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EC number: 232-088-3
CAS number: 7785-84-4
Repeated dose toxicity: oral;Four studies are available for this endpoint:- A key study (Hodge HC 1960) performed in rats demonstrates that there is not specific target organ toxicity when administered ad libitum in the diets of male and female rats for a period of 2 years. The data for this key study are sufficient to infer that that test material should not be classified for STOT-RE under the EU CLP Regulation. A toxicologist expert assessment of the key study is provided to support this conclusion.- There are also three supporting studies which support the findings of the key study for 90 day and 28 day testing periods. Above the thresholds for classification no target organ toxicity was noted at gross necroscopy.Based on exposure considerations (to be presented in the CSR), and the toxicokinetic and physicochemical properties of the test substance it was considered to be scientifically justifiable to waive in vivo testing for inhalation and dermal repeat dose administration.
NOAEL calculated in accordance with Appendix F, guidelines for the
preparation of toxicological working papers for the joint FAO/WHO expert
committee on food additives, December 2000.
TO THE STANDARD REGIMEN:
REPEATED-DOSE TOXICITY (SECTION 8.6.2):
to Annex IX, section 8.6.2, column 2 of Regulation No. 1907/2006
(REACH), a sub-chronic (90 day) study does not need to be conducted if:
a reliable chronic toxicity study is available. A two year oral feed
study is provided and therefore the sub-chronic (90 day) study is not
required for this substance.
to the ECHA's Guidance on information requirements and chemical safety
assessment Chapter R.7c: Endpoint specific guidance:
substances the processes of deposition of the substance on the surface
of the respiratory tract and the actual absorption have to be
differentiated. Both processes are influenced by the physico-chemical
characteristics of a chemical. The granulometry of trisodium
trimetaphosphate indicates that the substance is inhalable and therefore
the risks of inhalation need to be addressed in consideration of
specific target organ toxicity via repeat exposure (STOT-RE).
dusts, including the test material, may be absorbed directly from the
respiratory tract or, through the action of clearance mechanisms the
material can be cleared from the respiratory tract by the muco-cillary
escalator and then swallowed, adding to systemic toxicity via the oral
route. It has already been concluded that STOT-RE via the oral route is
of low potential systemic toxicity (EU CLP), therefore we can disregard
any potential risk from inhaled dust that is cleared from the airways
and subsequently swallowed.
regards to the potential of STOT-RE via absorption through the
epithelial lining of the respiratory tract and the potential damaging
effects which the test material may have on the organs of the
absorption; water-soluble dusts (such as trisodium trimetaphosphate)
would readily diffuse/ dissolve into the mucus lining of the respiratory
tract, however, trisodium trimetaphosphate is not a lipophilic substance
and therefore does not have the potential to be absorbed
directly across the respiratory tract epithelium. Another consideration
of systemic absorption are the aqueous pores lining the respiratory
tract, however, despite being hydrophilic the size of trisodium
trimetaphosphate (>200 mol. wt) makes this absorption via aqueous pores
unlikely. Given this evidence it can be suggested that the respiratory
tract will impede systemic absorption of trisodium trimetaphosphate.
is worth highlighting that the effect on the lungs themselves is likely
to be minimal based on the following considerations:
- The limit
test conducted for acute inhalation toxicity (Griffiths D, 2012) did not
result in toxicity, at gross necroscopy none of the animals tested
revealed any lesions or abnormality of the lung tissue.
discussed above, trisodium trimetaphosphate is readily absorbed by the
mucosal lining for clearance by the mucocilliary escalator.
assessment of eye irritation concluded that trisodium trimetaphosphate
did not have a significant effect on the delicate tissue of the eye,
therefore it is reasonable to assume that exposure to lung tissue would
be similarly unaffected.
together this evidence suggests that further in vivo testing for
repeated dose toxicity; short-term, sub-chronic and chronic, will not be
necessary, especially as orally administered test material was concluded
not to be classified (EU CLP).
to Annex VIII, Section 8.6.1, Column 2 and Annex IX, Section 8.6.2,
Column 2 of Regulation (EC) No. 1907/2006 (REACH) testing by the dermal
route is appropriate if 1) inhalation of the substance is unlikely, 2)
skin contact in production and/or use is likely and 3) physiochemical
and toxicological properties suggest potential for a significant rate of
absorption through the skin and 4) one of the following conditions is
is observed in the acute dermal toxicity test at lower doses than in the
oral toxicity test,
effects or other evidence of absorption is observed in skin and/or eye
• In vitro
tests indicate significant dermal absorption,
Significant dermal toxicity or dermal penetration is recognised for
route of exposure is possible for trisodium trimetaphosphate (based on
patterns of use), however due to the physical nature and known
toxicological properties trisodium trimetaphosphate is not anticipated
to pose a hazard via the dermal route for the following reasons:
trisodium trimetaphosphate is an inorganic ionic solid, with a molecular
weight of >200 and is unlikely to be lipophilic, the dermal route is not
considered to be a significant route of exposure as the substance is not
expected to penetrate the epidermis in any significant quantities and
therefore systemic toxicity is unlikely.
conclusion that trisodium trimetaphosphate is of low systemic toxicity
is supported by a lack of systemic effects or other evidence of
absorption in the skin or eye irritation studies conducted and a lack of
systemic toxicity when administered via the oral route for up to 2 years.
the rationale above and taking into consideration that oral exposure
represents a worst-case scenario for systemic uptake. No further testing
for repeated dose toxicity via the dermal route is considered to be
of the kidneys was noted in animals treated with trisodium
trimetaphosphate. However, this is not an effect that is sufficient to
result in a classification for STOT-RE (kidney) given that rats are
susceptible to kidney problems and no assessment of the historical
incidence in the strain investigated was made. In addition, the NOAEL
calculated from this study would not be sufficient for classification as
per the guidance values derived using Haber's rule for a 2 -year study
in accordance with the Guidance on the Application of the CLP Criteria.
used have been determined to be acceptable for assessment and no further
animal testing is justified. Trisodium trimetaphosphate is not
considered to be classified for STOT-RE, in accordance with Regulation
(EC) No 1272/2008 (EU CLP).
Conversion from % in diet to
mg/kg bw was calculated in accordance with Appendix F of
the guidelines for the preparation of toxicological
working papers for the joint FAO/WHO expert committee on
food additives, December 2000.
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.
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