2-naphthol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: expert assessment

Adequacy of study:

key study

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An assessment of the toxicokinetics behaviour of the substance was performed using results from existing toxicological studies

Data source

Reference

Reference Type:

other: expert assessment

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

An assessment of the toxicokinetics behaviour of the substance was performed using results from existing toxicological studies

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-naphthol

EC Number:

205-182-7

EC Name:

2-naphthol

Cas Number:

135-19-3

Molecular formula:

C10H8O

IUPAC Name:

2-naphthol

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Physicochemical properties of the substance suggest that it is likely to be absorbed following an exposure via the oral, inhalation or dermal route, which is supported or confirmed by available experimental data.

Main ADME results 2

Type:

distribution

Results:

2-naphthol is expected to be distributed in various compartment of the body, with higher concentrations identified in the lungs, kidneys and liver. Some adverse effects suggest that the substance or its metabolites reached the CNS.

Main ADME results 3

Type:

metabolism

Results:

The substance is metabolised mainly as glucuronide and sulphate.

Main ADME results 4

Type:

excretion

Results:

The urine is the main route of elimination of the substance, mainly in conjugated form.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral exposure:
2-naphthol is soluble in water (0.6 g/L) and can consequently be expected to dissolve upon oral exposure. Considering that the substance has a Log Kow of 1.89, it can be expected to be absorbed following an exposure via the oral route.
Several studies are available, investigating the toxicity of 2-naphthol following an acute or repeated exposure via the oral route. Signs of systemic toxicity were recorded as part of these studies, including – but not limited to – transient changes in the blood levels of creatinine, sodium and calcium. This confirms that absorption of 2-naphthol occurred following oral exposure.

Inhalation exposure:
2-naphthol has a vapour pressure of 0,0099 Pa at 20°C and a boiling point above 220°C therefore no exposure via inhalation to the substance as a vapour is expected.
The substance was shown to have a median particle size (D50) of 3011 µm, however, presence of particles of inhalable size cannot be excluded.
An acute toxicity study via inhalation was conducted using polyethylene glycol 400 / ethanol (1:1) as a vehicle to create an aerosol of 2-naphthol. Particle size distribution was investigated to confirm the presence of particles of inhalable size. The substance proved to be to hazardous to the animals when tested at up to 5.06 mg/L of air. Impairments of motility and reflex were noted, suggesting that absorption occurred following an exposure via inhalation.

Dermal exposure:
Since 2-naphthol has a molecular mass < 500 Da, it can theoretically be absorbed following a dermal exposure (Bos et al., 2000).
2-naphthol is soluble in water (0.6 g/L) and has a Log Kow = 1.89. According to ECHA (2017), these values are favourable for dermal absorption.
An in vivo skin irritation study was conducted on rabbits, during which no clinical signs were reported. It was concluded that the substance was not irritating or corrosive to the skin, therefore it will not induce damage to the skin leading to an enhanced dermal absorption.
2-naphthol was found to be sensitising to the skin when evaluated using a Guinea Pig Maximisation Test. Considering that the challenge was applied to intact skin, it can be concluded that some uptake of the test substance occurred as it is a prerequisite for skin sensitisation (ECHA, 2017). However, this absorption may have been limited to a small fraction of the dose applied.
Hemels (1972) investigated the excretion of 2-naphthol following a dermal absorption. A paste containing 2-naphthol at 20% was applied daily to human volunteers. Samples of blood and urine from persons exposed to the substance were collected during the treatment, and analysed to detect the parent compound as well as 2-naphthol in conjugated form. 2-naphthol and its metabolites were detected in plasma. About 5% of the dose of 2-naphthol applied was detected in urine after 24 hours as unchanged or conjugated substance. This demonstrates that dermal absorption occurred.

Details on distribution in tissues:

2-naphthol is slightly lipophilic as indicated by its Log Kow (1.89), therefore it is likely to distribute into cells, notably in fatty tissues.
Honda et al. (1991) administrated the test substance via the intraperitoneal route. After two hours, it was located mainly in lungs, liver and kidney.
Following a dermal absorption, Hemels (1972) identified the test substance in plasma of human volunteers, unchanged or conjugated.
A decreased of locomotor activity was recorded across several animal studies, which could suggest that the substance or its metabolites were distributed to the central nervous system, although it cannot be confirmed.
An increased creatinine level in blood was reported in male animals exposed for 28 days to 2-naphthol via the oral route, which could suggest a nephrotoxic effects. However, histopathological examination of the kidneys, urinalysis, and blood chemistry analysis conducted during this study did not allow to identify supporting evidence of nephrotoxic effects.

Details on excretion:

Capel et al. (1974) administrated the test substance to rats, pigs and cats. They identified that the substance was eliminated mainly via the urine route, mainly in a conjugated form. These results are supported by the human data generated by Hemels (1972).

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Capel et al. (1974) administrated 2-naphthol to mice subcutaneously, which resulted in 2-naphthol being excreted via the urine in conjugated form, mainly as glucuronide and sulphate.

Applicant's summary and conclusion

Conclusions:

An assessment of the toxicokinetics behaviour of the substance was performed using results from existing toxicological studies

Executive summary:

The absence of specific toxicokinetics data from animal testing means that it is not possible to make firm conclusions concerning the absorption, distribution, metabolisation and excretion of 2-naphthol. However, there are several data sources available investigating the toxicity of the test substance or specific mechanisms relevant when assessing the toxicokinetics behaviour of a substance.

Physicochemical properties of the substance suggest that it is likely to be absorbed following an exposure via the oral, inhalation or dermal route, which is supported or confirmed by available experimental data.

2-naphthol is expected to be distributed in various compartment of the body, with higher concentrations identified in the lungs, kidneys and liver. Some effects identified during acute and repeated-dose toxicity studies suggest that the substance or its metabolites reached the central nervous system, which cannot be confirmed by available experimental data.

The urine is the main route of elimination of 2-naphthol, mainly in conjugated form – glucuronide and sulphate.

It is not considered justified to perform animal studies on this substance to further investigate its toxicokinetics behaviour.