Propylidynetrimethanol, ethoxylated

Skin sensitisation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

- modified LLNA = Local Lymph Node Assay (LLNA) - Integrated Model for Differentiation of Skin reactions (IMDS)): Measurement of cell counts instead of radioactive labeling. In addition, measurements of ear swelling and ear weights were done to discrimina

Principles of method if other than guideline:

Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modifications are authorized in the OECD TG 429 and in the Note for Guidance SWP/2145/00 of the CPMP (2001). Information on validation of IMDS and scientific justification is given in: Vohr HW et al., Arch. Toxicol., 73, 501-509 (2000); Ehling G et al., Toxicology 212, 60-68 and 69-79 (2005).

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Propylidynetrimethanol, ethoxylated

EC Number:

500-110-3

EC Name:

Propylidynetrimethanol, ethoxylated

Cas Number:

50586-59-9

Molecular formula:

C3H5(CH2O(C2H4O)nH) sum of n: >1 - <6.5 mol EO

IUPAC Name:

Propylidynetrimethanol, ethoxylated

Details on test material:

- Physical state: liquid
- Name of test material (as cited in study report): Polyether V 533
- Content: 100%
- molecular weight: approx. 306 g/mol
- Stability under test conditions: analytically approved

In vivo test system

Test animals

Species:

mouse

Strain:

NMRI

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

0, 2, 10, 50 %

No. of animals per dose:

6

Details on study design:

TREATMENT PREPARATION AND ADMINISTRATION:
The test item in the formulation and the vehicle were applied epicutaneously onto the dorsal part of both ears of the animals. This  treatment was repeated on three consecutive days (d1, d2 and d3). The volume administered was 25µl/ear. The used concentrations were based on the experiences with the test system and the toxic properties of the test substance.
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application (d4). The appropriate organs were
then removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiiological saline (PBS).
Investigations:
- weight of lymph nodes
- cell counts in lymph nodes
- stimulation index is calculated by dividing the absolute number of weight or cell counts of the substance treated lymph nodes by the vehicle treated ones.
- ear swelling
- ear weight
- body weights

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

When it was statistically reasonable, the values from treated groups were compared with those from the control group by a one-way analysis of variance (ANOVA) when the variances are considered homogeneous according to a homogeneity testing like Cochran's test. Alternatively, if the variances are considered to be heterogenous (p<=0.05), a non-parametric Kruskal-Wallis test has been used (Kruskal-Wallis ANOVA) at significance levels of 5% . Two sided multiple test procedures were done according to Dunnett or Bonferroni-Holm, respectively. Outlying values in the LN weights were eliminated at a probability level of 99% by Nalimov's method. In addition, for the LLNA/IMDS the smallest significant differentes in the means were calculated by Scheffels method, which according to Sachs can be used for both equal and unequal sample sizes.

Results and discussion

Positive control results:

Alpha hexyl cinnamic aldehyde (3%, 10% and 30%), checked in regular intervals, shows a clear sensitizing potential in the local lymph node assay (IMDS).

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

Compared to vehicle-treated animals, none of the parameters measured in the test substance treated groups (Polyether V 533 in concentrations of 2 %, 10 % and 50 % in dimethylformamide, i.e. cell counts and weights of the draining lymph nodes reached or exceeded the 'positive levels' defined for this assay. The cell count indices were determined to be 0.78 (2 %), 1.01 (10 %) and 0.84 (50 %). Thus the "positive level", which is 1.4 for the cell count index, was never reached or exceeded in any dose group.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: modified LLNA; measurement of cell counts instead of radioactive labeling

Any other information on results incl. tables

The "positive level" of ear swelling which is 2 x 10-2 mm increase, i.e. about 10% of the control values, has not been reached or exceeded in any dose group. favorable. No substance specific effects were determined for ear weights either.

It has to be clarified that the "positive levels" mentioned above are exclusively defined for the NMRI outbred mice used for this study. Such positive limits have to be calculated for each strain of mice individually.

The body weights of the animals were not affected by any treatment.

Applicant's summary and conclusion

Interpretation of results:

other: no sensitizing potential; no indication for non-specific (irritant) activation

Executive summary:

The test substance showed no sensitizing potential in the modified Local Lymph Node Assay (IMDS) in female NMRI mice after dermal application of up to and including a 50 % concentration. Additionally, no indication for a non-specific (irritant) activation was detected. Therefore, the concentration of 50 % turned out to be the NOEL for the parameters investigated in this study with respect to skin sensitization.