Bottom residues resulting from the synthesis of propylene oxide and styrene from epoxidation of propylene with ethylbenzene hydroperoxide

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: LLNA Study accroding to OECD 429 under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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:

Bottom product of propylene oxide and styrene production

IUPAC Name:

Bottom product of propylene oxide and styrene production

Details on test material:

- Name of test material (as cited in study report): KORE grade V
- Substance type: UVCB
- Physical state: Brown viscous liquid
- Stability under test conditions: months
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/CaOlaHsd

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

25%, 50% and 100 %

No. of animals per dose:

4

Results and discussion

In vivo (LLNA)

Results

Parameter:

SI

Remarks on result:

other: see table

Any other information on results incl. tables

Calculation and Results of Individual Data

Vehicle: acetone:olive oil (4+1 v/v)

Test item concentration % (w/v)	Group	Measurement DPM	Calculation			Result
			DPM-BG^a)	number of lymph nodes	DPM per lymph node^b^)	S.I.
---	BG I	16	---	---	---	---
---	BG II	19	---	---	---	---
0	1	3468	3451	8	431.3	1.00
25	2	23507	23490	8	2936.2	6.81
50	3	31585	31568	8	3945.9	9.15
100	4	48672	48655	8	6081.8	14.10
25	5	24293	24276	8	3034.4	7.04

BG =  Background (1 mL 5% trichloroacetic acid) in duplicate

1    =  Control Group

2-4=  Test Groups

5    =  Positive Control Group

S.I. =  Stimulation Index

^a)   =  The mean value was taken from the figures BG I and BG II

^b)    =  Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled

The EC3 value could not be calculated, since all S.I.´s are above the threshold value of 3.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item bottom product of propylene oxide and styrene production - KORE GRADE V was found to be a skin sensitiser under the test conditions of this study.

Executive summary:

In order to study a possible contact allergenic potential of bottom product of propylene oxide and styrene production - KORE GRADE V, three groups each of four female mice were treated once daily with the test item at concentrations of 25%, 50% (w/v), and 100 % in acetone:olive oil (4+1 v/v) by topical application to the dorsum of each ear for three consecutive days. The highest concentration tested was the highest concentration that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation as confirmed by a pre-experiment. A control group of four mice was treated with the vehicle (acetone:olive oil (4+1 v/v)) only. A further group of mice was treated with the positive control item. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (³H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of³H-methyl thymidine measured in ab-scintillation counter.

All treated animals survived the scheduled study period and no signs of systemic toxicity or local skin irritation were observed.

A test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentration results in a 3-fold or greater increase in incorporation of³HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated concentration of test item required to produce a S.I. of 3 is referred to as the EC3 value.

In this study Stimulation Indices of 6.81, 9.15, and 14.10 were determined with the test item at concentrations of 25%, 50% (w/v), and 100 % in acetone:olive oil (4+1 v/v). A clear dose response was observed.A Stimulation Index of 7.04 was determined for the positive control, demonstrating the validity of the study.

The EC3 value could not be calculated, since all obtained SI´s were above the threshold value of 3.