Registration Dossier

Administrative data

Description of key information

sensitising (strong sensitiser; Cat 1A); S.I. values for 2.5, 5, 10%: 21.25, 35.7 and 47.06; no EC3 could be calculated, since all S.I. values were > 3 (mouse, LLNA; OECD TG 429; RL1; GLP)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 April 2018 - 22 May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
adopted 22 July 2010
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Horst, The Netherlands
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 15 to 23 g
- Housing: housed in suspended solid floor polypropylene cages furnished with softwood wood flakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK; ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
preliminary test: 50%, 25%, 10% and 5% v/v in acetone/olive oil 4:1
main test: 10%, 5% or 2.5% v/v in acetone/olive oil 4:1
No. of animals per dose:
preliminary test: 1
main test: 5
Details on study design:
PRE-SCREEN TESTS:
- Systemic toxicity: The animals treated with the test item at concentrations of 50% and 25%% v/v in acetone/olive oil 4:1 were humanely killed, on Day 3 or Day 5, due to the occurrence of clinical signs of toxicity that were considered to approach the moderate severity limit set forth in the UK Home Office Project License. No signs of toxicity or excessive irritation were noted ion the animals treated at concentrations of 5% and 10% v/v in acetone/olive oil 4:1.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response:
The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per animal and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).
The test item will be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test item failing to produce a threefold or greater increase in 3HTdR incorporation will be classified as a "non sensitizer".

TREATMENT PREPARATION AND ADMINISTRATION:
Test Item Administration:
daily application of 25 µL of the appropriate concentration of the test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The test item formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
A further group of five mice received the vehicle alone in the same manner.
The positive control animals were similarly treated to the test animals except that 25 µL of the positive control item, α-Hexylcinnamaldehyde, tech., 85%, at a concentration of 25% v/v in acetone/olive oil 4:1, was applied to the dorsal surface of each ear.

3H-Methyl Thymidine Administration:
Five days following the first topical application of the test item, vehicle control item or positive control item (Day 6) all mice were injected via the tail vein with 0.25 mL (250 µL) of phosphate buffered saline (PBS) containing 3H methyl thymidine (3HTdR: 80 µCi/mL, specific activity 2.0 Ci/mmoL, ARC UK Ltd) giving a total of 20 µCi to each mouse.

Observations:
Clinical Observations: All animals were observed twice daily on Days 1, 2 and 3 and on a daily basis on Days 4, 5 and 6. Any signs of toxicity or signs of ill health during the test were recorded.
Body Weights: The body weight of each mouse was recorded on Day 1 (prior to dosing) and Day 6 (prior to termination).

Terminal Procedures:
Termination: Five hours following the administration of 3HTdR all mice were killed by carbon dioxide asphyxiation followed by cervical separation. For each individual animal of each group the draining auricular lymph nodes were excised and processed. For each individual animal 1 mL of PBS was added to the lymph nodes.
Preparation of Single Cell Suspension: A single cell suspension of the lymph node cells for each individual animal was prepared by gentle mechanical disaggregation through a 200 mesh stainless steel gauze. The lymph node cells were rinsed through the gauze with 4 mL of PBS into a petri dish labeled with the study number and dose concentration. The lymph node cells suspension was transferred to a centrifuge tube. The petri dish was washed with an additional 5 mL of PBS to remove all remaining lymph node cells and these were added to the centrifuge tube. The lymph node cells were pelleted at 1400 rpm (approximately 190 g) for 10 minutes. The pellet was re suspended in 10 mL of PBS and re pelleted. To precipitate out the radioactive material, the pellet was re suspended in 3 mL of 5% Trichloroacetic acid (TCA).
Determination of 3HTdR Incorporation: After approximately 18 hours incubation at approximately 4 C, the precipitates were recovered by centrifugation at 2100 rpm (approximately 450 g) for 10 minutes, re suspended in 1 mL of TCA and transferred to 10 mL of scintillation fluid. 3HTdR incorporation was measured by  scintillation counting. The "Poly Q™" vials containing the samples and scintillation fluid were placed in the sample changer of the scintillator and left to stand in darkness for approximately 20 minutes. The purpose of this period of time in darkness was to reduce the risk of luminescence, which has been shown to affect the reliability of the results. After approximately 20 minutes, the vials were shaken vigorously. The number of radioactive disintegrations per minute was then measured using the Beckman LS6500 scintillation system (Beckman Instruments Inc, Fullerton, CA, USA).

Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Data was processed to give group mean values for disintegrations per minute and standard deviations where appropriate. Individual and group mean disintegrations per minute values were assessed for dose response relationships. Data was first assessed for suitability by analysis of normality and homogeneity of variance. If the assumptions that the data are both normally distributed and has homogeneity of variances, then parametric one way analysis of variance (ANOVA) and Dunnett’s multiple comparison procedure were used to determine statistical significance. If the assumptions were not met, non parametric Kruskal Wallis Rank Sum and Mann Whitney U test procedures were used.
Positive control results:
S.I. = 4.29 (positive)
Parameter:
SI
Value:
21.25
Test group / Remarks:
test item: 2.5% v/v in acetone/olive oil 4:1
Parameter:
SI
Value:
35.7
Test group / Remarks:
test item: 5% v/v in acetone/olive oil 4:1
Parameter:
SI
Value:
47.06
Test group / Remarks:
test item: 10% v/v in acetone/olive oil 4:1
Cellular proliferation data / Observations:
EC3 CALCULATION
An EC3 value could not be calculated, since all tested concentrations resulted in an S.I. >3

CLINICAL OBSERVATIONS:
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test.

BODY WEIGHTS
Body weight change of the test animals between Day 1 and Day 6 was comparable to that observed in the corresponding control group animals over the same period.

Individual Disintegrations per Minute and Stimulation Index

Treatment Group

Animal Number

dpm/
Animala

Mean dpm/Animal
(Standard Deviation)

Stimulation Indexb

Result

Vehicle
acetone/olive oil 4:1

1-1

578.14

646.71
(±166.91)

na

na

1-2

886.46

1-3

620.01

1-4

436.45

1-5

712.51

Test Item
2.5v/vin
acetone/olive oil 4:1

2-1

13285.92

13743.18**
(±1651.86)

21.25

Positive

2-2

12205.57

2-3

13811.24

2-4

16506.63

2-5

12906.54

Test Item
5v/vin
acetone/olive oil 4:1

3-1

29351.63

23084.47**
(±4665.87)

35.70

Positive

3-2

20994.83

3-3

23902.66

3-4

24478.24

3-5

16694.99

Test Item
10v/vin
acetone/olive oil 4:1

4-1

29032.68

30435.92**
(±3109.43)

47.06

Positive

4-2

31591.13

4-3

30843.87

4-4

26161.23

4-5

34550.67

Positive Control Item
25% v/vin
acetone/olive oil 4:1

5-1

4860.74

2771.32****
(±1213.29)

4.29

Positive

5-2

2295.43

5-3

1722.89

5-4

2352.30

5-5

2625.25

  


dpm=     Disintegrations per minute

a=         Total number of lymph nodes per animal is 2

b=         Stimulation Index of 3.0 or greater indicates a positive result

na=        Not applicable

**=       Significantly different from control group p<0.01

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
CGE-PMDA adduct was considered to be a sensitizer under the conditions of the test.
Executive summary:

A Local Lymph Node Assay according to OECD Guideline 429 was performed to assess the skin sensitization potential of CGE-PMDA adduct in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear.

Following preliminary screening tests in which no clinical signs of toxicity were noted at a concentration of 10% v/v, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of five females, were treated with 50 µL (25 µL per ear) of the test item as a solution in acetone/olive oil 4:1 at concentrations of 10%, 5% or 2.5% v/v. A further group of five animals were treated with acetone/olive oil 4:1 alone. A concurrent positive control test, using a group of five animals, was also performed with the known sensitizer, α‑Hexylcinnamaldehyde tech., 85%, at a concentration of 25% v/v in acetone/olive oil 4:1.

The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:

Treatment Group

Concentration

Stimulation Index

Result

Test Item

2.5% v/v in
acetone/olive oil 4:1

21.25

Positive

5% v/v in
acetone/olive oil 4:1

35.70

Positive

10% v/v in
acetone/olive oil 4:1

47.06

Positive

Positive Control Item

25% v/v in
acetone/olive oil 4:1

4.29

Positive

 

CGE-PMDA adduct was considered to be a sensitizer under the conditions of the test.

No EC3 could be calculated, since all S.I. values were > 3. Nevertheless, based on the results it can be concluded that the EC3 will be <<3. Thus, the substance is classified as Category 1A.

Endpoint:
skin sensitisation: in chemico
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
July 2015
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 limited documentation / justification
Justification for type of information:
1. SOFTWARE
Derek for Windows - Skin sensitisation

2. MODEL (incl. version number)
Derek Nexus v.4.1.0; Nexus: 2.0.0
(Derek KB 2014 1.0)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Skin Sensitization

5. APPLICABILITY DOMAIN
- Descriptor domain:
Derek is a knowledge-based system with data pertaining to skin sensitization being derived from public and proprietary sources. All substances that elicit skin sensitization fall within the descriptor domain of this knowledge-based system .

- Structural and mechanistic domains:
There are no structural fragments in the registered substance that would be expected to fall outside the applicability domain of this model

This model is based on eliciting skin sensitization as an apical endpoint without regard to mechanisms involved, which is varied and complicated. The registered substance was recognized to contain a structural feature that is common among specific known sensitizers. It is presumed plausible that the registered substance would be subject to the same mechanisms that drive sensitization with the known sensitizers.

6. ADEQUACY OF THE RESULT
The prediction of skin sensitization hazard fullfills the requirement for classification of this hazard for 1-10 tonnage band under Reach.
Qualifier:
equivalent or similar to
Guideline:
other: QSAR Prediction
Version / remarks:
DEREK Nexus v.4.1.0
Deviations:
not applicable
Principles of method if other than guideline:
- Principle of test:

DEREK™ (Deductive Estimation of Risk from Existing Knowledge) bases predictions on a collection of expert rules that define relationships between structural elements and known skin sensitization outcomes. The rules have been established by a board of experts and are periodically refined. Qualitative, rather than quantitative predictions are generated.

- Short description of test conditions:
The data are dervied skin sensitiization studies (Local Lymph Node Assays, Guinea pig Assays, Human studies, ...)from public, proprietary and regulatory sources.

- Parameters analysed / observed:
The prediction is based on the subject molecule(s) structural similarity with the structural features of known skin sensitizers.
GLP compliance:
no
Key result
Run / experiment:
QSAR prediction
Remarks on result:
positive indication of skin sensitisation
Remarks:
The DEREK Nexus QSAR program identified the major components with "Plausable" skin sensitizer potential.

Component

DEREK-Nexus Prediction

Alert

CGE-PMDA adduct

Plausible Skin Sensitizer

435: Diamine

Bis CGE-PMDA adduct

Plausible Skin Sensitizer

435: Diamine

Tris CGE-PMDA adduct

Plausible Skin Sensitizer

435: Diamine

CGE-water (Diol)

No Alert

None

CGE-impurity

No Alert

None

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The prediction of "Plausible" for skin sensitization potential for the principle components of the registered substance is based on the diamine structural feature. The potential for such a structural feature to drive the skin sensitization property of substances is sufficiently well grounded to accept the current prediction with high confidence.
Endpoint:
skin sensitisation: in chemico
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
Dec 2015
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:
1. SOFTWARE
OASIS TIMES

2. MODEL (incl. version number)
OASIS_TIMES v.2.27.16

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
https://qsardb.jrc.ec.europa.eu/qmrf/protocol/Q17-46-0053
- Defined endpoint:

Species: Mouse; guinea pigs
Endpoint: Human Health Effects: Skin sensitisation
Comment on endpoint: Semi quantitative potency score - strong, weak and non sensitising
Endpoint units:
LLNA – EC3, %
GPMT - % of animals showing reaction of skin
Dependent variable: Obs. Skin Sensitization effect
Experimental protocol: LLNA (the murine local lymph node assay); GPMT (the guinea pig maximization test)
Endpoint data quality and variability: High quality. The model was derived from a data set compiled from chemicals tested in the LLNA, GPMT as well as from the BfR (formerly BgVV) list

- Unambiguous algorithm:

Explicit algorithm: Equation
Descriptors in the model:
Descriptor: EHOMO - Energy of the Highest Occupied Molecular Orbital , [eV]
Descriptor: ELUMO - Energy of the Lowest Unoccupied Molecular Orbital , [eV] Descriptor: Molecular weight (MW)
Descriptor: Electronegativity – 0.5*(EHOMO –ELUMO) , [eV]
Descriptor: E_GAP – (EHOMO –ELUMO) , [eV]
Descriptor: Log Kow
Descriptor: ACCEPT_DLC – Acceptor superdelocalizability
Descriptor selection: Descriptors were selected by using the probabilistic approach for identifying common stereoelectronic (reactivity) patterns of the chemicals – COREPA

Algorithm and descriptor generation: The COREPA (COmmon REactivity PAttern) method [sect. 9.2, ref.3] was used to derive the sub-models incorporated in the TIMES-SS models. It is a probabilistic technique for identifying common stereoelectronic (reactivity) patterns of structurally diverse chemicals which may exert similar or differential biological effects. All energetically reasonable conformers are used to establish conformer distributions across the global and local stereoelectronic descriptors associated with the activity of studied chemicals. The COREPA model is derived in the form of a decision tree. Its logic boxes consist of decision rules based on the reactivity patterns described by a combination of global descriptors of molecular steric and electronic structure and local reactivity parameters associated with specific alerting groups

Two additional 3D QSAR models implemented into the TIMES-SS model were derived for predicting skin sensitization potential of Aldehydes and Michael acceptors:

1. 3D QSAR model distinguishing skin sensitizing from not skin sensitizing aldehydes:
-The chemicals used to derive the model were aldehydes;
-The decision tree is consisted of one node separating Strong from Weak and non-sensitizing aldehydes based on calculated EHOMO in the ranges [-11.7, -8.22] [-11.7, -11] and MW in the ranges [13.6, 184] [250, 254].
2. 3D QSAR model distinguishing skin sensitizing from not skin sensitizing Michael acceptors:
-The chemicals used to derive the model were Michael acceptor having a double bond adjacent to electron-withdrawing group.
The decision tree is consisted of two nodes. The first one separates Strong from Weak and Non-sensitizing chemicals based on calculated ELECTRONEGATIVITY in the ranges [-5.13, -4.23] [-6.02, -5.42] and E_GAP in the ranges [8.07, 10.5] [10, 10.9]. The second one separates Weak from Non-sensitizing Michael acceptors based on calculated Log(Kow) in the ranges [0.68, 6.53] [-1.61, -0.583] and ACCEPT_DLC in the ranges [0.229, 0.275] [0.233, 0.242].

Software name and version for descriptor generation
Name: COREPA-M software developed at Laboratory of Mathematical Chemistry

Chemicals/Descriptors ratio: 875/7=125

- Defined domain of applicability:

Description of the applicability domain of the model

The applicability domain of TIMES-SS model consists of the following layers:

1. General parametric requirements - includes ranges of variation of log KOW and MW. It specifies in the domain only those chemicals that fall in the range of variation of the MW and log Kow defined on the bases of the correctly predicted training set chemicals.

This layer of the domain is applied only on parent chemicals.

2. Structural domain - it is represented by list of atom - centered fragments extracted from the chemicals in the training set. The training chemicals were split into two subsets: chemicals correctly predicted by the model and incorrectly predicted chemicals. These two subsets of chemicals were used to extract characteristics determining the "good" and "bad" space of the domain. Extracted characteristics were split into three categories: unique characteristics of correct and incorrect chemicals (presented only in one of the subsets) and fuzzy characteristics presented in both subsets of chemicals.

Structural domain is applied on parent chemicals, only.

Mechanistic domain - in SS model it includes:

-Interpolation space: this stage of the applicability domain of the model holds only for chemicals for which an additional COREPA model is required. It estimates the position of the target chemicals in the population density plot built in the parametric space defined by the explanatory variables of the model by making use the training set chemicals. Currently, the accepted threshold of population density is 10%.

The mechanistic domain is applied on the parent structures and on their metabolites.

Method used to assess the applicability domain:

A stepwise approach for determining the applicability domain of the TIMES-SS model is proposed, distinguishing chemicals for which the model provides highly reliable predictions.

General parametric requirements are imposed in the first stage, specifying in the domain only those chemicals that fall in the range of variation of the physicochemical properties of the chemicals in the training set. The second stage defines the structural similarity between chemicals that are correctly predicted by the model. The structural neighborhood of atom-centered fragments is used to determine this similarity. The third stage in defining the domain is based on a mechanistic understanding of the modeled phenomenon. Here, the model domain combines the reliability of specific reactive groups hypothesized to cause the effect and the domain of explanatory variables determining the parametric requirements in order for functional groups to elicit their reactivity.

Software name and version for applicability domain assessment: Name: Domain Manager v.1.09 developed at Laboratory of Mathematical Chemistry University, "Prof. Assen Zlatarov," 1 Yakimov Str., Bourgas 8010, BULGARIA

Limits of applicability:In order to belong to the model applicability domain a target structure must meet the requirements of all the domain layers.


- Appropriate measures of goodness-of-fit and robustness and predictivity:
- Mechanistic interpretation:

5. APPLICABILITY DOMAIN
- Descriptor domain:
The Times-Oasis model specifies as “within the domain” only those parent chemicals that fall within the range of variation of MW and Log Kow defined in the correctly predicted training set chemicals.

- Structural and mechanistic domains:
The structural domain is represented by a list of “atom-centered” fragments derived from the training set chemicals. The atom-centred fragments are partitioned into subsets with respect to their association with correct, incorrect, or equivocal prediction of skin sensitization. The structural domain features are only applied to parent molecules.
A mechanistic domain is applied on to parent molecules and their metabolites. Where applicable (Aldehydes and Michael acceptors) a COREPA model is used to predict skin sensitization potential.


6. ADEQUACY OF THE RESULT
The positive prediction outcome for skin sensitization provides support for classification of the registered substance as a skin sensitizer. Skin Sensitizer Category 1
Qualifier:
equivalent or similar to
Guideline:
other: QSAR (OASIS-TIMES v.2.27.16)
Version / remarks:
OASIS-TIMES v.2.27.16
Deviations:
not applicable
Principles of method if other than guideline:
- Principle of test:
The OASIS-TIMES model serves to predict the skin sensitization potential of a substance and that of predicted metabolites. The model was derived from a data set compiled from skin sensitization testing of substances in the LLNA and GPMT as well as from the BfR list. The model utilizes structure activity and structure metabolism relationships to estimate metabolism and interactions with skin proteins. The model output predictions include Strong, Weak, or Non-sensitizing characterizations.

- Short description of test conditions:
The training data set included principally LLNA (the murine local lymph node assay) and GPMT (the guinea pig maximization test) study results.

- Parameters analysed / observed:
Skin Sensitization
GLP compliance:
no
Remarks:
QSAR
Details on study design:
Skin sensitisation (In chemico test system) : Oasis-Times (v.2.27.16)
Key result
Parameter:
other: CGE-PMDA adduct
Remarks:
parent substance
Remarks on result:
no indication of skin sensitisation
Key result
Parameter:
other: CGE-PMDA adduct predicted metabolites
Remarks:
Aldehyde metabolite
Remarks on result:
positive indication of skin sensitisation

 

i.         CGE-PMDA adduct:

           Skin Sensitization: parent substance: Negative

           Skin Sensitization: predicted metabolite: Positive

ii.        Bis CGE-PMDA adduct:

           Skin Sensitization: parent substance: Negative

           Skin Sensitization: predicted metabolite: Positive

iii.       Tris CGE-PMDA adduct:

           Skin Sensitization: parent substance: Negative

           Skin Sensitization: predicted metabolite: Positive

iv.       CGE-water (Diol): 

           Skin Sensitization: parent substance: Negative

v.        CGE-impurity:

           Skin Sensitization: parent substance: Negative

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A Local Lymph Node Assay according to OECD Guideline 429 was performed to assess the skin sensitization potential ofCGE-PMDA adductin the CBA/Ca strain mouse following topical application to the dorsal surface of the ear.

Following preliminary screening tests in which no clinical signs of toxicity were noted at a concentration of 10% v/v, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of five females, were treated with 50 µL (25 µL per ear) of the test item as a solution in acetone/olive oil 4:1 at concentrations of 10%, 5% or 2.5% v/v. A further group of five animals were treated with acetone/olive oil 4:1 alone. A concurrent positive control test, using a group of five animals, was also performed with the known sensitizer, α‑Hexylcinnamaldehyde tech., 85%, at a concentration of 25% v/v in acetone/olive oil 4:1.

The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:

Treatment Group

Concentration

Stimulation Index

Result

Test Item

2.5% v/v in
acetone/olive oil 4:1

21.25

Positive

5% v/v in
acetone/olive oil 4:1

35.70

Positive

10% v/v in
acetone/olive oil 4:1

47.06

Positive

Positive Control Item

25% v/v in
acetone/olive oil 4:1

4.29

Positive

 

CGE-PMDA adductwas considered to be a sensitizer under the conditions of the test.

No EC3 could be calculated, since all S.I. values were > 3. Nevertheless, based on the results it can be concluded that the EC3 will be <2. Thus, the substance is classified as Category 1A.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, CGE-PMDA adduct is classified as a Cat. 1A skin sensitiser according to CLP (1272/2008/EC) requirements.