid

increased in polarity as time progressed. Analysis by reversed-phase H P L C showed three peaks in the extracts with log K o w < 0.1, 2.1, and 3.1. The halflife of H H C B under these conditions was 21 h (21). A tentative mass balance calculation for the sludge digestion process, assuming no biodégradation during the sewage treatment process, showed that approximately 40 to 45% of A H T N and H H C B is removed during sludge digestion, probably by primary degradation (12). For the N M s , musk ketone and musk xylene, it was shown that during sewage treatment a major metabolism pathway is the reduction of the nitrogroups to form 2-amino-MK, 4-amino-MX, and 2-arnino-MX (22). These metabolites are more polar, e.g., log Kow of 4-amino-MX is 3.8 (23). The photodegradation of four nitromusks and A H T N was examined by irradiating an aqueous solution with artificial U V light (mercury-high pressure burner O M N I L A B TQ 150) at room temperature. The measured half-lives under these conditions are in the range of 2.0 to 8.2 min for the nitromusks and 1.25 min for A H T N . This degradation was also attained under sunlight but at a lower rate. At termination of the experiment with A H T N (after 5 hours), no metabolites could be detected even after 1000-fold concentration (24,25). The atmospheric oxidation was estimated as the rate in the reaction with hydroxyl radicals. Assuming a concentration of 1.5xl0 OH/cm , a light period of 12 h per day and 25 °C, the atmospheric half-lives for the nitromusks vary between 5 and 13 days. Under those conditions, the estimated half-lives for the polycyclic musks vary between 3 and 16 hours (14). 6

3


177


Environmental pathways

The major portion of the musk fragrances is used in private households in detergents, cleaning products, and personal care products that end up in domestic wastewater after use. During sewage treatment, a fraction of the load may be degraded, and the remainder partitions between the water phase and the organic matter of the activated sludge. Due to the lipophilic character of these substances, a high portion is sorbed to sludge. Removal percentages vary between 50 and more than 90%, depending on the treatment plants and sampling strategy (12). After discharge, the effluent of the treatment plants is diluted in surface water where the remainder of the substances further partitions between the suspended matter or sediment in the river, accumulates in fish and other aquatic organisms, and may be further biodegraded. Predatory birds or mammals may take up the material accumulated in fish. In some states, sewage sludge is disposed to land where it is possible that musks will end up in the terrestrial compartment. However, for AHTN, HHCB, and AHMI, it was shown that these substances may be degraded in soil. For the nitromusks these experiments have not been conducted. If present in soil, the musks may be available for terrestrial organisms (insects, worms, and other invertebrates) and be taken up by their predators (insectivores, small mammals, and birds). In the risk assessments carried out for musk ketone and musk xylene, as well as for AHTN and HHCB in Europe, the aquatic and terrestrial compartments were considered (11,12,13). For these risk assessments, calculations have been performed using the European Union System for the Evaluation of Substances (EUSES) (26). EUSES conservatively estimates the environmental fate and concentrations of the substances in a region modeling the highly populated western part of Europe (200 χ 200 km and 20 χ 10 inhabitants) (27). For AHTN and HHCB, the estimated concentrations in sludge were substituted with actual measured concentrations. In the meantime, more data from environmental samples have become available allowing a better estimation of the daily input per inhabitant of some musk ingredients to the sewage treatment plant (STP) and the distribution and degradation during the sewage treatment process and in the soil. This results in a flow diagram where the environmental pathways predicted by EUSES have been refined using empirical data. Figure 2 shows the environmental fate of HHCB as an example. 2

6

Example: Environmental fate of HHCB In the EU risk assessment, it was originally assumed that the total use volume of HHCB would be discharged to the sewer. This implied a daily discharge of 11.1 mg per person (inhabitant equivalent or I.E.). Based on the standard scenario of EUSES, the predicted concentrations in influent, effluent,


178


1482ton/yrinEU

1

11.1 mgi.eAcT = 100%

input to SIP

volatilisation

h

^

\r 'y/

:ion in digester (g) ι digester

volatilisation

soil (h)

soil 0.6%

dll

Figure 2. Fate of HHCB in the 'regional environment' of EUSES. See text for further explanation.



179 and sludge, however, were higher than the measured concentrations by a factor of 10 to 20, which implies that the fraction discharged to the sewer may be considerably lower than 1. Therefore the mass flow of H H C B has been further analyzed based on the partition processes between the compartments in EUSES and refinements derived from measurements. Effluent and sludge concentrations were measured in various European countries. The median effluent concentrations in these data sets varied between I. 4 and 2.3 μg/L (see also Fig. 3). Median concentrations in sludge were approximately 14 mg/kg in primary sludge, 4 to 28 mg/kg in activated sludge, and approximately 20 mg/kg in digested sludge (more details in next section). According to the tentative mass balance in the STP, the removal of H H C B during sludge digestion was estimated at 45% (12) [g in Fig. 2]. The input to the STP per I.E. is derived from the amount of H H C B on primary and activated sludge (1.35 mg/d) and from the effluent in the STP (0.34 mg/day), totalling 1.7 mg/d per i.e. [e in Fig. 2]. This is 15% of the estimated discharge per I.E. of II. 1 mg/day. In the EUSES model, sludge is used as an amendment on agricultural land. In mesocosm experiments where H H C B was applied to four different soil types, an average of 14% H H C B remained in the soil after 1 year (12) [h in Fig. 2]. EUSES assumes that 70% of the wastewater is treated in an STP and that 30% is directly discharged to surface water. Based on the above data and calculations and on the partition coefficients between the compartments, the generalized mass flow for H H C B as presented in Figure 2 predicts a concentration in sludge of 13 mg/kg [f in Fig. 2], an effluent concentration of 1.2 μg/L and a 'steady state' concentration in surface water of 0.03 μg/L in remote regions [c and d in Fig. 2]. Actually, the concentrations in a region will decrease from 1.2 μg/L in almost undiluted effluent directly after discharge, to 0.03 μg/L. The frequency of measured surface water concentrations in Figure 4 shows that measured H H C B concentrations fall in this range. The modeling of volatilization in the regional model of EUSES is based on the physico-chemical parameters of H H C B and the relative volumes of the environmental compartments. The loss of material by volatilization proves to be an important process, which may be explained by the large air volume as compared with the volumes of the other compartments [b in Figure 2]. In the same way, volatilization could be the major loss process during use of the household products or cosmetics. After all, they can only serve their function as a fragrance when they are in the air. Therefore, the fraction in the top of the scheme in Figure 2 [a] that is lost between the 'use per inhabitant' and 'detected in the STP' may be explained to a large extent by volatilization during/after use.


180

AHTN n=44


• Switz. ONL1

i

HNL2

J

UD-Ruhr i

HHCB n=47

Figure 3. Concentrations of AHTN and HHCB in STP effluents from Sweden (31), Switzerland (33), Netherlands NL1 (29), NL2 (30), D-Ruhr (6).


181

Environmental concentrations Musks have been detected in surface waters and sediment, biota, and in wastewater treatment plants. Often the results of these studies are summarized as a minimum and a maximum with occasionally a mean or median and a 90 percentile value. Thus it is often difficult to gain an insight in the relevance of the values. They may be part of a large or a limited sampling activity, and the maximum may be quite extreme. For a proper assessment of the environmental risk, the probability of occurrence of the environmental concentrations is of importance. Therefore a frequency distribution is more useful than a list of extremes. Downloaded by UNIV OF ARIZONA on July 28, 2012 | http://pubs.acs.org Publication Date: July 30, 2001 | doi: 10.1021/bk-2001-0791.ch010

th

Concentrations in sewage treatment plants Concentrations were measured in effluent samples of sewage treatment plants on the Ruhr (6), in Hamburg and Schleswig-Holstein in Germany (22,28), in The Netherlands (29,30), in Sweden (31), and in Switzerland (32,33) between 1993 and 1998. The concentration of musk ketone in effluents seems to vary around 0.2 μg/L, ranging from below the detection limits, to exceptional values around 1 μg/L. Figure 3 presents the frequency distributions of the available data for A H T N and H H C B . The median and 90 -percentile are 1.3 and 2.9 μg/L for A H T N and 1.6 and 4.5 μg/L for H H C B . The generic effluent concentration of 1.2 μg/L predicted above (see Fig. 2) for H H C B corresponds to the 36 -ρεΓ06ηηΐ6 in the distribution frequency of the measured data. This frequency distribution may be used as a reference for comparison with other effluent sample concentrations. ih

Λ

Concentrations measured in sludge in Germany (34), The Netherlands (35,29), and Switzerland (36) range roughly between 1 and 30 mg/kg for both A H T N and H H C B and between the detection limit to 0.06 mg/kg for musk ketone and musk xylene (12,37).

Surface water concentrations The concentrations found in surface water are highly variable, with higher concentrations clearly related to samples in close proximity to STP discharge points. The concentrations reported from a large number of studies are summarized in Figure 4. For H H C B , the median of the concentrations encountered in the Western European surface waters (n=209, excluding the North Sea samples) is 0.07 μg/L, and the 90 -percentile is 0.5 μg/L. Some extremely high concentrations were observed in surface waters in Berlin in th



182

Figure 4. Concentrations of AHTN and HHCB in surface water North Sea: German Bight (38), CH: Swiss rivers and lakes (33), CH: Glatt (39), Rhine and Meuse Dutch border (40), Netherlands surface waters NL1 (29), NL2 (30), Germany: D-Berlin, water system Berlin (41), D-Ruhr( 6), D-Elbel (38), D-Elbe2 (42), D-Elbe3 (43), Japan: Tama river (44). (Adapted with permissionfromreference 12, Copyright 1999 Elsevier Science).

which a high proportion of the flow consists of sewage treatment plant effluents. Of all the samples, 27% are < 0.03 μg/L, which corresponds to the generic concentration in remote areas as predicted above (see Fig. 2). Likewise, the concentrations of A H T N and musk ketone in over 200 surface water samples are presented in Figures 4 and 5. The median and ^-percentiles for Western Europe are 0.07 and 0.3 μg/L for A H T N and 67 μg/L), loss of caudal fin was observed. A t the next higher concentration (140 μg/L), larvae survival was 18% (13). The toxicity of the amino metabolites of musk xylene to D. magna was shown to be at the same level as for musk xylene (49). Other aquatic toxicity data are not available. The terrestrial toxicity of musk ketone, musk xylene, A H T N , and H H C B has also been reported (//, 13). For musk ketone, A H T N , and H H C B , tests were carried out with earthworms and springtails, whereas for musk xylene only an earthworm test was available. The P N E C for musk xylene was derived by equilibrium partitioning from the P N E C , and for the other substances an assessment factor of 50 was applied to the lowest test result after standardization for organic carbon according to the E U - T G D (27). The P N E C is 0.64 mg/kg dw for musk ketone, 0.23 mg/kg dw for musk xylene, and 0.32 mg/kg dw for A H T N and H H C B . These data are summarized in Table IV. The toxicity for predators in the natural environment is derived from data available for rats. The N O A E L s (No Observed Adverse Effect Level) are first converted to a dose in the daily food by multiplication with a factor of 10 for musk ketone and musk xylene, and 20 for A H T N and H H C B , respectively. For the derivation of the P N E C , the converted N O A E L is divided by an assessment factor of 30 according to the E U - T G D (27). The P N E C is 25 mg/kg food (ww) for musk ketone, 8 mg/kg ww for musk xylene, 10 mg/kg ww for A H T N , and 100 mg/kg ww for H H C B (11,13).


water

water

soil

predator

predator

Risk assessment In an environmental risk assessment, risk is expressed as the quotient of the exposure and the no-effect concentrations for the relevant organisms (Exposure


185 Concentration/PNEC). When the risk quotient is below 1, the environmental concentrations are not expected to cause an adverse effect. For an adequate risk evaluation, the exposure concentration should be presented in a probabilistic way and not by the extremes. For surface water, the 90 -percentiles of the measured concentrations were used, as these were derived from large data sets. Likewise, concentrations measured in fish were used to assess the risk to predatory birds and mammals. For the risk assessment for soil organisms, the measured concentrations in sludge were used to predict the concentration in agricultural soil. The exposure concentrations and no-effect concentrations used to calculate the risk quotients are given in Table V . The table shows that for musk ketone and musk xylene, all risk quotients are below 0.01, whereas for A H T N and H H C B , the risk quotients range from below 0.01 to 0.10. Downloaded by UNIV OF ARIZONA on July 28, 2012 | http://pubs.acs.org Publication Date: July 30, 2001 | doi: 10.1021/bk-2001-0791.ch010

th

Table V. Environmental concentrations (EC) in various compartments, Predicted No Effect Concentration (PNEC), and risk quotient (EC/PNEC) for musk fragrance ingredients. Musk ketone Aquatic organisms surface water concentration ^-percentile ^ g / L ] PNEC ^g/L] Risk quotient 4

0.04

Musk xylene 0.01

a

b

6.3 0.006

b

0.066 25

Risk quotient

0.003

0.012

0.001'

0.001

0.64*

0.23* 0.004

Soil predicted cone, in soil based on measured sludge concentrations [mg/kg ww] P N E C [mg/kg ww] Risk quotient

3.5

b

^-percentile [mg/kg ww] P N E C [mg/kg ww]

b

0.30

1.1 0.009

Fish-eating predators concentration in fish, max. or

e

HHCB 0.50

e

e

e

6.8 0.07

0.09

0.095 * 0.10 " 10

0.10"

0.01

0.001

e

b

0.002

AHTN

f

0.029

0.32

e

e

0.09

100

e

0.032

c

e

0.32 0.10

"data in Figure 5; Mata from (11); 'data from (12,13); ''PNEC in Figure 6; "data from (7,12,50,20); ^modified calculations from (11) using sludge data from (57)


186

Aquatic toxicity

10000

Ο

1000 .

α t -

Δ

10

OEC, c


ο

ο Χ

X Χ

Ζ 0.1

" Β

AHTN

HHCB

MK

MX

Ο

algae growth-72h

276

201

88

5600

•

Daphnia magna-21 d

196

111

169

56

Δ

fish growth-21d

89

93

62.5

>50

Ο

fish els-36d

35

68

200

Χ

PNEC

3.5

6.8

6.3

* 1.1

Figure 6. Aquatic toxicity data and the Predicted No Effect Concentration in the aquatic compartment PNEC (13). *fish growth test duration for MX was 14 days Table IV. Terrestrial and mammalian toxicity. 0

Musk ketone

Musk xylene

AHTN"

b

HHCB

0

Earthworm 8 weekNOECreprod. 1 4 d N O E C growth [mg/kg soil]

32

> 50

105

45

45

45

15

150

Springtail 4 weekNOECreprod. [mg/kg soil]

100

Rat 90 d N O A E L [mg/kg bw/d]

75

24 _ _

b

" data from 11; data from 13


187


Discussion and Conclusion In the present context, the musk fragrance ingredients are included in the Pharmaceutical and Personal Care Products group (PPCPs). In comparison with other members of the PPCPs, concentrations observed in effluents and surface water of the musk with the highest use volume, namely H H C B , are lower than for many of the other PPCPs detected in these compartments (1). A s a subset of the PPCPs, however, the musks are not intended to be biologically active and the aquatic toxicity of many pharmaceuticals is higher by orders of magnitude (52). This is not meant to trivialize the environmental relevance of the musk ingredients, but rather, to put the issue in a broader perspective. Musk fragrance ingredients have attracted the attention of the E U , OSPAR, and various national authorities because they have been detected in environmental and human samples. As a consequence, the substances are included in lists with recognized persistent and highly bioaccumulating groups of substances such as dioxins and PCBs. The available data, however, show that this is not justified. A H T N and H H C B are rapidly metabolized and excreted by fish and the measured bioaccumulation is considerably lower than that predicted on the basis of log Kow. Furthermore, the substances are biodegradable and biotransformable, as well as photodegradable. The risk assessments presented here are the result of an iterative process where initially the exposure was based on 'worst case' model predictions, and the effect assessment was based on a limited data set. Triggered by risk quotients above 1, empirical data were generated resulting in a more realistic evaluation of the environmental risks. In the present phase, the risk assessments still include various conservative assumptions, in particular for the estimation of the exposure and toxicity levels for soil organisms. Current environmental risk quotients of the N M s (musk ketone and musk xylene) and the PCMs ( A H T N and H H C B ) are at or below 0.1 for aquatic organisms, fish-eating predators, and terrestrial organisms. Keeping in mind the conservative approach taken, these data are reassuring that the environmental risks of these substances are low.

References 1. 2. 3.

Daughton, C.G.; Ternes, T.A. Environ. Health Perspect. 1999, 107(suppl. 6), 907-938. De Groot, A . C . ; Frosch, P.J. Contact Dermatitis 1997, 36, 57-86. Van de Plassche, E.J.; Balk, F. Environmental risk assessment ofpolycyclic

musks AHTN asnd HHCB according to the EU-TGD; R I V M report no. 601



188 503 008; National Institute of Public Health and the Environment R I V M : Bilthoven, N L , 1997. 4. Eschke, H.-D.; Traud, J.; Dibowski, H.-J. Vom Wasser 1994, 83, 373-383. 5. Eschke, H.-D.; Traud, J.; Dibowski, H.-J. UWSF. Z. Umweltchem. Ökotox. 1994, 6, 183-189. 6. Eschke H.-D.; Dibowski, H.J.; Traud, J. UWSF.Z. Umweltchem. Ökotox. 1995, 7, 131-138. 7. Eschke H.-D.; Dibowski, H.J.; Traud, J. Dt. Lebensm. Rdsch. 1995, 91, 375-379. 8. Rimkus, G.; Wolf, M. Chemosphere 1995, 30, 641-651. 9. Rimkus, G.; Wolf, M. Chemosphere 1996, 33, 2033-2043. 10. Tas, J.W.; Van de Plassche, E.J. Initial environmental risk assessment of musk ketone and musk xylene in the Netherlands in accordance with the EU-TGD; R I V M report 601503 002; National Institute of Public Health and the Environment R I V M : Bilthoven, N L , 1996. 11. Tas, J.W.; Balk, F.; Ford, R.A.; Van de Plassche, E.J. Chemosphere 1997, 35: 2973-3002. 12. Balk, F.; R . A . Ford Toxicol. Lett. 1999, 111, 57-79. 13. Balk, F.; R . A . Ford Toxicol. Lett. 1999, 111, 81-94. 14. SRC's Estimation Software; Environmental Science Center, Syracuse Research Corporation, N Y , 1996. 15. Chou, Y.-J.; Dietrich, D.R. Toxicol. Lett. 1999, 111, 17-25. 16. Yamagishi, T.; Miyazaki, S.; Horii, S.; Akiyama, K . Arch. Environ. Contam. Toxicol. 1983, 12, 83-89. 17. Rimkus, G.G.; Butte, W.; Geyer, H.J. Chemosphere 1997, 35, 1497-1507. 18. Boleas, S.; Fernandez, C.; Tarazona, J.V. Bull. Environ. Contam. Toxicol. 1996, 57, 217-222. 19. Butte, W.; Ewald, F. Kinetics of accumulation and clearance of the polycyclic musk compounds Galaxolide (HHCB) and Tonalide (AHTN); Poster University Oldenburg, Germany, 1999. 20. Rimkus, G. Toxicol. Lett. 1999, 111, 37-56. 21. Itrich, N.R.; Simonich, S.L.; Federle, T.W. Biotransformation of the polycyclic musk, HHCB, during sewage treatment; Environmental Science Department, Procter and Gamble, Poster S E T A C 19 Annual Meeting November 1998, Charlotte, N C U S A . . 22. Gatermann, R.; Hühnerfuss, H . ; Rimkus, G.; Attar, Α.; Kettrup, A . Chemosphere 1998, 36, 2535-2547. 23. Chou, Y . - J . ; D.R. Dietrich Toxicol. Lett. 1999, 111, 27-36. 24. Butte, W.; Schmidt, S; Schmidt, A . Photochemical degradation of nitrated musk compounds; Carl von Ossietzky University Oldenburg, Germany. Poster presented at 'Analytika', April 1996. th



189 25. Willenborg, R.; Butte, W. Photochemischer Abbau polycyclischer Moschusverbindungen; Carl von Ossietzky University Oldenburg, Germany. Poster presented at ' T a g der Chemie', November 1997. 26. EUSES, the European Union System for the Evaluation of Substances; R I V M , N L , Ed.; European Chemicals Bureau (EC/JRC): Ispra, Italy, 1996. 27. Technical Guidance Document in support of Directive 96/67/EEC on risk assessment of new notified substances and Regulation (EC) No. 1488/94 on risk assessment of existing substances; Office for Official Publications of the E C : Luxembourg, Lux., 1997; Part II. 28. Rimkus G.; Gatermann, R.; Hühnerfuss, H . Toxicol. Lett. 1999, 111, 5-15. 29. Verbruggen, E.M.J.; Van Loon, W . M . G . M . ; Tonkes, M.; Van Duijn, P; Seinen, W.; Hermens, J . L . M . Environ. Sci. Technol. 1999, 33, 801-806. 30. Rijs, G.B.J.; A.J. Schäfer Musken; R I Z A Report 99.006 (in Dutch). Institute for Inland Water Management and Waste Water Treatment RIZA, Lelystad, N L , 1999. 31. Paxéus, N. Wat. Res. 1996, 30, 1115-1122. 32. S A E F L Occurrence of nitromusk compounds in the aquatic environment in Switzerland. Swiss Agency for the Environment, Forests and Landscape S A E F L , Berne, C H , 1995. 33. S A E F L Occurrence of polycyclic musk compounds in the aquatic environment in Switzerland. Swiss Agency for the Environment, Forests and Landscape S A E F L , Berne, C H , 1998. 34. Sauer, J.; Antusch, E.; Ripp, Ch. Vom Wasser 1997, 88, 49-69. 35. Blok J. Measurement of musk fragrances in sludges of sewage treatment plants in The Netherlands. Report to R I F M , B K H Consulting Engineers, Delft, N L , 1997. 36. Herren, D.; Berset, J.D. Chemosphere 2000, 40, 565-574. 37. Background Document on Musk Xylene and other Musks, Series Point and Diffuse Sources No. 101, OSPAR Commission (2000), Copenhagen, Denmark. ISBN 094956553. 38. Bester, K . ; Hühnerfuss, H . ; Lange, W.; Rimkus, G.G.; Theobald, N. Wat. Res. 1998, 32, 1857-1863. 39. Müller, S.; Schmid, P.; Schlatter, C. Chemosphere 1996, 33, 17-28. 40. Breukel, R . M . A . ; Balk, F. Musken in Rijn en Maas; R I Z A Werkdocument 96.197x. National Institute for Inland Water management and Waste Water Treatment RIZA, Lelystad, N L . 41. Heberer, Th.; Gramer, S.; Stan, H.-J. Acta Hydrochim. Hydrobiolog. 1999, 27, 150-156. 42. Lagois, U. Wasser - Abwasser 1996, 137, 154-155. 43. Winkler, M.; Kopf, G.; Hauptvogel, C.; Neu, T. Chemosphere 1998, 37, 1139-1156.


190 44 Yun, S.-J.; Teraguchi, T.; Zhu, X.-M.; Iwashima, K . J. Environ. Chem. 1994, 4, 325-333 (in Japanese). 45. Gatermann, R.; Hühnerfuss, H . ; Rimkus,G.; Wolf, M.; Franke, S. Marine Pollut. Bull. 1995, 30, 221-227. 46. Geyer, H.J.; Rimkus, G.; Wolf, M; Attar, Α.; Steinberg, C.; Kettrup, A . UWSF-Z. Umweltchem. Oekotox. 1994, 6, 9-17. 47. Gatermann, R.; Rimkus, G.; Hecker, M.; Biselli, S.; Hühnerfuss, H . Bioaccumulation of synthetic musks in different aquatic species. Poster presented at S E T A C Europe 9 Annual Meeting, 25-29 May 1999, Leipzig, Germany. 48. Gatermann, R.; Hellou, J.; Hühnerfuss, H . ; Rimkus, G.; Zitko, V . Chemosphere 1999, 38, 3431-3441. 49. Giddings, J.M.; Salvito, D.T.; Putt, A . E . Wat. Res. 2000, 34, 3686-3689. 50. Draisci, R.; Marchiafava, C.; Ferretti, E.; Palleschi, L . ; Catellani, G.; Anastasio, A. J. Chromatogr. A 1998, 814, 187-197. 51. Background Document on Musk Xylene and other Musks, Series Point and Diffuse Sources No. 101, O S P A R Commission (2000), Copenhagen, Denmark. ISBN 094956553. 52. Halling-Sørensen, B . ; Nors Nielsen, S.; Lanzky, P.F.; Ingerslev, F.; Holten Lützhøft, H.C.; Jørgensen, S.E. Chemosphere 1998, 36, 357-393.


th


Pharmaceuticals and Care Products in the ... - ACS Publications

Recommend Documents