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Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Procter & Gamble ; n°batch I-38110
- Expiration date of the lot/batch: 14th January 2006
- Purity test date: No data
- Purity : 99.9% w/w

RADIOLABELLING INFORMATION
- Radiochemical purity: 96.9% (certificate of analysis)
- Specific activity: 10.5 mCi/mmmol ; 388.5 MBq/mmol
- Locations of the label: [14C]-1-naphthol (N°batch 020K9440/41)
- Expiration date of radiochemical substance: No data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient temperature in the dark
- Stability under test conditions: Yes
- Solubility and stability of the test substance in the solvent/vehicle: Yes
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING : No

FORM AS APPLIED IN THE TEST Cream
Radiolabelling:
yes
Remarks:
14C-1-naphthol
Type of coverage:
occlusive
Vehicle:
other: Blank formulation (Nice-n EasyTM tint)
Duration of exposure:
30 mn
Doses:
- Nominal doses: 2% w/w (400 µg/cm²)
- Actual doses: No data
- Actual doses calculated as follows: Liquid Scintillation counting
- Dose volume: 20 mg/cm²
- Rationale for dose selection: The dose used in this study were designed to simulate predicted normal human exposure to the test material.
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: The formulation was applied following a 1:1 w/w mix with two different developers (a peroxide developer and a placebo developer), both resulting in an nomial final dose concenration of 2% 1-Naphthol
- Method of storage: No data

APPLICATION OF DOSE: in the glass diffusion cells

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Amount(s) applied (volume or weight with unit): ca. 990 - 995 mg of developer
- Purity: No data
- Homegeneity and radioactive content were confirmed (triplicate samples - 10 ml - were diluted with scintillation fluid and each dilution were analysed by liquid scintillation counting).

TEST SITE
- Preparation of test site: glass diffusion cells
- Area of exposure: 2.54 cm²
- Type of cover : unoccluded after the exposure (30 mn) and during 48 hours

REMOVAL OF TEST SUBSTANCE
- Washing procedures and type of cleansing agent: the dose was washed from the surface of the skin using natural sponges soaked in 3% Teepol
- Time after start of exposure: 30 mn

SAMPLE COLLECTION/ PREPARATION
- All the sponges were combined and digested in Soluene 350
- Samples of the receptor fluid (0.5 ml) were taken at recorded intervals over a 48h period (0.5 ; 1 ; 2 ; 4 ; 6 ; 24 ; 29 and 48)
- Layers of stratum corneum removed using a tape stripping technique (at tne end of the experiment and after a new washing). The adhesive strips were soaked in Soluene 350.
- The donor Chamber was washed with ethanol and the sample analysed.

ANALYSIS
- Membrane Integrity : Yes (electrical resistane across the skin membrane).
- Test substance absorption : Yes
- Mass balance : yes by LSC

- Liquid scintillation counting results (cpm) converted to dpm as follows: 6 minutes or to a 0.5% standard deviation of the count
- Limits of quantification: 0.004 µg/ml (0.007 µg/cm²)

Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: surgery or post mortem
- Ethical approval if human skin: No data
- Type of skin: human dermatomed skin
- Preparative technique: six membranes were cut form the whole skin samples using an electric dermatome.
- Thickness of skin (in µm): 400
- Membrane integrity check: No data
- Storage conditions: -20°C on aluminium foil


PRINCIPLES OF ASSAY
- Diffusion cell: Yes (3.3 cm diameter)
- Receptor fluid: water
- Solubility od test substance in receptor fluid: Yes
- Static system: yes
- Flow-through system: No
- Test temperature: 32 +/-1°C
- Other: cells were selected such that each application (peroxide dilution or placebo dilution) was represented by 12 intact membranes from eight differents subjects.
Absorption in different matrices:
Peroxide developer mix
The fastest rate of penetration of 1-Naphthol form the peroxide developer mix (0.562 µg/cm²/h) occurred 0.5 - 2 h after application. Between 2 and 6h, the rate slowly reduced as the reservoir remaining in the skin depleted, following the washing at 0.5h. After 6h the penetration process was effectively complete.
The mean penetrated amount of 1-naphthol at 0.5h was 0.045 %g/cm² (0.0004% of dose),which increased to 0.214 µg/cm² (0.053%) at 1h, 2.07 µg/cm² (0.518%) at 6h and was 3.43 µg/cm² (0.857%) at the end of the experiment (48h). The mean residual amount in the remaining epidermis/ dermis, after tape stripping to remove the stratum corneum, was 0.149 %g/cm² (0.037%), thus the mean systemically available proportion of the dose (amounts penetrated + remaining epidermis/dermis) was 3.58 µg/cm² (0.894% of the dose).
The mean proportion of the dose recovered from the tape strips, representing the stratum corneum, was 1.621 µg/cm² (0.405%), while 1-naphthol recovered from the flange area was 0.064 µg/cm² (0.016%).
The greatest proportion of the applied 1-naphthol was removed from the surface of the skin by the washing procedure at 0.5h (394 µg/cm² ; 98.5%) with only a further 0.710 µg/cm² (0.178%) being removed by the later procedure at 48h.
The overall mean recovery of 1-Naphthol during this experiment was 100%.

Placebo developer mix
The fastest rate of penetration of 1-Naphthol from the placebo developer mix (0.624 µg/cm²/h) occured 0.5-1h after application. Between 1 and 6h, the rate slowly reduced as the reservoir remaining in the skin depleted, following the washing at 0.5h. After 6h the penetration process was effectively complete.
The mean penetrated amount of 1-Naphthol at 0.5h was 0.066 µg/cm² (0.017% of dose), which increased to 0.378 µg/cm² (0.095% of dose) at 1h, 2.22 µg/cm² (0.555%) at 6 hours and was 3.49 µg/cm² (0.873%) at the end of the experiment (48 hours). The mean residual amount in the remaining epidermis/dermis, after tape stripping to remove the stratum corneum, was 0.107 µg/cm² (0.027%), thus the mean systemically available proportion of the dose (amounts penetrated + remaining epidermis/dermis) was 3.60 µg/cm² (0.899% of the dose).
The mean proportion of the dose recovered from the tape strips, representing the stratum corneum, was 0.200µg/cm² (0.050%), while the amount of 1-naphthol recovered from the flange area was 0.042 µg/cm² (0.011%).
As with the peroxide mix, the greatest proportion of the applied 1-naphthol was removed from the surface of the skin by the washing procedure (402 µg/cm² ; 101%), with only a further 0.277 µg/cm² (0.069%) being removed by the later procedure at 48h.
The overall mean recovery of 1-naphthol during this experiment was 102%.
Key result
Time point:
48 h
Dose:
2%
Parameter:
amount
Remarks:
the mean systemically available proportion of the dose
Absorption:
ca. 0.899 %
Time point:
30 min
Dose:
2%
Parameter:
percentage
Remarks:
% of the mean penetrated
Absorption:
ca. 0.017 %
Time point:
1 h
Dose:
2%
Parameter:
percentage
Remarks:
% of the mean penetrated
Absorption:
ca. 0.095 %
Time point:
6 h
Dose:
2%
Parameter:
percentage
Remarks:
% of the mean penetrated
Absorption:
ca. 0.555 %
Time point:
48 h
Dose:
2%
Parameter:
percentage
Remarks:
% of the mean penetrated
Absorption:
ca. 0.873 %
Conclusions:
The fastest rate of penetration of 1-Naphthol from the placebo developer mix (0.624 μg/cm²/h) occured 0.5-1h after application. Between 1 and 6h, the rate slowly reduced as the reservoir remaining in the skin depleted, following the washing at 0.5h. After 6h the penetration process was effectively complete. The mean penetrated amount of 1-Naphthol at 0.5h was 0.066 μg/Cm² (0.017% of dose), which increased to 0.378 μg/cm² (0.095% of dose) at 1h, 2.22 μg/cm² (0.555%) at 6 hours and was 3.49 μg/cm² (0.873%) at the end of the experiment (48 hours). The mean residual amount in the remaining epidermis/dermis, after tape stripping to remove the stratum corneum, was 0.107 μg/cm² (0.027%), thus the mean systemically available proportion of the dose (amounts penetrated + remaining epidermis/dermis) was 3.60 μg/cm² (0.899% of the dose).
Executive summary:

The percutaneous absorption of 1-naphthol from a proprietary oxidative hair dye base containing 4% 1-naphthol was evaluated in an in vitro assay using human dermatomed skin. Prior to dosing, the formulation was mixed 1:1 with either A) a hydrogen peroxide developer solution to give a final concentration of 2% 1-naphthol or B) a placebo developer to give a final concentration of 2% 1-naphthol.

A dose of 20 mg of test formulation/cm2 skin (400 μg 1-naphthol /cm2 skin) was applied to the skin samples for 30 minutes followed by thorough rinsing with 3% Teepol®. Measurements of the 1-naphthol penetrating the skin into the receptor fluid were taken following the 30 minute exposure period and at set intervals during the 48 hour measurement period (1, 2, 4, 6, 24, 29 and 48 hours post application). At the end of the 48 hour measurement period, tape stripping was conducted and the levels of 1-naphthol in the tape strips and the remaining epidermis/dermis determined.

Results

a) In the oxidative formulation the amount considered absorbed was 3.58 ± 1.13 (range 1.31 to 5.46 μg/cm².

b) In the placebo, non-oxidative formulation the amount considered absorbed was 3.60 ± 1.80 (range 1.49 to 8.28) μg/cm² [0.899 ± 0.451 (range 0.373 to 2.07) % of the applied dose].

Endpoint:
basic toxicokinetics, other
Remarks:
collection of several in vivo and in vitro studies
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
GLP compliance:
not specified
Specific details on test material used for the study:
CAS 90-15-3
Species:
other: reports from several species described
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
various studies, including published reports
Route of administration:
not specified
Vehicle:
not specified
Details on exposure:
Depends on the study
Duration and frequency of treatment / exposure:
Varies
Remarks:
Depends on the type of study
Details on study design:
depends on the study type.
Details on dosing and sampling:
Varies
Details on absorption:
Please see the excutive summary on oral, dermal and inhalatory absorption of 1-naphthol.
Details on distribution in tissues:
Please see the excutive summary
Details on excretion:
Please see the excutive summary
Details on metabolites:
Please see the excutive summary
Bioaccessibility testing results:
Conclusion: Bioavailable

References cited:

Best, E. M. Jr., Murray, B. L.,J. Occupational .Med.4,507, 1962.

Carpenter, C. P., Weil, C. S., Palm. P. E.. Woodside, M. W.,Nair, J. H. III, Smyth, H. J., Jr.: J. Agr. Food Chem. 9, 30, 1961.

Doherty at al, Biochem Pharmacol 33(4): 543-9, 1984.

Doherty M D,Cohen GM,Gant TW,Naish S,Riley PA.Metabolism of 1-naphthol by tyrosinase.BiochemPharmacol.34(17):3167-72,1985.

Dechelotte, P., Varrentrapp, M., Meyer, H.J., and Schwenk, M. Conjugation of 1-naphthol in human gastric epithelial cells. Gut 34 (2): 177-80, 1993.

Knaak. J. B.. Tallant, M.J., Bartley, W. J., Sullivan L. J.: J. Agr. Food Chem. 13, 537, 1965.

Leeling, N.C., and Casida, JE.: Metabolites of Carbaryl (1-Naphthyl Methylcarbamate) in Mammals and Enzymatic Systems for Their Formation. J. Agr. Food Chem. Vol. 14 (3) 281-290, 1966.                                                          

Mehta R,Hirom PC,Millburn P. The influence of dose on the pattern of conjugation of phenol and 1-naphthol in non-human primates. Xenobiotica, 8(7): 445-52, 1978

P. Suwan-ampai, A. Navas-Acien, P.T. Strickland, and J. Agnew: Involuntary Tobacco Smoke Exposure and Urinary Levels of Polycyclic Aromatic Hydrocarbons in the United States, 1999 to 2002. Cancer Epidemiol Biomarkers Prev.:18(3)884-93, 2009.

Whitehurst, W.E., Bishop, E.T., Critchfield, F. E., Gyrisco, G. G., Huddleston. E. E.W.,Arnold, H., Lisk, D. L.: J. Agr. Food Chem., 11, 167, 1963.

Note: Other citations can be found at various endpoint summaries of this dossier.

Conclusions:
Toxicokinetics of 1-Naphthol:
Experimental data on the ADME (absorption, distribution, metabolism, and excretion) of 1-naphthol (CAS 3 90-15-3) based on the phys-chem properties, available information from animals studies submitted in the dossier, and from the published literature are briefly summarized thus providing the toxicokinetic behavior of the substance


It was concluded that the ADME profile of 1-naphthol suggests that is well absorbed, distributed in the body, metabolized, and excreted via urine and is assumed to be not significantly retained in the body.
Executive summary:

Toxicokinetics of 1-Naphthol: Experimental data on the ADME (absorption, distribution, metabolism, and excretion) of 1-naphthol (CAS 3 90-15-3) based on the phys-chem properties, available information from animals studies submitted in the dossier, and from the published literature are briefly summarized thus providing the toxicokinetic behavior of the substance

Absorption

Oral:

Generally, oral absorption is favored for molecular weights below 500 g/mol. This characteristic (Mol. Weight: 144.17 g/Mol), combined with the moderate lipophilic log Pow value (2.84 at 25 degrees C) and water solubility (1.1 g/L at 20 degrees C) allow dissolution of 1-naphtholin the gastro-intestinal fluids when in contact with the mucosal surface.

Repeated daily oral administration of 1-naphthol to Crl:CD/(SD)BR VAF/Plus rats for 13 weeks at 65, 130, or 400 mg/kg bw/day (Weiler, 2001) resulted in a number of altered urine and clinical chemistry parameters (which were considered non-adverse), treatment-related microscopic changes (restricted to the stomach and spleen). In gastric tissues, squamous hyperplasia and hyperkeratosis of the nonglandular stomach were present in all males and most females given 400 mg/kg bw/day and were due to the local irritating effect of the substance. That human gastric cells can metabolize 1-naphthol into its glucuronide and sulphate conjugates is known (Decollate et al, 1993). Microscopic changes in the spleen sections (increased pigment deposits [hemosiderin]) were minimally to slightly increased in the 400 mg/kg bw/day group. A NOAEL was set at 130 mg/kg bw/d. In CD-1 mice dosed by oral gavage for 30 days with 0, 50, 100, 200 mg/kg bw/day doses of 1-naphthol in propane-1,2-diol resulted in treatment-related changes in glandular stomach as focal mucosal erosion in three male mice dosed at high dose and two of these animals were killed in extremis on the 4th and 20th days of the study (Poole, 1989). A dose-related, but statistically insignificant increase in white blood cell counts was noted in female mice. Microscopic changes in the kidneys was observed. These studies support the absorption and systemic distribution of 1-naphthol from the gastrointestinal tract, and distribution in the body in rodents.

In an OECD 414 (developmental toxicity) study in rats, statistically significant numbers of rats in the 400 mg/kg bw/day dosage group had excess salivation, dilated pupils, decreased motor activity, ataxia, impaired righting reflex, lacrimation, lost righting reflex, lethargy, red, brown or orange perioral substance, urine stained abdominal fur, rales, chromorhinorrhea, twitches, body jerks and brown perinasal substance (Raymond, 2003). Additionally, dilated pupils, lacrimation, brown perioral substance and chromorhinorrhea occurred in one to five rats in the 100 mg/kg bw/day dosage group; the incidence of chromorhinorrhea was statistically significant. Maternal body weights were significantly reduced compared to the control group. Average fetal body weights were reduced by 4% as compared to controls in the 400 mg/kg bw/day dosage group; these reductions were significant for total and female fetal body weights and these might have been influenced by maternal toxicity. Again, these findings support absorption and distribution of 1-naphthol in rats.

Dermal

1-naphthol is likely to penetrate skin as the logPow value and water solubility favor dermal penetration. It is generally accepted that if a compound’s water solubility falls between 100-10000 mg/L, absorption can be anticipated to be moderate to high. Moreover, for substances with a logPow between 1 and 4 (2.84 at 25 degrees C for 1-naphthol), both penetration into stratum corneum and partition into the epidermis are likely to occur.

In a percutaneous absorption study of 1-naphthol from a proprietary oxidative hair dye base containing 4% (Hadfield, 2005; OECD 428), 1-naphthol was evaluated in an in vitro assay using human dermatomed skin. A dose of 20 mg of test formulation/cm2 skin (400 μg 1-naphthol /cm2 skin) was applied to the skin samples for 30 minutes followed by thorough rinsing with 3% Teepol®. Measurements of the 1-naphthol penetrating the skin into the receptor fluid were taken following the 30 minute exposure period and at set intervals during the 48 hour measurement period (1, 2, 4, 6, 24, 29 and 48 hours post application). At the end of the 48 hour measurement period, tape stripping was conducted and the levels of 1-naphthol in the tape strips and the remaining epidermis/dermis determined. The fastest rate of penetration of 1-Naphthol from the placebo developer mix (0.624 μg/cm²/h) occurred 0.5-1h after application. Between 1 and 6h, the rate slowly reduced as the reservoir remaining in the skin depleted, following the washing at 0.5h. After 6h the penetration process was effectively complete. The mean penetrated amount of 1-naphthol at 0.5h was 0.066 μg/Cm² (0.017% of dose), which increased to 0.378 μg/cm² (0.095% of dose) at 1h, 2.22 μg/cm² (0.555%) at 6 hours and was 3.49 μg/cm² (0.873%) at the end of the experiment (48 hours). The mean residual amount in the remaining epidermis/dermis, after tape stripping to remove the stratum corneum, was 0.107 μg/cm² (0.027%), thus the mean systemically available proportion of the dose (amounts penetrated + remaining epidermis/dermis) was 3.60 μg/cm² (0.899% of the dose).

Animal studies support the abovein vitrofindings. 1-Naphthol produced evidence of allergic contact sensitization in a mouse LLNA study when tested at 2.5% (Rosner, 2001). When a hair dye formulation containing 0.5% of 1 -naphthol was applied to rabbits twice weekly for 13 weeks, there was no evidence of systemic toxicity (Schulz, 1976). In a guinea pig maximization test (Middleton, 1978), no reaction was observed on the skin of any animal following challenge with either 0.05 or 0.1% 1-naphthol. It is not clear if the lower concentration used in the rabbit and G. pig studies or the use of non-standard methodologies resulted in a lack of skin sensitizing effects. The LLNA study results indicate that the substance has penetrated through the mouse skin to initiate the immune response. However, the effects may also be caused by the formation of reaction products between 1-naphthol and molecules present in the skin (haptenation). The assumptions of bioavailability based on the physico-chemical properties of the substance are further supported by the results from an acute dermal toxicity study performed on rabbits (Bio-FAX, EPA, 1991) where moderate erythema and edema were observed. Furthermore, skin irritation study in rabbits (EPA 86-920000514S) revealed moderate to severe erythema and edema after 72 hours (irritation score of 7.09/8.00) or moderately irritating or severely irritating to rabbit skin in various tests, resulting in classification of 1-naphthol as a Cat. 2 skin irritant. Therefore, its ability to cause local dermal injury can favor its absorption. 

Inhalation

In an acute toxicity study via inhalation of 1-naphthol as dust (CMU Report 43-92, 1980), signs of systemic toxicity observed included eye irritation, salivation and ataxia at high (>=97 mg/m3) concentration. Based on the low vapor pressure (0.4 Pa at 25 degrees C) the potential for inhalation exposure to 1-naphthol is considered to be low. Since the substance is a solid, it would have to effectively dissolve in the respiratory tract mucus before absorption directly across the respiratory tract epithelium by passive diffusion.

Taken together, physico-chemical properties and animal experimental data indicate bioavailability of 1-naphthol by oral, dermal and inhalation routes.

Distribution

1-Naphthol may be distributed into the interior part of cells due to its lipophilic properties and in turn the intracellular concentration could be higher than extracellular concentration particularly in adipose tissues. Direct transport through aqueous pores is likely to be an entry route to the systemic circulation. The results from the combined repeated dose toxicity studies and the developmental toxicity test support that distribution occurs. Penetration of the substance through the placenta could not entirely be excluded.

Metabolism

1-Naphtol is considered biodegraded to a level of 77.8% within the 10 day-window in a ready biodegradation test OCDE 301B (Whiting, 2007). 1-Naphthol may be hydrolyzed after being in contact with an aqueous solution as well as thermally degrade enzymatically. In the hydrolysis test (OECD Guideline 111) the preliminary test was performed at 50°C and pH 4, 7 and 9. Since less than 10% of hydrolysis was observed after 5 days at pH 4 and 50°C, the test item is considered stable at pH 4 and no additional test is required. It degrades at pH 7 with approximately 70% of the initial concentration after 5 days at 50°C, and at pH 9 (after 5 days at 50°C) it had approximately 18% of the initial concentration. At pH 7 and 9 the test item is not stable and had a half-life of 9.74 and 2.02 days, respectively. The results of the hydrolysis tests at a pH range of 4 to 9 are somewhat representative for the conditions found in the GIT with the stomach having an acidic milieu (~ pH 1.4 to 4.5) and the intestine a slightly acidic to slightly alkaline milieu (~ pH 5 to 8).

The conjugation of 1-naphthol by human gastric epithelial cells was assessedin vitroby Dechelotte et al., 1993). In cultured cells, the 1-hour turnover of 1 uM 1-naphthol to its glucuronide and sulphate conjugate averaged 35% and 8% respectively. These results suggest that the human gastric mucosa is a detoxifying organ. 1-Naphthol can be metabolized by the polyphenol oxidase, tyrosinase, primarily to 1,2-naphthoquinone and to small amounts of 1,4-naphthoquinone as well as to covalently bound products. (Doherty, 1985). It is known that the toxicity of 1-naphthol may be mediated by the formation of 1,2-naphthoquinone and/or 1,4-naphthoquinone, which may be metabolized by one electron reduction to naphthosemiquinone radicals. These in turn, may covalently bind to important cellular macromolecules or enter redox cycle with molecular oxygen thereby generating active oxygen species. Both of these processes appear to play a role in producing the cytotoxic effects of 1-naphthol (Doherty at al, 1984).

Excretion

Hydrolysis and metabolism are expected and conjugation of Phase I-metabolites may further increase hydrophilicity. The degradation products, assuming they have low molecular weights, and are miscible with water, may either directly be excreted by urine or further metabolized by Phase II enzymes before excretion. Excretion via urine is assumed to be the main elimination pathway of metabolites formed due to their molecular weight (<300 g/mol in rat). In fact, in Capuchin monkeys, only a small amount of sulfate was excreted, but glucuronic acid conjugation was the major metabolism at various dose levels (Metha et al, 1978).

1-naphthol derived from carbaryl metabolism is assumed to be conjugated and excreted in the urine as l-naphthyl glucuronide by humans, rats, and guinea pigs (Best and Murray, 1962; Carpenter et al, 1961, and Whitehurst et al., 1963, all three as cited by Leeling and Casida, 1966). In another report, the glucuronides and sulfates of 1-naphthol were identified in the urine of carbaryl-treated rats and guinea pigs (Knaak et al., 1965).  Naphthols can serve as biomarkers for livestock and humans exposed to polycyclic aromatic hydrocarbons such as cigarette smoke.For instance, 23 metabolite isomers of the nine parent PAH (polycyclic aromatic hydrocarbons) compounds, including naphthalene were found in the urine samples of humans exposed to tobacco smoke (P. Suwan-ampai et, 2009). Therefore, exposure to naphthalene in humans can occur indirectly also.

 

In conclusion, the ADME profile of 1-naphthol suggests that is well absorbed, distributed in the body, metabolized, and excreted via urine and is assumed to be not significantly retained in the body. 

Description of key information

The mean penetrated amount of 1-Naphthol at 0.5h was 0.066 μg/Cm² (0.017% of dose), which increased to 0.378 μg/cm² (0.095% of dose) at 1h, 2.22 μg/cm² (0.555%) at 6 hours and was 3.49 μg/

cm² (0.873%) at the end of the experiment (48 hours). The mean residual amount in the remaining epidermis/dermis, after tape stripping to remove the stratum corneum, was 0.107 μg/cm² (0.027%), thus

the mean systemically available proportion of the dose (amounts penetrated + remaining epidermis/dermis) was 3.60 μg/cm² (0.899% of the dose).

Key value for chemical safety assessment

Absorption rate - dermal (%):
0.899

Additional information