Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: toxicokinetic assessment
Adequacy of study:
key study
Study period:
2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Alkylated Naphthalene, EC Number 700-826-8 is a close structural analog of alkyl naphthalene. The substances have similar chemical and physical properites and the toxicokinetic assessment for Alkylated Naphthalene, EC Number 700-826-8 can be used as read-across to alkyl naphthalene.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The available toxicity and chemistry test data for the substance are evaluated using expert judgement and currently accepted principles of absorption, distribution, metabolism and excretion.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Substance: UVCB (Alkylated Naphthalene)
Description: Clear amber slightly viscous liquid (determined at WIL Research Europe B.V.)
Purity: UVCB
Radiolabelling:
no

Results and discussion

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: low bioaccumulation based on Log Kow (>8.2) and low water solubility
In view of the properties of the substance and according to the criteria given in the REACH Guidance, for risk assessment purposes the absorption is estimated to be 10% for dermal, 10% for oral and 10% for inhalation exposure.
Executive summary:

Toxicokinetic Assessment for Alkylated Naphthalene

A substance can enter the body via the lungs, the gastrointestinal tract, and the skin. To determine the absorption rate, the different routes need to be assessed individually.

 

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration [1]. Alkylated Naphthalene has a very low water solubility (<2 μg/l), therefore dissolving into the gastrointestinal fluids will be limited. Alkylated Naphthalene is a UVCB substance. Its approximate molecular weight is moderate to high, absorption is thus not favoured by its size. Alkylated Naphthalene has a high log Pow (> 8.2 at 20°C), which makes the compound very hydrophobic. This characteristic will enable micellular solubilisation by bile salts in the gastro-intestinal tract which allows crossing of lipid biomembranes.

 

In light of risk assessment purposes, the low water solubility and the moderate molecular weight of Alkylated Naphthalene do not favour oral absorption, uptake by passive diffusion is thus expected to be very limited. The high log Pow indicates that crossing lipid biomembranes is possible to some extent as a result of micelllular solubilisation by bile salts. Consequently, oral absorption of Alkylated Naphthalene is considered to be limited, and for risk assessment purposes is set at 10%.

 

Once absorbed, wide distribution of the test substance throughout the body is not expected based on the fact that it hardly dissolves in water. Alkylated Naphthalene has a moderate to high molecular weight. In general, the smaller the molecular, the wider the distribution. A molecular weight around 500 or above will not favour wide distribution. Based on its size and its low water solubility, distribution is expected to be limited. Excretion of Alkylated Naphthalene will occur via the bile (high molecular weight) or the urine (low molecular weight). Based on its high partition coefficient (>8.2 measured at 20 °C), it can generally be assumed that Alkylated Naphthalene can distribute into cells and accumulate in adipose tissue. However, for highly hydrophobic substances, experimental data now demonstrate that both the bioconcentration factor and the bioaccumulation factor tend to decrease with increasing log Kow (above 6 and above 7.5 resp.; [2]) therefore the likelihood of bioconcentration and accumulation is relatively low.

The low vapour pressure (8.4 × 10-7Pa at 20 °C) indicates that Alkylated Naphthalene has a low volatility and is not expected to evaporate and become available via inhalation. However, if aerosols are formed, inhalation of small droplets may reach the respiratory tract. If Alkylated Naphthalene reaches the tracheobronchial region, it is not likely to dissolve within the mucus lining of the respiratory tract due to its very limited water solubility. However, based on its high log Pow, micellular solubilisation can occur which will enable uptake of the substance by crossing of biomembranes.

Based on the above data, for risk assessment purposes the inhalation absorption of Alkylated Naphthalene is set at 10% [3].

 

When Alkylated Naphthalene comes in contact with the skin, the first layer of the skin, the stratum corneum, forms a barrier for hydrophilic compounds. Alkylated Naphthalene has a log Pow > 6, suggesting that the substance can be taken up in the stratum corneum. Due to its very low water solubility (<2 μg/l), the transfer between the stratum corneum and the epidermis will be limited.

According to the criteria given in the REACH Guidance (4), 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. As the physical/chemical properties of Alkylated Naphthalene meet the criteria for limited dermal absorption (High MW and Log Pow >8.2) and oral absorption was also estimated to be 10%, for risk assessment purposes dermal absorption should be set at 10%.

References

1.  Martinez, MN , Amidon GL. Mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J Clin Pharmacol 2002; 42: 620-43.

2. Review of QSAR Models for Bioconcentration. Manuela Pavan, Andrew P. Worth and Tatiana I. Netzev. 2006 EUR 22327 EN.

3. Guidance for the Implimentation of Reach. Chapter R.7c. Endpoint Specific Guidance, European Chemical Agency 2008