Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1998-07-07 - 1998-12-29
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented guideline study in compliance with GLP (conducted with a read-across substance)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: viscous liquid
Details on test material:
- Molecular formula (if other than submission substance): C28H62NO4P (for a representative structure: Phosphoric acid, di(C8)ester, compds with C12 amine)
- Molecular weight (if other than submission substance): 507.76
- Smiles notation (if other than submission substance): CCCCCCCCCCCCN.O=P(O)(OCCCCCCCC)OCCCCCCCC
- InChl (if other than submission substance): InChI=1/C12H27N/c1-2-3-4-5-6-7-8-9-10-11-12-13/h2-13H2,1H3
- Physical state: liquid
- Storage condition of test material: room temperature in the dark
- Other: Data relating to the identity, purity and stability of the test material are the responsibility of the Sponsor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 204 to 222g (males); 204 to 215g (females)
- Housing: housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet/Water (e.g. ad libitum): free access to mains drinking water and food (except overnight fast before dosing and 3-4 h after dosing); Rat and
Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23
- Humidity (%): 50 to 62
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg (Range-finding Study); 2000 mg/kg (Main Study)
No. of animals per sex per dose:
1 male/ 1 female (Range-finding Study)
5 males / 5 females (Main Study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days (Range-finding Study); 14 days (Main Study)
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 5 (Range-finding Study) or 14 days (Main Study).
- Necropsy of survivors performed: yes (Main Study)
-Others: Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes (Range-finding Study). Individual bodyweights were recorded prior to dosing on day 0 and on days 7 and 14.
Statistics:
not applied

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Hunched posture was noted in all animals during the day of dosing and persisted in all females and one male one day after dosing.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Other observations were not performed.

Any other information on results incl. tables

Experimental Preparation

For the purpose of the study the test material was freshly prepared, as required, as a solution at the appropriate concentration in arachis oil BP. Preparation

was aided by the use of a vortex mixer and by heating the formulation in a warming bath at approximately 80 °C. The formulation was allowed to cool

prior to dosing. Determination by analysis of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not specified

in the Study Plan and is not a requirement of the Test Guideline.

Procedure

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was

calculated according to its fasted bodyweight at the time of dosing.

Table 1. Individual Clinical Observations and Mortality Data in the Range-finding Study

Dose Level mg/kg Animal Number and Sex Effects Noted After Dosing (Hours) Effects Noted During Period After Dosing (Days)
 1/2 1 2 4 1 2 3 4 5
2000 1-0 Male 0 0 0 0 0 0 0 0 0
2-0 Female 0 0 0 0 0 0 0 0 0

0 = no signs of systemic toxicity

Table 2. Individual Clinical Observations and Mortality Data in the Main Study

Dose Level mg/kg Animal Number and Sex Effects Noted After Dosing (Hours) Effects Noted During Period After Dosing (Days)
1/2 1 2 4 1 2 3 4 5 6 7 8 9 I 10 11 12 13 14
2000 3-0 Male H H H H 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3-1 Male H H H H H 0 0 0 0 0 0 0 o o 0 0 0 i0
3-2 Male 0 0 H H 0 0 0 0 0 0 0 0 0 o 0 0 0 0
3-3 Male 0 0 H H 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3-4 Male H H H H 0 0 0 0 0 0 0 0 0 0 0 0 0 0
4-0 Female H H H H H 0 0 0 0 0 0 0 0 0 0 0 0 o
4-1 Female 0 0 0 H H 0 0 0 0 0 0 0 0 0 0 0 0 0
4-2 Female H H H H H 0 0 0 0 0 0 0 0 0 0 0 0 0
4-3 Female H H H H H 0 0 0 0 0 0 0 0 0 0 0 0 0
4-4 Female H H H H H 0 0 0 0 0 0 0 0 0 0 0 0 0

H = hunched posture; 0 = no signs of systemic toxicity

Table 3. Individual Bodyweights and weekly Bodyweight Changes in the Main Study

Dose Level mg/kg Animal Number and Sex Bodyweight (g) at Day Bodyweight Gain (g) During Week
0 7 14 1 2
2000 3-0 Male 216 267 314 51 47
3-1 Male 204 240 274 36 34
3-2 Male 222 263 305 41 42
3-3 Male 221 282 330 61 48
3-4 Male 210 250 297 40 47
4-0 Female 215 238 260 23 22
4-1 Female 210 233 251 23 18
4-2 Female 206 230 252 24 22
4-3 Female 204 223 231 19 8
4-4 Female 215 228 231 13 3

Table 4. Individual Necropsy Findings in the Main Study

Dose Level mg/kg Animal Number and Sex Time of Death Macroscopic Observations
2000 3-0 Male Killed Day 14 No abnormalities detected
3-1 Male Killed Day 14 No abnormalities detected
3-2 Male Killed Day 14 No abnormalities detected
3-3 Male Killed Day 14 No abnormalities detected
3-4 Male Killed Day 14 No abnormalities detected
4-0 Female Killed Day 14 No abnormalities detected
4-1 Female Killed Day 14 No abnormalities detected
4-2 Female Killed Day 14 No abnormalities detected
4-3 Female Killed Day 14 No abnormalities detected
4-4 Female Killed Day 14 No abnormalities detected

Evaluation of Data

Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities

including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. According to Regulation (EC) No 1272/2008, the test substance is not classified as acutely toxic by oral route of exposure.
Executive summary:

A OECD Guideline 401 study was performed to assess the acute oral toxicity of phosphoric acid, mono- and di-(C8 -C10) ester, compds. with C12 -14 amine in the Sprague-Dawley CD strain rat in compliance with GLP. Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material as a solution in arachis oil BP at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

There were no deaths. Hunched posture was noted in all animals up to one day after dosing. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.