Oxy alkylation products of glycerol and sucrose with propylenoxid (>1 - <6.5 mol PO)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

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:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Federal register, August 22, 1978, 43:37359-60

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Oxy alkylation products of sucrose with propylenoxid

Cas Number:

9049-71-2

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Oxy alkylation products of sucrose with propylenoxid

Constituent 2

Reference substance name:

Sucrose, propoxylated

EC Number:

500-029-3

EC Name:

Sucrose, propoxylated

Cas Number:

9049-71-2

Molecular formula:

C12H14O11-(C3H6O)nH8 sum of n: >1 - <16.5 mol PO

IUPAC Name:

Sucrose, propoxylated

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ray Nicols Rabbitry, Lumberton, Texas

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye served as a control.

Amount / concentration applied:

TEST MATERIAL
1) Group A: 0.1 ml of the undiluted test substance was instilled into the conjunctival sac of the right eye of 6 rabbits
- 2) Group B: 0.1 ml of the undiluted test substance was instilled into the conjunctival sac of the right eye of 3 additional rabbits. Following 30-second exposure period these eyes were washed for 1 minute with tepid, flowing tape water.

Duration of treatment / exposure:

30 sec exposure

Observation period (in vivo):

7 days post-instillation

Number of animals or in vitro replicates:

9

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed and unwashed groups


SCORING SYSTEM:
Scoring system time points: 1, 2, 3, 4, and 7 days following instillation

TOOL USED TO ASSESS SCORE: penlight

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #1

Time point:

other: 24 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 2

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #2

Time point:

other: 24 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 3

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #3

Time point:

other: 24 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 4

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #4

Time point:

other: 24 hour

Score:

2

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 5

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #5

Time point:

other: 24 hour

Score:

2

Max. score:

110

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Unwashed eyes

Results 6

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #6

Time point:

other: 24 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 7

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #1

Time point:

other: 48 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 8

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #2

Time point:

other: 48 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 9

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #3

Time point:

other: 48 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 10

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #4

Time point:

other: 48 hour

Score:

2

Max. score:

110

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Unwashed eyes

Results 11

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #5

Time point:

other: 48 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 12

Irritation parameter:

other: Primary Irritation Score

Basis:

animal #6

Time point:

other: 48 hour

Score:

0

Max. score:

110

Remarks on result:

other: Unwashed eyes

Results 13

Irritation parameter:

other: Primary Irritation Score

Basis:

animal: 7

Time point:

other: 24 hour

Score:

0

Max. score:

110

Remarks on result:

other: Washed eyes

Results 14

Irritation parameter:

other: Primary Irritation Score

Basis:

animal: 8

Time point:

other: 24 hour

Score:

0

Max. score:

110

Remarks on result:

other: Washed eyes

Results 15

Irritation parameter:

other: Primary Irritation Score

Basis:

animal: 9

Time point:

other: 24 hour

Score:

0

Max. score:

110

Remarks on result:

other: Washed eyes

Irritant / corrosive response data:

Group A (unwashed): slight redness of conjunctiva was observed 2/6 rabbits at 24 hours (group average score = 0.67) and 1/6 rabbits at 48 hours (group averaqge score = 0.33). No corneal injury was observed.
Group B (washed): no irritation and injury observed

Other effects:

Upon instillation of test substance rabbits experienced slight to moderate discomfort, characterized by blinking and/or rubbing the eye with a paw. No irritation was observed 3 days post-instillation.

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 Glycerol) 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

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is slightly irritating to the eye. The findings do not warrant classification.