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Description of key information

The skin sensitization potential of Trichloroacetaldehyde (75-87-6) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Trichloroacetaldehyde (75-87-6) was predicted to be non-sensitizing to the skin of guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction is done using OECD QSAR Toolbox version 3.3 with logKow as the primary descriptor.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
- Name of test material (as cited in study report): trichloroacetaldehyde
- Molecular formula (if other than submission substance): C2HCl3O
- Molecular weight (if other than submission substance): 147.388 g/mol
- Substance type: organic
- Physical state: liquid
- Purity: no data
- Impurities (identity and concentrations): no data
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
no data
Details on study design:
no data
Positive control substance(s):
yes
Remarks:
hexyl cinnamic aldehyde
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 5, 25 and 100%
No. of animals per dose:
5 animals
Details on study design:
no data
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Parameter:
SI
Value:
ca. 1.7
Remarks on result:
no indication of skin sensitisation based on QSAR/QSPR prediction
Parameter:
EC3
Value:
ca. 18.1
Remarks on result:
no indication of skin sensitisation based on QSAR/QSPR prediction
Remarks:
15.6, 14.1, 13.8, 13.9, 16.0, 11.9 and 14.7%.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aldehydes (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Schiff base formation by aldehyde formed after metabolic activation AND AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives AND AN2 >> Shiff base formation for aldehydes AND AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives AND SN2 AND SN2 >> Acylation involving a leaving group  AND SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives AND SN2 >> Acylation involving a leaving group after metabolic activation AND SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives AND SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation AND SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Schiff base formers AND Schiff base formers >> Direct Acting Schiff Base Formers AND Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Schiff base formation AND Schiff base formation >> Schiff base formation with carbonyl compounds AND Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Schiff Base Formers AND Schiff Base Formers >> Direct Acting Schiff Base Formers AND Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 2-Alken-1-als (MA) OR Highly reactive (GSH) >> Cinnamaldehydes (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> alpha-chloro toluenes (SN2) OR Moderately reactive (GSH) >> Substituted 2-Alken-1-als (MA) OR Slightly reactive (GSH) OR Slightly reactive (GSH) >> Substituted haloacetamides (SN2) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aldehyde AND Alkyl halide AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acetoxy OR Alcohol OR Alkane branched with quaternary carbon OR Alkane, branched with tertiary carbon OR Alkoxy OR Alkyl arenes OR Allyl OR Aryl OR Aryl halide OR Benzodioxole OR Bridged-ring carbocycles OR Carboxylic acid OR Carboxylic acid ester OR Cycloalkane OR Cycloalkene OR Dialdehydes OR Ether OR Isopropyl OR Oxocarboxylic acid OR Oxolane OR Phenol OR Saturated heterocyclic fragment OR tert-Butyl by Organic Functional groups (nested)

Domain logical expression index: "o"

Similarity boundary:Target: O=CC(Cl)(Cl)Cl
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.173

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.68

Interpretation of results:
not sensitising
Conclusions:
The skin sensitzation [otential of trichloroacetaldehyde was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.
Executive summary:

The skin sensitization potential of trichloroacetaldehydew as estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

trichloroacetaldehyde was estimated to be not sensitizing to the skin of mouse.

Based on the estimated results, trichloroacetaldehyde can be considered not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization

In different studies, Trichloroacetaldehyde (75-87-6) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical Trichloroacetaldehyde (75-87-6) and its structurally similar read across substances Chloroform (67-66-3) and Propionaldehyde (123-38-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

 

The skin sensitization potential of Trichloroacetaldehyde (75-87-6) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Trichloroacetaldehyde (75-87-6) was predicted to be non-sensitizing to the skin of female guinea pig.

 

Supported by experimental study conducted byNational Technical Reports library (NTRL) 1992) to evaluate the skin sensitizing potential of Trichloroacetaldehyde (75-87-6) in guinea pig. A test for sensitization revealed that allergic contact dermatitis did not develop. A 2% solution was not irritating to the skin of guinea pig.It can be concluded that the Trichloroacetaldehyde is not sensitizing.

 

It is further supported by experimental study conducted byEuropean Union Risk Assessment Report(2002) to evaluate the skin sensitizing potential of read across substance Chloroform (67-66-3) in guinea pigs. Chloroform were administered intradermally to 5 guinea pigs as primary sensitization (Day 1).One day after (as secondary sensitization), chloroform was applied as an occlusive patch for 48 hours (Day 9, patch sensitization).For challenge, another 3 guinea pigs in the control group were used as a control group, and chloroform was applied to 5 guinea pigs in the sensitization group as an occlusive patch for 24 hours in the same manner (Day 22). Evaluation was according to the Draize criteria 48 and 72 hours after the start of challenge.In the evaluation at 48 and 72 hours after the start of challenge, erythema (score 1 or 2, slight to mild) was observed in all 8 animals including the control group. Sensitization could not be definitely evaluated due to this strong irritation reaction,

but since skin reactions were comparable in the chloroform sensitization group and the control group, chloroform sensitization was concluded to be negative in GPMT. Chloroform is not sensitizing to the skin of guinea pig tested by Guinea Pig Maximization Test (GPMT).

 

Also supported by experimental study conducted byEuropean Union Risk Assessment Report(2002) to evaluate the skin sensitizing potential of read across substance Chloroform (67-66-3) in mouse.Using 4 groups with 5 animals per group,1. 25 uL/ear chloroform; 2. 25 uL/ear acetone:olive oil (4:1); 3. 25 uL/ear 10 % hexyl cinnamic aldehyde in chloroform; 4. 25 uL/ear 10 % hexyl cinnamic aldehyde in acetone:olive oil (4:1) Application of test solutions to both auricles of the mice for three consecutive days. 3 days later, 3H-methyl thymidine (Amersham Pharmacia Biotech, Inc.) was administered intravenously (250 uL, 2.96 MBq/mL). Five hours later, animals were euthanised. The auricular lymph nodes were removed, in order to compare reactions to HCA with chloroform as vehicle and with acetone:olive oil as vehicle. Cells were isolated from the lymph nodes, cell suspensions prepared and radioactivity was measured with a beta scintillation counter.The lymphoproliferative activity is used as an index of sensitization in LLNA, but since primary irritation also activates lymph cell proliferation through inflammatory cytokine effects. SI was obtained by dividing the mean measured value in each test substance administration groups by the mean measured value in the vehicle administration groups, the AOO and chloroform administration groups. SI for chloroform alone was obtained using the value for AOO as the vehicle administration group.Sensitization was judged to be positive if SI was 3 or more and there was statistically significant difference from the vehicle control group. In Local Lymph Node Assay (LLNA, RI Method). No positive reaction was observed. On the basis of SI 2.4 value obtained it can be concluded that the Chloroform is not sensitizing.

Also supported by experimental study conducted byNational technical Repots Library (NTRL),1999) to evaluate the skin sensitizing potential of read across substancePropionaldehyde(123-38-6)in guinea pigs.In this study upto 80% of the animals of the test group were observed with the erythematous reactions after the first challenge with Propionaldehyde at the highest non-irritating concentration of 30% in water. No skin reactions were observed in the negative control group.

 

Thus based on the above predictions onTrichloroacetaldehyde (75-87-6)as well as its read across and applying weight of evidence, it can be concluded thatTrichloroacetaldehyde (75-87-6)is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Trichloroacetaldehyde (75-87-6) can be considered as not classified for skin sensitization.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, Trichloroacetaldehyde (75-87-6) can be considered as not classified for skin sensitization.