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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Annex XI of Regulation 1907/2006 and the REACH Guidance (R 6.2) permits the grouping of chemicals (chemicals categorisation). Barratt and Illing (2007, revised 2009a; 2009b, see attachments in section 13 of IUCLID data set) set out justification for an initial grouping of the polyols (oligomers and polymers) using a named core substance, with varying numbers of attached propoxy groups (or propoxy and ethoxy groups). The properties of the core substance and the repeating unit should be reflected in the polyols. The repeating unit is essentially non-toxic. If there are toxic properties associated with a core substance, these properties should reduce with increasing numbers of repeating units (i.e. increasing molecular weight).If both the core substance and the repeating unit are non-toxic, it can be anticipated that there will be no toxicity in the polyol.
Justification for type of information:
Justification cf. field "any other information on results incl. tables"

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
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)

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd, Staffs, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23g

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
5/mice/group were treated with the test material at concentrations of 0.5%, 5% or 50% w/v in acetone/olive oil 4:1
No. of animals per dose:
5/mice/group
Details on study design:
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT

Five days following the first topical application of the test material (Day 5) all mice were injected via the tail vein with 250 µl of phosphate buffered saline containing 3 H-methyl thymidine (3HTdR:80µCi/ml, specific activity 2.0 Ci/mmol) giving a total of 20 µCi to each mouse.

The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph nodes from each individual animal and as the ratio of 3 HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index (SI)).

TREATMENT PREPARATION AND ADMINISTRATION:
The mice were treated by daily application of 25 µl of the appropriate concentration of the test material to the dorsal surface of each ear for three consecutive days (Days 0, 1, 2).
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
other: Eugenol... (see attached file)
Statistics:
Linear regression analysis followed by one way analysis of variance (ANOVA) incorporating Levene’s test for homogeneity of variance. Where variances were shown to be homogenous pairwise comparisons were conducted using Dunnett’s test. Where Levene’s test showed unequal variances the data were analysed using non-parametric methods: Kruskal-Wallis ANOVA and Mann-Whitney ’U’ test.

Results and discussion

In vivo (LLNA)

Results
Parameter:
SI
Remarks on result:
other: Proliferative Response of Lymph Node Cells: A stimulation index (SI) of less than 3 was recorded for the three concentrations of the test material SI of the 0.5% group: 1.07 SI of the 5% group: 1.03 SI of the 50% group: 0.84

Any other information on results incl. tables

Annex XI of Regulation 1907/2006 and the REACH Guidance (R 6.2) permits the grouping of chemicals (chemicals categorisation).Barratt and Illing (2007, revised 2009a; 2009b, see attachmentsin section 13 of IUCLID data set) set out justification for an initial grouping of the polyols (oligomers and polymers) using a named core substance, with varying numbers of attached propoxy groups (or propoxy and ethoxy groups). The properties of the core substance and the repeating unit should be reflected in the polyols. The repeating unit is essentially non-toxic. If there are toxic properties associated with a core substance, these properties should reduce with increasing numbers of repeating units (i.e. increasing molecular weight).If both the core substance and the repeating unit are non-toxic, it can be anticipated that there will be no toxicity in the polyol.

 

A second round of grouping was based on allocation of the NLP polyols formed from different named core substances to one of two categories. The first group was those NLP polyols linked to the core substance by an ether linkage (category 1) and the second group (category 2) was those linked by a secondary/tertiary amine linkage.

Category 1 consists of:

·        Sucrose, propoxylated, >1-16.5 moles propoxylated

·        propylidyne trimethanol, propoxylated, >1-6.5 moles propoxylated

·        Glycerin, propoxylated, >1-6.5 moles propoxylated

·        Propan-1,2-diol, propoxylated, >1-4.5 moles propoxylated

·        Pentaerythritol, propoxylated, >1-8.5 mol propoxylated.

·        Nitrilotriethanol, propoxylated, 1-6.5 moles propoxylated.

For details see attached documents ‘Grouping of NLP Polyols and their toxicokinetics assessments’ (Barratt and Illing (2007, revised 2009a) and PROPOSALS FOR FURTHER TESTING FOR THE NLP ‘POLYOLS’ (2009b) in section 13 of IUCLID data set. 

The registered substance is a complex substance (UVCB) which can be regarded as a mixture of Sucrose, PO and Glycerin, PO, two members of the grouping "NLP polyols linked to the core substance by an ether linkage" (= category 1). As, in all cases, the ether linked NLP polyols are non-toxic, it is anticipated that any mixture of them or any co-initiated polyol formed using a mixture of initiators will have a similar lack of toxicity. Thus the hazard profile for the multicomponent substance can be sufficiently described by the information of the individual constituents and it is unnecessary to test this co-initiated polyol

The physico-chemical properties of these source substances and the target substance are very similar as displayed in Table 1 (test material is highlighted in yellow).

Table 1: Comparison of physico-chemical properties of source substances with target substance

 

 

Source Substances

Target Substance

 

Glycerin + PO

Sucrose + PO

Glycerin + Sucrose + PO

Appearance

liquid

liquid

liquid

Melting point

no MP

no MP

no MP

Boiling point

Decomposition >= 290°C

no BP

Decomposition >= 210°C

Relative density

1.08 (20°C)

1.122 (20°C)

1.132 (20°C)

Partition coefficient

> -1.82 < -0.73

> -3.60 < -3.25

> -0.7 < 1.1

Water solubility

completely miscible

240 g/L (25°C)

completely miscible

Surface tension

53 nM/m (20°C; at 1 mg/L)

54.54 nM/m (20°C; at 1 mg/L)

61.3 nM/m (20°C; at 1 mg/L)
(Glycerol + PO)

Flashpoint

163°C (no information on pressure available)

149.5°C (1003 hPa)

198°C (1013 hPa)

Auto flammability

305°C (1014 ha)

355°C (1000 hPa)

350°C (1008 hPa)

Flammability

no pyrophoric properties
does not emit flammable gases in contact with water

no pyrophoric properties
does not emit flammable gases in contact with water

no pyrophoric properties
does not emit flammable gases in contact with water

Explosiveness

no explosive properties

no explosive properties

no explosive properties

Oxidising properties

no oxidising properties

no oxidising properties

no oxidising properties

Viscosity

560.6 mPa (20°C)

26.63 Pa s (20°C)

21.47 mPa s (20°C)

 

Therefore, in line with Annex XI, 1.2 of Regulation (EC) No 1907/2006, read-across (many-to-one) was chosen for the registered substance (Polyether Sucrose + Glycerin+ PO) and thus no toxicological study has been performed with registered substance itself.

The model being used to justify read-across (many-to-one) is that the toxicity of the polyether polyol is derived from the core substance (initiator) and the repeating unit. While for propoxylated polyols the repeating unit is probably not classifiable, any toxicological property requiring classification is derived from the core substance. The fact, that the target chemical is formed from core substances (Sucrose and Glycerin) which are the same for two source substances (Sucrose, PO and Glycerin, PO), suggests that there are no major differences between these source substances and the target substance which may affect the toxicological properties. Due to the closeness of the compounds, polyols grouping data (= source substances data) is lead for Polyether Sucrose + Glycerin + PO (= target substance) according to Table 2 (see section 13 of IUCLID data set).

Applicant's summary and conclusion

Conclusions:
The test material was considered to be a non-sensitiser under the conditions of the test.