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Administrative data

Link to relevant study record(s)

Description of key information

A toxicokinetic assessment was conducted in accordance with REACH Annex VIII 8.8.1. The substance tridecanedioic acidis a solid.  It is an organic mono constituent substance.
A full ADME toxicokinetic study in the rat is not available. An in vitro/vivo study on metabolism in humans/animals of tridecanedioic acid is available (Mortensen and Gregersen, 1982). The toxicokinetic analysis is based on data from physicochemical data and in vivo animal models. In vivo studies for the acute oral and dermal routes and an in vivo skin sensitization study are available for Tridecanedioic acid. In vivo read across studies from dodecanedioic acid (CAS 693-23-2) for the oral subacute route (Combined Repeated Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test) and oral subchronic route (90 day repeated dose toxicity) are available.There are no studies covering the inhalational route available. Further details on endpoints are available in the IUCLID 5 registration dossier.
Absorption ….
Based on the substance data, the absorption rates of 50 % (oral), 50 % (dermal) and 100 % (inhalation) are accepted for chemical risk assessment purposes

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Physicochemical properties

In accordance with the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7C Section R.7.12 (Endpoint Specific Guidance), the physicochemical properties can provide an insight into the potential behaviour of Tridecanedioic acid in the body. This information can be combined with the in vivo study data for the toxicokinetic assessment.

Absorption

The molecular weight of Tridecanedioic acid (244.33 g/mol) is in the range for favourable oral absorption (<500 g/mol). The log P of Tridecanedioic acid(3.0 @ 25 °C) indicates it is lipophilic and is in the range of favourable oral absorption by passive diffusion. The water solubility (10.15 mg/L @20°C) indicates it is slightly soluble and as solids typically have to dissolve before they can be absorbed, this may impair absorption via the oral route.

The water solubility of Tridecanedioic acid (10.15 mg/L) is favourable for low to moderate dermal uptake and the log P (3.0) is in the optimal range to favour dermal absorption. However the molecular weight of Tridecanedioic acid (244.33 g/mol) is above the range for favorable dermal absorption (<100 g/mol) and the physical state indicate that dermal absorption is likely to be low.

The particle size distribution report for Tridecanedioic acid indicates the following volume median diameters: d10: 12.9±0.28 µm; d50: 82.1±1.94 µm; d90: 454.3±33.56 µm. This indicates that Tridecanedioic acid particles have the potential to be available in the inhalable fractions of air and may reach the thoracic (<50 µm) and alveolar regions (<15 µm).As the substance is slightly water soluble (10.15 mg/L), it may diffuse/dissolve into the mucus lining the respiratory tract and as the log P is > 0, it may have the potential to be absorbed directly across the respiratory tract epithelium. However, Tridecanedioic acid has a very low vapour pressure (9.5 X 10E-8) and high melting point (113.6 °C at 101.32 kPa) so the potential for the generation of inhalable forms is low and thus absorption via the inhalation route is expected to be low. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur.

Distribution/Metabolism

A wide distribution Tridecanedioic acid is favourable as it has a relatively small molecular weight and moderate lipophilicity. Based on the log P value (3.0), Tridecanedioic acid is unlikely to accumulate with intermittent exposure. The physicochemical properties of Tridecanedioic acid (low molecular weight, lipophilic) suggest it can cross the placenta.

Excretion

The substance is expected to be excreted in the urine due to its low molecular weight (<300) and good water solubility.

Information from other studies in the dossier and public literature

Oral/GI absorption

In the acute oral toxicity study (LD 50: 2000 mg/kg (female), no treatment-related mortalities, clinical signs, necropsy findings or changes in body weight were observed. Systemic effects were noted in the subchronic oral toxicity study (read across dodecanedioic acid, NOAEL: 1800 mg/kg bw/day);it is assumed that oral absorption of Tridecanedioic acid occurs during repeated exposure.The in vivo study data together with the physicochemical information indicates that the substance may be absorbed via the oral route. For chemical safety assessment purposes, an oral absorption rate of 50% is acceptedbased on all the information in the dossier.

Dermal absorption

The acute dermal toxicity study did not indicate any effects up to the limit dose (LD50: >2000 mg/kg). In the skin sensitisation test in guinea pigs according to Magnusson and Kligman (Maximisation test), Tridecanedioic acid was not sensitising.The available in vivo data together with the physicochemical dataindicates that any significant dermal absorption is unlikely.The ECHA guidance criteria (Chapter R.7C) state that 10% dermal absorption is used when the molecular weight of the substance is >500 and the log P is <-1 or >4, otherwise 100% dermal absorption is used. In general, dermal absorption will not be higher than oral absorption, so for chemical safety assessment purposes a dermal absorption rate of 50% is accepted.

Respiratory absorption-Inhalation

There are no inhalation studies available for the substance.The available physicochemical data (vapour pressure, melting point) indicate that the potential for the generation of inhalable forms is low and thus absorption via the inhalation route is expected to be low. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. However, as no direct data is available, for chemical safety assessment, an inhalation absorption rate of 100% is accepted.

Distribution/Metabolism

From the dodecanedioic acid read across study (90 day repeated dose oral toxicity study), there is evidence of a wide distribution; it is assumed that similar distributionmay occur forTridecanedioic acid.

Excretion

The beta-oxidation of C8 -C16 -dicarboxylic acids to short-chain dicarboxylic acids was investigated (Mortensen and Gregersen, 1982):

The beta-oxidation in vivo was evaluated from the excretions of C6-C10-dicarboxylic acids in urine from rats given C8-C16-dicarboxylic acids. Correspondingly, the beta-oxidation in vitro was determined from the rise in concentration of C6-C10(12)-dicarboxylic acids in the postnuclear (600Xg) fraction of rat liver homogenates incubated with C8-C16-dicarboxylic acids. The results showed that C10-C14-dicarboxylic acids were far better substrates for beta-oxidation than were C8- and C16-dicarboxylic acids.