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Description of key information

The assessment of the toxicokinetic behaviour of the substance is based on the relevant available information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
10
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
10

Additional information

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]. Zinc bis( di C8-C10, branched, C9 rich, alkylnaphthalene sulphonate) has a measured water solubility of < 15 mg/L and therefore it is expected to dissolve into the gastrointestinal fluids to a small extent. Uptake by passive diffusion is possible, but limited due to the high molecular weight of the salt (average MW 984) and its dissociation product DNNSA (MW 461). ZnDNNSA was concluded to have a high log Pow (> 6.5), which makes the compound relatively hydrophobic. This characteristic will enable micellular solubilisation by bile salts in the gastro-intestinal tract which allows some crossing of lipid biomembranes. The structure contains an ionizable group (SO3H), which might hamper diffusion across biological membranes. In addition, the molecular size of the molecule of ca.19 Å does not favor uptake across the biological membranes.

In the repeated dose toxicity test on the structural analogue BaDNNSA, effects seen on the kidney (tubular crystals) indicate that the substance has poor solubility in bodily fluids, is excreted via urine and is unlikely to be widely distributed and absorbed in most tissues. The additional observation in the OECD 422 study of congestion and discoloration in the mesenteric lymph nodes suggests the filtering action of the lymph nodes towards some of BaDNNSA that passes through the intestinal wall. This filtering action may further reduce bioavailability and systemic exposure.

For risk assessment purposes, the logPow, water solubility, the high molecular weight and the molecular size of ZnDNNSA do not favor absorption via the oral exposure route. Therefore, absorption of ZnDNNSA by the oral route is set at 10%, based on the evidence for some systemic toxicity as seen in the OECD 422 study on the analogue BaDNNSA.

 

The metabolism of DNNSA salts is mainly contingent on both the nature of the alkyl groups and the nature and extent of naphthalene ring substitutions. There are currently no metabolism studies of ZnDNNSA, however, the US EPA has evaluated the metabolism of analogs in the sodium alkyl naphthalenesulfonate cluster (SANS), a group of sodium salts of naphthalenesulfonic acids[2]. In a US EPA final rule for SANS, it was stated that “the 1- or 2-sulfonic acid sodium salt moieties on the naphthalene ring may provide a handle by which these compounds can be readily conjugated and eliminated.”  Though the available information is not definitive for ZnDNNSA, where the alkyl chains are much larger than for the naphthalenesulfonic acids evaluated by EPA, it is expected that the metabolism of the substance will be a factor, enhancing elimination.

 

If absorbed, wide distribution of the test substance throughout the body is not expected based on its molecular size (19 Å). In general, molecules of this size do not pass readily through cell membranes, thus limiting wide distribution. Based on its size and its water solubility, distribution is expected to be limited. Excretion of ZnDNNSA and its potential metabolites will occur via the bile (high molecular weight) or the urine (low molecular weight).

 

The low vapor pressure (estimated <1E-08 Pa at 20°C) indicates that ZnDNNSA has a very low volatility and is not expected to evaporate and be available via inhalation. Moreover, aerosols with inhalable or respirable droplets which would reach the respiratory tract are not expected from the current uses of this substance. If ZnDNNSA reaches the tracheobronchial region, the uptake via biological membranes would be limited based on its molecular size.

Based on the above data, for risk assessment purposes the inhalation absorption of ZnDNNSA is set at 10%.

 

When ZnDNNSA comes in contact with the skin, the first layer of the skin, the stratum corneum, forms a barrier for hydrophilic compounds. The logPow > 6.5 suggests that the substance can be taken up in the stratum corneum. However, the water solubility (<15 mg/l) will limit the transfer between the stratum corneum and the epidermis to a certain extent.

The structure contains an ionisable group (-SO3H) that is expected to hamper penetration of the substance, because ionized substances do not readily diffuse across biological membranes. An acute dermal toxicity study showed that ZnDNNSA is not toxic via skin application, which is also indicative of low absorption. In general DNNSA salts are irritating to the skin, but not corrosive, a characteristic that might enhance dermal absorption.  

According to the criteria given in the REACH Guidance [1], 10% dermal absorption will be considered in cases where the MW >500 and log Pow <-1 or >4. Weight of evidence indicates that ZnDNNSA can be assumed to have a dermal absorption of 10%: 1) the molecular weight (984) greatly exceeds the criterion 2) the logPow is considerably outside the stated range (>6.5) 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 ZnDNNSA is set at 10%.

[1] Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance, Nov 2012

[2]Sodium Alkyl Naphthalenesulfonate; Exemption from the Requirement of a Tolerance. 40 CFR 180.Federal Register Number: E9-18702. August 5, 2009.