3,3'-thiodi(propionic acid)

Endpoint summary

Description of key information

Guinea pig skin sensitisation test: negative

Human maximisation test: negative

Human photoallergenicity test: negative

Literature search and handbook information: no contact allergy or skin sensitisation reported

QSAR prediction (molcode model) moderate sensitiser near the lower class limit

QSAR prediction (OECD Toolbox): no protein binding structural alerts for skin sensitisation  

QSAR prediction (Toxtree): low or no potential to cause skin sensitisation

QSAR prediction (VEGA): low or no potential to cause skin sensitisation

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The data were derived from a secondary source (Cosmetic Ingredient Review (CIR) report) without access to original data. However, the data were peer-reviewed by an expert panel and the information presented is generally accepted as scientifically valid.

Principles of method if other than guideline:

The test solution was injected intradermally into one side of the back of the guinea pigs; a saline injection on the opposite side served as control.

GLP compliance:

no

Remarks:

The study was conducted prior to implementation of GLP.

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Route:

intradermal

Vehicle:

other: saline

Concentration / amount:

0.8 mg/mL (80% (w/v)

Day(s)/duration:

no data

Adequacy of induction:

not specified

Route:

other: no data

Vehicle:

other: saline

Concentration / amount:

0.8 mg/mL (80% (w/v)

Day(s)/duration:

unknown

Adequacy of challenge:

not specified

No. of animals per dose:

no data

Details on study design:

0.1 mL of the test solution containing 0.8 mg/mL TDPA was injected intradermally into one side of the back of the guinea pigs; a saline injection on the opposite side served as control. There were no further details reported in the CIR report.

Challenge controls:

not specified

Positive control substance(s):

not specified

Reading:

rechallenge

Hours after challenge:

0

Group:

positive control

Dose level:

0.8 mg/mL

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

local irritations rather than sensitization

Remarks on result:

no indication of skin sensitisation

Remarks:

hours of challende and animal number unknown

The TDPA solution caused slight erythema and oedema following the injections, but these reactions did not increase in intensity or duration throughout the experiment and thus were considered local irritation rather than sensitisation.

Interpretation of results:

not sensitising

Remarks:

Migrated information The TDPA solution caused slight erythema and oedema following the injections, but these reactions did not increase in intensity or duration throughout the experiment and thus were considered local irritation rather than sensitisation. Criteria used for interpretation of results: expert judgment

Reference 2

Endpoint:

skin sensitisation, other

Remarks:

other: QSAR prediction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Accepted calculation method

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSAR's R.6, May/July 2008

Deviations:

no

Principles of method if other than guideline:

OECD QSAR Toolbox v3.2. QSAR prediction of the skin sensitisation potential of the test substance. The potential for DNA binding and protein binding and the presence of structural alerts that may indicate a skin sensitising potential are assessed.

GLP compliance:

no

Key result

Remarks on result:

other: No indication of skin sensitisation based on (Q)SAR prediction

The predicted skin sensitisation potential of 3,3'-thiodi(propionic acid) was modelled in the OECD QSAR Toolbox.

The test substance was run against the following databases: DNA-binding potential by OASIS v1.2; DNA-binding potential by OECD; Protein binding by OASIS v1.2; Protein binding by OECD; Protein binding alerts for skin sensitisation by OASIS v1.2; Skin irritation/corrosion inclusion rules by BfR; Eye irritation/corrosion rules by BfR. No structural alerts were flagged. Therefore, 3,3'-thiodi(propionic acid) is not expected have a skin sensitising potential.

Interpretation of results:

other: Not sensitising based on (Q)SAR prediction

Conclusions:

The predicted skin sensitisation potential of 3,3'-thiodi(propionic acid) was modelled in the OECD QSAR Toolbox. No structural alerts were recognised for the databases DNA-binding potential by OASIS v1.2; DNA-binding potential by OECD; Protein binding by OASIS v1.2; Protein binding by OECD; Protein binding alerts for skin sensitization by OASIS v1.2; Skin irritation/corrosion inclusion rules by BfR; Eye irritation/corrosion rules by BfR. Therefore, 3,3'-thiodi(propionic acid) is not expected have a skin sensitising potential.

Reference 3

Endpoint:

skin sensitisation, other

Remarks:

other: QSAR prediction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Accepted calculation method

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSAR's R.6, May/July 2008

Deviations:

no

Principles of method if other than guideline:

The QSAR Toxtree v2.6.0 is a full-featured open source application. It is able to estimate toxic hazard by applying a decision tree approach (http://toxtree.sourceforge.net/). The skin sensitisation potential of 3,3'-thiodi(propionic acid) was assessed by running it in the skin sensitisation module of Toxtree.

GLP compliance:

no

Remarks on result:

other: No indication for skin sensitisation based on (Q)SAR prediction.

The skin sensitisation potential of 3,3'-thiodi(propionic acid) was assessed by running it in the skin sensitisation module of the QSAR Toxtree. This QSAR model uses a decision tree to estimate a toxic hazard. The SMILES code O=C(O)CCSCCC(O) was used as the identifier. The results of the decision tree were:

 

Alert for SN2 identified. = NO

Alert for Schiff base formation identified. = NO

Alert for SNAr Identified. = NO

Alert for Acyl Transfer agent identified. = NO

Alert for Michael Acceptor identified. = NO

 

No skin sensitisation reactivity domains alerts identified. = YES

The results indicate that 3,3'-thiodi(propionic acid) has low or no potential to cause skin sensitisation.

Interpretation of results:

other: No indication for skin sensitisation based on (Q)SAR prediction.

Conclusions:

The skin sensitisation potential of 3,3'-thiodi(propionic acid) was assessed by running it in the skin sensitisation module of the QSAR Toxtree. No skin sensitisation reactivity domains alerts were identified. The results indicate that 3,3'-thiodi(propionic acid) has low or no potential to cause skin sensitisation.

Reference 4

Endpoint:

skin sensitisation: in chemico

Remarks:

other: QSAR prediction

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSAR's R.6, May/July 2008

Deviations:

no

Principles of method if other than guideline:

VEGA is a platform of QSAR models that may be used to predict the property of a chemical, using information from its structure. In VEGA, the Skin sensitisation model (CAESAR v2.1.5) was applied to predict the skin sensitisation potential of the test substance.

GLP compliance:

no

Details on the study design:

Skin Sensitisation model (CAESAR) (version 2.1.5)
QSAR classification model for Skin sensitisation based on a Adaptive Fuzzy Partion. The model
extends the original CAESAR Skin model 1.0. The original model was developed inside the CAESAR
Project
(http://www.caesar-project.eu/)

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

no indication of skin sensitisation

 The CAESAR skin sensitisation model was applied to 3,3'-thiodi(propionic acid) to predict the potential of the substance to induce skin sensitisation. The results show that 3,3'-thiodi(propionic acid) is not predicted to be a skin sensitiser, within the defined parameters of the model.

The output of the model in detail was:

Prediction for compound 1 (Molecule 1)

Compound: 1

Compound SMILES: O=C(O)CCCSCCC(=O)O

Experimental value: -

Prediction: NON-Sensitizer

O(Active): 0.32

O(Inactive): 0.68

Reliability: Compound could be out of model Applicability Domain

Remarks for the prediction: None

 

Prediction: Reliability:

Model assessment: Prediction is NON-Sensitizer, but the result shows some critical aspects, which require to be checked:

- only moderately similar compounds with known experimental value in the training set have been found

- similar molecules found in the training set have experimental values that disagree with the predicted value

- some atom centered fragments of the compound have not been found in the compounds of the training set or are rare fragments

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The skin sensitisation potential of 3,3'-thiodi(propionic acid) was assessed by running it in the skin sensitisation module of CAESAR v2.1.5. The prediction for the substance was it is a non-sensitiser. The results indicate that 3,3'-thiodi(propionic acid) has low or no potential to cause skin sensitisation.

Reference 5

Endpoint:

skin sensitisation, other

Remarks:

other: QSAR prediction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Accepted calculation method

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSAR's R.6, May/July 2008

Deviations:

no

Principles of method if other than guideline:

Predicted endpoint: Human health effects. Score index (by local lymph node assay) for skin sensitation

Remarks on result:

other: Moderate sensitizer based on (Q)SAR prediction.

Descriptor values: Average nucleophilic reactivity index (AM1) for H atoms: 0.001076; Relative number of N atoms: 0; Global softness: 1/(LUMO - HOMO) (AM1): 0.1087; HA dependent HDCA-1 (AM1) (all): 22.93; Highest e-e repulsion (1 -center) (AM1) for Br atoms: 0; RNCG Relative negative charge (QMNEG/QTMINUS) (AM1) 0.1642; Highest n-n repulsion (AM1) for N - O bonds: 0:

Domains: Structural fragment domain 3,3 thiodipropionic acid is structurally similar to the training set compounds, the training set of the model consists of diverse organic compounds, including carboxylic acids and compounds containing sulphur atoms. Mechanism domain 3,3 thiodipropionic acid is considered to be in the same mechanistic domain as the molecules in the training set. The structural analogues in the training set are somewhat of shorter chain than 3,3 thiodipropionic acid, they are in the same chemical space in terms of size and principle of polarity. The training set is not from one lab but a collection. However, it has been shown to be of reasonable quality. 3,3 thiodipropionic acid is a dicarocylic acid of a thio-ether, no such compounds are found in the training set, but both thio- groups and dicarboxylic acids are present. Skin sensitization is believed to be underpinned by mechanisms based on chemical reactivity (with the chemical behaving as an electrophile). One of the most important descriptors is the 1/HOMO–LUMO energy gap which accounts for the stability and reactivity of the molecule. This molecular feature was confirmed also by other authors (related to the mechanism of action). Other charge distribution and hydrogen bonding related descriptors contribute to the frontier orbital energy gap.

Interpretation of results:

other: Moderate sensitizer based on (Q)SAR prediction.

Conclusions:

Predicted value (model result): LLNA Score index (S) = 0.547, class: moderate sensitizer (nearer the weak sensitizer class limit). Moderate sensitizer near the lower limit of the class, according to five scale classification (non-sensitizers, weak sensitizers, moderate sensitizers, strong sensitizers, extreme sensitizers)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitising potential of 3,3-thiodipropionic acid (TDPA) was assessed by means of weight of evidence approach. Data from a Cosmetic Ingredient Review (CIR) report (Diamante et al., 2010) are available. In this publication, a risk assessment on TDPA and five of its most prominent dialkyl esters frequently used in cosmetics was conducted. For the skin sensitisation endpoint both animal and human data for TDPA, as well as information on the photoallergenicity of TDPA in man are available. However, these data must be considered as reliability 4 according to the Klimisch scoring system, as there was no access granted to the original data. Nevertheless, the data published were peer-reviewed by an expert panel and the information presented is generally accepted as scientifically valid. Among this, the dossier contains 4 different QSAR models, which were applied to predict the skin sensitising potential of TDPA based on its chemical structure.

 

Experimental data:

The members of the CIR expert panel summarised a study conducted by Tullar (1947, as cited in Diamante et al., 2010), in which a solution of TDPA was intradermally injected into one side of the back of guinea pigs. A saline injection on the opposite side served as control.The TDPA solution caused slight erythema and oedema following the injections, but these reactions did not increase in intensity or duration throughout the experiment. The authors thus considered the effects as local irritation rather than sensitisation.

The CIR expert panel further evaluated a study on skin sensitisation of TDPA with human volunteers (KGA, 2004, as cited in Diamante et al., 2010). Face cream containing 2% of the registered substance was tested in a maximisation test with 26 subjects(9 male and 17 female), out of which 25 subjects completed the study. During the induction phase, sodium laureth sulphate (SLS) was applied to a site on the upper outer arm, volar forearm, or back of each subject under an occlusive patch for 24 h to enhance a possible skin reaction caused by the test material. Upon removal of the SLS patch, an occlusive patch mounted with the test material was applied to the same site for 48 h (or 72 h on the weekends). The site was examined upon patch removal. If no irritation waspresent, the same SLS patch test patch sequence was repeated. This continued for a total of 5 induction exposures. If irritation developed at any point of the induction phase, the SLS patch was omitted. The subjects were challenged after a 10-day non-treatment period. A previously untreated site was pre-treated with an occlusive patch of 0.5 mL of 5% SLS for 1 h followed by an occlusive patch containing 0.05 mL of the face cream containing 2% ofThiodipropionic acid (TDPA)for 48 h.Of the remaining 25 subjects, no adverse or unexpected reactions were observed during the induction phase, and no evidence of sensitisation was seen at challenge. The researchers concluded that a face cream containing 2% TDPA did “not possess a detectable contact-sensitising potential.”

Additional data on photoallergenicity were reviewed by the CIR expert panel (KGA, 2005, as cited in Diamante et al., 2010). Face cream containing 2% of the registered substance was tested in a repeated insult patch test (RIPT), in which the test material was applied to the lower back of each subject for 24 h. Upon patch removal, the test site was exposed to UV radiation and then left uncovered for 48 h. A patch was then applied to the same test site following the same procedure; this was repeated twice weekly for 3 weeks for a total of 6 exposures.Eleven days after the last induction dose, the subjects received a single challenge exposure. Duplicate occlusive patches were applied to a previously untreated area of the lower back for 24 h. One patch was removed, and the site was irradiated with solar-simulated radiation (SSR) and UVA radiation. The duplicate patch site served as a non-irradiated control site. All test sites were scored on a scale of 0 to 3 at 48 and 72 h after UV exposure.No adverse effects were observed in any of the 28 remaining subjects and the face cream containing 2% TDPA did “not possess a detectable photocontact-sensitising potential in human skin.”

 

Prediction of the skin sensitising potential of TDPA by means of QSAR

In addition, four Quantitative Structure-Activity Relationship (QSAR) models were applied to predict the skin sensitising potential of TDPA:

1) The Molcode model (Molcode model development team, 2010) establishes a score index (by Local Lymph Node Assay, LLNA) for skin sensitisation. Hereby, the non-linear QSAR uses an artificial neural network for classification of skin sensitisation potential. In the LLNA, the classification (Score index S) is based on the chemical concentration necessary to induce a three-fold or greater increase in lymph node cell proliferation activity in treated groups relative to the control. This concentration, known as the EC3 value, is estimated by linear interpolation of skin sensitisation factors above and below the value of three on the LLNA dose response plot. A close association between the EC3 values and the relative skin sensitising potential of chemicals among humans has been observed. Thus, based on the EC3 results obtained, a chemical can be classified as being extreme (1), strong (0.725), moderate (0.5), weak (0.25), or non-sensitising (0).

Skin sensitisation is believed to be underpinned by mechanisms based on chemical reactivity (with the chemical behaving as an electrophile). One important descriptor is the 1/HOMO (highest occupied molecular orbital)–LUMO (lowest unoccupied molecular orbital) energy gap which accounts for the stability and reactivity of the molecule. Other charge distribution and hydrogen bonding related descriptors contribute to the frontier orbital energy gap.

The training set of the model consisted of diverse organic compounds, including carboxylic acids and compounds containing sulphur atoms.The structural analogues in the training set are somewhat of shorter chain than TDPA, they are in the same chemical space in terms of size and principle of polarity.The training set is not from one lab but a collection. However, it has been shown to be of reasonable quality. TDPA is a dicarboxylic acid of a thio-ether, no such compounds are found in the training set, but both thio- groups and dicarboxylic acids are present. TDPA was therefore considered structurally similar and to be in the same mechanistic domain as the molecules in the training set.

Applying the Molcode model for the skin sensitisation potential of TDPA resulted in the predicted value of LLNA Score index (S) = 0.547, which means that TDPA isa moderate sensitiser at the lower class limit (nearer the weak sensitiser class limit)according to five scale classification system of the Molcode model. However, the overall classification is only 77% correct.

 

2) The OECD QSAR Toolbox was further applied to predict the skin sensitising potential of TDPA. The OECD QSAR Toolbox v3.2 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry (2013). It contains several different databases with data on chemicals. The model was used to predict the skin sensitisation potential of the test substance. One of the necessary steps for a substance to cause skin sensitisation is the formation of a stable association with a skin protein. This is most likely to be a covalent association between the test substance (electrophile) and the skin protein (nucleophile). The Toolbox is used to identify structural alerts, like chemical groups, in the test substance that may indicate a protein binding potential.

TDPA was run against the following databases: DNA-binding potential by OASIS v1.2; DNA-binding potential by OECD; Protein binding by OASIS v1.2; Protein binding by OECD; Protein binding alerts for skin sensitisation by OASIS v1.2; Skin irritation/corrosion inclusion rules by BfR; Eye irritation/corrosion rules by BfR. TDPA was considered to fall within the model applicability domain.

For the protein binding alerts for skin sensitisation by OASIS v1.2, the following reaction mechanisms were considered:

-Acylation (acyl transfer via nucleophilic addition reaction; direct acylation involving a leaving group; ester aminolysis; ester aminolysis or thiolysis; isocyanates and related chemicals; ring opening acylation.

-Ionic interaction (electrostatic interaction of tetraalkylammonium ion with protein carboxylates; substituted guanidines).

-Michael addition (α, β-unsaturated carbonyl compounds; addition on conjugated systems with electron withdrawing group; addition on azoxy compounds; addition on phosphoranylidene compounds; addition on unsaturated sultones; polarised alkenes; polarised alkynes; polarised azo compounds; quinoide type compounds; quinone type chemicals.

-Nucleophilic addition (addition to carbon-hetero double bonds, addition reaction at polarised N-functional double bond).

-Radical reactions (free radical formation).

-Schiff base formation (benzoyl formation; direct acting Schiff base formers; pyrazolones and pyrazolidinones derivatives; formation with carbonyl compounds).

-SN1 (carbenium ion formation – enzymatic; nucleophilic substitution SN1 on alkyl or aryl mercury cations).

-SN2 (activated allyl type fragment; interchange reaction with Sulphur containing compounds; nucleophilic substitution at a nitrogen atom; nucleophilic substitution at sp3 carbon atom; nucleophilic substitution at the central carbon atom of N-nitroso compounds; nucleophilic substitution on a sulphur atom; nucleophilic substitution on benzylic carbon atom; nucleophilic substitution on heteroarenesulfenamides; protein azidation via an SN2-like reaction; ring opening SN2 reaction; reaction at a halo atom; reaction at a sp2 carbon atom; reaction at a sp3 carbon atom; reaction at a sulfur atom).

-SN2 ionic (nucleophilic substitution at protein disulphide bonds involving O- or S- nucleophiles).

-SNAr (nucleophilic aromatic substitution on activated aryl and heteroaryl compounds; nucleophilic aromatic substitution on activated halogen, cyano, isocyano, sulfo, sulfonyl groups; nucleophilic aromatic substitution on halogenated nitrophenols).

-SNVinyl (nucleophilic vinylic substitution on activated halogens; SNVinyl at a vinylic (sp2) carbon atom.

The total number of structural alerts examined amounted 100.No protein binding structural alerts for skin sensitisation by OASIS v1.2 were detected. Therefore, 3,3'-thiodi(propionic acid) is not expected to have a skin sensitising potential under the conditions defined for the OECD QSAR Toolbox.

 

3) As a third QSAR model the Toxtree v2.6.0 was applied (Patlewicz et al., 2008), which is a full-featured open source application. It is able to estimate toxic hazard by applying a decision tree approach. The skin sensitisation potential of TDPA was assessed by running it in the skin sensitisation module. This QSAR model uses a decision tree to estimate a toxic hazard. The SMILES code O=C(O)CCSCCC(O) was used as the identifier.

There were no structural alerts detected for SN2, Schiff base formation, SNAr, Acyl Transfer agent, or Michael Acceptor. There were no skin sensitisation reactivity domains alerts identified. The results thus indicate that TDPA has low or no potential to cause skin sensitisation.

 

4) The fourth and last QSAR model applied was the skin sensitisation model within VEGA (Chaudhry et al., 2010). VEGA is a platform of QSAR models that may be used to predict the property of a chemical, using information from its structure. In VEGA, the Skin sensitisation model (CAESAR v2.1.5) was applied to predict the skin sensitisation potential of TDPA. CAESAR uses a dataset of substances that are sensitisers as a comparison basis (Gerberick et al., 2005) and a set of identifiers to assess the ability of the substance to be capable of one of five electrophilic-nucleophilic reactions.

The results show that TDPA is not predicted to be a skin sensitiser within the defined parameters of the model, thus indicating that TDPA has low or no potential to cause skin sensitisation in vivo.

 

Further information

Apart from data on TDPA, peer-reviewed data from the expert panel (CIR) are available for prominent dialkyl esters of TDPA frequently used in cosmetics (Diamante et al, 2010). Just as TDPA, DLTDP (Dilaurylthiodipropionate) was not sensitising in a guinea pig sensitisation test. Moreover, human data are available, showing that just alike TDPA, DLTDP was not sensitising in man and did not exhibit a photocontact-sensitising potential in humans. Based on these data the CIR expert panel concluded that neither TDPA, nor its dialky ester DLTDP are sensitising in animals or man and their use in cosmetics was regarded as safe. This is further supported by information gathered from a handbook. Although used as antioxidant or chelating agent in cosmetic products, topical and systemic drugs used in dermatology, or other therapeutic modalities used by dermatologists, no contact allergy or any other side effects were reported for TDPA (de Groot et al., 1994). An extensive literature search on the skin sensitising potential of TDPA was conducted by the registrant (file attached to this endpoint summary). Despite wide use in cosmetics and in food packaging films, the literature search revealed no case reports or any other information on potential skin sensitising properties of TDPA. In contrast, TDPA was classified as “Generally Recognized As Safe” (GRAS) food substance by the U.S. Food and Drug Administration (FDA, 1979).

 

Summary and conclusion

In summary, three out of four QSAR models applied predicted TDPA to have low or no potential to cause skin sensitisation. Among these, TDPA was tested negative in the OECD Toolbox for a total of 100 structural alerts, which are generally recognised for potential skin sensitising properties of a substance. In contrast, only one QSAR model, the Molcode model, predicted TDPA to be a moderate to weak sensitiser. However, it was reported, that the overall classification for TDPA in this model is only 77% correct. It can thus be concluded that according to the chemical structure TDPA has low or no potential to cause skin sensitisation in vivo. A risk assessment conducted by an expert panel (CIR) revealed that TDPA just alike its dialkyl ester DLTDP is not a skin sensitiser and use in cosmetics was regarded as safe. Similarly, the FDA classified TDPA as safe food substance. Based on the overall available information, TDPA is therefore regarded as not sensitising and classification for skin sensitisation is not warranted.

 

Further references:

FDA (1979). Select Committee on GRAS Substances (SCOGS) Opinion: Thiodipropionic acid. SCOGS-Report Number: 79

Gerberick, G.F.et al.(2005).Compilation of historical local lymph node data for evaluation of skin sensitization alternative methods, Dermatitis 16:157-202.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The available data on the skin sensitisation do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but nor sufficient for classification.