Estr-5(10)-en-17-one, 3,3-dimethoxy-

Endpoint summary

Description of key information

Skin irritation (rabbit): not irritating [Kurth, 2000a] 
Eye irritation (rabbit): not irritating [Kurth, 2000b]

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:

Feb to Mar 2000

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:

17 January 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Weight at study initiation: males: 2.7-2.9 kg; females: 2.7-2.9 kg
- Housing: in conventional metal cages, individually
- Diet (e.g. ad libitum): pell. Altromin® K ; ad libitum
- Water (e.g. ad libitum): demineralized water; ad libitum
- Acclimation period: ≥ 14 days; during this period the animals were vaccinated against rabbit hemorrhagic disease (Arvilap®)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 54-62
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

other: the untreated skin served as control

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

2 males and 2 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 6 cm² each
- Type of wrap if used: The sites (compound·treated and vehicle-treated) were covered with a piece of gauze (semiocclusive) fixed on the skin with Leukoflex ®.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure the gauze was removed and the treated and untreated skin areas were wiped carefully with lukewarm tap water and paper towels.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
The application sites were evaluated 1 , 24, 48 and 72 hours after end of exposure. Clinical observation was performed in each animal as long as findings occurred, at least until day 4 (72 hours after treatment). Body weight was recorded for the individual animal on the day of compound administration (day 1) and at the end of the observation period (day 4).

SCORING SYSTEM:
- Method of calculation: According to the system of evaluation recommended for EU.

Irritation parameter:

erythema score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Other effects:

- Other adverse local effects: Slight to moderate reddening and scab formation were seen only outside of the administration sites in two out of four animals on day 4 of the test. These findings were not considered to be compound-related but due to shearing injuries.

No signs of local intolerance were observed after dermal administration of test item as a paste. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.

Conclusions:

A single dermal administration of the test substance (0.5 g applied as a paste) for 4 hours to male and female rabbits was tolerated without any local irritations. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.

Executive summary:

In a primary dermal irritation study according to OECD TG 404 (adopted 12 May 1981), groups of young adult New Zealand White rabbits (2/sex) were dermally exposed to Dimethoxyketal in physiological saline for 4 hours at a dose 0.5g. Animals then were observed for 4 days. Irritation was scored by the method as recommended by the guideline.

The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.
In this study, the test item is not a dermal irritant.

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:

Apr 2000

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:

24 February 1987

Deviations:

yes

Remarks:

- 4 instead of 3 animals

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Weight at study initiation: males: 3.2 - 3.9 kg; females: 3.4 - 3.6 kg
- Housing: individually, in conventional metal cages
- Diet (e.g. ad libitum): pell. Altromin® K, ad libitum
- Water (e.g. ad libitum): demineralized water, ad libitum
- Acclimation period: ≥ 14 days; du ring this period the animals were vaccinated against rabbit hemorrhagic disease (Arvilap®)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 64-66
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye, which remained untreated, served as control.

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

test substance remained in the eye (eye was not rinsed)

Observation period (in vivo):

4 days

Number of animals or in vitro replicates:

2 males and 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: Evaluation of the local tolerance on the conjunctiva of the rabbits was performed according to the score system recommended for the EU

Irritation parameter:

chemosis score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

no swelling of the eye lids or the nictating membranes was reported but swelling of the conjuntivae was reported

Irritation parameter:

cornea opacity score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal: #1, #2, #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Table 1: Results of the study

 

		Irritant effects (score)
Animal no. (sex)	Irritation parameter	24 h	48 h	72 h	Mean scores
1 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
2 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	0	0	0.33
	Conjunctiva (swelling)	0	0	0	0.0
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0

 

The control eyes were without findings.

 

The single application of 0.1 mL of the test item into the conjunctival sac of the right eye provoked slight conjunctival reddening in one out of four animals only 24 hours after administration.

Conclusions:

In a local tolerance test on the rabbit eye according to OECD TG 405 a single application of the test substance into the conjunctival sac provoked slight conjunctival reddening in one out of four animals only 24 hours after administration.The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea, iris and conjunctival swelling as well as 0.08 for conjunctival reddening. According to EU classification criteria the test item need not be labelled as an eye irritant.

Executive summary:

In a primary eye irritation study similar to OECD TG 405, 0.1 mL corresponding to 50.9-56.9 mg of Dimethoxyketal was instilled into the conjunctival sac of the right eye of young adult female and male New Zealand White rabbits (2/sex) and the animals were observed for 4 days. The eyes were not washed. Irritation was scored by the method described in the guideline.

The single application of 0.1 mL of the test item into the conjunctival sac of the right eye provoked slight conjunctival reddening in one out of four animals only 24 hours after administration. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea, iris and conjunctival swelling as well as 0.08 for conjunctival reddening. In this study, the test item is not an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a primary dermal irritation study according to OECD TG 404 (adopted 12 May 1981), groups of young adult New Zealand White rabbits (2/sex) were dermally exposed to Dimethoxyketal in physiological saline for 4 hours at a dose 0.5g. Animals then were observed for 4 days. Irritation was scored by the method as recommended by the guideline.

The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.
In this study, the test item is not a dermal irritant.

In a primary eye irritation study similar to OECD TG 405, 0.1 mL corresponding to 50.9-56.9 mg of Dimethoxyketal was instilled into the conjunctival sac of the right eye of young adult female and male New Zealand White rabbits (2/sex) and the animals were observed for 4 days. The eyes were not washed. Irritation was scored by the method described in the guideline.

The single application of 0.1 mL of the test item into the conjunctival sac of the right eye provoked slight conjunctival reddening in one out of four animals only 24 hours after administration. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea, iris and conjunctival swelling as well as 0.08 for conjunctival reddening. In this study, the test item is not an eye irritant.

 

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.