7-[2-(2-hydroxymethylethoxy)methylethoxy]tetramethyl-3,6,8,11-tetraoxa-7-phosphatridecane-1,13-diol

Endpoint summary

Description of key information

Eye and skin irritation studies were conducted in the rabbit.  Only very slight irritation was seen in both studies, fully resolved within 24 hours for skin and 72 hours for eye.

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:

2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle: the photoperiod was between 7:00 and 19:00 hrs daily. Any variations to these conditions were recorded in the raw data and had no effect on the outcome of the study.AccommodationAnimals 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). Acclimatization period was at least 5 days before start of treatment under laboratory conditions.DietPelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period.WaterFree access to tap water. 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.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL neat

Duration of treatment / exposure:

4 hours

Details on study design:

Each animal was treated by dermal application of 0.5 mL of the test substance. The test substance was 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.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: only slight erythema (1) seen in all 3 rabbits at 1 hour, resolved at 24 hours

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

Four hours exposure to 0.5 mL of Weston 430 resulted in very slight erythema in the treated skin areas of the three rabbits. The skin irritation resolved within 24 hours after exposure in all animals.

Other effects:

There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed and no test substance remnants were seen.No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The test material caused very slight erythema in the treated skin areas of the three rabbits. The skin irritation resolved within 24 hours after exposure in all animals.There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed and no test substance remnants were seen.7.4.Toxicity / MortalityNo symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Executive summary:

The test material caused only very slight erythema which was completely resolved in 24 hours post exposure. The results indicated that tris dipropylene glycol phosphite should not be classified as a skin 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:

2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

ConditionsEnvironmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle: the photoperiod was between 7:00 and 19:00 hrs daily. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study. AccommodationAnimals 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).Acclimatization period was at least 5 days before start of treatment under laboratory conditions.DietPelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period.WaterFree access to tap water. 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.

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye in each animal used as control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

Each animal was treated by instillation of 0.1 mL of the test substance, 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. The other eye remained untreated and served as the reference control.Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH, Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection.After the final observation, two of the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands). The other animal was removed from the study alive.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible

Remarks:

72 hours

Remarks on result:

other: redness only

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Slight irritant was observed in all animals at 1 hour, irritation was fully resolved in 1 animal at 24 hours, 2 animals at 48 hours and in all three animals at 72 hours.

Executive summary:

Tris dipropylene glycol showed only limited eye irritation when tested neat in the rabbit. Based on these results it is not classified as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Results did not show effects at a level that would trigger classification as a skin or eye irritant.