Dodecanoic acid, ester with oxybis[propanediol]

Endpoint summary

Description of key information

Based on read-across from surrogate substances the substance Reaction products of lauric acid and oxybis(propanediol) is not irritating to the skin (OECD 404; GLP) and not irritating to eyes (FDA, 1959).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: National guideline study with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology, FDA, according to Draize (1959)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.4-2.6 kg
- Housing: animales were housed individually
- Diet: standard diet (Höing 222), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12

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 g

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

7 days
Reading time points: 1, 2, 8, 24, 48 and 72 h and 4, 5, 6 and 7 days

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72-96 h

Remarks on result:

other: individual mean scores ranged from 0 to 1.0

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 48 h - 6 days

Remarks on result:

other: individual mean scores ranged from 0.3 to 2.0

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h - 6 days

Remarks on result:

other: individual mean scores ranged from 0.3 to 1.7

Irritant / corrosive response data:

At the 1, 2 and 8 h reading time points, no corneal opacity and no iritis were observed in any animal. Whereas at this time points, slight to moderate conjunctival redness and moderate to strong chemosis and discharge were seen in all animals (see Table 2 under “Any other information on results incl. tables”). In 2/6 animals corneal opacity was observed and was fully reversible within 48 h and 72 h, respectively.
No effects on the iris were observed in any animal during the study period.
Slight to moderate conjunctival redness was observed in all animals 24 h post-instillation being fully reversible within 48 h (2 animals), 72 h (1 animal) and 5 days (3 animals).
24 h post application, slight to strong discharge was observed in all animals. Effects were fully reversible within 72 h in 5 animals and 4 days (1 animal).

Other effects:

No further local or systemic effects were reported.

Table 1. Results of eye irritation study.

Rabbit number #	Time [h]	conjunctivae score		iris	cornea
		redness	swelling
1	1	1	2	0	0
	24	2	1	0	0
	48	2	1	0	0
	72	1	1	0	0
	average	1.7	1.0	0.0	0.0
2	1	1	2	0	0
	24	2	1	0	0
	48	1	1	0	0
	72	1	1	0	0
	average	1.3	1.0	0.0	0.0
3	1	1	2	0	0
	24	2	2	0	0
	48	1	1	0	0
	72	0	0	0	0
	average	1.0	1.0	0.0	0.0
4	1	1	3	0	0
	24	1	1	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.3	0.0	0.0
5	1	1	2	0	0
	24	2	1	0	1
	48	2	1	0	1
	72	2	1	0	1
	average	2.0	1.0	0.0	1.0
6	1	2	2	0	0
	24	2	2	0	1
	48	2	2	0	1
	72	1	1	0	0
	average	1.7	1.7	0.0	0.7
	Time [h]	conjunctivae score		iris	cornea
		redness	swelling
average scores	1	1.17	2.17	0.00	0.00
	24	1.83	1.33	0.00	0.33
	48	1.33	1.00	0.00	0.33
	72	0.83	0.67	0.00	0.17
	24+48+72	1.33	1.00	0.00	0.28

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

There are no data available on the skin irritating properties of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1).

In order to fulfil the standard information requirements set out in Annex VII, 8.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related surrogate substance, octanoic acid, monoester with glycerol (CAS No. 26402-26-6) and available data on the expected metabolite lauric acid (CAS No. 143-07-7) were considered for assessment and read-across was conducted based on an analogue and weight of evidence approach.

The predicted metabolite lauric acid (CAS No. 143-07-7) and the structural surrogate octanoic acid, monoester with glycerol (CAS No. 26402-26-6), were tested in studies according to the OECD guideline 404 in compliance with GLP (Koopmans and Daamen, 1989; Guest, 1989).

In each study, 3 New Zealand White rabbits were exposed to 0.5 g or 0.5 mL of the test substance, applied to the shaved skin for 4 h using a semi-occlusive dressing. Thereafter, the remaining test substance was removed, the treated skin was observed and evaluated at 1, 24, 48 and 72 h and 7 days post-application.

In the study with lauric acid, the observed skin irritation consisted of very slight erythema 1 h post-application in all animals. These effects were fully reversible within 24 h in 1 animal, in the second animal within 48 h post-application and in the third animal within 7 days. The resulting mean erythema scores over 24, 48 and 72 h were 1.0, 0.0 and 0.3 in animal #1, #2 and #3, respectively. No oedema formation or further local or systemic effects were apparent in any animal during the study period.

In the study with octanoic acid, monoester with glycerol, no oedema formation or systemic effects were noted in any animal. Very slight erythema was noted in all animals 1 h after treatment. In 2 animals the erythema was persistent up to the 48 h reading time point and in 1 animal up to 72 h post-application resulting in mean erythema scores of 0.67, 0.0 and 1.0 over 24, 48 and 72 h in animal #1, #2 and #3, respectively. All skin reactions were fully reversible at the latest within 7 days.

In summary, the available data on the metabolite and the structural surrogate, do not provide evidence for a dermal irritation potential of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1).

Eye irritation

There are no data available on the eye irritation properties of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1). In order to fulfil the standard information requirements set out in Annex VII, 8.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related structural surrogate, 2,3-dihydroxyproypl laurate (CAS No. 142-18-7), was considered for read-across and assessment was conducted based on an analogue approach.

The eye irritation properties of 2,3-dihydroxyproypl laurate were tested in a study in New Zealand White rabbits according to the "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology, FDA, according to Draize (1959)” (Sterner, 1977).

In a group of 6 rabbits, 0.1 g of the undiluted test substance was applied into one eye (the untreated eye served as control), in a single application without washing. The eyes were observed and reactions were evaluated 1, 2, 8, 24, 48 and 72 h and 4, 5, 6 and 7 days after application.

Slight to moderate conjunctival redness resulting in a mean conjunctivae score of 1.3 out of all 6 animals over 24, 48 and 72 h and moderate to strong chemosis were seen in all 6 animals (mean chemosis score out of all 6 animals over 24, 48 and 72 h = 1). 24 h post-application corneal opacity was observed in 2/6 animals being fully reversible within 48 h and 72 h, respectively. Slight to moderate conjunctival redness was observed in all animals 24 h post-instillation being fully reversible within 48 h, 72 h and 5 days in 2, 1 and 3 animals, respectively. Slight to strong discharge was observed in all animals 24 h post-instillation. The effects were fully reversible within 72 h and 4 days in 5 and 1 animal, respectively. No further local or systemic effects were observed in any animal during the study period.

Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from structural surrogates. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across from a structural surrogate. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from surrogate substances following an analogue approach, the available data on the skin and eye irritating potential of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.