Registration Dossier
Registration Dossier
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EC number: 220-585-8 | CAS number: 2825-82-3
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
The available evidence suggests that the substance is potentially bioavailable via the oral, dermal and inhalation routes. The substance is expected to be metabolised by the liver and mainly excreted in urine and has low potential to bioaccumulate.
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 100
- Absorption rate - inhalation (%):
- 100
Additional information
According to section 8.1.1 of Annex X of Regulation (EC) No 1907/2006 (REACH) and R7.c guidance, in absence of toxicokinetic data on the registered substance, the toxicokinetic profile of the substance (i.e. absorption, distribution, metabolism and elimination) was derived from the relevant available information collated in the dossier. The physical chemical characteristics, the results obtained from acute, repeated-dose and reproductive toxicity studies on the substance, as well as information gained from genotoxicity assays were used to predict its toxicokinetic behaviour.
Structure and physical-chemical properties:
THDCPD - Tetrahydrodicyclopentadiene is a monoconstituent, having a molecular weight of 136,24 g/mol. The substance is a fluid liquid at ambient temperature. It is less dense than water, has low solubility (2.87 mg/L at 25°C) and low potential for bioaccumulation (4.8 at 25°C. (estimated by QSAR)). The substance is not considered to have surface-active potential. It has low volatility based on its vapour pressure (260 Pa at 20°C).
Absorption:
Oral/GI absorption:
The physical chemical characteristics described above suggest that the target substance is of adequate molecular size (< 500 g/mol) to participate in endogenous absorption mechanisms within the mammalian gastrointestinal tract. The absorption may be potentiated by the ability of the substance to dissolve into gastro-intestinal fluids and hence make contact with the mucosal surface.
These hypotheses are supported by oral systemic effects observed in the acute toxicty studies in rats, hamsters and mice. Deaths occurred within 48 hours of dosing with convulsions and necropsy revealed congested lungs and GI tract. In 28-day repeated dose toxicity study (OECD 407) performed on the test substance in rats by diet, hematological and biochemical changes and kidneys effects observed at 15000 ppm in males. These effects were considered not adverse. The NOAEL was considered to be 15000 ppm (equivalent to 1205 mg/kg bw/day in males and 1165 mg/kg bw/day in females).
In addition, in developmental toxicity studies in rats and mice, There was a decreased weight gain in the higher dose groups and tremors and mild convulsions were observed. The NOAEL developmental toxicity was considered 748 and 1000 mg/kg bw/d for mice and rats respectively.
The observation of systemic effects indicates the oral bioavailability of the substance and/or its metabolites. In light of these data, and the lack of specific information, the target substance was assumed to be 100% bioavailable by oral route for the DNELs calculation in the purpose of human health risk assessment.
Dermal absorption:
The substance is irritating to the skin which may upon high-dose contact favour dermal penetration of the substance.
In light of these data, and the lack of specific information on the test substance, a dermal absorption of 100% was conservatively assumed for the DNELs calculation in the purpose of human health risk assessment.
Respiratory absorption:
The potential for inhalation toxicity was evaluated in acute and developmental toxicity studies. In an acute inhalation toxicity study performed in male and female rats, and female mice exposed to varying concentrations of test material during 4 hours. Male Golden Syrian hamsters were exposed to saturated vapor pressure concentrations during 6 hours. Gross signs of toxicity during exposure included tremors and ataxia were observed. LC50 after a 4-hour exposure period were 1221 and 1194 ppm for male and female rats, respectively and 930 ppm for female mice. The test substance is classified as toxic if inhaled.
In a developmental toxicity in rats, many animals in the treated group exhibited tremors and a few also had mild convulsions.
The NOAEC(6h/d) for maternal toxicity cannot be determined and the NOAEC(6h/d) for developmental toxicity in rats is considered to be higher than the test dose of 600 ppm, ca. 3343 mg/m3.
The observation of systemic effects indicates the oral bioavailability of the substance and/or its metabolites. In light of these data, and the lack of specific information on respiratory absorption, the substance was conservatively assumed to be 100% bioavailable by inhalation for the DNEL calculation in the purposes of human health risk assessment.
Distribution:
Systemic distribution of the substance can be predicted from its physical chemical characteristics. Considering that the substance is highly lipophilic (log Pow >4) and slightly water soluble, it is suggested that, upon systemic absorption, the substance may be transported through the circulatory system in association with a carrier molecule such as a lipoprotein or other macromolecule. Afterwards, based on its lipophilic character, the substance will readily cross cellular barriers or will be distributed into fatty tissues with a potential to accumulate. However, the substance seems to be metabolised by the liver, probably into more soluble and excretable metabolites.
Metabolism:
The results of the the 28-day repeated dose toxicity study (OECD 407) performed in the rat with the test substance showed liver and kidney changes that are consistent with the increased metabolism associated with detoxification of a xenobiotic. This liver induction confirmed that a non-negligible part of the substance is metabolised following gastrointestinal tract absorption. The results of the in vitro gene mutation study also shows cytotocity in the presence of S9 metabolising system, corresponding to signs of metabolisation and detoxification process.
Excretion:
The substance, having a molecular weight lower than 500 g/mol, is expected to be mainly excreted in urine unchanged or as glucuronide and sulfate conjugates following oral exposure and inhalation. A minor amount (< 10%) may be excreted in bile as such or as metabolites following metabolism.
Any substance that is not absorbed from the gastro-intestinal tract, following oral ingestion, will be excreted in the faeces.
Following dermal exposure, as the substance, that have penetrated the stratum corneum is likely to be absorbed in the blood following excretion in urine unchanged or as glucuronide and sulfate conjugates if metabolisation in the liver occurs.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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