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Description of key information

Toxicokinetic assessment of Diacid 1550 and its potassium salt

Background

Diacid 1550 is a substance of Unknown or Variable composition, Complex reaction products or Biological material (UVCB substance). Diacid 1550 consists of isomers of branched, C-21 or C-23 dicarboxylic acid composed of saturated alkyl chains and a cyclohexene or cyclohexadiene branch. The substance is placed on the market as such or neutralized with caustic potash as a potassium salt.

No studies on toxicokinetics are available for Diacid 1550 or its potassium salt, and the available toxicity studies provide little information on absorption, distribution, metabolism and excretion of the substance. Therefore, the following assessment is primarily based on physicochemical properties, supported by some toxicological indications.

Physical/chemical properties

The physical/chemical properties that are of importance to assess the toxicokinetic behaviour of Diacid 1550 and its potassium salt are:

- Water solubility: 15.72 mg/L (acid) and 13.1 g/L (potassium salt, determined as critical micelle conc.)

- Molecular weight range: 351 to 378 g/mol for 65% - 95% of the UVCB (acid)

- Log Kow – ranges from 3.36 - 7.61 at 30 °C and pH 7. The main constituents (73.4%) of the UVCB show a Log Kow of 6.36 - 6.61 (values for the free acid)

- Vapour pressure – 4.5 x 10-5Pa (25 °C)

 

Absorption

Oral

Diacid 1550 is a lipophilic substance (having an overall log Kow of 6.36 to 6.61 for the UVCB), therefore, its absorption from an oral route of exposure via passive diffusion is expected to be limited. If any absorption occurs, micellular solubilisation will likely be the major mechanism involved, based on the relatively low water solubility (i.e., 15.72 mg/L) and moderately low molecular weight (i.e., 351 to 378 g/mol for 65 -95% of the UVCB) of Diacid 1550. Death of the animals receiving the 2 highest doses (6,834 and 10,250 mg/kg bw) in the acute oral toxicity study (Hintz and Kretchmar, 1973) due to gastroenteritis, as well as the clinical signs of hypoactivity, ruffed fur, laboured breathing, and muscular weakness are all indicative of systemic absorption of Diacid 1550 from the oral route of exposure. In a 28-day feeding toxicity study (Clubb, S.K. and Jardine L, 2005), Diacid 1550 was found to cause significant changes in liver-related clinical chemistry parameters at the lowest dose tested (500 ppm). In the mid- and high-dose groups, these changes were accompanied with changes in liver weights and histopathology of the liver, indicating presence of systemic toxicity as a result of oral absorption.

Inhalation

Respiratory exposure to Diacid 1550 is unlikely to occur on a large scale, due to the very low vapour pressure (~0.000045 Pa) and therefore, low volatility of the substance. However, when exposure occurs as an aerosol, some respiratory exposure may be possible. Any inhaled Diacid 1550 may be absorbed through the inhalation tract to the same extent and for the same reasons as for oral absorption.

Dermal

Considering the liquid state, medium molecular weight, and the low vapour pressure of Diacid 1550, it is likely that it will be absorbed to some extent following dermal route of exposure. Based on its log Kow, Diacid 1550 is expected to be sufficiently lipophilic to cross the lipid rich barrier of the stratum corneum, but due to its low to moderate water solubility, the substance's partition from the stratum corneum into the epidermis may be limited. This understanding is in agreement with the results of two GLP-compliant in vitro studies assessing the potential of Diacid 1550 to cause skin irritation as well as an in vivo study with rabbits using the potassium salt, showing skin irritation and an acute dermal toxicity study in rats with the potassium salt, in which irritation scores were seen that were fully reversible within one week. The results of these studies indicated that Diacid 1550 and its potassium salt are a skin irritant, but do not have skin corrosive properties, likely due to its limited penetration into the epidermis following dermal exposure. As the potassium salt is solid at ambient temperature and more lipophilic (ionic salt), absorption through skin of the potassium salt is expected being lower than absorption of the free acid.

Distribution

Based on it physico-chemical properties (high log Kow and low water solubility), Diacid 1550 is likely to be distributed into cells and adipose tissues and to a lower extent into the extracellular spaces.

Metabolism and excretion

No information on metabolism and excretion is available.

Conclusions

In the absence of studies specifically addressing the toxicokinetic properties of Diacid 1550 and its potassium salt, and based on the available data, it is anticipated that the adsorption of Diacid 1550 mainly occurs via oral and dermal routes, with limited potential for respiratory absorption. Based on the information on the physico-chemical properties of Diacid 1550, the substance is expected to be distributed into cells and adipose tissues and to a lower extent into the extracellular spaces.

For risk assessment, absorption by oral and inhalation route is conservatively estimated being 100%, whereas absorption by dermal route is estimated being only 10% for the potassium salt.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information