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EC number: 701-316-8 | CAS number: -
Endpoint summary
Administrative data
Description of key information
The Target Substance is anticipated not to possess skin sensitising potential.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation, other
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- This endpoint study record is part of a Weight of Evidence approach comprising of six QSAR model predictions and a read-across from three analogue source substance studies. The results of the QSAR and the read-across studies agree as to the skin sensitisation potential and are sufficient to fulfil the information requirements as further explained in the provided skin sensitisation endpoint summary.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Data for propane-1,2,3-triol (glycerol; CAS No. 56-81-5), formic acid, sodium salt (1:1) (sodium formate; CAS No. 141-53-7), formic acid, potassium salt (1:1) (potassium formate; CAS No. 590-29-4), formic acid, potassium salt (2:1) (potassium diformate; CAS No. 20642-05-1), formic acid, calcium salt (2:1) (calcium formate; CAS No. 544-17-2), 1,2-ethanediol, 1,2-diformate (ethylene diformate; CAS No. 629-15-2), 1,2-ethanediol (ethylene glycol; CAS No. 107-21-1) and formic acid (CAS No. 64-18-6) is used to address the toxicological data requirements for propane-1,2,3-triol and its esterification products with formic acid (EC No. 701-316-8) in an analogue read-across approach. The basis for this read-across approach is that, upon oral administration, the target substance is expected to undergo stepwise transformation by esterases in which the triformate constituent is converted into diformate constituents, diformate constituents are converted to monoformate constituents, and monoformate constituents to free glycerol, with formic acid being released at each step, as illustrated in Figure 1. The toxicity of the glycerol constituent/metabolite will be assessed using information on glycerol, and the toxicity of the formic acid metabolite will be assessed using information on sodium formate, potassium formate, potassium diformate, calcium formate, ethylene diformate, ethylene glycol and formic acid.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target Substance: Propane-1,2,3-triol and its esterification products with formic acid; 701-316-8
Source Substance 1: Propane-1,2,3-triol ; 200-289-5 ; 56-81-5
Source Substance 2: Formic acid, sodium salt (1:1) ; 205-48-0 ; 141-53-7
Source Substance 3: Formic acid, potassium salt (1:1) ; 209-677-9 ; 590-29-4
Source Substance 4: Formic acid, potassium salt (2:1) ; 243-934-6 ; 20642-05-1
Source Substance 5: Formic acid, calcium salt (2:1) ; 208-863-7 ; 544-17-2
Source Substance 6: 1,2-Ethanediol, 1,2-diformate ; 211-077-7 ; 629-15-2
Source Substance 7: 1,2-Ethanediol ; 203-473-3 ; 107-21-1
Source Substance 8: Formic acid ; 200-579-1 ; 64-18-6
[See attached JUSTIFICATION FOR READ-ACROSS OF TOXICOLOGICAL INFORMATION for further details.]
The TS is a UVCB substance of 100% purity. On this basis, the source substances collectively represent 100% w/w of the target substance. The purities of the samples of source substances that were tested are not specifically known, but it is assumed that they would not have been sufficiently impure as to substantially affect the study results. On this basis, the applicability of the data on the source substances to the TS is not expected to be compromised by the presence of impurities in any of the substances.
3. ANALOGUE APPROACH JUSTIFICATION
The basis for this read-across approach is that, upon oral administration, the TS is expected to undergo stepwise hydrolysis by esterases in which the triformate constituent is converted into diformate constituents, diformate constituents are converted to monoformate constituents, and monoformate constituents to the free glycerol constituent, with formic acid being released at each step.
The TS is manufactured from a 1:1 molar ratio of glycerol and formic acid reactants and will therefore metabolize back to those same proportions of those same reactants. An exposure of an organism to the TS is therefore considered to be essentially equivalent to an exposure to a 1:1 molar mixture of glycerol and formic acid.
Refer to the attached JUSTIFICATION FOR READ-ACROSS OF TOXICOLOGICAL INFORMATION for further details as to how the source substances relate to the target substance.
For the following toxicity endpoints:
8.2 serious eye damage / eye irritation
8.3 skin sensitisation
8.5.1 acute toxicity by oral route
8.4.1 in vitro gene mutation study in bacteria;
8.4.2 mutagenicity: in vitro cytogenicity study in mammalian cells;
8.4 mutagenicity: in vivo genotoxicity;
8.6.3 long-term repeated dose toxicity: ≥ 12 months; and
8.7.2 developmental toxicity
information on the glycerol constituent/metabolite and the formic acid metabolite of the target substance will be used to predict the properties of the target substance.
4. DATA MATRIX
Refer to the attached JUSTIFICATION FOR READ-ACROSS OF TOXICOLOGICAL INFORMATION for data matrix details. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Group:
- test chemical
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- GHS criteria not met
- Executive summary:
No skin sensitisation data were available for the TS; however, in silico data was generated for the TS.
The ToxTree Version 3.1.0 program was used to predict the skin sensitisation potential of the TS. The SMILES (Simplified Molecular Input Line Entry System) representative structures of the constituent components of the TS were uploaded into the model. Based on the modeled predictions, the TS is estimated not to possess skin sensitisation potential.
Skin sensitisation data were identified for the analogue source substances SS1, SS4, and SS8.
The skin sensitisation potential of SS1 was assessed in a study where adult white male guinea pigs (12/group) were injected with 0.1 mL of a 0.1% solution of SS1 in isotonic sodium chloride solution (Hine, et al., 1953). A total of 10 injections were administered on alternate days. After a 2-week resting period, animals were challenged with 0.05 mL injection of the test substance and skin reactions were observed in 24 hours. No responses to the challenging injection were noted, except a barely perceptible papule at the site, which was classified as both colourless and negative on Landsteiner’s scale.
Information on skin sensitisation of formic acid and its salts was reviewed as part of the OECD SIDS Initial Assessment Report for formic acid and formats (OECD SIDS, 2008). The assessment report noted that SS4 and SS8 were not sensitising in a guinea pig maximisation study nor the Buehler study, respectively. The studies were performed according to OECD Test Guideline 406 and in accordance with good laboratory practice (GLP). The animals (20 in test group, 10 in control group) were induced at concentrations dissolved in purified water of 0.5 and 15% for SS4 and 7.5% for SS8 and challenged at 10% for SS4 and 2% for SS8. No skin reactions were observed in any animals at 24 or 48 hours after challenge.
Here, the lack of skin sensitising potential of either SS1, representing the glycerol component of the TS, or of SS4 and SS8, representing the formate content of the TS, indicate that it is reasonable to conclude that the TS will also not possess skin sensitizing potential.
On the basis of the skin sensitisation information presented, the TS is anticipated not to possess skin sensitising potential.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
Justification for classification or non-classification
As per Regulation (EC) 1272/2008 as amended, the target substance does not meet the criteria for classification. The substance
is anticipated not to possess skin sensitising potential.
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