Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 605-076-4
CAS number: 156928-09-5
No toxicokinetic data (animal or
human studies) are available on this substance.
Based on the moderate
molecular weight (130.14 g/mol), High water solubility (>10000 mg/L),
and moderate partition coefficient (log Kow 1.055 at pH 5), it can be
expected that oral, dermal and respiratory absorption rates are moderate
to high. The adverse effects of the 28-day oral repeated dose gavage
toxicity study confirm oral absorption since oral administration
resulted in adverse changes of different test parameters (clinical signs
and biochemistry, mortality, food consumption and body weight) in all
dose groups. However, the reproduction/developmental toxicity screening
test showed no adverse effects up to 15 mg eq/kg. Furthermore, a dermal
acute toxicity test showed no clinical signs, no mortality, nor gross
pathology and T002675 was found to be not irritating to skin (OECD 404,
(CAS 156928-09-5) is light yellow to yellow liquid with a moderate
molecular weight of 130.14 g/mol. A K2 GLP study was performed
according to OECD guideline 105 and EU Method A.6 (flask method).
T002675 was found completely miscible (>10 g/L) in water in all
proportions tested (Paulus, 2007). The partition coefficient was
determined to be log Kow 1.055 at pH 5 and the vapour pressure was
assessed to be 0.19 Pa at 25°C.
backbone of the substance is a hexahydrofurofuran group with a
hydroxyl substituent on position 3.
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 the
moderate partition coefficient (–1 < log Kow < 4) indicates that
the substance is favourable for absorption. T002675 was also
determined to be very miscible. Water soluble substances most
likely dissolve into the gastrointestinal fluids. Passive
diffusion through aqueous pore or through epithelial barrier by
bulk passage of water is also possible given that the molecular
weight is below 200 g/mol. It is generally assumed that the
absorption along the gastrointestinal tract predominantly takes
place in the small intestine since it has a very large surface
area and the longest transit time.
an acute oral toxicity study (OECD 423), 3 female rats were
treated with a single oral gavage of either 300 or 2000 mg/kg and
observed for 14 days. All animals treated with 2000 mg/kg died
spontaneously 2 or 3 days after treatment, whereas no deaths
occurred in the animals treated with 300 mg/kg. Consequently, the
LD50 of T002675 determined was greater than 300 mg/kg bw and less
than 2000 mg/kg bw.
28-days repeated dose toxicity test (OECD 407, Brunke et al.,
2007) has been performed by oral gavage with T002675 on Wistar
(Han) rats (50 animals in total) applying following doses: 50, 150
and 450 mg/kg/day (and a control group). The oral administration
resulted in adverse changes of different test parameters (clinical
signs and biochemistry, mortality, food consumption and body
weight) in all dose groups. Test item-related adverse changes were
observed at the lowest test dose of 15 mg/kg bw/day, such as
elevated bilirubin, changes in the red blood cell count and
elevated absolute and relative liver weights in males. Mortality
before scheduled necropsy, liquid contents of the gastrointestinal
tract and a reduced size of spleen were observed in animals
treated with 150 mg/kg bw/day.
a reproduction/developmental toxicity screening test, T002675 was
administered daily to Wistar rats at dose levels of 5, 15 and 50
mg/kg/day and a control group (10 rats/sex/dose level) (OECD 421,
Beekhuijzen, 2018) for a minimum of 14 days of treatment for the
males and females, until detection of mating was confirmed. The
following observations and examinations were evaluated: mortality
/ viability, clinical signs, body weight and food consumption,
estrous cycle determination, measurement of thyroid hormone T4,
macroscopy at termination, organ weights, reproductive function
and histopathology on a selection of tissues.
results of the first parental anmimals show no clinical signs of
toxicity were noted during the observation period at dose levels
up to 15 mg eq/kg. It was decided to terminate the high dose group
of 50 mg eq/kg on day 15, based on the severe body weight loss of
the animals (up to 12% vs initial weight on pre-mating Day 1), at
this point not considered sufficiently healthy for mating. At 15
and 5 mg eq/kg, body weight gain was similar to controls for the
males and females during premating and the females during the
lactation phase. The statistically significantly increased serum
T4 levels in males at 5 mg eq/kg were considered not to represent
a sign of toxicological relevance. There were no test item-related
alterations in organ weights up and microscopic observations to 15
mg eq/kg and no gross observations at the dose up to 50 mg eq/kg.Length
and regularity of the estrous cycle were considered not affected
by treatment up to 50 mg eq/kg and stage aware evaluation of the
testes did not show any indication for abnormal spermatogenesis.
As all animals at 50 mg eq/kg were sacrificed in the premating
period, reproduction data is available for females up to 15 mg
eq/kg only. The total number of offspring born compared to the
total number of uterine implantations was considered not to be
affected by treatment up to 15 mg eq/kg. The results of the first
generation showed no clinical signs, no mortality up to 15 mg
eq/kg, no change in body weight, no macroscopic findings, no
change in thyroid hormone T4, and no influence on sex ratio.
on the physicochemical properties and the results of the toxicity
studies, the oral absorption factor is set to 50%.
its low volatility (vapour pressure < 0.5 kPa), the availability
of T002675 for inhalation as a vapour is limited.
liquids readily diffuse/dissolve into the mucus lining of the
respiratory tract. In the case of T002675, the high water
solubility will favor the rate at which the particles dissolve
into the mucus. Very hydrophilic substances such as T002675 might
be absorbed through aqueous pores especially with its molecular
weight is <200 g/mol. T002675 can also be retained in the mucus
and transported out of the respiratory tract. The moderate log Kow
(between -1 and 4) would indicate favourable absorption directly
across the respiratory tract epithelium by passive diffusion but
to a limited extend since the log Kow is only 1.055.
on the physicochemical properties, the respiratory absorption
factor is set to 100%.
is a liquid substance and therefore it is more easily taken up by
the skin in comparison to solid products. In order to cross the
skin, a compound must first penetrate into the stratum corneum
(non-viable layer of corneocytes forming a complex lipid membrane)
and may subsequently reach the viable epidermis, the dermis and
the vascular network. It is expected that the penetration of
T002675 into the lipid rich environment of the stratum corneum
will be favoured to a small extent due to the limited lipophilic
character (log Kow of 1.055) of the substance resulting in a low
to moderate dermal absorption. Considering, its high water
solubility, dermal uptake of T002675 is expected to be moderate to
high. It is soluble enough in water to partition from the stratum
corneum into the epidermis (water solubility >10000 mg/l). A
dermal acute toxicity test (OECD 402, Esposito 2007), performed on
both female and male rats (10 animals in total), treated with a
single dose of 2000 mg/kg bw, showed no clinical signs, no
mortality, nor gross pathology. The LD50 was determined to be
greater than 2000 mg/kg bw. Furthermore,
T002675 was found to be not irritating to skin (OECD 404,
a result, the dermal absorption factor is set to 50%.
high water solubility of T002675 can favour its distribution in
the body through aqueous channels and pores. the substance will
distribute into the cells to a limited extent. Based on the
toxicological studies, the target organs may be the liver, the
gastrointestinal tract and the spleen. The liver being the most
sensitive organ since it is affected at the lowest dose in the
28-day study (OECD 407).
on these observations it can be concluded that T002675 will
distribute within the body to a limited extent.
on the liquid form of T002675 no accumulation is expected within
the lungs. T002675 is only moderately lipophilic it is not
expected to accumulate within the adipose tissue or the stratum
on the structure, T002675 was found completely miscible in water,
the hydroxyl group already part of the molecule can undergo a
conjugation reactions (phase II) such as glucuronidation (by the
enzyme glucuronosyltransferase) and sulfation (by the enzyme
sulfotransferase). The Phase II conjugation reactions will further
increase the water solubility and hydrophilic character of the
substance. Metabolism mainly takes place in the liver, causing
route specific presystemic (or first pass) effects, especially
after oral intake. Other metabolic changes may take place in the
gastrointestinal (GI) flora or within the GI tract epithelia
(mainly in the small intestine), respiratory tract epithelia (in
the nasal cavity, trachea-bronchial mucosa and alveoli and skin),
water soluble conjugated metabolites of T002675 from Phase II
biotransformation will be excreted from the systemic circulation
through the urine. Most of them will have been filtered out from
the blood by the kidneys, though a small amount can enter the
urine directly by passive diffusion. There is also the potential
for re-absorption into the systemic circulation across the tubular
epithelium. Another route of excretion of conjugated derivatives
(such as glucuronides) is the bile. The excretion via the bile is
highly influenced by hepatic function since metabolites formed in
the liver may be excreted directly into the bile without entering
the bloodstream. Products in the bile pass through the intestine
before excretion in the faeces and can thus undergo enterohepatic
recycling which will prolong their half-life.
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.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again