Phosphoric acid, butyl ester, sodium salt

Endpoint summary

Description of key information

oral: The LD50 of the test item is greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

Please refer to the attached read-across justification in section 13.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

Preliminary study:

In preliminary experiments undertaken to set the dose, no male or female fatalities were observed even on administration of 2000 mg/kg.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of the read across-substance dibutyl phosphate (CAS 107-66-4) was found to be > 2000 mg/kg bw.

Executive summary:

A study of the acute oral toxicity of the read across-substance dibutyl phosphate (CAS 107-66-4) in rats was undertaken. No fatalities were observed after administration of 2000 mg/kg bw (chosen on the basis of the results of preliminary test). The symptoms of toxicity observed in males and females after dosing were as follows: there were symptoms of systemic suppression such as decreased locomotor activity, deepening respiration and eyelid ptosis. Abdomina were urine-stained and on the day after dosing inhibition of body weight increase or body weight decrease was observed. Some animals exhibited transient salivation and the excretion of red urine. There was recovery such that by 4 days after dosing none of these changes were observed anymore. Necropsy revealed no visible abnormalities of the organs. From these results it was concluded that the minimum lethal dose and thus also the LD50 is higher than 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1978

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Control animals:

no

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item was found to be >5000 mg/kg bw.

Executive summary:

A study was conducted to assess the acute oral toxicity of the test item in rats. As a result, the LD50 value was determined to be >5000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., l,lanston, Kent, U.K
- Age at study initiation (main study): five to eight weeks old
- Weight at study initiation: males weighed 153 - 170g, and the females 135 -157g
- Fasting period before study: overnight before dosing
- Housing: The animals were housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet: Rat and Mouse Expanded Diet No. l, Special Diet Services Limited, Witham, Essex, U.K)
- Water: ad libitum)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 46-70
- Air changes (per hr): appr. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.9 mL/kg bw

Doses:

only one (limit) dose: 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, external examination, opening of the abdominal and thoracic cavities, appearance of macroscopic abnormalities

Preliminary study:

A range-finding study was performed to determine a dosing regime. 1 male and 1 female rat received a dose of 2000 mg/kg bw. No deaths occured.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortalitiy occured

Clinical signs:

other: Hunched posture was noted in all animals for two hours folIowing dosing. Lethargy was also noted in four animals. All animals recovered four hours after dosing.

Gross pathology:

No abnormalities were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of the test item was found to be >2000 mg/kg bw.

Executive summary:

A study according to OECD guideline 401 was conducted with Sprague Dawley rats to identify the acute oral median lethal dose (LD50) of the test material. 5 males and 5 females of each sex were dosed (gavage, single application of 2000 mg/kg bw) and observed for 14 days for mortality and clinical signs. As no deaths occurred, the LD50 was determined to be greater than 2000 mg/kg bw.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2007-05-28 to 2007-04-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

no details given in report

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Rationale for the selection of the starting dose:
Following a sighting test in which there were no mortalities at dose levels of 300 and 2000 mg/kg bw, the main test was started.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not necessary

Preliminary study:

In preliminary experiments undertaken to set the dose, none of the exposed females died at dose levels of 300 or 2000 mg/kg bw.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

other: none

Gross pathology:

No abnormalities were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of the test substance is > 2000 mg/kg bw.

Executive summary:

A study of the acute oral toxicity of the test item in rats was undertaken following OECD Guideline No. 420 (fixed dose-procedure). No mortality and no clinical signs were observed during the 14 days-observation period after the administration of 2000 mg/kg bw (chosen on the basis of the results of a preliminary test). At necropsy, no abnormalities were detected. From these results it was concluded that the LD50 value of the test item is higher than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The weight-of evidence approach included guideline and GLP-studies, which were assessed to be suitable for assessment.

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

Several studies are available which were used to assess the oral toxicity of the substance based on a weight of evidence-approach:

Read across to dibutyl phosphate (CAS 107-66-4), OECD 420

A study of the acute oral toxicity of the read across-substance dibutyl phosphate (CAS 107-66-4) in rats was undertaken. No fatalities were observed after administration of 2000 mg/kg bw (chosen on the basis of the results of preliminary test). The symptoms of toxicity observed in males and females after dosing were as follows: there were symptoms of systemic suppression such as decreased locomotor activity, deepening respiration and eyelid ptosis. Abdomina were urine-stained and on the day after dosing inhibition of body weight increase or body weight decrease was observed. Some animals exhibited transient salivation and the excretion of red urine. There was recovery such that by 4 days after dosing none of these changes were observed anymore. Necropsy revealed no visible abnormalities of the organs. From these results it was concluded that the minimum lethal dose and thus also the LD50 is higher than 2000 mg/kg bw.

OECD 401

A study according to OECD guideline 401 was conducted with Sprague Dawley rats to identify the acute oral median lethal dose (LD50) of the test material (as aqueous solution, 80 % water). 5 males and 5 females of each sex were dosed (gavage, single application of 2000 mg/kg bw) and observed for 14 days for mortality and clinical signs. As no deaths occurred, the LD50 was determined to be greater than 2000 mg/kg bodyweight.

OECD 420

A further study of the acute oral toxicity of the test item (aqueous solution, 45 % water) in rats was undertaken following OECD Guideline No. 420 (fixed dose-procedure). No mortality and no clinical signs were observed during the 14 days-observation period after the administration of 2000 mg/kg bw (chosen on the basis of the results of a preliminary test). At necropsy, no abnormalities were detected. From these results it was concluded that the LD50 value of the test item is higher than 2000 mg/kg bw.

Similar to OECD 401

A study was conducted to assess the acute oral toxicity of the test item (aqueous solution, 80 % water) in rats. As a result, the LD50 value was determined to be >5000 mg/kg bw. The study documentation is very limited, therefore it was allocated to reliability 4 (not assignable).

Taken together, no mortality was observed in the available studies and therefore it was concluded that the LD50 of the test substance is > 2000 mg/kg bw.

Even though only studies with the test substance itself at lower purity (aqueous solutions) are available, the substance was judged to be not toxic after acute oral administration, taking also the results of the analogue substance into account.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008 (CLP). As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the twelth time in Regulation (EU) No 2019/521.