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Administrative data

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-OH and isostearyl isostearate' 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
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:
read-across source
Qualifier:
according to
Guideline:
other: notification No. 118 of the Pharmaceuticals Affairs Bureau, 15 Feb 1984, Toxicity Test Guideline
Deviations:
no
Qualifier:
equivalent or similar to
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 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:
- Piloerection in 20/20 animals in treated group; recovery on Day 3
- No clinical signs in control group
Body weight:
- No difference between treated animals and 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 -OH and isostearyl isostearate'.

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+), alcohol (i.e., hexadecanol) and isoalkylester (i.e., isostearyl isostearate). 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:

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).

Constituent: Isoalkylester:

A study was conducted to determine the acute toxicity of isooctadecyl isooctadecanoate (purity not specified), according to a method adapted from French Pharmacopoeia 9thedition, dose fixed taking account of the OECD Guideline 401. The test 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 were 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 test substance in mice was determined to be >5000 mg/kg bw (Dufour, 1991).

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-OH and isostearyl isostearate', 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-OH and isostearyl isostearate', does not warrant a classification for acute oral or dermal toxicity, according to the EU CLP criteria (Regulation 1272/2008/EC).