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Description of key information

Short description of key information on bioaccumulation potential result:
An assessment of the toxicological behaviour of the substance has been conducted to the extent that can be derived from relevant available information. The material is expected to have low potential to bioaccumulate.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

Test Material

EC 202-228-8 substance is light tan solid in its pure form.

Significance of Route of Exposure

Dermal route: This is considered the principal route for occupational exposure. 

Oral route: This is not considered a significant route for occupational exposure or the general population. Slight exposure may occur via accidental hand-to-mouth contact. 

Inhalation route: Under conditions of normal handling and use, the Registration substance will not be aerosolized and, based on its physico-chemical properties, there is negligible potential for volatilisation and inhalation exposure

Absorption

Dermal route:  Percutaneous Absorption, the physical chemical properties that influence dermal absorption are molecular weight, water and lipid solubility, and degree of ionization. EC 202-228-8 is of a relatively low molecular weight (188.225), is relatively water soluble (363.4 mg/L) and has a log Powof 1.44. These physical chemical properties are likely to favour dermal absorption.

No adverse effects were reported in both the acute dermal and the LLNA studies. However a developmental toxicity study in the structurally similar material 2-phenoxyethanol (as detailed in IUCLID 7.8.2) reveals maternal systemic toxicity occurs at doses of 600 and 1000 mg/kg/day when administered dermally. It is considered read across from 2-phenoxyethanol to EC 202-228-8 is applicable and the justification for this is outlined in IUCLID section 13. Therefore it is concluded that EC 202-228-8 will likely be able to penetrate and be absorbed through the skin.

Oral Route: The same physical chemical factors that affect dermal absorption also affect absorption from the gastrointestinal (GI) tract. The difference being that log Kow between 0 and 4 are optimal for GI absorption. EC 202-228-8 physico-chemical characteristics therefore are likely to favour GI absorption. 

Adverse effects were observed in the OECD 423 acute oral gavage study conducted in rats. Clinical observations considered test substance-related included hunched posture, decreased motor activity, bradypnea, slight excess salivation, ptosis, ataxia, lacrimation, impaired righting reflex, low carriage and coldness to the touch. The adverse clinical observations were first observed at approximately 30 minutes postdose. These clinical observations persisted for approximately two hours in the 300 mg/kg dose groups and until the end of day post-checks in the 2000 mg/kg dose groups. All rats appeared normal on Day 2 and continued to be normal for the remainder of the study. It is considered that these clinical observations indicate that EC 202-228-8 was absorbed across the GI tract of the rats. Systemiceffects were reported at 150 and 450 mg/kg/day in a 28 day oral repeat dose study, most notably in the form of changes to clinical chemistry,which again supports the conclusion drawn above that EC 202-228-8 is absorbed across the GI tract of the rats.

Distribution

Some of the factors that affect absorption will also affect the distribution of chemicals within the body. In general, the more lipophilic the substance, the more readily it will move into the tissues, especially fatty tissues and the more highly perfused tissues such as heart, liver and kidney. EC 202-228-8 has a relatively low log Pow,of 1.44 and it is therefore considered that it is unlikely to partition into fatty tissue and bio-accumulate. Plasma protein binding can influence the movement of chemicals from blood to tissue, however no information on the materials ability to bind to plasma proteins is available. No specific tissue effects were seen in any of the in vivo studies conducted therefore it is not clear whether EC 202-228-8 partitions into any specific tissues.

 

Metabolism

The results of the 28 day oral toxicity study showed no clear evidence of an adaptive response in the livers of rats, which is normally associated with enhanced metabolism. There was however some changes in serum chemistry observed that could not be attributed to specific organ toxicity; it was considered that these were likely related to adaptive metabolic changes. The in vitro chromosome aberration assay shows evidence that addition of the S9 metabolising system and hence further metabolism enhances the activity of the substance. The material is hydrolytically stable under physiological conditions. The material was demonstrated to be not readily biodegradable in an OECD 301F study (IUCLID section 5.2.1), however this may have been due to inhibition of microorganism as demonstrated in the OECD 209 assay (IUCLID section 6.1.7). It is concluded that EC 202-228-8 is likely to undergo metabolism prior to excretion, this is further supported in publication detailed in IUCLID section 7.1.1 which demonstrates that both non-conjugated and conjugated metabolites of EC 202-228-8 can be detected in the urine of rabbits post intravenous and intra-peritoneal administration of the registration material.

 

Excretion

Given the material is of low molecular weight and is relatively soluble in water it is considered that elimination in the urine is the most likely route of excretion. This is supported by the findings of the publications detailed in IUCLID section 7.1.1 which demonstrate that after intravenous or intra-peritoneal administration EC 202-228-8 is rapidly eliminated from the blood and that the material and its metabolites can be detected in the urine. Any material not absorbed across the GI tract will be excreted in the faeces.