Contains naphtha benzoyl
Naphthalene / naphthols and human biomonitoring
- Opinion of the Commission "Human Biomonitoring" of the Environment Agency -
(Federal Health Gazette No. 10/2007 p. 1357)
As a combustion product of organic materials (among other things as a component of tobacco smoke), naphthalene is ubiquitous in the human environment. For a long time, naphthalene, unlike other polycyclic aromatic hydrocarbons (PAH), was not considered to be carcinogenic. On the basis of new findings from animal experiments, the Senate Commission for the Examination of Harmful Working Materials of the German Research Foundation carried out a reassessment in 2001 and classified naphthalene in Category 2 as a substance that is to be regarded as carcinogenic for humans . When characterizing the risk, the EU also comes to the conclusion that carcinogenic effects are possible, but classifies naphthalene in category 3 because it does not consider the data situation to be sufficient for classification in category 2 .
It is currently unclear whether there is a relevant health risk from naphthalene for the general population. Knowledge of the exposure is a prerequisite for assessing a risk.
Naphthalene (chemical molecular formula: C10 H8) consists of 2 condensed benzene rings and is thus the smallest representative of the PAH. Its colorless crystals are only slightly soluble in water (30 mg / l) and are subject to slow sublimation at room temperature (vapor pressure at 25 ° C: 10.5 Pa). The melting point is 80.2 ° C, the boiling point 218 ° C [2, 3].
Naphthalene is metabolized in the human body to form 1- and 2-naphthol (1- and 2-hydroxynaphthalene), among other things, which are excreted conjugated in the urine. These metabolites are suitable for human biomonitoring. As sensitive test methods are now available for the quantitative determination of naphthols in urine, the internal exposure of the person can be determined in this way.
Due to the available data, reference values cannot yet be derived. The Human Biomonitoring Commission has therefore compiled the available data in order to enable an orienting assessment of event-related measurement results.
Use and distribution
PAHs result from incomplete combustion of organic material. A large number of polycyclic aromatics are formed by pyrolysis. This applies to industrial processes (e.g. energy supply, waste incineration, petrochemicals, steel production, hard coal coking) as well as traffic, private households (e.g. food preparation, heating, tobacco smoke) and natural processes such as forest fires [4, 5].
In the processes mentioned, naphthalene is also formed; it is also a component of diesel and aircraft fuels [6, 7] and tar-containing paints  such as Creosot - a coal tar distillate that is used as a wood preservative for railway sleepers and wooden masts.
Coal tar, which contains naphthalene, is an active ingredient in some pharmaceuticals for the treatment of skin diseases [2, 8]. As a repellent against clothes moths, naphthalene is only used sporadically in Germany; it is even more widespread in the US .
Naphthalene is mainly produced industrially by distilling coal tar or from crude oil. The annual production volume in the EU is around 200,000 tonnes [2,10]. It is used in the chemical industry (in addition to o-xylene) for the synthesis of phthalic anhydride, which is further converted to phthalates (e.g. DEHP or diisononyl phthalate) . Phthalates are widely used as plasticizers for plastic products made from PVC.
In addition, naphthalene is required as a raw material for the production of azo paints and naphthalene sulfonic acid, which is processed into aggregates for cement and plasterboard, into dispersants and into tannins.
1- and z-naphthol are manufactured as industrial intermediates. Finally, among other things, carbaryl (i-naphthyl-N-methylcarbamate), a carbamate insecticide, is synthesized.
Entry into the environment and sources of human exposure PAH are ubiquitous in the environment. Limit and guide values generally relate to benzo [a] pyrene, which is often used as a key component in PAH mixtures.
Naphthalene is mainly introduced into the environment through traffic emissions . Naphthalene concentrations in the air are usually lower in rural areas than in cities and densely populated regions. In the open air, the concentrations are usually below 1 µg / m3 [10, 12], but higher values are also possible at traffic hotspots .
The representative environmental survey in Germany in the mid-1980s showed a geometric mean indoor value of 2.0 ug / m3 (maximum value: 14 ug / m3) for measurements in 479 living rooms . In more recent studies, somewhat lower concentrations in indoor air were found in the western federal states .
The use of naphthalene-containing moth repellants and tobacco smoke increase the concentrations in indoor air. With values of up to 46 µg naphthalene per cigarette, larger quantities were measured in sidestream smoke than in mainstream smoke . Naphthalene can also be emitted from moisture barriers or from leaks from mineral oil tanks in basement rooms. Joints in the parquet floor, which was laid with old tar glue, are also conceivable as sources [3,16].
The US Environmental Protection Agency (EPa) has an average concentration of 5.2 µg / m3 Estimated air to which humans are exposed . According to their statements, this results in an average daily naphthalene uptake through respiration of 1.1 µg / kg body weight (BW) for adults and 4.5 µg / kg for children. In addition, a reference concentration (RfC) of 3 µg / m3 which, however, does not take into account the carcinogenic potential of naphthalene . The RfC describes the daily inhalation exposure at which a life-long exposure to human health is considered unlikely.
Food is particularly contaminated with PAHs if it has been smoked or cooked on an open fire (grilling). Details for
Naphthalene range from <1 to 176 µg / kg . The EPa estimates the average daily naphthalene intake from food to be 0.04-0.24 µg / kg body weight (children: 0.20-0.94 µg / kg) .
The concentration of naphthalene in drinking water is generally well below 1 µg / l [2,10].
In addition to the sources mentioned, there is also absorption via dust, especially in small children. Because of the volatility of naphthalene, this route of absorption is likely to play less of a role than with PAHs with a larger ring system. The EPa estimate shows a daily intake of 0.24 µg / kg body weight for adults and 3.3 µg / kg body weight for children .
In addition, naphthalene can be found in household products and consumer goods. For example, tests carried out on behalf of the Öko-Test magazine (07/2003) found naphthalene in concentrations of up to 129 mg / kg in swimming aids made of PVC. It is conceivable that other PVC products also contain naphthalene as an impurity in the phthalates used. Systematic scientific work on this problem is not yet available. It is currently not known to what extent such residues are released when these products are used and to what extent they make a relevant contribution to the exposure of the general population to naphthalene.
At certain workplaces where raw materials containing PAHs such as tar or pitch are used or PAHs are released through pyrolysis processes, PAH concentrations are significantly higher than in the environment. Industries with a significant naphthalene load are in particular: the impregnation with Creosot, the production of mothballs from naphthalene as well as the naphthalene production in general as well as the coal tar distillation and coking. With considerable fluctuations within the same branch, naphthalene concentrations of a few µg to several mg per m3 can be reached at the workplace . In a current study at various workplaces in Germany, a maximum of 0.7 mg / m3 measured .
In animal experiments, the target tissues of the eye, the hematopoietic system and the respiratory tract were identified [19, 20, 21]. Mice and rats reacted differently to the tissue in the lungs and nose . This species difference is attributed to different metabolic rates in the tissues of the two animal species. In humans, cataract formation and haemolytic anemia, among other things, have been observed .
A two-year inhalation study in rats found naphthalene concentrations of 0, 50, 160 and 320 mg / m, respectively3 were exposed in male rats in all concentration levels and in females from 160 mg / m3 a significantly increased incidence of adenomas of the respiratory epithelium of the nose. The incidence of neuroblastomas in the olfactory epithelium was also dose-dependently increased . In addition, there was chronic inflammation of the nasal mucous membrane. On the basis of these new findings, various scientific committees have rated naphthalene as potentially carcinogenic for humans [1, 2, 17, 23].
Uptake, metabolism and carcinogenicity of naphthalene
As a highly volatile PAH, naphthalene is mainly absorbed by inhalation. However, absorption into the body is also possible dermally and orally [4, 24, 25]. In test animals, naphthalene is initially metabolically activated in analogy to the other PAHs. Cytochrome P45o forms naphthalene-1,2-epoxide (2 stereoisomers), the half-life of which is a few minutes . The epoxide can be partially converted into glutathione conjugates, which are ultimately eliminated renally as naphthyl mercapturic acids [26, 27, 28].
1- and 2-naphthol and 1,2-dihydro-1,2-dihydroxynaphthalene are also formed from the epoxide. Other metabolites are 1,2- and 1,4-dihydroxynaphthalene and 1,2- and 1,4-naphthoquinone. To date, a total of 30 naphthalene metabolites have been identified in the urine of mammals .
There are considerable differences between rats, mice and humans in terms of the enzymes and naphthalene metabolism in tissue . This could explain why, after inhalation, with the same naphthalene concentrations in the breath, the concentration of toxic metabolites in human tissues is lower than in rodents. For details, please refer to the statement of the adhoc working group "Indoor reference values" .
In humans, r- and 2-naphthol and 1,2- and 1,4-dihydroxynaphthalene have been described as metabolites in the urine , as well as 1,4-naphthoquinone . The excretion of i-naphthol occurs biphasic with half-lives of 1-2 h and 14-46 h. After inhalation, 6.3-8.5% of the naphthalene was excreted as i-naphthol in the 24-hour urine . Bieniek  gives a half-life of 4 hours. Metabolic pathways can also be induced by PAHs and cigarette smoke [33, 34].
In contrast to the PAHs with more rings in the molecule, according to the current state of the art it can be assumed that the actual carcinogenic agents are not the epoxide or a diol epoxide, but rather a. the naphthoquinones [35, 36].
There are currently two main hypotheses regarding the mechanism of the carcinogenic effects of naphthalene: On the one hand, the naphthoquinones could increase the concentration of reactive oxygen species via a redox cycle, which damage the DNA by oxidation . On the other hand, naphthoquinones form covalent bonds with nucleophilic functional groups. Protein adducts have been found in workers exposed to naphthalene  and suggest that DNA adducts can also be formed.
The Adhoc Working Group of the Indoor Air Hygiene Commission of the Federal Environment Agency and the Supreme State Health Authorities (Adhoc AG IRK / AOLG) have derived guideline values for naphthalene for indoor air based on the toxicological endpoint "inflammation of the nasal mucosa". In animal experiments, long-term inhalation of naphthalene resulted in chronic inflammation of the nasal and lung mucosa, as well as hyperplasias, neuroblastomas and adenomas in the same organs. In contrast, inflammation and cancer caused by naphthalene in humans have not yet been identified. The main reasons for this could be seen in the different anatomy and physiology of the nasal and pharynx in experimental animals compared to humans. Rats and mice are mandatory nasal breathers. Other possible reasons are the lower respiratory volume relative to the body mass and a lower sensitivity of humans to naphthalene due to metabolic differences. In the opinion of the adhoc working group, sufficient protection against the carcinogenic effects of naphthalene can be assumed if the occurrence of signs of inflammation is avoided. Under these conditions, a guideline value II (hazard value) of 20 µg naphthalene / m was established3 and a guideline value of 1 of 2 µg naphthalene / m3 derived . The guideline values of the US-EPa and the ATSDR (Agency for Toxic Substances and Disease Registry) as RfC of 3 µg / m are of the same order of magnitude3 or as a minimum risk level (MRL) of 4 pg / rn3 
Analytical determination of naphthols in urine
The parameters 1- and 2-naphthol in urine have proven themselves in numerous occupational and environmental medical studies . In the published analytical methods, the conjugates are usually first enzymatically cleaved. In earlier studies, however, hydrochloric acid was used for the hydrolysis of sulfates and glucuronides. However, this can lead to analytical problems due to undesired side reactions. Hill et al.  reported that the internal standard used due to acid13 C.6-1-naphthol was degraded. Yang et al.  found a lower naphthol yield compared to conjugate cleavage by enzymatic hydrolysis. These analytical problems with acid hydrolysis have been confirmed by current comparative studies . In order to obtain comparable results, the uniform application of the gentler enzymatic hydrolysis with beta-glucuronidase / aryl sulfatase is therefore recommended.
The quantification of 1- and 2-naphthol can then be carried out by means of high pressure liquid chromatography (HPLC) with fluorescence detection or, alternatively, by coupling capillary gas chromatography to mass spectrometry. An overview of the analytical methods is given in Table 1. For routine analysis, a method should be selected with which 1- and 2-naphthol can be determined in parallel with a limit of quantification of a maximum of 5 µg / l each. This makes it possible to detect increased concentrations of just one naphthol. This is important because, in addition to exposure to naphthalene, the following sources can also contribute to the excretion of just one naphthol isomer.
Exposure to carbaryl causes increased excretion of 1-naphthol . The insecticide is not approved for agricultural use in Germany. However, imported fruit can contain carbaryl. For example, residues of up to 1.9 mg / kg were found in pears from Argentina and Chile .
Another possible disruptive factor for the detection of naphthalene exposure via the quantitative determination of naphthols in urine is possible exposure to naphthols. For example, 1-naphthol is used in various chemical hair colors. In addition, contact with residues of 2-naphthol is conceivable, which is used as a chemical intermediate for azo dyes, tanning agents and as a preservative for glue, wood and leather. It is excreted in the urine of humans both unchanged and conjugated . The significance of exposure to naphthols compared to naphthalene exposure for the general population cannot yet be conclusively assessed.
Table 1: Analytical methods for the determination of 1- and 2-naphthol in urine
|Authors [literature]||hydrolysis||Analytes||Int. default||method||Derivatization||NWG / BG|
|Preuss, Angerer ||enzyme||1-N and 2-N||without||HPLC-FD||1.5 µg / l|
0.5 µg / l
|Kuusimäki et al. ||enzyme||2-N||without||HPLC-FD||1 µg / l BG|
|Andreoli et al. ||without||1-N|
1-N-glucuronide and 2-N-sulfate
|without||LC-MS||0.1 mg / l|
|Elovaara, et al. ||enzyme||1-N and 2-N||without||HPLC-FD||4 µg / l BG|
1.5 µg / l BG
|Hansen et al. ||enzyme||1-N||without||HPLC-FD||5.5 µg / l|
|Kim et al. ||enzyme||2-N||without||HPLC-FD||0.13 µg / l BG|
|Heikkiläetal. ||HCI||1-N||without||GC-ECD||Pentafluorobenzyl bromide||10 µg / l|
|Bieniek ||HCI||1-N and 2-N||without||GC-FID||without||100 µg / l|
|Bouchard et al. ||enzyme||1-N and 2-N||without||GC-MS-SIM||Acetic anhydride / K2 CO3||0.1 µg / l|
|Hill et al. ||enzyme||1-N and 2-N||13C6-IN|
|GC-MS-MS||Chloriodopropane||1 µg / l|
|Jansen et al. ||Enzyme and acid||1-N and 2-N||2H7-1 N||GC-MS-SIM||Benzoyl chloride||0.7 µg / l|
|Keimig, Morgan ||HCI||1-N and 2-N||without||GC-ECD||Pentafluorobenzyl bromide / K2 CO3||10 µg / l|
|Serdar et al. ||enzyme||1-N and 2-N||2H7-1 N||GC-MS-SIM||Silylation||0.3 µg / l|
|Smith et al. ||enzyme||1-N and 2-N||7306-1 N||GC-HRMS according to||Silylation||0.016 µg / l|
0.011 µg / l
|Petropoulou et al. ||enzyme||1-N and 2-N and carbaryl||N-ethyl-p-methyl-3-carboxamide||SPME GC-MS / MS||Trifluoroacetic anhydride / triethylamine||0.2 µg / l BG|
|Hardt et al. ||enzyme||1-N and 2-N||2H7-1 N||GC-MS-SIM||Acetic anhydride / K2CO3||0.5 µg / l BG|
|Yang et al. ||Enzyme> HCI||1-N and 2-N||2H10 anthracene||GC-MS-SIM||Pentafluorobenzyl bromide / K2CO3||0.27 µg / l|
1-N: 1-naphthol, 2-N: 2-naphthol BG: limit of quantification, ECD: electron capture detector, FD: fluorescence detector, FID: flame ionization detector, GC: gas chromatography, (HP) LC: (high pressure) liquid chromatography, HR: high resolution, MS: mass spectrometry, NWG: detection limit, SIM: selected ion monitoring, SPME: solid phase microextraction.
The parallel determination of i- and 2-naphthol, however, ensures the specificity of these parameters for naphthalene exposure, since the two metabolites correlate well . After occupational exposure (n = 277), the concentration of 1-naphthol was approximately 1.2 times that of 2-naphthol . Serdar et al.  also found slightly higher 1- than 2-naphthol values in workers exposed to naphthalene, and a concentration ratio of approximately one in control persons. According to Yang et al.  tobacco smoke influences the ratio of 1- to 2-naphthol: the quotient was approx. 1.2 for smokers and 1.5 for non-smokers. The specified concentration ratios were derived on the basis of the collective investigations; deviations are possible on an individual basis [9, 47]
For the sake of completeness, it should be pointed out that in addition to the naphthols in urine, other metabolites can in principle be used for human biomonitoring of naphthalene. For example, 1,2- and 1,4-dihydroxynaphthalene have been determined in the urine of occupationally exposed persons. The measured concentrations correlated with those of the naphthols . Unmetabolized naphthalene was also measured in the urine of workers exposed to PAH .
However, only 3- and 2-naphthol have so far been determined on a larger scale and have also proven to be suitable for environmental medicine issues.
Internal exposure of the general population
The concentrations of i- and 2-naphthol in the urine of people who were not exposed to naphthalene at work are shown in Table 2. It must be pointed out that the compiled values, with the exception of those from the USA, which do not come from representative collectives.
Table 2: Naphthol concentrations in the urine of the general population
|Smoking status + country||Age||N||1-naphthol in the urine||2-naphthol in the urine||Authors [literature]|
|NOa Germany||from 10y||63 MU||Md 5.0 µg / l (<1.5-29.4 µg / l)|
P95 19.7 µg / l
|Md 3.6 µg / l (<0.5-23.6 µg / l)|
P95 17.1 µg / L
|Preuss et al. |
|NOa Germany||2,5-6,51||35 MU||Md 3.0 µg / l ≪ 1.5-12.0 µg / l)|
P95 10.7 µg / l
|Md 2.6 µg / l (<0.5-35.4 µg / l)|
P95 9.8 µg / l
|Preuss et al. |
|NOb Germany||25-51 J w||67 MU||Md 3.6 µg / l (<1.5-82.4 µg / l)|
P95 29.9 µg / l
|Md 2.1 µg / l (<0.5-22.9 µg / l)|
P95 16.9 µg / l
|Holz and Wilhelm |
|NOb Germany||5-7 y||94 MU||Md 2.4 µg / l (<1.5- 82.6 µg / l)|
P95 20.9 µg / l
|Md 1.5 µg / l (<0.5-68.3 µg / l)|
P95 6.5 µg / l
|Holz and Wilhelm |
|NOc Germany||25-51 J w||48 MU||Md 2.6 µg / l (<1.5-68.4 µg / l)|
P95 24.0 µg / l
|Md 2.0 µg / l (<0.5-62.4 µg / l)|
P95 21.9 µg / l
|Holz and Wilhelm |
|NOc Germany||5-7 y||91 MU||Md 2.7 µg / l (<1.5-252 µg / l)|
P95 12.6 µg / l
|Md 2.4 µg / l (<0.5-93.2 µg / l)|
P95 12.8 µg / L
|Holz and Wilhelm |
|NOed Germany||from 18 y||50 MU||Md 1.0 µg / l (<0.5-18.3 µg / l)||Md 1.0 µ / l (<0.5-28.4 µg / l)||Hardt et al. |
|NR Finland||20||GM 1.9 µg / gK (<0.9-4.5 µg / gK)||GM 2.2 µg / gK (<0.9-5.4 µg / gK)||Väänänen |
|NR Finland (winter)||46||-||Md 1.7 µg / gK||Kuusimäki et al. [58)|
|NR Finland (summer)||38||-||Md 2.9 µg / gK||Kuusimäki et al. |
|NR Canada||26 MU||Md 1.3 µg / gK|
P95 8.7 µg / gK
|Md 1.2 µg / gK|
P95 6.4 µg / gK
|Bouchard et al. |
|NOe Canada||30 MU||Md 3.4 µg / gK|
P95 10.7 µg / gK
|Md 2.6 µg / gK|
P95 6.3 µg / gK
|Bouchard et al. |
|NR Japan||56 MU||GM 3.0 µg / l||GM 1.1 µg / l||Yang et al. |
|NR Korea||12 +/-1 1||137 MU||Md 2.8 (0.3-74.6) µg / gK||Kang et al. |
|NR Korea||62||-||Md 1.6 (0.4-11.3) µg / gK|
P95 7.0 µg / gK
|Kim et al. |
|NR Korea||87||GM 2.0 µg / gK||Nan et al. |
|NR China||19||GM 3.2 µg / l||GM 3.3 µg / l||Serdar et al. |
|R.a Germany||from 101||9 MU||Md 20.61 µg / l (3.6-56.3 µg / l)||Md 19.5 µg / l (2.2-48.3 µg / l)||Preuss et al. |
|R.f Germany||26-44 J, f||35 MU||Md 13 µg / l (2-36 µg / l)|
P95 32.9 µg / l
|Md 17 µg / l (1-92 µg / l)|
P95 52.01 µg / L
|Holz and Wilhelm |
|R Japan||63 MU||GM 8.3 µg / l||GM 7.8 mg / l||Yang et al. |
|R Korea||67||Md 5.1 µg / gK (0.9-16.4 µg / gK)|
P95 11.2 µg / gK
|Kim et al. |
|R Korea||41||-||GM 5.0 µg / gK||Nan et al. |
|R, NR USA||983||Md 4.4 µg / l ≪ 1-2500 µg / l)|
P95 43 µg / l
|Md 3.4 mg / l (<1-88 µg / l)|
P95 30 µg / l
|Hill et al. |
|R, NR USA||from 20.1||1626||Md 1.9 µg / l|
P95 23 µg / l
|Md 2.4 µg / l|
P95 28 µg / l
|(R), NR USA||6-11 y||387||Md 1.2 µg / l|
P95 12 µg / l
|Md 1.7 mg / l|
P95 7.7 µg / l
|R, NR Denmark||119||Md 2.5 µg / gK||-||Hansen et al. |
|28 R, 8 NR Poland||36||P95 12.1 µg / gK|
GM 9.9 µg / gK
|GM 5.8 µg / gK||Bienik |
|(Range), GM: geometric mean, Y: years, Md: median, MU: morning urine, N: number of samples examined, NR: non-smoker, P95: 95th percentile, R: smoker, µg / gK: µg / g creatinine , w: female|
a) includes in-house control collective in a bitumen processing company,
b) unencumbered control collective,
c) residents of a coking plant who did not differ from the unpolluted control collective with regard to 1-naphthol values,
d) patients in an environmental clinic,
e) residents in the vicinity of a Creosot impregnation system,
f) Residents of a coking plant and unpolluted control collective who did not differ with regard to naphthol values.
Table 3: Brief overview
|Investigation medium||parameter||method||Limits of quantification|
|HPLC fluorescence or GC-MS||<5 Ng / l|
|Reference values: currently not derivable|
|Orientation values for non-smokers:|
1-naphthol <30 µg / l
2-naphthol <20 µg / l
|swell||excretion||Effects at high exposure|
|Tobacco smoke, smoked food and food grilled over an open fire, diesel fuel, small combustion systems, traffic, moth protection containing naphthalene, contaminated consumer goods||Elimination in the urine with 2 different half-lives (approx. 1-2 or 14-46 h)||Hemolytic anemia, respiratory disease, cancer risk|
First repeat measurements, whereby the creatinine concentration of the sample should be in the range of 0.5 to 2.5 µ / l. If necessary, determine 1-hydroxypyrene in the urine, evaluate using reference values. If the naphthol values increase again: initiate a search for sources (see above)
As expected, smokers show higher values than non-smokers. In the German studies, the median values for smokers were about 5 times as high as for non-smokers [47, 49]
The smoking status is the dominant influencing variable in the general population not exposed to occupational stress. A meaningful interpretation of the naphthol concentrations in the urine is therefore only possible for non-smokers. From the compiled data it follows that the following concentrations are generally measured in adults who are not occupationally exposed and who do not smoke:
1-naphthol in the urine below 30 µg / l, 2-naphthol in the urine below 20 µg / l.
Because of the small German collectives, these values are subject to considerable uncertainty [47, 49]. The concentrations mentioned reflect the current state of knowledge and serve as a preliminary orientation. Investigations in patients at an environmental outpatient clinic in southern Germany  showed lower median values than the other two German studies mentioned.
The data from the USa  indicate that the concentrations related to the urine volume in children (investigated collective: 6-n years old) could be somewhat lower. The currently available data from Germany do not allow any valid statements in this regard.
Measures in the event of abnormal measured values
In those cases in which the stated orientation values are exceeded and tobacco smoke can be excluded as a source, control measurements are indicated. In order to be able to better assess the result of a control measurement, it must be ensured that the creatinine concentration of the urine sample is in the range of 0.5 to 2.5 g / l .
If multiple, reliable measurements have confirmed an increased naphthol excretion, the causes of this exposure must be determined within the framework of the proportionality. In addition to tobacco smoke, possible sources include indoor air pollution from building materials, naphthalene-containing moth repellants and open fireplaces, as well as the consumption of grilled and smoked food and contact with consumer goods that are contaminated with naphthalene. The latter are e.g. products made of PVC with phthalate plasticizers, which can be contaminated with naphthalene. Leakage in diesel tanks and the use of tar paints should also be considered as possible sources.
The therapeutic external use of ointments containing tar for certain skin diseases can lead to high naphthol concentrations in the urine  and must be subjected to an individual risk assessment in each individual case.
It should be expressly pointed out that a priori toxicological assessment is not possible on the basis of the orientation values mentioned.
If there is a suspicion of additional exposure to other PAHs, the determination of the parameter i-hydroxypyrene in the urine should be considered and assessed using the published reference value [54. 55].
Naphthalene is metabolized to 1- and 2-naphthol, which are usually excreted in comparable amounts. In contrast, carbaryl residues on food lead to an isolated increase in the excretion of i-naphthol . This is also to be expected for the use of certain hair dyes that contain i-naphthol. In
In cases in which the concentration of i-naphthol exceeds that of 2-naphthol blatantly (e.g. by a factor of 4-5), abnormal values can usually not be attributed to exposure to naphthalene. This applies analogously to the opposite constellation with an isolated increased 2-naphthol excretion, the causes of which are still unclear.
- German Research Foundation (DFG) Substances that are harmful to health. Toxicological and occupational medical justifications for MAK values. Naphthalene (33rd delivery 2001) - Weinheim, Whiley-VCH
- European Commission (Ed.) (2003): Naphthalene - European Union Risk Assessment Report, 1 "Priority List, Volume 33. Self-published
- Sagunski H, Heger W (2004) Guide values for indoor air: naphthalene. Bundesgesundheitsbl Gesundheitsforsch Health Protection 47: 705 - 712
- National Toxicology Program NTP (2000) Toxicology and carcinogenesis studies of naphthalene in F344 / N rats (inhalation studies), Technical report series 500, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health
- IARC (1983) International Agency for Research on Cancer: Monographs on the evaluation of carcinogenic risk of the chemical to humans. Polynuclear aromatic compounds, Part 1. Chemical, environment and experimental data. Vol. 32, IARC, Lyon
- Clark C, Henderson T, Royer R, et al. (1982) Mutagenicity of diesel exhaust particulate extracts: influence of fuel composition in two diesel engines. Fundam Appl Toxicol 2: 38-43
- Serdar B, Egeghy PP, Waidyanatha S, et al. (2003) Urinary biomarkers of exposure to jet fuel (JP-8). Environ Health Perspect 111: 1760-1764
- Red List (2005) List of Medicines for Germany. Frankfurt / Main
- Preuss R (2005) Development of an analytical process for the biomonitoring of naphthalene and its application in environmental and occupational medicine diagnostics. Dissertation, Friedrich-Alexander University Erlangen-Nuremberg
- Preuss R, Angerer J, Drexler H (2003): Naphthalene - an environmental and occupational toxicant. Int Arch Occup Environ Health 76: 556-576
- Weissermel K, Arpe HJ (1994) Industrial Organic Chemistry - Important preliminary and intermediate products. VCH, Weinheim, 4th edition
- Bouchertall F (1986) Volatile hydrocarbons in the atmosphere of the Kiel Bight (Western Baltic). Marine Chem 19: 153-160
- Khalili NR, Scheff PA, Holsen TM (1995) PAH source fingerprints for coke ovens, diesel and gasoline engines, highway tunnels, and wood combustion emissions. Atmos Environ 29: 533-542
- Federal Health Office (1993) Announcements of the Federal Health Office: Assessment of indoor air quality. Bundesgesundhbl No. 36,117-118
- Schmeltz I, ToskJ, Hoffmann D (1976) Formation and determination of naphthalenes in cigarette smoke. Anal Chem 48: 645-650
- Dieckow P, Ullrich D, Seifert B (1999) Occurrence of polycyclic aromatic hydrocarbons (PAH) in apartments with parquet floors. Federal Environment Agency. Institute for Water, Soil and Air Hygiene, WaBoLu Issue 2/99, Berlin
- EPa (2002) U.S. Environmental Protection Agency: Health Effects Support Document for Naphthalene, external review draft. EPa 822-R-02-031; Washington (DC)
- Preuss R, Drexler H, Böttcher M, et al. (2005) Current external and internal exposure to naphthalene of workers occupationally exposed to polycyclic aromatic hydrocarbons in different industries. Int Arch Occup Environ Health 78: 355-362
- Shopp GM, White KL, Holsapple MP, et al. (1984) Naphthalene toxicity in CD-1 mice: general toxicology and immunotoxicology. Fundam Appl Toxicol 4: 406-419
- Van Heyningen R (1979) Naphthalene cataract in rats and rabbits: a resume. Exp Eye Res 28: 435-439
- Zheng J, Cho M, Jones AD, Hammock BD (1997) Evidence of quinone metabolites of naphthalene covalently bound to sulfur nucleophiles of proteins of murine clara cells after exposure to naphthalene. Chem ResTox 10: 1008-1014
- Buckpitt A, Boland B, Isbell M, et al. (2002) Naphthalene-induced respiratory tract toxicity: metabolic mechanisms of toxicity. Drug Metab Rev 34: 791-820
- IARC (2002) International Agency for Research on Cancer: Monographs on the evaluation of carcinogenic risks to humans: some traditional herbal medicines, some mycotoxins, Naphthalene and Slyrene, Vol. 82, IARC, Lyon
- Turkall RM, Skowronski GA, Kadry MA, Abdel-Rahman MS (1994) a comparative study of the kinetics and bioavailability of pure and soilabsorbed naphthalene in dermally exposed male rats. Arch Environ Contam Toxicol 26: 504-509
- Chao YCE, Kupper LL, Serdar B, et al. (2006) Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel cell maintenance workers. Environ Health Perspect 114: 182-185
- Pakenham G, Lango J, Buonarati M, et al. (2002) Urinary naphthalene mercapturates as biomarkers of exposure and stereoselectivity of naphthalene epoxidation. Drug Metab Dispos 30: 247-253
- Chen KC, Dorough HW (1970) Glutathione and mercapturic acid conjugations in the metabolism of naphthalene and 1-naphthyl-N-methylcarbamate (carbaryl). Drug Chem Toxicol 2: 331-354
- Stillwell WG, Horning MG, Griffin GW, Tsang WS (1982) Identification of new sulfur-containing metabolites of naphthalene in mouse urine. Drug Metab Dispos 10: 624-631
- Wu R, Waidyanatha S, Henderson AP, et al. (2005): Determination of dihydroxynaphthalenes in human urine by gas chromatographymass spectrometry, J Chromatogr B 826: 206-213
- Bieniek G (1997) Urinary naphthols as an indicator of exposure to naphthalene. Scand J Work Environ Health 23: 414-420
- Heikkilä P, Luotamo M, Pyy L, Riihimäki V (1995) Urinary 1-naphthol and 1-pyrenol as indicators of exposure to coal tar products. Int Arch Occup Environ Health 67: 211-217
- Bieniek G (1994) The presence of 1-naphthol in the urine of industrial workers exposed to naphtha-Iene. Occup Environ Med 51: 357-359
- WHO (1998) Selected nonheterocyclic polycyclic aromatic hydrocarbons. Environmental Health Criteria 202. Self-published, Geneva
- Serdar B, Egeghy PP, Gibson R, Rappaport SM (2004) Dosedependent production of urinary naphthols among workers exposed to jet fuel (JP-8). Am J Ind Med 46: 234-244
- Palackal NT, Burczynski ME, Harvey RG, Penning TM (2001) The ubiquitous aldehyde reductase (AKR1A1) oxidizes proximate carcinogen transdihydrodiols to oquinones: potential role in polycyclic aromatic hydrocarbon activation. Biochemistry 40: 10901-10910
- Sugiyama K, Wang TC, Simpson JT, et al.(1999) Aldose reductase catalyzes the oxidation of naphthalene-1, 2-dihydrodiol for the formation of orthonaphthoquinone. Drug Metab Dispos 27: 60-67
- Bolton JL, Trush MA, Penning ™, et al. (2000) Role of quinones in toxicology. Chem Res Toxicol 13: 135-160
- Waidyanatha S, Zheng Y, Serdar B, Rappaport SM (2004) Albumin adducts of naphthalene metabolites as biomarkers of exposure to polycyclic aromatic hydrocarbons. Cancer Epidemiol Biomarkers Prev 13: 117-124
- TERa (Toxicology Excellence for Risk Assessment) & Concurrent Technologies Corporation (2005) International Toxicity Estimates for Risk Database. http://www.tera.org/iter/
- Hill RH, Shealy DB, head SL, et al. (1995) Determination of pesticide metabolites in human urine using an isotope dilution technique and tandem mass spectrometry. J Anal Toxicol 19: 323-329
- Yang M, Koga M, Katoh T, KawamotoT (1999) a study for the proper application of urinary naphthols, new biomarkers for airborne polycyclic aromatic hydrocarbons. Arch Environ Contam Toxicol 36: 99-108
- Hardt J (2006) Acidic and enzymatic hydrolysis of samples in urine naphthol determination, Clin Chem Lab Med 44: A119
- Hill RH, head SL, Baker S, et al. (1995) Pesticide residues in urine of adults living in the United States: reference range concentrations. Environ Res 71: 99-108
- Chemical and Veterinary Investigation Office Stuttgart (2006) Residues of pesticides in pome fruit 2004/5 - general report. Self-published, Stuttgart
- BG Chemie (1995) Toxicological Evaluations No. 135: (3-Naphthol. Www.bgchemie.de
- Serdar B, Waidyanatha S, Zheng Y, Rappaport SM (2003) Simultaneous determination of urinary 1-and 2-naphthols, 3- and 9-phenanthrols, and 1-pyrenol in coke oven workers. Biomarkers 8: 93-109
- Hölzer J, Wilhelm M (2006) personal communication
- Campo L, Addario L, Buratti M, et al. (2006) Biological monitoring of exposure to polycyclic aromatic hydrocarbons by determination of unmetabolized compounds in urine, Toxicol Lett 162: 132-138
- Preuss R, Koch HM, Wilhelm M, et al. (2004) Pilot study on the naphthalene exposure of German adults and children by means of urinary 1- and 2-naphthol levels. Int J Hyg Environ Health 207: 441-445
- Hardt J, Schulze M, Ehret W (2006) Biomonitoring of naphthalene by determining 1- and 2-naphthol in urine (abstract). Umweltmed Forsch Prax 11: 214-215
- CDC (2005) Third national report on human exposure to environmental chemicals. Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta. www.cdc.gov/ exposurereport
- Commission "Human Biomonitoring" of the Federal Environment Agency (2005) Standardization of substance content in urine - creatinine. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 48: 616-618
- Hansen AM, Poulsen OM, Menne T (1993) Longitudinal study of excretion of metabolites of polycyclic aromatic hydrocarbons in urine from two psoriatic patients. Acta Derm Venereol 73: 188-190
- Commission "Human Biomonitoring" of the Federal Environment Agency (1996) Concept of reference and human biomonitoring (HBM) values in environmental medicine. Bundesgesundhbl. 39: 221-224
- Commission "Human Biomonitoring" of the Federal Environment Agency (2005) 1-hydroxypyrene in urine as an indicator of internal exposure to polycyclic aromatic hydrocarbons (PAH) - reference value for 1-hydroxypyrene in urine. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 48: 1194-1206
- Meeker JD, Barr DB, Serdar B, et al. (2006) Utility of urinary 1-naphthol and 2-naphthol levels to assess environmental carbaryl and naphthalene exposure in an epidemiology study. J Expo Sci Environ Epidemiol 1-7
- Preuss R, Angerer J (2004) Simultaneous determination of 1- and 2-naphthol in human urine using anline cleanup columns switching liquid chromatography fluorescence detection. J Chromatogr B 801: 307-316
- Kuusimäki L, Peltonen Y, Mutanen P, et al. (2004) Urinary hydroxymetabolites of naphthalene, phenanthrene and pyrene as markers of exposure to diesel exhaust. Int Arch Occup Environ Health 77: 23-30
- Andreoli R, Manini P, Bergamaschi E, et al. (1999): Determination of naphthalene metabolites in human urine by liquid chromatographymass spectrometry with electrospray ionization. J Chromatogr a 847: 9-17
- Elovaara E, Väänänen V, Mikkola J (2003) Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with betanaphthoflavone induction in the rat. Arch Toxicol 77: 183-193
- Hansen AM, Poulsen OM, Christensen JM, Hansen SH (1992) Determination of anaphthol in human urine by high performance liquid chromatography. J Liquid Chrom 15: 479-499
- Kim H, Kim YD, Lee H, et al. (1999) Assay of 2-naphthol in human urine by high performance liquid chromatography. J Chromatogr B 734: 211-217
- Bieniek G (1996) Simultaneous determination of phenol, cresol, xylenol isomers and naphthols in urine by capillary gas chromatography. J Chromatogr B 682: 167-172
- Bouchard M, Pinsonneault L, Tremblay C, Weber JP (2001) Biological monitoring ofenvironmental exposure to polycyclic aromatic hydrocarbons in subjects living in the vicinity of a creosote impregnation plant. Int Arch Occup Environ Health 74: 505-513
- Jansen EHJM, Schenk E, Denengelsman G (1995) Use of biomarkers in exposure assessment of polycyclic aromatic hydrocarbons. Clin Chem 41: 1905-1906
- Keimig SD, Morgan DP (1986) Urinary 1-naphthol as a biological indicator of naphthalene exposure. Appl Ind Hyg 1: 61-65
- Smith CJ, Walcott CJ, Huang W, et al. (2002) Determination of selected monohydroxy metabolites of 2-, 3- and 4-ring polycyclic aromatic hydrocarbons in urine by solidphase microextraction and isotope dilution gas chromatographymass spectrometry. J Chromatogr B 778: 157-164
- Petropoulou SSE, Gikas E, Tsarbopoulos A, Siskos Pa (2006) Gas chromatographictandem mass spectrometric method for the quantitation of carbofuran, carbaryl and their main metabolites in applicators' urine. J Chromatogr a 1108: 99-110
- Väänänen V, Hämeilä M, Kontsas H, et al. (2003) Air concentrations and urinary metabolites of polycyclic aromatic hydrocarbons among paving and remixing workers. J Environ Monit 5: 739-746
- Kang JW, Cho SH, Kim H, Lee CH (2002) Correlation of urinary 1-hydroxypyrene and 2-naphthol with total suspended particulates in ambient air in municipal middleschool students in Korea. Arch Environ Health 57: 377-382
- Kim H, Cho SH, Kang JW, et al. (2001) Urinary 1-hydroxypyrene and 2-naphthol concentrations in male Koreans. Int Arch Occup Environ Health 74: 59-62
- Nan HM, Kim H, Lim HS, et al. (2001) Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1, GSTM1 and GSTT1 an urinary 1-hydroxypyrene and 2-naphthol concentrations. Carcinogenesis 22: 787-793
- Hansen AM, Omland 0, Poulsen OM, et al. (1994) Correlation between work process related exposure to polycyclic aromatic hydrocarbons and urinary levels of alphanaphthol, betanaphthylamine and 1-hydroxypyrene in iron foundry workers. Int Arch Occup Environ Health 65: 385-394
- Do audible credits ever expire
- What are the alternatives for porn
- Has Bob Seger ever sung the blues
- How is Robespierre a hero
- How is an INTJ mom
- What is user-centered research
- The air quality is getting worse from year to year
- How is an eccentric sander used
- Is an efficient compilation of repetitive expressions possible
- What should individual Indian men think about
- What if Comcast buys Viacom
- What is the source of beryllium
- This is how you create more attractive products
- What's the best way to make 100 waste of money
- Has associated hydrogen gas with bubbling
- How can I soften hard brownies
- It's time to buy Sun Pharma
- Is addiction to something bad
- What can you learn from observing
- How is the education minister in Jammu
- What is the difference between stalagmites and stalagmites
- How can I get free inmate information
- One Direction will return by 2018
- How can I master chess endings
- Why did Modi set up free bank accounts
- Students in ait receive a scholarship return
- What is a radical standard form
- Which Skinprove Serum
- Hypnotherapists hypnotize themselves as therapy
- Which is better RTU or MBM
- Which browser has the standard incognito mode?
- What made Adidas Boost shoes so popular
- What is the grueling Cambrian patrol
- How powerful is Young Thor