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: 204-528-4
CAS number: 122-20-3
Starting point is a NOAEL of 272 mg/kg bw. A
factor 0.9 (90/100) is applied for route to route extrapolation, oral to
inhalation. An 8h respiratory volume of 0.19 m3/kg bw for dogs is used
for conversion (calculated according to AIT recommended method
(Alexander et al. (2008), Inhal Toxicol 20, 1179 -1189), default
bodyweight values were used). Correction for activity driven difference
of respiratory volumes in workers compared to workers in rest are used.
272 mg/kg * (90/100) * (1/0.19) * (6.7/10) =
According to the REACH “Guidance on
information requirements and chemical safety assessment”, a leading
DN(M)EL needs to be derived for every relevant human population and
every relevant route, duration and frequency of exposure, if feasible.
Kinetics (absorption figures for
oral, dermal and inhalation route of exposure)
No data on inhalation absorption are
available. Therefore for the DNEL derivation the default as reported in
the REACH guidance will be used, i.e. 100%.
Orally administered TIPA was rapidly
and extensively absorbed by the rat. The principle route of excretion
was urine, which contained 81-85% of the total dose, 3-5% was eliminated
as14CO2 and <2% was recovered in the tissues/carcass and final cage
wash. The amount of 14C in the traps for volatile organics was
negligible. Therefore, an oral absorption percentage of 90% is assumed
for TIPA (feces contained 4-7%).
For dermal absorption, the specific
DIPA figure will be used (20%). This is considered a worst case scenario
since DIPA is a smaller molecule and therefore expected to penetrate the
skin more readily than the larger TIPA molecule.
Long-term, systemic effects, inhalation
The derivation of a POD for the most
sensitive effect for the inhalation route is based on the results of the
highest dose from a repeated dose toxicity study in dogs due to its most sentive
derived no exposure limit (DNEL).
Besides, no adverse effects were observed in
the reproductive toxicity study, according to US FDA guidelines.
For comparison, the NOAEL from the
developmental toxicity study in rabbits, according to OECD 414, is used
as to derive a an inhalatory DNEL:
Considering the NOEAL from the key
reproduction oral toxicity study in rabbits as relevant dose descriptor
and taking the starting point modification and assessment factors into
account, the worker DNEL can be calculated as follows:
(following the ECHA Guidance on information
requirements and chemical safety assessment – Chapter 8:
Characterisation of dose [concentration]-response for human health)
Relevant dose descriptor (NOAEL): 440 mg/kg
Modification for the absorption differences:
experimentally derived oral absorption 90% / inhalatory conservative
Modification of respiratory volume: 1/0.23
(6.7 m3/person/8h human / 70 kg * allometric scaling rabbit =
Modification for light activity at work:
0.67 (human resting respiratory volume / human light activity
respiratory volume = 6.7 m3/kg bw/8h / 10 m3/kg bw/8h)
NOAEC = 440 mg/kg * (90/100) * (1/0.23) *
(6.7/10) = 1153 mg/m3
Intrapecies factor (rabbit-to-worker): 5
Intrerspecies factor: 1 (The AF has already
been handled within the correction of the modification of the dose
descriptor. Therefore, no additional factor has to be applied. Besides,
allometric scaling should not be applied in cases where doses in
experimental animal studies are expressed as concentrations (e.g. in
mg/m3 air, ppm in diet, or mg/L in the drinking water) as these are
assumed to be already scaled according to the allometric principle,
since ventilation rate and food intake directly depend on the basal
Exposure duration factor: 1 (no time
extrapolation is required for developmental toxicity as increasing
exposure duration does not increase the incidence or severity of adverse
Extrapolation factor (NOAEC): 1
Quality of database factor: 2 (POD is based
on a read across approach
worker DNEL (long-term inhalation exposure)
= 1153 mg/m3 /(2 × 5) = 115 mg/m3
A modification of the POD (NOAEL) is not
essential as no route-to-route extrapolation is performed.
there are no consumer uses for TIPA, CAS 122-20-3, the systemic
long-term oral DNEL for the general population is necessary for the
assessment of indirect exposure of humans via the environment (ECHA GD
R.16, v 3.0, Feb 2016).
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