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

Endpoint summary

Description of key information

- Acute toxicity by oral route: The acute oral median lethal dose (LD50) of Di-tert-butyl phosphate in rat was calculated to be greater than 2372 mg/kg bw.
- Acute toxicity by inhalation route: no data available.
- Acute toxicity by dermal route: no data available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

2012-07-23 to 2012-12-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across with Di-tert-butyl potassium phosphate. Study conducted in compliance with international standard guidelines under GLP conditions. The study report was well documented with all mandatory information included.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: 12 NohSan N° 8147, JMAFF 2002

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Remarks:

(2012-09-07)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group (from 159g to 173 g)
- Fasting period before study: Yes
- Housing: in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK
- Water (e.g. ad libitum): free access to mains drinking
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

IN-LIFE DATES: From: 20 September 2012 To: 18 October 2012

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
For the 2000 mg/kg dose level:
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on results of available data

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

3 per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
+ Observations: The first day: 0.5h, 1h, 2h, 4h and then once daily
+ Weighing: day 0, 7 and 14

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Statistics:

No statistics were performed.

Preliminary study:

Not applicable.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks:

DTBPOK

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 372 mg/kg bw

Based on:

act. ingr.

Remarks:

di-tert-butyl phosphate

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No data.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions of this study, the acute oral median lethal dose (LD50) of Di-tert-butyl potassium phosphate in rat was estimated to be greater than 2000 mg/kg bw. The acute oral median lethal dose (LD50) of Di-tert-butyl phosphate in rat was calculated to be greater than 2372 mg/kg bw.

Executive summary:

The acute oral toxicity study was assessed on the potassium salt analogue of the target substance, di-tert-butyl potassium phosphate, in a study according to acute toxicity class method procedure (OECD Guideline 423; EC test method B1.tris, EPA OPPTS 870.1100 and Japanese MAFF, 2000) and in accordance with GLP.

No abnormalities were detected in the two groups tested at 2000 mg/kg bw.

Under the test conditions of this study, the acute oral median lethal dose (LD50) of Di-tert-butyl potassium phosphate in rat was estimated to be greater than 2000 mg/kg bw. The acute oral median lethal dose (LD50) of Di-tert-butyl phosphate in rat was calculated to be greater than 2372 mg/kg bw. Based on these data, no classification is required for both Di-tert-butyl potassium phosphate and Di-tert-butyl phosphate according to EU criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Key study performed according to the OECD 423 guideline study and in compliance with the GLP (Klimisch score = 2).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

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. By analogy with Di-tert-butyl potassium phosphate, the median lethal dose (LD50) of Di-tert-butyl phosphate in rat was calculated to be greater than 2372 mg/kg bw. Heptane is not classified by oral route in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation). Based on these data, the test substance is considered as not harmful if swallowed.

Justification for selection of acute toxicity – oral endpoint
Only one study was available.

Justification for classification or non-classification

The substance considered in the present dossier is manufactured as a 15% solution in 85% n-heptane.

- As n-heptane is not classified by oral route in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation) and LD50 calculated of Di-tert-butyl phosphate in rat is > 2372 mg/kg bw, the test substance is not classified by oral route according to CLP Regulation (1272/2008) criteria.

- As n-heptane is classified as Asp. Tox. 1 (H304) in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation), therefore the test substance in 85% n-heptane is classified as Asp. Tox. 1 (H304) according to CLP Regulation (1272/2008) criteria.

- As n-heptane is classified as STOT SE 3 (H336) in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation), therefore the test substance in 85% n-heptane is classified as STOT SE 3 (H336) according to CLP Regulation (1272/2008) criteria.