Phosphoric acid, bis(1,1-dimethylethyl) ester

Endpoint summary

Description of key information

- Skin irritation: irritating to skin
- Eye irritation: corrosive to eyes.
- Respiratory irritation: no data available.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

between 1997-06-02 to 1997-07-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study in accordance with OECD guideline.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Remarks:

(1996-21-02)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 16 weeks
- Weight at study initiation: 3.32 kg
- Housing: suspended metal cage
- Diet (e.g. ad libitum): ad libitum (STANRAB SQC Rabbit diet, special diets services, Witham, Essex, UK)
- Water (e.g. ad libitum):ad libitum
- Acclimation period: yes, at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 21 °C
- Humidity (%): 51 to 70%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: To: 2 June 1997 to 23 June 1997

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (Approximately 20 mg)

Duration of treatment / exposure:

Only one treatment.

Observation period (in vivo):

just after the administration of the test item, 1h, 24h, 48h, 72h (according to the numerical evaluation from Draize J H 1977 "Dermal and Eye Toxicity test")
Additional observation were made on Days 7, 14 and 21 to assess the reversibility of the ocular test.

Number of animals or in vitro replicates:

1 animal

Details on study design:

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

SCORING SYSTEM: according to the numerical evaluation from Draize J H 1977 "Dermal and Eye Toxicity test" in: Principles and Procedures for evaluating the toxicity of Household Substances, National Academy of sciences, Washington DC p 48-49

TOOL USED TO ASSESS SCORE: standard ophtalmoscope

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 1h

Max. score:

57

Reversibility:

not fully reversible within: 21 days.

Irritant / corrosive response data:

Individual and total scores for ocular irritation are given in table 1.

Areas of translucent corneal opacity were noted in the treated eye one hour after treatment with area of diffuse corneal opacity at the 24 and 48-hour observations, areas of translucent corneal opacity at 72-hour observation and diffuse corneal opacity at the 7 and 14-day observations. Sloughing of the cornea was noted in the treated eye at the 72-hour observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour and 7-day observations. No other iridial affect were noted

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24, 48 72-hour and 7-day observation with minimal conjunctival irritation at the 14 and 21-day observations. Pale green discolouration of the nictitating and conjunctival membranes was noted in the treated eye one hour after treatment. An off white appearance of the nictitating membrane and approximately half of the lower conjunctival membrane was noted in the treated eye at the 24, 48 and 72-hour and 7-day observations. An area of haemorrhage approximately 3 mm² in size on the conjunctival membrane of the lower eyelid was noted in the treated eye at 48 and 72-hour and 7-day observations. An abnormally shaped nictitating membrane was noted in the treated eye at the 14 and 21 day observations.

Table 1: Acute irritation test in the rabbit: Individual Scores and total Scores for Ocular Irritation   Rabbit Number and Sex (Bodyweight kg) IPR = 3 63 Female (3.32) Time after Treatment 1 hour 24 hours 48 hours 72 hours 7 days 14 days 21 days CORNEA   E = Degree of Opacity 2 1 1 2 SI 1 1 0 F = Area of opacity 4 4 4 3 3 1   Score (E x F) x 5 40 20 20 30 15 5 0 IRIS   D 1 1 1 1 1 0 0 Score (D x 5) 5 5 5 5 5 0 0 CONJUNCTIVAE   A = redness 2G 2W 2WH 2WH 2WH 1AB 1AB B = Chemosis 2 2 2 2 2 1 0 C = discharge 2 3 3 1 1 0 0 Score (A +B + C) x 2 12 14 14 10 10 4 2 Total Score 57 39 39 45 30 9 2   IPR = Initial Pain Reaction AB = Abnormally shaped nictitating membrane G = Pale green discolouration of the nictating and conjunctival membrane of lower eyelid H = Area of haemorrhage approximately 3 mm² located on conjuntival membrane of lower eyelid W = off white appearance of nictating membrane and approximately half of the lower conjunctival membrane SI = sloughing of corneal membrane

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions of this study, Potassium Dibenzyl Phosphate is considered as corrosive to eyes.

Executive summary:

In an eye irritation study performed similarly to the OECD No. 405 guideline, 0.1 mL of undiluted test item was instilled into the right eye of 1 female New Zealand White Rabbits. After the instillation the substance was not remained. Animal was then observed for 21 days for eye oedema and erythema of the conjunctive, corneal opacity and iris lesion.

Eye irritation was assessed and scored according to the Draize scale at 24, 48 and 72 hrs after the instillation of the substance and then at days 7, 14 and 21. The highest score was observed 1 hour after treatment. The effects was not fully reversible during the 21 days of observation, with still effect on conjonctivae (redness ans abnormally shaped nictitating membrane).

Under the test condition of this study, the test item is considered as corrosive to eye rabbit ans is therefore classified as Eye Irr. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP) and as Xi; R41 according to the Directive 67/548/EEC. By analogy with Potassium Dibenzyl Phosphate, Di-tert-butyl phosphate is considered as corrosive to eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

- Skin irritation: the substance considered in the present dossier is manufactured as a 15% solution in 85% n-heptane (CAS: 142 -82 -5). No data are available on the test substance. n-heptane (CAS: 142 -82 -5) is classified as irritating to skin into category.2 (H315) in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation). Based on these data the test substance is considered as irritating to skin.

- Eye irritation: the substance considered in the present dossier is manufactured as a 15% solution in 85% n-heptane (CAS: 142 -82 -5).

No data available on the test substance. An analogy approach was used with Potassium Dibenzyl Phosphate (OECD 405 , GLP, Kr. 2) and Dibutyl hydrogen phosphate (CAS: 107-66-4, ECHA C&L inventory). Both substances are self classified as corrosive to eyes.

This analogy is used as the worst case in absence of data. Therefore, the test substance is classified as corrosive to eyes.

n-heptane (CAS: 142 -82 -5) is not classified as corrosive or irritating to eyes in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation).

Justification for selection of eye irritation endpoint:
Only one study was available.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

The substance considered in the present dossier is manufactured as a 15% solution in 85% n-heptane (CAS: 142 -82 -5).

- Skin irritation: As n-heptane is classified as skin irritant into category 2 (H315) in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation), therefore Di-tert-butyl phosphate in 85% n-heptane is classified as irritating to skin into category 2 (H315) according to CLP Regulation (1272/2008) criteria.

- Eye irritation: by analogy with Potassium Dibenzyl Phosphate (effects not fully reversible during the 21 days of observation, OECD 405, GLP, Kr. 2) and Dibutyl hydrogen phosphate (CAS: 107 -66 -4, ECHA C&L inventory), Di-tert-butyl phosphate is considered as corrosive to eyes and classified into category.1 (H314) according to CLP Regulation (1272/2008) criteria.