2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid

Endpoint summary

Description of key information

The test item showed no irritant effects on the skin of female rabbits in a study according to an OECD 404 (LPT, 2016). The test item causes irreversible damage to eyes in a study according to OECD 405 in male rabbits (LPT, 2016).

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:

2016-03-08 to 2016-03-29

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:

adopted July 28, 2015

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS: 
- Source: Manfred Bauer Kaninchen, Lohe 7/1, 74632 Neuenstein, Germany
- Sex: female
- Age: approx.4 months
- Weight at study initiation: 3.7 kg - 4.3 kg
- Housing: single
- Diet: ad libitum, Commercial diet, ssniff® K-H V2333 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimatisation period: at least 20 days
- Controls: untreated skin surrounding the application area
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30% - 70%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 ml test item/patch and animal

Duration of treatment / exposure:

4 hour(s)

Observation period:

Postexposure period: 72 hours (Because no effects have been observed the period of observation is not 14 days but 72 hours.)

Number of animals:

3

Details on study design:

ADMINISTRATION/EXPOSURE
- Preparation of test substance: unchanged
- Area of exposure: dorsal area of trunk, shaved 24 hours in advance,  approx. 6 cm2
- Concentration: 0.5 mL of the test item was applied to the test site (area: approx. 6 cm2).
- Occlusion: gauze patch held in place by semi-occlusive non-irritating  tape dressing
- Inital test:
Three test patches were applied sequentially to the animal. The first patch was removed after three minutes
As no serious skin reaction was observed, a second patch was applied at a different site and removed after one hour.
No skin reactions were observed, neither. So a third patch was applied and removed after 4 hours.
After the end of exposure time, no residual test item had to be removed.
- Confirmatory test:
As no skin reactions were observed in the initial test, the test was completed using two additional animals, each with one patch only, for an exposure period of 4 hours.
- Washing: at the end of the exposure time no residual test item had to be removed.
EXAMINATIONS
- After the 4-hour exposure period the patch was removed and the skin sites were evaluated.
- Examination time points: 60 minutes, 24, 48, 72 hours,
- Scoring system: Draize (0-4 possible scores each for erythema/eschar  and for edema)

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48, 72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

AVERAGE SCORE
- Erythema: 0
- Edema: 0

Other effects:

no other effects

Findings                                Examination                  Skin irritation scores

of the skin                            schedule                      

animal no.

1             2            3

E/Oe          E/Oe        E/Oe

          500 mL substance/patch/animal

 

erythema and

eschar formations/               before dosing             0/0           0/0          0/0

oedema formation

time after removal after 3 -minute appl (patch 1) 0/0

after 1 hour appl (patch 2) 0/0

after 4 hour exp (patch 3) 0/0

of the patch

(4-hour exposure) patch 3 patch 1 patch 1

60 min                        0/0          0/0          0/0

24 hours                      0/0           0/0          0/0

48 hours                      0/0           0/0          0/0

72 hours                      0/0           0/0          0/0

 

0   no pathological findings    

E   erythema and eschar formations 

Oe  oedema

Conclusions:

According to the study, the test item showed no irritant effects on the skin of female rabbits.

Executive summary:

The purpose of this study was to examine the test item for acute dermal irritation/corrosion properties in rabbits (patch test).

Under the present test conditions, none of three rabbits exposed for 4 hours to 0.5 mL test item/patch (semi-occlusive conditions) revealed any skin reaction.

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:

2016-05-26 to 2016-06-07

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:

adopted October 02, 2012

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted May 30, 2008

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: 
- Species / Strain: Rabbit / New Zealand White
- Source: Manfred Bauer Kaninchen, Lohe 7/1, 74632 Neuenstein, Germany
- Sex: male
- Age: Approx. 3 months
- Weight at study initiation: Animal no. 1: 2.6 kg
- Housing: single
- Diet: ad libitum, Commercial diet, ssniff® K-H V2333 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany,
- Water: ad libitum, tap water
- Acclimatisation period: at least 20 days
- Controls: identical animal, second eye
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30% - 70%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: identical animal, left eye

Amount / concentration applied:

Amount: 0.1 mL of the test item was administered to the right eye of one animal.

Duration of treatment / exposure:

Single administration into the conjunctival sac of the right eye

Observation period (in vivo):

24 hours

Number of animals or in vitro replicates:

1 male rabbit

Details on study design:

ADMINISTRATION:
The test was performed initially using one animal. Due to the severe findings on cornea, iris and conjunctiva the test was stopped 24 hours after instillation. No further animal was employed.
0.1 mL of the test item was administered to the right eye of one animal.
The test item was placed into the conjunctival sac of the right eye of the animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material.
The left eye, which remained untreated, served as a control.


REMOVAL OF TEST SUBSTANCE
- Washing: test item was not rinsed

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE:
The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1 and 24 hours after the administration.
The eye reactions were observed and registered.
One day before and 24 hours after administration, fluorescein was applied to the eyes before being examined to aid evaluation of the cornea for possible lesions.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Max. score:

2

Remarks on result:

other: not evaluable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Irritant / corrosive response data:

SCORE
- Cornea: 4
- Iris: not evaluable - no examination
- Conjunctivae (Redness): 2
- Conjunctivae (Chemosis): 4

Other effects:

no other effects

Examination of the treated eye

Time after administration	C O R N E A	I R I S	C O N J U N C T I V A E		F L U O R E S C E I N T E S T
	Opacity		Redness^#1	Chemosis^#2	Grade	Area
	A n i m a l n o. : 1
right eye: 0.1 mLTest item/animal
before dosing	0	0	0	0	0	0
60 minutes	3	^#3	3	3	-	-
24 hours	4	^#3	2	4	4	4

^#1    refers to palpebral and bulbar conjunctivae; excluding cornea and iris

^#2    swelling: refers to lids and/or nictitating membrane

^#3     not evaluable

-    no examination

Conclusions:

The test substance causes irreversible damage to eyes in a study according to OECD 405 in rabbits.

Executive summary:

The purpose of this study was to obtain information on the influence of test item on rabbit eyes (irritation/corrosion test).

Under the present test conditions, a single instillation of 0.1 mL test item into the conjunctival sac of the right eye of one rabbit caused the following effects:

Corneal opacity was observed at 60 minutes (grade 3) and 24 hours (grade 4) after instillation.

The fluorescein test revealed corneal staining (whole surface) 24 hours after instillation.

Iridial response was not evaluable.

Conjunctival redness was observed at 60 minutes (grade 3) and 24 hours (grade 2) after instillation.

Chemosis was observed at 60 minutes (grade 3) and 24 hours (grade 4) after instillation.

As lesions such as a grade 4 corneal opacity are generally not reversible, the study was stopped 24 hours after instillation and the animal was humanely killed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data the test item is not irritating to skin and therefore must not be classified according to criteria of EC Regulation 1272/2008.

Based on the available data the test substance causes irreversible damage to eyes and hence according to criteria of EC Regulation 1272/2008 the test substance is classified as eye damage Cat. 1; H318 "Causes serious eye damage".