Phosphoric acid C12-alkyl and C18-alkyl esters, potassium salts

Endpoint summary

Description of key information

Based on a weight of evidence-approach using two read across-studies, the acute oral LD50 of the test substance was determined to be >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

Justification for type of information:

ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only one sex tested, limitations in study reporting

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

10 490 mg/kg bw

95% CL:

> 9 833 - <= 11 191

Interpretation of results:

not classified

Conclusions:

The median lethal dose of the test item (LD50) was 10490 mg per kg body weight. Based on the result of this study the test item is not subject for labelling and classification requirements according to regulatory requirements.

Executive summary:

Based on results of the study conducted equivalent to OECD Guideline No 401 in rats, the median lethal dose of the read across item (CAS 39322-78-6) was 10490 mg per kg body weight.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

ANALOGUE APPROACH JUSTIFICATION
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)

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 females was determined to be > 2000 mg/kg bw.

Executive summary:

The acute oral toxicity in rats was determined according to the method recommended in the OECD Guideline No. 420, "Acute Oral Toxicity - Fixed Dose Procedure", December 2001, and the commission directive 2004/73/EC "B.1 bis Acute Oral Toxicity: Fixed Dose Procedure", April 2004. The study was initiated with a sighting study, in which one female rat was given the read across-substance (CAS 68987 -29 -1) in a 2000 mg/kg bw dose. Slight signs of toxicosis (piloerection) were observed in this rat. Based on the results from the sighting study, the main study was carried out with four more female animals each given a dose of 2000 mg/kg bw. All animals in the main study survived the treatment, weight gain was normal and apart from piloerection no other clinical signs were observed. The gross necropsy of the animals revealed no pathological abnormalities. The oral LD50 females was determined to be > 2000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2007-01-17 to 2007-02-16

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)

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Name of test material: Silastol H 200
- CAS No.: 68987-29-1

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 0-97633 Sulzfeld
- Weight at study initiation: 164 g - 176 g.
- Fasting period before study: overnight prior to dosing
- Housing: Macrolone cages type 3 (2-3 per cage)
- Diet: Altromin 1314, Altromin GmbH, 0-32791 Lage, Lippe ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): air changes 10 times/ hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Sighting study: 1 female
main study: 4 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed 30 min., 2, 4 and 6 hours after the administration and thereafter daily. Body weight was recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes; all rats were killed by inhalation of CO2 on day 14 and subjected to a gross necropsy examination.
- Other examinations performed: clinical signs, body weight

Preliminary study:

The animal included in the sighting study survived the treatment and showed slight signs of toxicosis, piloerection was observed 30 minutes, 2, 4 and 6 hours after the application of the test item. The post mortem inspection revealed no pathological abnormalities.

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the female rats died.

Clinical signs:

They did not show marked signs of toxicosis. Piloerection was observed 30 minutes and 2 hours after the application of the test item, whereas normal behaviour was observed after 4 and 6 hours. From day 1 to the end of the observation period on day 14 no abnormalities were revealed.

Body weight:

The rats had a normal body weight gain during the study period.

Gross pathology:

The gross necropsy of the animals revealed no pathological abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 females was determined to be > 2000 mg/kg bw.

Executive summary:

The acute oral toxicity in rats was determined according to the method recommended in the OECD Guideline No. 420, "Acute Oral Toxicity - Fixed Dose Procedure", December 2001, and the commission directive 2004/73/EC "B.1 bis Acute Oral Toxicity: Fixed Dose Procedure", April 2004. The study was initiated with a sighting study, in which one female rat was given SILASTOL H 200 in a 2000 mg/kg bw dose. Slight signs of toxicosis (piloerection) were observed in this rat. Based on the results from the sighting study, the main study was carried out with four more female animals each given a dose of 2000 mg/kg bw. All animals in the main study survived the treatment, weight gain was normal and apart from piloerection no other clinical signs were observed. The gross necropsy of the animals revealed no pathological abnormalities. The oral LD50 (females) was determined to be > 2000 mg/kg bw.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Sept 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent to OECD401; performed before GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only one sex tested, limitations in study reporting

GLP compliance:

no

Remarks:

performed before GLP guidelines

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Hoe WISKf(SPF71)
- Source: Hoechst AG Kastengrund - SPF breed
- Weight at study initiation: 90-112 g (female); (mean = 100 g; n = 60)
- Age at study initiation: no data
- Fasting period before study: 16 hours before and 2 hours after application
- Diet: Altromin 1324 (Altromin GmbH, Lage/Lippe), ad libitum
- Water: Tap water ad libitum
- Acclimatization period: no data

ENVIRONMENTAL CONDITIONS
- Housing: in groups, in plastic cages, softwood pellets

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- concentration in vehicle: 25 % (w/v)

Doses:

6300 mg/kg
8000 mg/kg
9000 mg/kg
10000 mg/kg
12500 mg/kg
15000 mg/kg

No. of animals per sex per dose:

10 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations after application / Weighing once weekly
- Necropsy of survivors performed: yes

Statistics:

Probit analysis (method by Linder and Weber);
Confidence limits according to Cavalli-Sforza

Preliminary study:

Preliminary experiments did not show differences related to gender. Therefore only females used for main study.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

10 490 mg/kg bw

95% CL:

> 9 833 - <= 11 191

Mortality:

Sex: female, Dose: 6300 mg/kg bw, Mortality rate: 0 / 10
Sex: female, Dose: 8000 mg/kg bw, Mortality rate: 0 / 10
Sex: female, Dose: 9000 mg/kg bw, Mortality rate: 0 / 10
Sex: female, Dose: 10000 mg/kg bw, Mortality rate: 5 / 10
Sex: female, Dose: 12500 mg/kg bw, Mortality rate: 9 / 10
Sex: female, Dose: 15000 mg/kg bw, Mortality rate: 10 / 10

Clinical signs:

Mortally poisened animals died within 1-2 days after application.
Following symptoms were observed: disturbance of equilibrium, spasm.
The test substance was vomitted.

Body weight:

- normal body weight gain in all surviving animals.

Gross pathology:

Dissection of rats killed at the end of the observation period revealed no macroscopic findings.
Necropsy of the deceased animals revealed following macroscopic findings: Stomach and oesophagus were filled with white foam.

Interpretation of results:

not classified

Conclusions:

The median lethal dose of the test item (LD50) was 10490 mg per kg body weight. Based on the result of this study the test item is not subject for labelling and classification requirements according to regulatory requirements.

Executive summary:

Based on results of the study conducted equivalent to OECD Guideline No 401 in rats, the median lethal dose of the test item was 10490 mg per kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and Guideline conform studies

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

Oral:

No data on the substance itself is available. The test substance is a mixture of C12 and C18 chain phosphoric acid esters. Therefore, read-across approach to the C12 and C18 phosphoric acid esters separately was applied.

Two read across studies are available assessing the acute oral toxicity of CAS 39322-78-6 and CAS 68987-29-1, respectively. These studies were used in a weight of evidence-approach.

Based on results of a study conducted equivalent to OECD Guideline No 401 in rats, the median lethal dose of the read across item (CAS 39322-78-6) was 10490 mg per kg body weight in rats.

Furthermore, the acute oral toxicity of the second read across substance (CAS 68987-29-1) in rats was determined according to the method recommended in the OECD Guideline No. 420, "Acute Oral Toxicity - Fixed Dose Procedure", December 2001, and the commission directive 2004/73/EC "B.1, Acute Oral Toxicity: Fixed Dose Procedure", April 2004. The study was initiated with a sighting study, in which one female rat was given the read across-substance in a 2000 mg/kg bw dose. Slight signs of toxicosis (piloerection) were observed in this rat. Based on the results from the sighting study, the main study was carried out with four more female animals each given a dose of 2000 mg/kg bw. All animals in the main study survived the treatment, weight gain was normal and apart from piloerection no other clinical signs were observed. The gross necropsy of the animals revealed no pathological abnormalities. The oral LD50 females was determined to be > 2000 mg/kg bw.

Therefore, as an overall conclusion, the acute oral toxicity of the test substance was considered to be >2000 mg/kg bw.

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. Based on this data, the substance is considered not to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.