1,3-Diazaspiro[4.5]decane-2,4-dione, 8-methoxy-, sodium salt (1:1), cis-

Endpoint summary

Description of key information

Skin irritation in vivo (Rabbit, GLP, OECD TG 404): not skin irritating

Skin corrosion in vitro (RhE, GLP, OECD TG 431): not corrosive

Eye irritation (Rabbit, GLP, OECD TG 405): not irritating to eye

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 01 - November 07, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)

Version / remarks:

2004

GLP compliance:

yes

Test system:

human skin model

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

60 min

Value:

94.53

Negative controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 min

Value:

100.83

Vehicle controls validity:

not specified

Negative controls validity:

valid

No scores on irritation parameters can be provided as the study is an in vitro study using recontructed human epidermis.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was not characterised by a significant impact on cell viability after the 3 min and after the 60 min period.
Thus, it should not be labelled as corrosive to skin.

Executive summary:

This study for predicting non-specific, corrosive potentials of compounds by using reconstructed human skin (RHS) was performed in 2008. The experiment was carried out on a reconstructed human epidermis EST-1000 (CellSystems, St. Katharinen, Germany) for detection of topically applied skin corrosives with the test item.

A 100% concentration was tested on the skin/epidermal equivalents in triplicate. For the determination of time related cytotoxic effects the incubation periods were 3 min and 60 min, respectively. Thus the study was conducted in accordance with the OECD 431 guideline draft as well as with an EC draft guideline (amending Council Directive 67/548/EEC, B.40 Skin corrosion) using the test item concentrations and incubation periods recommended there. 

The test item was applied at a 100% concentration, i.e. 25 mg per insert. The MTT (Methylthiazoletetrazolium) method has determined the following values of viability after 3 min. or after 60 min. of incubation: 100.83% and 94.53%, respectively.
Thus, the results show that no corrosive property of the test item was determined by the assay used.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 14 - September 28, 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

GLP compliance:

yes

Species:

rabbit

Strain:

other: Crl:KBL(NZW)BR

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Controls:

no

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3/female

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

There were no systemic intolerance reactions.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is not an irritant to the skin.

Executive summary:

The irritant / corrosive potential of of the test item was studied on the skin of rabbits. The method used complied with the OECD - Guideline for Testing of Chemicals No. 404 -" Acute Dermal Irritation/Corrosion"; adopted: 24th April 2002; EEC Directive 67/548 Annex V - Method B.4. (1967) in its current version, and the principles of the EPA Health Effects Test Guidelines (OPPTS 870.2500), United States, EPA 712-C-98-196 (1998).
According to classification criteria the test item is not an irritant to the skin.
There were no systemic intolerance reactions.

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:

May 16 - September 28, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002-04-24

GLP compliance:

yes

Species:

rabbit

Strain:

other: Crl:KBL(NZW)BR

Controls:

yes, concurrent no treatment

Duration of treatment / exposure:

24 h

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3/female

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.88

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

The treatment did not result any effect on body weight.
There were no systemic intolerance reactions.

 

 

 

Summary of Irritant Effects (Score)

 

Animal		24 h	48 h	72 h	Mean scores	Response	Reversible (days)
1	Corneal opacity	0	0	0	0.0	-	na
	Iritis	0	0	0	0.0	-	na
	Redness conjunctivae	2	2	2	2.0	-	7
	Chemosis conjunctivae	0	0	0	0.0	-	1*
2	Corneal opacity	0	0	0	0.0	-	na
	Iritis	0	0	0	0.0	-	na
	Redness conjunctivae	2	2	1	1.7	-	7
	Chemosis conjunctivae	0	0	0	0.0	-	1*
3	Corneal opacity	0	0	0	0.0	-	na
	Iritis	0	0	0	0.0	-	na
	Redness conjunctivae	3	2	1	2.0	-	14
	Chemosis conjunctivae	0	0	0	0.0	-	1*

 

response:

corneal opacity              : mean scores   < 2 = -,              ≥ 2 <3 = +,        ≥ 3 = ++

irits                              : mean scores   < 1 = -,              ≥ 1 <2 = +,        = 2 = ++

conjunctival redness      : mean scores < 2.5 = -,               ≥ 2.5 = +

conjunctival oedema      : mean scores   < 2 = -,                   ≥ 2 = +

na : not applicable

*: in respect of the result 1 h post application

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not cause eye irritation.

Executive summary:

The irritant / corrosive effects of the test item were tested on the eye of rabbits.

The method used complied with the OECD - Guideline for Testing of Chemicals No. 405 -"Acute Eye Irritation/Corrosion"; adopted: 24th April 2002; EEC Directive 67/548 Annex V - Method B.5. (1967) in its current version, and the principles of the EPA Health Effects Test Guidelines (OPPTS 870.2400), United States, EPA 712-C-98-195 (1998), with the exception that recognized differences exist between OECD - Guideline 405 and EPA - Guideline OPPTS 870.2400.

According to classification criteria the test item is not irritating to eyes.
There were no systemic intolerance reactions.

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Based on the study results for skin and eye irritation no classification is warranted according to Regulation (EC) No. 1272/2008 (CLP).