Octanoic acid, 1,1'-(1,3-propanediyl) ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

03 Jun -10 Jun 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS# 68583-51-7 referred as source substance) is proposed as structural analogues for the target substance 1,3-propanediol dioctanoate (CAS# 56519-71-2). Both substances are diesters with propanediol (1,3-propanediol or 1,2-propanediol) of similar molecular size, containing the same functional groups. Due to the lack of human health data on eye irritation by 1,3-propanediol dioctanoate, an eye irritation study with the source substance as suggested to be used for closing the respective data gap in the target substance dossier. Similarities in structure and physico-chemical properties are supposed to form a basis for the analogue approach. This study with the source substance CAS# 68583-51-7 has been performed according to OECD and/or EC guidelines and according to GLP principles. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Decanoic acid, mixed diesters with octanoic acid and propylene glycol

EC Number:

271-516-3

EC Name:

Decanoic acid, mixed diesters with octanoic acid and propylene glycol

Cas Number:

68583-51-7

Molecular formula:

C21H44O6

IUPAC Name:

decanoic acid; octanoic acid; propane-1,2-diol

Details on test material:

- Name of test material (as cited in study report): [trade name], Polypropylenglykol-di-Fettsäureester
- Physical state: yellowish liquid
- Analytical purity: no data
- Smiles notation (if other than submission substance): CCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC
- Physical state: liquid
- Melting point: -40 °C (pour point)
- Boiling point: 342 °C
- Relative density: 0.92
- Vapour pressure: ca. 0.00001 (calc. SPARC v4.5)
- log Kow: >8.0
- Water solubility: <0.05 mg/L

Test animals / tissue source

Species:

rabbit

Strain:

other: Kleinrusse Chbb:HM

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: adult animals
- Weight at study initiation: mean 2457.5 g
- Housing: single holding in cage
- Diet: Altromin-Haltungsdiät 2023 (Altomin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Identification of animals: Ear tattoo and cage labelling
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single application without wasching

Observation period (in vivo):

72 h
Reading time points: 1, 6, 24, 48 and 72 h

Number of animals or in vitro replicates:

4 males

Details on study design:

PRELIMINARY CONTROL:
The eyes of the animals were visually controlled and with fluorescein, 24 h prior to application.

MAIN STUDY:
A control of the treated eye with fluorescein was conducted, 24 h after application and after macroscopic control of the eye.

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 4 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 4 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 4 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 4 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Cornea: no effects were observed during the study period in any animal.
Iris: no effects were observed during the study period in any animal.
Conjunctivae: after 1 h mild redness was observed in 2 of 4 animals. In one of theses animals the effect was fully reversible within 6 h after application. The second animal showed mild redness until 6 h after application being fully reversible after 24 h as well.
Chemosis: no effects were observed during the study period in any animal.
Exsudation: no effects were observed during the study period in any animal.

Other effects:

No further local or systemic effects were reported.

Any other information on results incl. tables

Analogue approach justification

 

Structure and PC parameters

 The structural difference between the target and source chemicals is that the Propanediol moiety in the source substance is 1,2-propanediol, whereas in the target substance it is 1,3-propanediol. In addition,

one hydrocarbon chain of the source substance is two CH2 – groups longer compared to the length in target substance (C10 instead of C8). These feature accounts for differences in PC-parameters (see Data Matrix). The melting point of the source substance is lower than the one of the target substance. This may be correlated with the lower symmetry of the source molecule. Both substances are liquids at ambient conditions. They are non-volatile substances of similar density, boiling at temperatures exceeding 340 °C. The logarithmic partition coefficients are both =>7 and water solubilities are below 0.1 mg/L.

Eye irritation

With the help of OECD QSAR Toolbox v2.2 it can be determined, whether inclusion and exclusion rules are fulfilled for the target substance as well as for the source substance (experimentally non-irritating). Inclusion rules are based on structural alerts and exclusion rules are based on physico-chemical parameters. Both sets of rules are referred to as BfR Inclusion/Exclusion Rules, because they were developed at or in cooperation with German Federal Institute for Risk Assessment (BfR - Bundesinstitut für Risikobewertung).

 

1. Inclusion rules for eye irritation/corrosion:

The structures were examined for the presence of 17 structural alerts (literature references: Tsakovska et al, SAR QSAR Environ Res. 2007, 18 (3-4): 221-35; Saliner et al, SAR QSAR Environ Res. 2007, 18 (3-4): 331-42; OECD(2002), Acute Eye Irritation/Corrosion, OECD Guidelines for Testing of Chemicals, Vol.405, 14pp. Paris, France: OECD Publication Office). As no alerts were detected, both substances are predicted neither irritating nor corrosive for the eye with respect to this set of rules.

 

2. Exclusion rules for eye irritation/corrosion.

 

As both substances contain only C, H and O atoms, the following rules (literature reference: Gerner et al, Altern Lab Anim 2005, 33: 215-37) are applicable (Table 1):

 

Rule	Class of substances	Positive for:	If positive, than NOT:
log Kow > 9	all	none	R34, R35, R36, R41
water solubility < 0.1 mg/L	all	both	R34, R35, R36, R41
melting point > 55 °C	C, H, O only	none	R34, R35
molecular weight > 380 g/mol	C, H, O only	none	R34, R35, R36, R41
lipid solubility < 0.01 g/kg	all	none*)	R34, R35, R36, R41

*) High lipid solubilities can be deduced from high log Kow’s and low water solubilities.

Table 1 Performance of BfR Exclusion Rules for Eye Irritation/Corrosion

 

The two substances have the same profiles with respect to BfR Inclusion and Exclusion Rules. It is the water solubility rule from the latter set that accounts for a non-irritant character of both substances.

Thus, read across is justified for this endpoint because of similarity in structure, PC parameters and rule-based profiles of target substance and the source substance.

Data matrix

Endpoint	Target substance	Source substance
Physical state	liquid	liquid
Melting point [°C]	6	-40 (pour point)
Boiling point [°C]	352	342
Relative density	0.93	0.92
Vapour pressure [Pa]	8E-4	ca. 1E-5 (calc. SPARC v4.5)
log Kow	7.6	> 8.0
Water solubility [mg/L]	< 0.01	< 0.05
Eye irritation (in vivo)	RA: not irritating	Not irritating
Skin sensitisation	RA: non-sensitising	-

Data are experimental determinations (Klimisch 1 or 2) unless otherwise indicated.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Executive summary:

Based on the study results, the criteria for classification and labelling according to DSD (67/548/EEC) and CLP (EC 1272/2008) are not fulfilled. Therefore, 1,3-propanediol dioctanoate is not irritating to the eyes.