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Description of key information

Short description of key information on bioaccumulation potential result: 
Assessment of toxicokinetik properties from existing data

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Toxicokinetic parameters such as uptake, distribution, metabolism and excretion form the essential toxicological profile of a substance. An approximate indication of the toxicokinetic pattern can be gained from the physico-chemical properties taking into account the molecular weight, the number of atoms (hydrogen bond donors and acceptors), the solubility in solvents, log POW, etc. and the results of basic toxicity testing of the test article. The assessment of the toxicokinetic properties of Triazin UV-Absorber given below is based on the results obtained for, the following toxicological endpoints:

 

·        Acute oral toxicity in rats

·        Acute dermal toxicity in rats

·        In vivo skin irritation in rabbits

·        In vivo eye irritation in rabbits

·        Skin sensitization (Local lymphnode assay in mice)

·        Bacterial reverse mutation test

·        In vivo micronucleus test in rats

·        Subacute (28-day) oral toxicity in rats

Allstudieswere carried out according to the principles of Good Laboratory Practice and met the requirements of the OECD and EU-Guideline for the Testing of Chemicals.

Physico-chemical properties

Name:                                 Triazin UV-Absorber

Chemical name:              2-[4-(4-ethoxyphenyl)-6-phenyl-1,3,5-triazin-2-yl]phenol

Physical state:                   solid, powder

Empirical formula:        C23H19N3O2

Molecular weight:          369 g/mol                                           (>500 daltons = bad absorption)

Water solubility:             <19 µg/L                                             (= insoluble in water)

Partition coefficient:      log Kow > 6.5                                    (<-0.4 or >5.6 = bad absorption)

Surface tension:               NA                                                        (>60 = no activity)

Vapor pressure:               5.9E-11 hPa                                        (= not volatile)

Atom count:                     47                                                           (>70 = bad bioavailability)

H-bond acceptor:           1                                                             (>10 = bad bioavailability)

H-bond donor:               2                                                             (>5 = bad bioavailability)

Toxicological Profile:

Triazin UV-Absorber was tested for acute oral toxicity in female rats. After application of 2000 mg/kg body weight by gavage, neither lethality nor any clinical signs occurred. Based on the results of this study the oral medial lethal dose (LD50) of Triazin UV-Absorber in the rat is greater than 2000 mg/kg body weight. Dermal treatment with 2000 mg/kg body weight caused also neither mortality nor local or systemic clinical signs. There were no macroscopically visible changes in all animals killed at study end. Testing for skin irritating properties of Triazin UV-Absorber did not result in any local or systemic effects. It is most likely that due to its bad water solubility, Triazin UV-Absorber has no significant dermal absorptive potential, as no effects attributable to dermal absorption were noted in any of the studies conducted.

The administration of Triazin UV-Absorber into the conjunctival sac of rabbit eyes had no effect on the cornea or iris. All rabbits had slight redness of the conjunctiva 24 hours after application. Consequently, Triazin UV-Absorber is not irritating to eyes.

Testing for sensitizing properties of Triazin UV-Absorber was performed in the Local Lymphnode Assay (LLNA) in female mice. Dose levels tested were 5%, 2.5%, and 1%. No evidence of skin sensitizing properties was found.

To assess the toxicity of Triazin UV-Absorber after repeated administration, male and female rats received the test substance at dose levels of 62.5, 250, or 1000 mg/kg body weight per day for a period of 29 days by oral gavage. 14-day recovery groups (controls and high dose animals) were included in the study.

Triazin UV-Absorber caused neither test item related mortality, nor clinical changes following administration by oral gavage, daily for at least 28 days, at up to and including 1000 mg/kg bw/day in CRL:(WI)BR rats. All the animals were normal during the 14-day recovery period. One male at 1000 mg/kg bw/day died due to a dosing failure between Day 9 and Day 10. The behaviour and the general condition of the test animals were normal during the study. There was no treatment-related effect on motor activity or in the functional observation battery tests across groups of treated male or female animals and no findings indicative of neurotoxicity were observed. Evaluation of the vaginal smears prior to necropsy showed the expected distribution of the oestrus cycle phases within the normal population of female Wistar rats. There were no toxicologically significant changes in body weight, body weight gain or animal food consumption between the control and test item treated groups. There were no test item related differences in the examined haematological and clinical chemistry parameters. There were no macroscopic or microscopic findings, or changes in the absolute or relative organ weights that could be ascribed to Triazin UV-Absorber-administration.

In conclusion, under the conditions of this study, the no observed effect level (NOEL) for Triazin UV-Absorber is considered to be 1000 mg/kg bw/day.

 

Triazin UV-Absorber was tested negative for bacterial mutagenicity. The experiments were carried out using histidine-requiring auxotroph strains of Salmonella typhimurium (TA98, TA100, TA1535 and TA1537), and the tryptophan-requiring auxotroph strain of Escherichia coli (WP2 uvrA) in the presence and absence of a metabolic activation system, which is a cofactor-supplemented post-mitochondrial S9 fraction prepared from rat liver.

Triazin UV-Absorber has been assessed for its clastogenic and aneugenic potential in an in vivo Micronucleus Assay in the rat. This assessment was included in the 28-day repeat dose study. No induction of micronuclei in bone marrow erythrocytes was observed, thus, there was no evidence of any genotoxic activity of the test item.

Evaluation and Assessment

Based on all available data, Triazin UV-Absorber does not exhibit a conspicuous toxicokinetic behavior. The data of the acute dermal toxicity, dermal irritation test and skin sensitization testing indicate low dermal permeability, owing to the fact that neither systemic nor irritating or sensitizing effects were observed. This is in accordance with the extremely low solubility of the test substance in water.

In the subacute oral toxicity study, Triazin UV-Absorber was dissolved in an organic solvent (PEG400); hence, the low water solubility should not play a major role in the bioavailability in this study. According to its molecular weight, atom count and H-bond donors and acceptors, Triazin UV-Absorber should be absorbed from the gastrointestinal tract to some extent, whereas the high log Kow indicates a low absorption of the test substance. As no test substance-related effects were noted during the 28 days of treatment, this could either be due to the fact that there was no adsorption of the test substance, or due to a very low toxicity of the test substance. According to the molecular weight, excretion of Triazin UV-Absorber is most likely predominantly eliminated via intestine, as substances with a molecular weight above 300 g/mol are preferentially excreted via the feces in rats. However, it is most likely that the test compound is at least partly eliminated via kidneys/urine, too.

Taking the results of the bioaccumulation modeling into account, a significant bioaccumulation potential can most probably be excluded. Additionally, Triazin UV-Absorber was also not genotoxic in an in-vitro cell mutagenicity test and an in-vivo MNT test. Therefore, a metabolisation towards genotoxic structures can most probably be excluded.

Summary

The results of basic toxicity testing give no reason to anticipate unusual characteristics with regards to the toxicokinetics of Triazin UV-Absorber. The data indicate that there is little or no dermal absorption. No signs of a significant systemic toxicity associated with absorption potential have been observed. Bioaccumulation of Triazin UV-Absorber can most probably be excluded due to the available data. Based on the results of genotoxicity assays, a metabolisation towards genotoxic metabolites can also be excluded.

On the basis of the results, it is anticipated that the substance does not undergo significant metabolic activity; rather it is metabolized for excretion with little subsequent toxicity. The substance is therefore not considered to be of concern for ADME related effects.