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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study, Source substance for RA information according to analogue justification.
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V.
- Age at study initiation: 10-11 weeks (beginning of treatment)
- Weight at study initiation: animals of comparable size and weight
- Housing: group housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days prior to the start of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-2
- Humidity (%): 45 – 65%
- Air changes (per hr): ca. 10/h
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
dimethylformamide
Concentration:
25 %, 50 % and 100 %
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS:
At the tested concentrations (50 % and 100 %) the animals did not show any signs of systemic toxicity. On days 3 and 4, both treated animals showed an erythema of the ear skin (Score 1). Other signs of irritation or signs of systemic toxicity were not observed.
Thus, the test item in the main study was assayed at 25, 50% (w/w), and 100%.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: OECD 429
- Criteria used to consider a positive response:
A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled:
- First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the Stimulation Index.
- Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear with test item concentrations of 25, 50% (w/w), and 100% in dimethylformamide. The application volume, 25 μL/ear/day, was spread over the entire dorsal surface of each ear once daily for three consecutive days. A further group of mice (control animals) was treated with an equivalent volume of the relevant vehicle alone.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated in the body weight tables, for the ear weights, the lymph node weights and lymph node cell count, and for the DPM values (group mean DPM ± standard deviation).
A statistical analysis was conducted on the DPM values, the ear weights, the lymph node weights and the lymph node cell count to assess whether the difference was statistically significant between test item groups and negative control group. For all statistical calculations SigmaStat for Windows (Version 2.0) was used. A One-Way-Analysis-of-Variance was used as statistical method. In case of significant results of the One-Way-ANOVA, multiple comparisons were performed with the Dunnett test or the Student Newman Keuls test. Statistical significance was set at the five per cent level (p < 0.05). The Dean-Dixon-Test and/or Grubb’s test was /were used for identification of possible outliers (performed with Microsoft Excel 2003).
However, both biological and statistical significance were considered together.
Parameter:
SI
Remarks on result:
other: S.I. control: 1.0 25 %: 0.60 50 %: 1.14 100 %: 0.71
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Vehicle: 742.3 dpm 25 %: 445.3 dpm 50 %: 844.5 dpm 100 %: 524.1 dpm

Viability / Mortality

No deaths occurred during the study period.

Clinical Signs

No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

Body Weights

The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

Lymph Node Weights and Cell Counts

The measured lymph node weights and –cell counts of all animals treated were recorded after sacrifice. A statistically significant or biologically relevant increase in lymph node weights was not observed in any of the test item treated groups in comparison to the vehicle control group. For BALB/c mice, a cutoff-value for the lymph node cell count index of 1.55 was reported for a positive response. The indices determined for the lymph node cell count did not exceed this threshold.

Ear Weights

The measured ear weights of all animals treated were recorded after sacrifice. A statistically significant or biologically relevant increase in ear weights was not observed in any treated group in comparison to the vehicle control group.

For BALB/c mice, a threshold for the ear weight index of 1.1 was reported for a positive response. The indices determined for the lymph node cell count did not exceed this threshold. Furthermore, according to OECD guideline 429, an increase in ear weight exceeding the threshold value of 25% was considered to be indicative for excessive local skin irritation. This threshold was not exceeded in any test item treated group.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:

In order to study a possible skin sensitisation potential of 2-Propyn-1-ol, compd. with methyloxirane, 3 groups each of 5 female mice were treated once daily with the test item at concentrations of 25, 50% and 100% in dimethylformamide by topical application to the dorsum of each ear for three consecutive days according to OECD 429 in compliance with GLP.

A control group of 5 mice was treated with the vehicle (dimethylformamide) only. All treated animals survived the scheduled study period and no signs of systemic toxicity or local skin irritation were observed. 

The Stimulation Indices (S.I.) of 0.60, 1.14, and 0.71 were determined with the test item at concentrations of 25, 50% (w/w) and 100% in dimethylformamide, respectively. An outlier was identified in the mid dose group but it did not change the overall test result and was not excluded from calculation.A statistically significant increase in DPM value, lymph node weight and also in lymph node cell count was not observed in any of the tested dose groups in comparison to the vehicle control group. Furthermore, the cutoff-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was not exceeded in any dose group.

An EC3 value could not be calculated, since none of the tested concentrations induced a S.I. greater than the threshold value of 3.

The test item 2-Propyn-1-ol, compd. with methyloxirane was not a skin sensitiser under the test conditions of this study (BASF, 2012).

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

Justification for grouping of substances and read-across

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

 

 

Substance

Sensitization

Target substance

2-Propyn-1-ol, polymer with ethylene oxide

(CAS 25749-64-8)

 --

Source substance (Read across)

2-Propyn-1-ol, compd. with methyloxirane

(CAS 38172-91-7)

Not a skin sensitizer

 

 Lack of data for a given endpoint is indicated by “--“.

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2-Propyn-1-ol, polymer with ethylene oxide (CAS# 25749-64-8).

Since no studies are available for 2-Propyn-1-ol, polymer with ethylene oxide(CAS 25749-64-8)investigating the skin sensitization,a read-across from the structurally related analogue substance2-Propyn-1-ol, compd. with methyloxirane (CAS 38172-91-7) was usedin accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5.

 

OECD guideline study:  

Source substance (Read across) 2-Propyn-1-ol, compd. with methyloxirane (CAS 38172-91-7)

 

LLNA:

In order to study a possible skin sensitization potential of 2-Propyn-1-ol, compd. with methyloxirane (a.i. 54,7%), 3 groups each of 5 female mice were treated once daily with the test item at concentrations of 25, 50% and 100% in dimethylformamide by topical application to the dorsum of each ear for three consecutive days according to OECD 429 in compliance with GLP. A control group of 5 mice was treated with the vehicle (dimethylformamide) only. All treated animals survived the scheduled study period and no signs of systemic toxicity or local skin irritation were observed. The Stimulation Indices (S.I.) of 0.60, 1.14, and 0.71 were determined with the test item at concentrations of 25, 50% (w/w) and 100% in dimethylformamide, respectively.A statistically significant increase in DPM value, lymph node weight and also in lymph node cell count was not observed in any of the tested dose groups in comparison to the vehicle control group. Furthermore, the cutoff-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was not exceeded in any dose group. An EC3 value could not be calculated, since none of the tested concentrations induced a S.I. greater than the threshold value of 3.

Therefore, the test item 2-Propyn-1-ol, compd. with methyloxirane was not a skin sensitizer under the test conditions of this study (BASF, 2012).

Key study assignment:

As there is only one study available with suitable reliability and relevance this study is used as key study.

 

Conclusion

The cutoff-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was not exceeded in any dose group for a close homologue to the target substance. Concluding based on the available data, also the target substance 2-Propyn-1-ol, compd. with ethylene oxide is assumed to be not a skin sensitizer as it contains similar structure elements.



Migrated from Short description of key information:
Skin sensitisation (OECD 429, LLNA, mouse, GLP, RA to CAS 38172-91-7 ): not a skin sensitizer (BASF, 2012)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitization was observed in a skin sensitization local lymph node assay with the source substance2-Propyn-1-ol, compd. with methyloxirane. The scores obtained from the study led to no classification for skin sensitization according to GHS (Regulation (EU) 1272/2008). This classification was also supposed for the target substance 2-Propyn-1-ol, polymer with ethylene oxide.

 

Labelling skin/respiratory sensitization:

 

GHS: no classification