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Description of key information

 No toxicokinetic data (animal or human studies) are available on this substance.

Based on the moderate molecular weight (329.18 g/mol), a particle size of 230.22 µm (Mass Median Aerodynamic Diameter or MMAD), a moderate water solubility (0.144 g/L), a moderate partition coefficient (log Kow of 2.4 at pH 9, unionized form; log Kow of 2.7 at pH 7, ionized form) and a low volatility (vapour pressure of <5.3E-10 kPa at 25°C), it can be expected that oral, dermal and respiratory absorption rates are moderate. The adverse effects of the 28-day oral repeated dose gavage toxicity study confirm the moderate oral absorption rate.

Distribution in the body cells is not expected to be wide based on the lipophobic character and the elimination of the product will mainly occur through the bile.

Key value for chemical safety assessment

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

Additional information

T001159 (CAS 84682-23-5) is a white powder with a moderate molecular weight (329.18 g/mol), a particle size of 230.22 µm (Mass Median Aerodynamic Diameter or MMAD), a moderate water solubility (0.144 g/L), a moderate partition coefficient (log Kow of 2.4 at pH 9, unionized form; log Kow of 2.7 at pH 7, ionized form) and a low volatility (vapour pressure of <5.3E-10 kPa at 25°C).

The backbone of T001159 is a 1,3-dioxolanylmethanol group with 2 substituents at position 2 which are a 2,4-dichlorophenyl-group and a 1H-imidazolylmethyl-group. Due to the presence of the imidazole group, the substance is considered a weak base. This implies that the product will be protonated in an acidic environment. From the calculated pKa values based on the Perrin calculation method (Reingruber, 2016), it is confirmed that the test item is (partly) ionized in environments with a pH <9.

No toxicokinetic data (animal or human studies) are available on this substance. The data present in this dossier are based on physicochemical and toxicological parameters and will allow a qualitative assessment of the toxicokinetic behaviour of T001159.


Oral/GI absorption:

T001159 is considered favorable for absorption since its molecular weight < 500 g/mol, its log Pow value between -1 and 4 and its moderate water solubility leading to dissolution of the substance into the gastrointestinal fluids and absorption through passive diffusion. It is generally assumed that the absorption along the gastrointestinal tract predominantly takes place in the small intestine.

In an acute oral toxicity study (OECD 423; Latour; 2016), T001159 was administered via oral gavage on a single occasion to 2 subsequent groups of 3 female Wistar rats at 2000 mg/kg body weight. No mortality or abnormalities were observed at gross pathology. Hunched posture and piloerection was noted for 4 animals on days 1 or 2. No adverse effects were demonstrated with LD50 established as greater than 2000 mg/kg body weight.

In a combined 28-day repeated dose toxicity with the reproductive/developmental toxicity screening test (OECD 422, van Otterdijk; 2016), T001159 was administered by daily oral gavage to male and female Wistar Han rats at dose levels of 50, 150 and 500 mg/kg body weight/day. Results showed that at the high dose level (500 mg/kg body weight/day), T001159 was tolerated without observations of mortality, toxicologically relevant clinical signs, or changes in functional observation tests. At this dose level, adverse histopathological findings were noted in the liver (scattered centrolibular vacuolation and higher liver weight) and in the thyroid gland (follicular cell hypertrophy). The effects in the thyroid gland were considered secondary to the hepatocellular hypertrophy in the liver and adverse in nature. Moreover, at 500 mg/kg body weight/day, a lower gestation index, lower post implantation survival index, lower mean number of pups per and lower pup body weights were recorded, and were considered developmental adverse effects.

There is thus a significant uptake of the test item following oral administration.

Based on the physicochemical properties and the results of the toxicity studies, the oral absorption factor is set to 50%.


Respiratory absorption:

Because T001159 has a low volatility, the availability of the powder for inhalation as a vapour is limited. As its MMAD is larger than 100 µm, the majority of the solid particles will not be inhaled. Based on the above, the absorption of T001159 through inhalation is expected to be very low.

Its lipophilic character (logKow>0) implies that the product has the potential to be subsequently absorbed across the respiratory tract epithelium by passive diffusion. However,the moderate water solubility and the molecular weight higher than 200 g/mol will cause the substance to be retained within the mucus and transported out of the respiratory tract rather than being absorbed after inhalation.

Therefore, the respiratory absorption factor is estimated to be 50%.

Dermal absorption:

Since T001159 is a solid, the uptake of the product will be more limited compared to liquid products. The dry product has to dissolve into the surface moisture of the skin before uptake can take place. Based on its moderate water solubility (0.144 g/L), dermal uptake is expected to be moderate since the substance is sufficiently soluble in water to partition from the stratum corneum into the epidermis. From its moderate logKow value of 2.7 (at pH 7) it can be derived that the substance is rather lipophilic and therefore easily crosses the lipid rich environment of the stratum corneum leading to dermal uptake.

An acute dermal toxicity study (according to OECD guideline 402; Latour, 2016) where 2000 mg/kg of T001159 was applied to 5 male and 5 female Wistar rats, demonstrated no significant adverse effects related to the test material except for local clinical effects at the treated skin area (scales, scabs and erythema maculate), confirming the expectations described above. Piloerection and chromodacryorrhoea were observed during the first two days after treatment but appeared to be reversible effects. Furthermore, the substance is not irritating to skin based in anin vivoacute dermal irritation study (equivalent to OECD guideline 404; Sanders, 2004).

In a Local Lymph Node Assay (equivalent to OECD guideline 429; Sanders, 2005), beside the fact the test item was not considered a sensitizer under the conditions of the test, no signs of systemic toxicity were noted. This confirms that dermal absorption of T001159 is not extensive.

As a result, the dermal absorption factor is set to 50%.


Due to its moderate water solubility and moderate molecular weight T001159 is expected to distribute through the body due to diffusion through aqueous channels and pores. Since the substance is lipophilic (log Kow >0 at pH 7), the substance is likely to distribute into cells leading to a higher intracellular concentration in comparison to the extracellular concentration particularly in fatty tissues. Based on the 28-day repeated oral gavage toxicity study described above, the product distributes to the liver after ingestion.


Since T001159 is a moderately water soluble and has a log Kow of 2.7, no or only limited accumulation is expected within the body.


Once absorbed, T001159 might undergo phase I biotransformation (including reduction, oxidation or hydroxylation) followed by conjugation reactions (phase II) such as glucuronidation and sulfation, increasing the hydrophilicity.


Given the moderate molecular weight, moderate water solubility and ionization of the molecule at the pH of urine, T001159 and its possible metabolites (such as conjugated glucuronides) will most likely be excreted through the urine. Most of the metabolites will have been filtered out of the blood by the kidneys, though a small amount may enter the urine directly by passive diffusion. Furthermore, T001159 may also be actively secreted through the bile.