Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 May 2018 - 21 Jun 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was conducted in accordance with international guidelines and in accordance with GLP. All guideline validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Commission Regulation (EC) No. 440/2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, No. 2-1-1 "Acute oral toxicity studies", 12 Nousan No. 8147
Version / remarks:
24 Nov 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

1
Reference substance name:
Reaction products of triphenyl phosphite, oleyl alcohol and alcohols, C10-16
EC Number:
947-909-7
Molecular formula:
Not applicable - UVCB substance
IUPAC Name:
Reaction products of triphenyl phosphite, oleyl alcohol and alcohols, C10-16
Test material form:
liquid
Details on test material:
Although the test item used within this test contains different identifiers as compared to the subtance that is being registered, the tested substance is within the boundary composition of the substance being registered. Therefore, this particular batch of the tested substance, can be considered as the same substance as (Z,Z)-di-9-octadecenyl phosphonate. It can be considered that all tests conducted on Reaction products of triphenyl phosphite, oleyl alcohol and alcohols, C10-16, Batch 2955, are considered relevant and reliable for (Z,Z)-di-9-octadecenyl phosphonate.
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark
- Stability under test conditions: Not reported
- Solubility and stability of the test substance in the solvent/vehicle: Not reported
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not reported

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item formulated in arachis oil BP within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.
- Preliminary purification step (if any): N/A
- Final dilution of a dissolved solid, stock liquid or gel: Not reported
- Final preparation of a solid: N/A

FORM AS APPLIED IN THE TEST (if different from that of starting material): Light yellow liquid

OTHER SPECIFICS: Homogeneity of formulation confirmed by visual inspection.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: body weight variation did not exceed ±20% of the mean body weight at the start of treatment
- Fasting period before study: yes overnight and for approximately 3 - 4 hours post dosing
- Housing: housed in groups of up to 4 individuals in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK)
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12

IN-LIFE DATES: Not clarified in the study report

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
Arachis oil BP used for 300 mg/kg bw dose only
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg total
- Justification for choice of vehicle: Arachic oil was used because the test item did not dissolve/suspend in distilled water
- Lot/batch no. (if required): n/d
- Purity: n/d

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw (300 mg/kg bw) and 2.24 mL/kg bw (2000 mg/kg bw)

DOSAGE PREPARATION (if unusual): applied unchanged

CLASS METHOD (if applicable) - a fixed dose procedure was used
- Rationale for the selection of the starting dose: In the absence of data regarding toxicity of the test item, 300 mg/kg bw was chosen as the start dose for one female. In the absence of effects at this dose level a further female was tested at 2000 mg/kg bw. As not effects were found here a further 4 females were tested at the maximum guideline required concentration of 2000 mg/kg bw. This is in accordance with the OECD 420 (2001).
Doses:
300, 2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Each animal was given single dose of 10 mL/kg dose volume of 2000 mg/kg of the test item of 30 mg/mL concentration.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing then daily thereafter until day 14 post-dose.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight
Statistics:
not required

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No deaths reported
Clinical signs:
There were no signs of systemic toxicity noted during the course of the study with excepttion of hunched posture was noted within four hours post dosing in animals treated at a dose level of 300 mg/kg and four animal treated at 2000 mg/kg.
Body weight:
All animals showed expected weight gain. The animal dosed at 300 mg/kg bw gained 16 g in the first week and 11 g in the second week (27 g total). The animals dosed at 200 mg/kg bw gained 16 g in the first week and 11 g in the second week (27 g total).
Gross pathology:
No abnormality noted at necropsy

Any other information on results incl. tables

Table 1:   Number of animals dead (and with evident toxicity)

Dose

(mg/kg bw)

Mortality

(# dead / total)

Time range of deaths

(hours)

Number with evident toxicity

(# / total)

Male

Female

Combined

Male

Female

Combined

300

-

0 / 5

0 / 5

n/a

 

0 / 5

0 / 5

2000

-

0 / 5

0 / 5

n/a

-

0 / 5

0 / 5

Table 2:   Number of animals hunched at observations time x

Dose

(mg/kg bw)

Hunched

(# hunched / total)

Time (h)

Male

Female

Combined

300

0.5

-

0 / 1

0 / 1

1

 

1 / 1

1 / 1

2

 

1 / 1

1 / 1

3

 

1 / 1

1 / 1

4

 

1 / 1

1 / 1

1-14 (days)

 

0 / 1

0 / 1

2000

0.5

 

4 / 5

4 /5

1

 

4 / 5

4 /5

2

 

4 / 5

4 /5

3

 

4 / 5

4 /5

4

 

4 / 5

4 /5

1-14

-

0 / 5

0 / 5

Table 3:   Body weight gain (g)

Body weight gain (g)

Animal #

Week 1

Week 2

Female 1-0

16

11

Female 2-0

19

16

Female 3-0

23

16

Female 3-1

23

27

Female 3-2

27

9

Female 3-3

27

14

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).
Executive summary:

OECD 420 (2018) - In an acute oral toxicity study, a group of fasted, 8-12 week old female Wistar rats were given a single oral dose of test item at a single dose rate of 2000 mg/kg bw (limit test) and observed for 14 days. A sighting study in line with the guideline with 1 animal dosed at 300 mg/kg bw was also conducted.

In the absence of mortality during the observation period, the oral LD50 was estimated to be greater than 2000 mg/kg bw.

In addition, there were no treatment related clinical signs, necropsy findings or changes in body weight observed in any of the individuals.