Registration Dossier

Toxicological information

Eye irritation

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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:
other: Federal register, August 22, 1978, 43:37359-60
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

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

Resultsopen allclose all
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.