Registration Dossier

Administrative data

Description of key information

Skin irriation (OECD 439, GLP): negative (RA CAS 10023-48-0)

Eye irritation (OECD 437, GLP): negative (RA CAS 10023-48-0)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Mean of three tissues
Value:
90.39
Vehicle controls valid:
not applicable
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
no indication of irritation
Remarks:
Source: CAS 10023-48-0, 7.3.1-1
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Conclusions:
Under the conditions of the RHE test method the test substance did not show irritant properties. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in skin irritation potential.
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Irritation parameter:
in vitro irritation score
Run / experiment:
mean value of 3 corneae
Value:
1.4
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Remarks on result:
no indication of irritation
Remarks:
Source: CAS 10023-48-0, 7.3.2-1
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Conclusions:
Under the conditions of the BCOP assay, the test substance did not show irritant properties towards eyes. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in eye irritation potential.
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

There are no reliable data available regarding irritation/corrosion for 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate (CAS 136-09-4). Read-across from an appropriate substance 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium (CAS 10023-48-0) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.1 and 8.2. Common functional groups, structural similarities and comparable toxicological properties (according to the joint consideration in Annex VI to CLP) of the source and target substance are the basis of read-across. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Skin irritation

CAS 10023-48-0

The skin irritancy potential of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium was determined in an in vitro skin irritation study using a human skin model according to OECD TG 439 and GLP (reference 7.3.1-1). The negative control OD (2.450, 2.313 and 2.318) was in the acceptance criteria range of ≥ 0.8 and ≤ 3.0 for all three tissues. Exposure to the positive control dodecyl sulfate sodium salt induced a decrease in the relative absorbance as compared to the negative control to 1.13%. Thus, negative and positive controls met the acceptance criteria and can be considered as valid. The mean tissue viability after treatment with the test substance was determined to be 90.39% for all three tissues, thus indicating a clear negative result and the test substance did not show any irritating properties towards human-derived epidermal keratinocytes.

Under the specific circumstances it is possible to conclude that the test substance is not expected to cause skin irritating properties and does not require classification.

 

Eye irritation

CAS 10023-48-0

To exclude corrosive properties towards the eyes, a bovine corneal opacity and permeability (BCOP) test according to OECD Guideline 437 and in compliance with GLP was conducted (reference 7.3.2-1). After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 1.0 and, therefore within three standard deviations of the current historical mean of the negative control (IVIS: -1.5 to 3.5). After treatment with the positive control (20% imidazole) the calculated IVIS was 107.7 and therefore falls within two standard deviations of the current historical mean of the positive control (IVIS 78.2 to 135.3). Thus, negative and positive controls met the acceptance criteria and can be considered as valid. Application of the test substance to bovine corneae resulted in a calculated mean IVIS of 1.4.

Under the specific circumstances, it is possible to conclude that the test substance is not expected to cause eye irritating properties and does not require classification.

Overall conclusion

3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium (CAS 10023-48-0) did not exhibit a skin or eye irritation potential. Therefore based on the analogue approach, 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate (CAS 136-09-4) is not considered to exhibit hazardous properties to the skin and towards the eyes.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

The available data on skin and eye irritation from the source substance 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.

Therefore, applying the RA-A approach, the target substance 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate is also considered no to meet the classification criteria for skin and eye irritation.