Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Expert assessment
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Brown liquid
UVCB treated as 100% purity

Results and discussion

Applicant's summary and conclusion

Conclusions:
Interpretation of results: low bioaccumulation potential based on study results
The oral absorption for risk assessment purposes of DNNSA is set at 100%. This is based primarily on observed effects on the upper GI tract in the repeat dose testing. The inhalation and dermal absorption is set at 10% based on chemical properties and other test results. Once absorbed, wide distribution of the test substance throughout the body is not expected based on its low water solubility and molecular size. Based on the high log P and the results of QSAR modeling, DNNSA is not expected to significantly bioaccumulate in animal tissue.
 
Executive summary:

A toxicokinetic assessment for Di C8–C10, branched, C9-rich, Alkylnaphthalene Sulphonic Acid (DNNSA) has been made based on the physical and chemical properties of the substance, the available toxicity studies and the QSAR model BCFWIN/BCFBAF (EPIWIN Suite). 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.

Oral Absorption

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration. DNNSA has a low water solubility (0.229 mg/l), therefore it is expected to dissolve to a small extent into the gastrointestinal fluids. Uptake by passive diffusion is thus limited, but it will occur. DNNSA is a UVCB substance. Its approximate molecular weight is moderate (MW = 459), absorption is thus not influenced by its size. DNNSA has a high log Pow (> 6.6 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. The structure contains a ionisable group (SO3H), which might hamper diffusion across biological membranes.

The effects seen on the GI tract after 28 days repeated exposure by gavage (hyperkeratosis of the forestomach epithelium, mucosal hyperplasia and increased severity of lymphogranulocytic inflammation in the caecum and increased amounts of mucus in the large intestines) are most probably related to the acidic nature of the material. Based on these data it is concluded that the substance interferes with the integrity of the epithelium lining the GI tract, which will enhance absorption.

In light of risk assessment purposes, the high log Pow, low water solubility and the moderate molecular weight of DNNSA do not favour oral absorption. However, oral absorption of DNNSA is set at 100%, based on its irritation effects on the epithelium of the GI tract as seen in the 28 days subacute study.

 

Distribution and Bioaccumulation

Once absorbed, wide distribution of the test substance throughout the body is not expected based on its low water solubility. DNNSA has an approximate molecular weight of 459. In general, the smaller the molecular, the wider the distribution. A molecular weight around 500 will not favour wide distribution. Based on its size and its low water solubility, distribution is expected to be limited. Excretion of DNNSA will occur via the bile (high molecular weight) or the urine (low molecular weight). Based on its high partition coefficient (>6.6 measured at 20°C; 8.52 based on EPIWIN calculation), it might be assumed that DNNSA will distribute into cells and accumulate in adipose tissue. However, for highly hydrophobic substances, e.g. with log Kow > 6, experimental data now demonstrate that bioaccumulation factor (BCF) values tend to decrease with increasing log Kow above 6. The fish BCF value (calculated applying the BCFWIN/BCFBAF model) was found to be 56 and 10 (based on measured or calculated log Pow resp.). Since both values are considerably less than the EU PBT criterion of 2000 for BCF, it is concluded that the bioaccumulation potential is low.

Inhalation

The low vapour pressure (3.3 × 10-7hPa at 20°C) indicates that DNNSA has a low volatility and is not expected to evaporate and be available via inhalation. The uses of substance as a lubricant additive also do not indicate a significant potential for inhalation exposure. Moreover, if DNNSA reaches the tracheobronchial region, it is not likely to dissolve within the mucus lining the respiratory tract due to its low water solubility. Based on its high log Pow, some 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 DNNSA is set at 10%.

 

Dermal

When DNNSA comes in contact with the skin, the first layer of the skin, the stratum corneum, forms a barrier for hydrophilic compounds. DNNSA has a log Pow > 6, suggesting that the substance can be taken up in the stratum corneum. Due to its low water solubility (0.229 mg/l), the transfer between the stratum corneum and the epidermis will be limited.

The structure contains a ionisable group (-SO3H), since it is generally thought that ionized substances do not readily diffuse across biological membranes, penetration of the substance is hampered. A rabbit skin irritation study showed that DNNSA was moderately irritating to skin but the study does not report any skin corrosion which might enhance dermal absorption. 

 

According to the criteria given in the REACH Guidance (3), 10% dermal absorption will be considered in cases where the MW >500 and log Pow <-1 or >4. The weight of evidence of the following factors indicates that DNNSA can be assumed to have a dermal absorption of 10%: 1) the molecular weight (459) approaches the criterion 2) the log P is considerably outside the stated range (8.52) and 3) skin irritation testing did not report any corrosive effects which would enhance absorption.

 

In conclusion, the dermal absorption for risk assessment purposes of DNNSA is set at 10%.