Reaction mass of bis[4-(vinyloxy)butyl] hexane-1,6-diylbiscarbamate and 9,18-dioxo-3,8,19-trioxa-10,17-diazapentacos-1-en-25-yl [6-({[4-(vinyloxy)butoxy]carbonyl}amino)hexyl]carbamate

Endpoint summary

Description of key information

In vivo studies are available performed according to OECD-EC guidelines and GLP principles. This data shows that the substance has no corrosive or irritating effects on skin or eyes.

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:

31 March 2015 - 11 April 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The in vivo study was performed as a data requirement for a registration in China. In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, a weight of evidence analysis was performed prior to the start of this in vivo skin irritation study in the rabbit.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008, including most recent amendments.

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines

Version / remarks:

2000, including the most recent revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

d.d. 03 november 2015

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: 16 and 17 weeks old
- Weight at study initiation: 3062 - 3380 g
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet: approx 100 grams per day pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy). Hay and wooden sticks were available during the study period.
- Water: Tap water,ad libitum
- Acclimation period: at least 5 days

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.

ENVIRONMENTAL CONDITIONS (set conditions)
- Temperature (°C): 18 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Controls:

other: Adjacent areas of the untreated skin of each animal

Amount / concentration applied:

Test material:
0.5 grams was applied to skin moistened with 0.5 mL with 50% watery ethanol

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 males

Details on study design:

Study Design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 8 days later, after considering the degree of skin irritation observed in the first animal. Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.5 mL of the vehicle and applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

Observations:
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and after the final observation.
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.
No histopathology was performed.

Scoring system:
Draize scale

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritant / corrosive response data:

No irritant effects were observed during the study period.

Interpretation of results:

GHS criteria not met

Conclusions:

A primary skin irritation study was performed according to OECD guideline 404 and EU method B.4 and according to GLP principles. Based on the results URALAC P 1920C is not classified for skin irritation according to GHS and CLP criteria.

Executive summary:

Three male rabbits were exposed in a step-wise manner to URALAC P 1920C for 4 hours using a semi-occlusive dressing, according to OECD 404 test guideline and GLP principles. This in vivo study was performed as a data requirement for a registration in China. No skin irritation was caused by URALAC P 1920C at any point during the experiment. There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on these results it is concluded that URALAC P 1920C is not irritating to skin and no classification is needed according to EC regulation 1272/2008.

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:

09 April 2015 - 27 April 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The study was performed as a data requirement for a registration in China. In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, a weight of evidence analysis was performed, prior to the start of this in vivo eye irritation study in the rabbit.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2012

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008, including most recent amendments

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines

Version / remarks:

2000, including the most recent revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

d.d. 3 November 2015

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: 17 and 19 weeks old
- Weight at study initiation: 3101 - 3501 g
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet: approx 100 grams per day pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy). Hay and wooden sticks were available during the study period.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.

ENVIRONMENTAL CONDITIONS(set to maintain)
- Temperature (°C): 18 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

63.4 – 63.7 mg (approx 0.1 mL)

Duration of treatment / exposure:

Single instillation on day 1.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

Study Design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 11 days later, after considering the degree of eye irritation observed in the first animal. Animals were treated by instillation of, on average, 63.6 mg (range 63.4 – 63.7 mg) of the test substance (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

Analgesia:
One hour prior to instillation, the rabbits were subcutaneouslyinjected with 0.01 mg/kg buprenorphine and 5 minutes prior to instillation, two drops of topical anesthetic alcaine 0.5% were applied to both eyes.
After fluorescein examination, 0.01 mg/kg buprenorphine and 0.5 mg/kg meloxicam were subcutaneously injected.

Observations:
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation) and after the final observation.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance.
Other: Local effects were recorded.

Scoring system:
Draize scale

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not relevant

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not relevant

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not relevant

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not relevant

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Irritation of the conjunctivae in the form of redness, chemosis and discharge was observed. All irritation effects had resolved after 7 days.

Other effects:

Remnants of the test substance on the outside of the eyelids was observed 1 hour after installation.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an eye irritation study performed according to OECD guideline 405 and EU method B.5, URALAC P 1920C is not classified for adverse effects on the eye according to CLP and GHS criteria.

Executive summary:

An eye irritation study was performed according to OECD guideline 405 and EU method B.5. This in vivo study was performed as a data requirement for a registration in China. Three rabbits were exposed in a step-wise manner by a single instillation of 63.4 – 63.7 mg (approx 0.1 mL) test item in one eye. Minor rrritation of the conjunctivae in the form of redness, chemosis and discharge was observed. All irritation effects had resolved after 7 days. Based on the results, URALAC P 1920C is not classified according to CLP and GHS criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

Three male rabbits were exposed in a step-wise manner to URALAC P 1920C for 4 hours using a semi-occlusive dressing, according to OECD 404 test guideline and GLP principles. This in vivo study was performed as a data requirement for a registration in China. No skin irritation was caused by URALAC P 1920C at any point during the experiment. There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Eye in vitro:

The substance was screened for its eye irritancy potential using the BCOP test performed according to OECD 437 guideline and GLP principles.

The negative control responses of the opacity and permeability values were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas.The mean in vitro irritancy score of the positive control (20% (w/v) Imidazole) was 159 and within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. The substance did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 0 after 240 minutes of treatment. Since the substance induced an IVIS ≤ 3, the substance does not need to be classified for Eye irritation.

Eye in vivo:

An eye irritation study was performed according to OECD guideline 405 and EU method B.5. This in vivo study was performed as a data requirement for a registration in China. Three rabbits were exposed in a step-wise manner by a single instillation of 63.4 – 63.7 mg (approx 0.1 mL) test item in one eye. Minor irritation of the conjunctivae in the form of redness, chemosis and discharge was observed. All irritation effects had resolved after 7 days. Based on the results, URALAC P 1920C is not classified according to CLP and GHS criteria.

Justification for classification or non-classification

The registered substance is not classified and has no obligatory labelling requirement for skin irritation and eye irritation according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.