[No public or meaningful name is available]

Endpoint summary

Description of key information

Overall, based on available weight of evidence from studies for substances representative of the main constituents, the test substance can be considered to have a low acute oral toxicity potential with LD50 value exceeding 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.

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 constituents, 'mono- and di- cetyl phosphate esters and their potassium salts', 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, 'potassium hexadecyl hydrogen phosphate' (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 constituents, 'mono- and di- cetyl phosphate esters and their potassium salts'.

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.

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 the constituents, 'mono- and di- cetyl phosphate esters and their potassium salts' was determined to be >16000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute toxicity of the read across substance, 'dihexadecyl hydrogen phosphate (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 constituents, 'mono- and di- cetyl phosphate esters and their potassium salts'.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

1976

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.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

the analytical purity of the test substance is not reported

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 176-296 g
- Fasting period before study: overnight
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50%
- Amount of vehicle (if gavage): 5 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

Doses:

5000 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: observations of mortality and signs of toxicity were made 1, 3, 4, 6 and 24 h after administration and daily thereafter; animals were weighed prior to dosing and prior to necropsy.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to >2500 mg/kg bw (based on 50% test substance use in test)

Mortality:

One male rat died on day 4 after administration. No information on the cause of death was provided.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

No substance-related findings were noted during the necropsy.

Interpretation of results:

other: Not classified

Conclusions:

Based on the results of the read across study, the oral LD50 value of the constituent, 'linear or branched esters' is considered to be >5000 mg/kg bw (i.e., equivalent to >2500 mg a.i./kg bw).

Executive summary:

A study was conducted to determine the acute toxicity of the read across substance, 'tetradecyl myristate (50% in corn oil)' according to the method equivalent to the OECD Guideline 401. Five Wistar rats per sex were treated with single oral dose of 5000 mg/kg bw read across substance and observed for 14 days post exposure. Observations of mortality and signs of toxicity were made 1, 3, 4, 6 and 24 h after administration and daily thereafter; animals were weighed prior to dosing and prior to necropsy. Necropsy of survivors was performed. One male rat died on day 4 after administration. No information on the cause of death was provided. No clinical signs of toxicity and effect on body weight were noted up to the end of the 14-day observation period. No substance-related findings were noted during the necropsy. Under the study conditions, the oral LD50 value of the read across substance was determined to be >5000 mg/kg bw (i.e., equivalent to >2500 mg a.i./kg bw) (CPT, 1976). Based on the results of the read across study, similar oral LD50 value is expected for the constituent, 'linear or branched esters'.

Reference 4

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 March 13, 1991 to March 19, 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Refer to section 13 of IUCLID for details on the read-across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

The LD50 of the test substance was determined by administering 5 female mice 5000 mg/kg bw orally. The animals were observed for mortality and signs of toxicity for 6 days post-treatment, and the body weight was determined at the start and end of the study period.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: NMRI EOPS

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals
- Weight at study initiation: 18 - 20 g

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 6 d
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight and mortality

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality during the study period.

Clinical signs:

other: No signs of toxicity were observed during the study period.

Interpretation of results:

other: not classified based on EU CLP criteria

Conclusions:

Based on the results of the read across study, the LD50 of the constituent 'linear or branched esters' is considered to be >5000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute toxicity of the read across substance, 'Isooctadecyl isooctadecanoate (purity not specified)', according to a method adapted from French Pharmacopoeia 9^thedition, dose fixed taking account of the OECD Guideline 401. The read across substance was administered to 5 female mice at 5000 mg/kg bw orally. The animals were observed for mortality and signs of toxicity for 6 d post-treatment, and the body weight was determined at the start and end of the study period. There was no mortality or no other signs of toxicity which were observed during the study period. No effect on body weight was noted. Under the study conditions, the LD50 of the read across substance in mice was determined to be >5000 mg/kg bw (Dufour, 1991). Based on the results of the read across study, similar oral LD50 value is expected for the constituent, 'linear or branched esters'.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

No data available

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

no guideline followed

Principles of method if other than guideline:

No information

GLP compliance:

not specified

Test type:

other: Not specified

Species:

mouse

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 3 200 mg/kg bw

Based on:

not specified

Interpretation of results:

other: Not classified

Conclusions:

Under the study conditions, the acute oral LD50 in mice was determined to be 3200 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, Hexadecanol in mice. Under the study conditions, the acute oral LD50 in mice was determined to be 3200 mg/kg bw (Opdyke, 1978).

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

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

In absence of acute toxicity studies with the test substance, the endpoint has been assessed based on studies for read across substances representative of the main constituents, which can be categorised as phosphate esters (PSE i.e., mono- and di C16 PSE, K+: 10 -40%), alkyl esters (i.e., C16-18 linear and branched fatty acid esters: 39 -87%) andalcohols (i.e., C16 -18 linear or branched alcohol: 10 -30%). 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, 'potassium hexadecyl hydrogen phosphate' (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). Based on the results of the read across study, similar absence of acute toxicity potential can be expected for the phosphate ester constituent of the test substance.

Study 2: A study was conducted to determine the acute toxicity of the read across substance, 'dihexadecyl hydrogen phosphate' (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, similar absence of acute toxicity potential can be expected for the phosphate ester constituent of the test substance.

Constituent: Alkyl ester (linear) - read across studies 

Study 1:A study was conducted to determine the acute toxicity of the read across substance, ‘tetradecyl myristate (50% in corn oil)’, according to the method equivalent to the OECD Guideline 401. Five Wistar rats per sex were treated with single oral dose of 5000 mg/kg bw and observed for 14 days post exposure. Observations of mortality and signs of toxicity were made 1, 3, 4, 6 and 24 h after administration and daily thereafter; animals were weighed prior to dosing and prior to necropsy. Necropsy of survivors was performed. One male rat died on day 4 after administration. No information on the cause of death was provided. No clinical signs of toxicity and effect on body weight were noted up to the end of the 14-day observation period. No substance-related findings were noted during the necropsy. Under the study conditions, the oral LD50 value of the read across substance was determined to be >5000 mg/kg bw (i.e., equivalent to >2500 mg a.i./kg bw) (CPT, 1976). Based on the results of the read across study, similar absence of acute toxicity potential can be expected for the alkyl ester constituent of the test substance. 

Constituent: Alkyl ester (branched) - read across studies 

Study 1:A study was conducted to determine the acute toxicity of the read across substance, ‘Isooctadecyl isooctadecanoate (purity not specified)’, according to a method adapted from French Pharmacopoeia 9thedition, dose fixed taking account of the OECD Guideline 401. The read across substance was administered to 5 female mice at 5000 mg/kg bw orally. The animals were observed for mortality and signs of toxicity for 6 d post-treatment, and the body weight was determined at the start and end of the study period. There was no mortality or no other signs of toxicity which were observed during the study period. No effect on body weight was noted. Under the study conditions, the LD50 of the read across substance in mice was determined to be >5000 mg/kg bw (Dufour, 1991). Based on the results of the read across study, similar absence of acute toxicity potential can be expected for the alkyl ester constituent of the test substance. 

Constituent: Alcohol - study on hexadecan-1 -ol:

A study was conducted to determine the acute oral toxicity of the test substance, hexadecanol in mice. Under the study conditions, the acute oral LD50 in mice was determined to be 3200 mg/kg bw (Opdyke, 1978).

Supporting studies on alcohol from OECD SIDS dossier:

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). Based on the results of the read across study, similar absence of acute toxicity potential can be expected for the alcohol constituent of the test substance.

Further, the presence of branched alcohols in the test substance are not expected to show difference in toxicity compared to the linear alcohols.

Overall, based on available weight of evidence from studies for substances representative of the main constituents, the test substance, ‘Reaction products of hexadecyl dihydrogen phosphate, dihexadecyl hydrogen phosphate, hexadecan-1-ol, stearic acid, esters of C18 (branched and linear) fatty acids with C18 (branched and linear) alcohols, and potassium hydroxide’ can be considered to have a low acute oral toxicity potential with LD50 value exceeding 2000 mg/kg bw.

Inhalation:

The substance appears as solid waxy pellets and has a low vapour pressure (0.0079 Pa) at room temperature. Due to its physical state and physical chemical properties, it is unlikely that this substance will form inhalable dust, mist or fumes during normal processing and use conditions. In case inhalable forms of the substance are created under particular conditions (e.g. spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.

Dermal:

As per Annex VIII (8.5.3), the acute dermal toxicity testing is not needed as the substance does not meet the criteria for classification for acute toxicity and STOT SE for the oral route (based on read across studies). This is also supported by the absence of any systemic effects in thein vivoskin sensitisation studies available with the substance representing the constituents (i.e., PSE, alcohol and alkylester). Moreover, given the physico-chemical properties of the test substance, the dermal LD50 value is less likely (due to lower absorption potential of dermal route) to be lower than oral LD50 or the oral doses showing clinical signs. Hence, testing via dermal route will less likely result in any additional hazard identification and testing is therefore considered unnecessary.

Justification for classification or non-classification

Overall based on the available weight of evidence, the test substance does not warrant a classification for acute oral or dermal toxicity, according to the EU CLP criteria (Regulation 1272/2008/EC).