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Description of key information

One reliable study is available for the Reaction mass of AminoPhosphonium salt and Bisphenol AF (XA 31) for the acute oral toxicity.

In an acute oral study in rats, no animals died and no signs of overt toxicity were observed at the limit dose-level of 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:
experimental study
Adequacy of study:
key study
Study period:
2012-2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
On occasions the relative humidity was outside the target range of 30 to 70%. This was considered not to affect the purpose or integrity of the study.
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
yes
Remarks:
On occasions the relative humidity was outside the target range of 30 to 70%. This was considered not to affect the purpose or integrity of the study.
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: 3706OB
- Expiration date of the batch: 31 December 2018
- Purity test date: > 99%


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:room temperature in the dark


Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: eight to twelve weeks of age.
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:acclimatization period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

:
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE:
The test item was freshly prepared, as required, as a solution in dimethyl sulphoxide. Dimethyl sulphoxide was used because the test item did not dissolve/suspend in distilled water.
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 300 mg/kg was chosen as the starting dose.In the absence of toxicity at a dose level of 300 mg/kg, the dose level of 2000 mg/kg was tested.

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 the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
Dose level 300 mg/Kg : 1 female
Dose level 2000 mg/Kg : 1 female
Dose level 2000 mg/Kg : 4 females
A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing /Other examinations performed:
Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed: yes
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality. (See Table 1 in "any other information on results incl. tables")
Clinical signs:
No signs of systemic toxicity were noted during the observation period. (See Table 1 in "any other information on results incl. tables")
Body weight:
The animal showed expected gains in body weight over the observation period. (See Table 2 in "any other information on results incl. tables")
Gross pathology:
No abnormalities were noted at necropsy. (See Table 3 in "any other information on results incl. tables")

Dose Level - 300 mg/kg

 - Mortality: There was no mortality.

 - Clinical Observations: No signs of systemic toxicity were noted during the observation period.

 - Body Weight: The animal showed expected gains in body weight over the observation period.

 - Necropsy: No abnormalities were noted at necropsy.

Dose Level - 2000 mg/kg

Table 1 :   Individual Clinical Observations and Mortality Data - 2000 mg/kg

Dose level mg/k

Animal Number and Sex

Effects Noted After Dosing (Hours)

Effects Noted During Period After Dosing (Days)

 

 

 

0.5

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Table 2:     Individual Body Weights and Body Weight Changes - 2000 mg/kg

Dose Level mg/kg

Animal Numberand Sex

Body Weight (g) at Day

Body Weight gain (g) during week

 

 

0

7

14

1

2

2000

2-0 Female

203

227

230

24

3

 

3-0 Female

171

182

200

11

18

 

3-1 Female

169

190

196

21

6

 

3-2 Female

170

184

200

14

16

 

3-3 Female

186

203

216

17

13

Table 3:    Individual Necropsy Findings - 2000 mg/kg

Dose Level mg/kg

Animal Number and Sex

Time of Death

Macroscopic observations

2000

2-0 Female

Killed Day 14

No abnormalities detected

 

3-0 Female

Killed Day 14

No abnormalities detected

 

3-1 Female

Killed Day 14

No abnormalities detected

 

3-2 Female

Killed Day 14

No abnormalities detected

 

3-3 Female

Killed Day 14

No abnormalities detected

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.
According to the Globally Harmonized Classification System, the test does not meet the criteria for classification.
Executive summary:

The acute oral toxicity of the test item in the Wistar strain rat was assessed using the Fixed Dose Procedure according to the OECD Test Guideline 420.

The study was conducted in compliance with the principles of Good Laboratory Practice.

A sighting test at dose levels of 300 mg/kg and 2000 mg/kg was initially performed. Then a further group of four fasted females was given a single oral dose of test item, as a solution in dimethyl sulphoxide, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored over the 14-day observation period. All animals were subjected to gross necropsy.

In this study, no deaths occurred and no signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight and finally no abnormalities were noted at necropsy.

Therefore, 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. Thus, according to the Globally Harmonized Classification System, the test does not meet the criteria for classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The study is GLP-compliant and is scored 1 according to Klimisch reliability criteria.

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

Justification for classification or non-classification

The acute oral median lethal dose (LD50) was greater than 2000 mg/kg body weight. According to the Globally Harmonized Classification System, the test does not meet the criteria for classification.