Phosphoric acid, hexadecyl phosphate esters, potassium salts with cetostearyl alcohol

Endpoint summary

Description of key information

Based on the available weight of evidence from studies for substances representing the main constituents, the test substance, 'mono- and di- C16 PSE, K+ and C16-18-OH' can be considered to have a low acute oral toxicity potential with LD50 value >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:

From June 02, 1987 to June 17, 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to section 13 of IUCLID for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Ibm: RORO (SPF), also known as Fü-albino SPF rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals
- Age at study initiation: about 6 weeks
- Weight at study initiation: female 114-117 g; male 116-124 g
- Fasting period before study: 18 h
- Housing:
- Diet: NAFAG standard rat maintenance diet, No. 850 (cubic), ad libitum
- Water: tap water, ad libitum
- Acclimatisation period: seven days under laboratory conditions

Environmental conditions
- Temperature: 20-24°C
- Humidity: 45-65 %
- Air changes: air-conditioned room
- Photoperiod: 12/12 h dark / light

Route of administration:

oral: gavage

Vehicle:

other: Standard Suspending Vehicle (SSV), please see below in " Details on oral exposure"

Details on oral exposure:

Vehicle
The test article was suspended in Standard Suspending Vehicle (SSV)
1000 mL SSV contain:
5 g sodium carboxy methyl cellulose of median viscosity,
4 mL Tween 80,
5 mL benzylalcohol pro analysis,
9 g sodium-chloride pro analysis,
aqua destillata ad 1000 mL.

- Amount of vehicle: 10 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 d
- Frequency of observations and weighing: daily for clinical signs and weighing on Day 1, 4, 8, 11, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (respiratory distress, crust around nose, hunched posture, crust around eyes, exitability), body weight, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: i.e., equivalent to >4000 mg a.i./kg bw

Mortality:

No compound-related deaths occurred.
One male was found dead early in the morning of Day 8. This case of death was considered to be a result of an application injury. This male rat showed a marked respiratory distress and a marked loss of weight. The histopathological examination of the lung of this animal revealed aspiration pneumonia.

Clinical signs:

other: The main symptom was respiratory distress seen in 3 males and 1 female. This symptom developed in consequence of aspiration of a little test suspension. The other findings were of no toxicological significance.

Gross pathology:

In the urinary bladder of male rat 2694, gritty contents were observed. This finding was of a spontaneous nature. No other macroscopic organ changes were seen.

Other findings:

Histopathology: Bronchopneumonia caused the respiratory distress and itself was caused by aspiration of test suspension (by the male rat that died at Day 8).

Interpretation of results:

other: not classified based on EU CLP Criteria

Conclusions:

Based on the results of the read across study, LD50 for the test substance, is considered to be >4000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, 'mono- and di- C16 PSE, K+ (purity: ca. 85%)', according to the OECD Guideline 401, standard acute method, in compliance with GLP. Five male and 5 female Fü-albino SPF rats were randomly selected for an acute oral toxicity study. Fasted rats were given a single dose of the test substance suspended in SSV (Standard Suspended Vehicle) by gavage at a dose level of 5000 mg/kg bw. They were observed for 15 d for toxic signs, mortality and body weight changes. All rats were examined for gross lesions. No compound-related deaths occurred. No compound-related incompatibility reactions were observed. No compound-related effect on body weight development appeared. No compound-related gross or microscopic lesions were observed. The LD50 was determined at >5000 mg/kg bw (i.e., equivalent to >4000 mg a.i./kg bw) (Bremer, 1987). Based on the results of the read across study, a similar oral LD50 value can be considered for the test substance, 'mono- and di- C16 PSE, K+ and C16-18-OH'.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

From August 30, 1985 to September 13, 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Refer to section 13 of IUCLID for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: notification No. 118 of the Pharmaceuticals Affairs Bureau, 15 Feb 1984, Toxicity Test Guideline

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: CFY (Sprague-Dawley origin)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals
- Source: Interfauna UK Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 4 to 6 weeks
- Weight at study initiation: 109 to 150 g
- Fasting period before study: yes; overnight prior to and 4 h after dosing
- Housing: in groups by sex in metal cages with wire mesh floor
- Diet (e.g. ad libitum): standard laboratory rodent diet (Labsure LAD 1), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 8 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 62% mean
- Air changes (per hr): ca. 15/h
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

Vehicle
- Concentration in vehicle: 80%
- Amount of vehicle (if gavage): 20 mL/kg bw

Doses:

0, 16.0 g/kg bw

No. of animals per sex per dose:

preliminary study: 2
main study: 10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: preliminary study 5 d; main study 14 d
- Frequency of observations and weighing: (a) bodyweights: Day 1 (day of dosing), 4, 8, 15 (b) clinical signs: soon after dosing, then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least once in the morning and once at the end of the experimental day (on Saturdays and Sundays app. 11:30 a.m.)
- Necropsy of survivors performed: yes

Statistics:

none

Preliminary study:

0/4 animals died in the preliminary test.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Based on:

test mat.

Mortality:

0/20 animals died in the main study

Clinical signs:

other: - Piloerection in 20/20 animals in treated group; recovery on Day 3 - No clinical signs in control group

Gross pathology:

- Terminal autopsy findings were normal

Other findings:

None

Interpretation of results:

other: Not classified based on EU CLP criteria

Remarks:

'mono- and di- C16 PSE, K+ and C16 -OH and isostearyl isostearate'.

Conclusions:

Under the study conditions, the oral LD50 in rats for test substance was determined to be >16000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute toxicity of the read across substance, di- C16 PSE (purity: 100%), according to the notification no. 118 of the Pharmaceuticals Affairs Bureau, 15 Feb 1984, Toxicity Test Guideline (similar to OECD guideline 401). Groups of fasted, 4 to 6 weeks old CFY (Sprague-Dawley origin) rats, 10/sex were given a single oral dose of test substance in distilled water at doses of 0 (control) and 16 g/kg bw and observed for 14 d. No mortality occurred. Piloerection was observed in all animals in the treated group, however, the animals had recovered on Day 3. No effects on body weight were observed. Terminal necropsy findings were found to be normal. Under the study conditions, the oral LD50 in rats for test substance was determined to be >16000 mg/kg bw (Kynoch, 1985). Based on the results of the read across study, a similar oral LD50 value can be considered for the test substance, 'mono- and di- C16 PSE, K+ and C16 -18-OH'.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

other: In house protocol

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test organism: Rat (Sprague-Dawley)
- Source: Not reported
- Weight at study initiation: 200-245 g

Route of administration:

oral: gavage

Vehicle:

other: 0.5% gum tragacanth

Details on oral exposure:

Administration: Gavage
- Doses per time period: single
- Volume administered or concentration: 20% aqueous suspension in in 0.5% gum tragacanth.
- Post dose observation period: 14 d

Examination: Mortality was recorded.

Doses:

2, 4, 5 and 10 g/kg (based on range finding test)

No. of animals per sex per dose:

5 animals per dose (No clear details about how the sexes were distributed among the dose levels as the report states both were used)

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: Not reported

Gross pathology:

Not carried out

Interpretation of results:

other: not classified based on EU CLP criteria

Conclusions:

Under the study conditions, the oral LD50 in rats for test substance was determined to be >10000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute toxicity of the test substance, Alcohols, C16-18 (>=90%), according to a method similar to OECD Guideline 401. Doses of test substance were selected based on the range finding study. Groups of fasted, Sprague-Dawley rats (200 - 245 g), 5/dose were given 20% aqueous suspension of test substance in 0.5% gum tragacanth, corresponding to doses of 2, 4, 5 and 10 g/kg bw and observed for 14 d. It was not clear how the sexes were distributed among the dose levels as the report stated both were used. No mortality occurred in any test substance dose group. There were no potential target organ toxicities identified. Under the study conditions, the oral LD50 in rats for test substance was determined to be >10000 mg/kg bw (OECD SIDS, 2006).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good quality 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

In absence of acute oral toxicity study with the test substance, the endpoint has been assessed based on studies for substances representative of the main constituents, which can be categorised as phosphate esters (PSE; i.e., mono- and di- C16 PSE, K+) and alcohol (i.e., alcohols, C16-18). The results are presented below:

Constituent PSE - read across studies:

Study 1: A study was conducted to determine the acute oral toxicity of the read across substance, mono- and di- C16 PSE, K+ (purity: ca. 85%), according to the OECD Guideline 401, standard acute method, in compliance with GLP. Five male and 5 female Fü-albino SPF rats were randomly selected for an acute oral toxicity study. Fasted rats were given a single dose of the test substance suspended in SSV (Standard Suspended Vehicle) by gavage at a dose level of 5000 mg/kg bw. They were observed for 15 d for toxic signs, mortality and body weight changes. All rats were examined for gross lesions. No compound-related deaths occurred. No compound-related incompatibility reactions were observed. No compound-related effect on body weight development appeared. No compound-related gross or microscopic lesions were observed. The LD50 was determined at >5000 mg/kg bw (i.e., equivalent to 4250 mg a.i./kg bw) (Bremer, 1987).

Study 2: A study was conducted to determine the acute toxicity of the read across substance, di- C16 PSE (purity: 100%), according to the notification no. 118 of the Pharmaceuticals Affairs Bureau, 15 Feb 1984, Toxicity Test Guideline (similar to OECD guideline 401). Groups of fasted, 4 to 6 weeks old CFY (Sprague-Dawley origin) rats, 10/sex were given a single oral dose of test substance in distilled water at doses of 0 (control) and 16 g/kg bw and observed for 14 d. No mortality occurred. Piloerection was observed in all animals in the treated group, however, the animals had recovered on Day 3. No effects on body weight were observed. Terminal necropsy findings were found to be normal. Under the study conditions, the oral LD50 in rats for test substance was determined to be >16000 mg/kg bw (Kynoch, 1985).

Constituent alcohol:

Study 1: A study was conducted to determine the acute toxicity of the test substance, Alcohols, C16-18 (>=90%), according to a method similar to OECD Guideline 401. Doses of test substance were selected based on the range finding study. Groups of fasted, Sprague-Dawley rats (200 - 245 g), 5/dose were given 20% aqueous suspension of test substance in 0.5% gum tragacanth, corresponding to doses of 2, 4, 5 and 10 g/kg bw and observed for 14 d. It was not clear how the sexes were distributed among the dose levels as the report stated both were used. No mortality occurred in any test substance dose group. There were no potential target organ toxicities identified. Under the study conditions, the oral LD50 in rats for test substance was determined to be >10000 mg/kg bw (OECD SIDS, 2006).

Study 2: A study was conducted to determine the acute oral toxicity of hexadecan-1-ol (purity: >95%), according to OECD Guideline 401, in compliance with GLP. Five male and five female fasted Sprague-Dawley CD rats were exposed to the 2000 mg/kg bw (based on range finding test) of test substance in arachis oil by oral gavage. The rats were observed for clinical signs of toxicity and mortality 30 minutes, 1, 2 and 4 h after dosing and thereafter daily throughout the observation period. Body weights were recorded prior to dosing on Day 0 and then at 7 and 14 d. All animals were subject to gross pathological examination at the end of the observation period. No compound-related deaths occurred. No compound-related target organ toxicity were observed. No clinical signs of systemic toxicity were observed. All animals showed the expected body weight gain over the observation period. No compound-related gross or microscopic lesions were observed. Under the study conditions, the LD50 for the test substance was determined to be >2000 mg/kg bw (i.e., >1900 mg a.i./kg bw) (OECD SIDS, 2006).

Overall, based on available weight of evidence from studies for substances representative of the main constituents, the test substance, 'mono- and di- C16 PSE, K+ and C16-18-OH', can be considered to have a low acute oral toxicity potential with LD50 value exceeding 2000 mg/kg bw.

Justification for classification or non-classification

Overall based on the available weight of evidence, the test substance, 'mono- and di- C16 PSE, K+ and C16-18-OH', does not warrant classification for acute oral toxicity, according to the EU CLP criteria (Regulation 1272/2008/EC).