Reaction mass of (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl palmitate and (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl stearate

Endpoint summary

Description of key information

The test substance showed no skin irritation potential in a guideline study performed under GLP (RCC, 848425, 2003) and no eye irritation potential in a guideline study performed under GLP (RCC, 848426, 2003).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 12 weeks
- Weight at study initiation: 2020 - 2142 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 11/03) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Fullinsdorf, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30 - 70
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 (2 female, 1 male)

Details on study design:

TEST SITE
- Area of exposure: 4 cm x 4 cm
- Type of wrap if used: semi-occlusive dressing wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tap water
- Time after start of exposure: 4 h

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

not irritating

Remarks:

Migrated information

Conclusions:

The test item is considered to be "not irritating" to rabbit skin.

Executive summary:

The primary skin irritation potential of the test substance was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 mL to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no other clinical signs of substance related effects were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

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:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 14-15 weeks
- Weight at study initiation: 2358 g male, 2248 g and 2488 g females.
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 28/03) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Fullinsdorf, ad libitum
- Acclimation period: 5 days (1 animal), 6 days (2 animals)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30 - 70
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/2

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

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

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3.
As it was suspected that the test item might produce irritancy, a single animal (one female) was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 1 - and 24-hour examinations, the test was completed using the two remaining animals.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no, the eye was kept unrinsed

SCORING SYSTEM: According to EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours, as well as 7 days after application.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzeriand).

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.55

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Individual body weights

Animal No.	Sex	First Day of Acclimatization	Day of Treatment	Last day of Observation
1	male	2358	2552	2694
2	female	2488	2593	2756
3	female	2248	2443	2685

Interpretation of results:

not irritating

Remarks:

Migrated information

Conclusions:

The test item is considered to be "not irritating" to the rabbit eye.

Executive summary:

The primary eye irritation potential of the test substance was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 mL into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects

was performed approximately 1, 24, 48 and 72 hours, as well as 7 days after test item application. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the

conjunctivae, separately. The instillation of the test substance into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no other clinical signs of substance related effects were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye and is considered to be "not irritating" to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

According to regulation (EC) No 1907/2006, Annex XI, paragraph 1.5., substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or "category" of substances. Environmental effects or environmental fate may be predicted from data for reference substance(s) within the group by interpolation to other substances in the group (read-across approach).

The source (CAS 376588-17-9) and target (EC 936-831-9) substance share identical structural elements, the only difference being the length of the carbon chain at the ester function. The source chemical is esterified with stearic acid (C18), whereas the target compound is a mixture of stearate (C18) and palmitate (C16), with the stearate version accounting for about 60% of the chemicals present in the target compound. Therefore, 60% of the target compound are identical with the source chemical and the remaining molecules of the target compound are nearly identical with the only difference being the chain length at the ester group. It is expected that the structural difference between the octadecanoate and the hexadecanoate does not affect the physico-chemical properties, the toxicological and ecotoxicologocal profile as well as the environmental fate. Both substances are characterized by similar values for water solubility, vapor pressure and log POW. Furthermore, it can be assumed that the degradation products of CAS 376588-17-9 are very similar to the degradation products of the mixture containing the octadecanoate and the hexadecanoate. In addition, both substances triggered comparable (eco)toxicological effects.  Therefore read-across to CAS 376588-17-9 is scientifically justified for physico-chemical properties, the toxicological and ecotoxicological profile as well as environmental fate. For more information on the read-across approach, please refer to the Chapter 13 (attached read-across justification).

The irritation/corrosion potential was evaluated in two GLP compliant guideline studies according to OECD 404 (RCC, 848425, 2003) and OECD 405 (RCC, 848426, 2003) with the source substance. According to the analogues approach, no additional information is needed to conclude for classification and labelling. The test substance was not irritating to the skin or the eye.

Justification for classification or non-classification

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for skin and eye irritation is not warranted under Regulation (EC) No.1272/2008.