Biphenyl-4,4'-diyl tetrakis(2,6-dimethylphenyl) bis(phosphate)

Endpoint summary

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:

7-10 December 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Data have been generated according to current internationally recognised study guidelines and in accordance with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species and strain: New Zealand White rabbits
Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY Justification of strain: The New Zealand White albino rabbit is one of the standard strains used for acute irritation toxicity studies.
Animal health: Only animals in acceptable health condition were used for the test.
Number of animals: 3
Age of animals at treatment: ~11 weeks old
Sex: Male Body weight range at the beginning of the life phase: 2770-2799 g at the end of the life phase: 2934-2961 g
Date of receipt: 01 December 2010
Acclimation time: 6 days
Animal identification: The animals were identified by engraved ear tags. The cages were marked with individual identity cards with information about study code, sex, cage number, dose group and individual animal number.

Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20±3°C
Relative humidity: 30-70 %
Housing/Enrichment: Rabbits were individually housed in AAALC approved metal wire rabbit cages (65x65 cm with height of 45 cm). Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour

Animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum.
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A single dose of 0.5 g was applied to the test area. Sufficient water to damp the material were used to ensure good contact with the skin

Duration of treatment / exposure:

4 hrs

Observation period:

24, 48 and 72 hours after patch removal

Number of animals:

3, male

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

At observation 1 hour after patch removal, very slight oedema (score 1) was observed in one animal.

At observation 24 hours after patch removal, very slight erythema (score 1) was observed in one animal.

At observation 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals.

As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.33, 0.00 and 0.00 respectively.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.11.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance caused minor skin responses up to 24 hours after exposure. The substance is not irritating to skin.

Executive summary:

The acute skin irritation of the substance was measured following exposure to the intact skin of shaved New Zealand white rabbits as prescribed in the OECD 404 test method in accordance with GLP. The substance caused minor skin responses up to 24 hours after exposure. The substance is not irritating to skin.

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:

9-12 February 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Data have been generated according to current internationally recognised study guidelines and in accordance with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The eye of the rabbits was rinsed with distilled water, however saline solution was indicated in the Study Plan.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species and strain: New Zealand White rabbits
Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, Hungary
Justification of strain: The New Zealand White rabbit is one of the standard strains used for acute irritation toxicity studies.
Animal health: Only animals in acceptable health condition were used for the test. Both eyes of each animal provisionally selected for testing were examined approximately one hour before starting the study. Animals showing eye irritation, ocular defects or pre-existing corneal injury were not used.

Number of animals: 3 animals
Age of animals at treatment: ~16 weeks old (adult)
Sex: Male Body weight range at the beginning of the life phase: 3794 - 4250 g end of the life phase: 3803 - 4244 g
Date of receipt: 29 December 2010 Acclimatization time: 42 days
Animal identification: The individual identification was by engraved ear tag. The cages were marked with individual identity cards with information about study code, sex, dose group, cage number and individual animal number.

Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20 ± 3 °C
Relative humidity: 24 - 96%
Housing/Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages
Ventilation: 15-20 air exchanges/hour

Animal received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A single dose of 0.1 g of the solid test item was administered to each animal.

Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals that had a normal eye condition and any with ocular lesions were rejected. An initial test was performed using one animal. The test item was instilled into the conjunctival sac of the left eye. The eyelids were held closed for several seconds to prevent the loss of the test item. The contralateral eye served as the control.
Immediately after the administration of the test item, an assessment of the initial pain reaction was made according to the six point scale.
After consideration of the ocular responses produced in the first animal, two additional animals were treated.

Duration of treatment / exposure:

The treated eye of the rabbits was rinsed at 1 hour after application.

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of ill- health during the study were recorded.

Number of animals or in vitro replicates:

3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1 h

Score:

0.6

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24h

Score:

0.6

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24h, 48h and 72h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 48h and 72h

Score:

0

Max. score:

0

Reversibility:

not fully reversible within:

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance caused minor responses in the eyes up to 24 hours after exposure. The substance is not irritating to eyes.

Executive summary:

The acute eye irritation of the substance was measured following exposure to the eyes of New Zealand white rabbits as prescribed in the OECD 405 test method in accordance with GLP. The substance caused minor eye responses up to 24 hours after exposure. The substance is not irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Data have been generated according to current internationally recognised study guidelines and in accordance with GLP

Justification for selection of eye irritation endpoint:
Data have been generated according to current internationally recognised study guidelines and in accordance with GLP

Justification for classification or non-classification

The acute skin irritation of the substance was measured following exposure to the intact skin of shaved New Zealand white rabbits as prescribed in the OECD 404 test method in accordance with GLP. The substance caused minor skin responses up to 24 hours after exposure. The substance is not irritating to skin.

The acute eye irritation of the substance was measured following exposure to the eyes of New Zealand white rabbits as prescribed in the OECD 405 test method in accordance with GLP. The substance caused minor eye responses up to 24 hours after exposure. The substance is not irritating to eyes.