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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 September 2017 - 09 October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
Most recent version
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Benzyltriphenylphosphonium, salt with 4,4'- [2,2,2- trifluoro-1- (trifluoromethyl)ethylidene]bis[phenol] (1:1)
Cas Number:
75768-65-9
IUPAC Name:
Benzyltriphenylphosphonium, salt with 4,4'- [2,2,2- trifluoro-1- (trifluoromethyl)ethylidene]bis[phenol] (1:1)
Test material form:
solid
Details on test material:
Purity: 98 %
Specific details on test material used for the study:
Purity: > 98%

Test animals

Species:
rat
Strain:
other: Crl:CD (SD)
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Age at study initiation: Young adult animals (approx. 6-8 weeks old)
- Weight at study initiation: 140 g - 181 g
- Fasting period before study: Overnight
- Housing: Individually in wire mesh cages
- Diet: Free access to PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002 (meal)
- Water: Free access to municipal water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2 – 22.5
- Humidity (%): 39.3 - 54.4
- Air changes (per hr): a minimum of 10
- Photoperiod (hrs dark / hrs light): 12/12



IN-LIFE DATES: From: 12 September 2017 to 09 October 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
0.5% in deionized water
Details on oral exposure:
FREQUENCY: single dosage, on Day 0.

VEHICLE: 0.5% methylcellulose (400 cps) in deionized water.


MAXIMUM DOSE VOLUME APPLIED:
10 mL/kg body weight.


DOSAGE PREPARATION:

The test substance formulations were prepared on each day of dosing as single formulations for each dose level. The test substance formulations were stirred continuously throughout the preparation and dose administration procedures.

Doses:
175 mg/kg body weight
550 mg/kg body weight
2000 mg/kg body weight
No. of animals per sex per dose:
175 mg/kg body weight (1 female rat)
550 mg/kg body weight (1 female rat)
2000 mg/kg body weight (1 and 2 female rats dosed in a stepwise manner)
Control animals:
no
Details on study design:
STUDY DESIGN:
The test substance was administered once orally via gavage to 1 fasted female albino rat at a dose level of 175 mg/kg body weight, as no mortality was observed. Another female rat was dosed at 550 mg/kg body weight, as no mortality was observed. A third female rat was dosed at 2000 mg/kg body weight, as no mortality was observed. 2 additional female rats were dosed at 2000 mg/kg body weight.


- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: At study day 0, 7, and 14
Clinical signs: The rats were observed at the time of dosing, approximately 15 ± 5 minutes and 1, 2, and 4 hours post dosing on study day 0, and once daily thereafter for 14 days.
- Necropsy of survivors performed: All rats were euthanized by carbon dioxide inhalation. The major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.
- Other examinations performed: none.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Clinical signs observed in all animals were mucoid or soft feces and/or brown material around the anogenital area at approximately 4 hours following dose administration. One animal in dose group 2000 mg/kg bodyweight showed brown material around the anogenital area on study days 1 and 2. On female in the 175 mg/kg group was noted with dilated pupils at approximately 1 hour following dose administration; this single occurrence was not considered test substance-related.
Body weight:
There were no remarkable body weight changes noted during the study.
Gross pathology:
There were no macroscopic findings at the necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study with rats performed according to OECD test guideline 425 and GLP principles, an LD50 > 2000 mg/kg body weight was determined. According to GHS criteria the substance does not need be classified.
Executive summary:

An acute oral toxicity study was performed in female rats according to OECD test guideline 425 and GLP principles. The doses applied were 175 mg/kg body weight (1 female), subsequently 550 mg/kg body weight (1 female), then 2000 mg/kg body weight, (1 female and 2 female in a stepwise manner). No mortality occurred in all doses. Clincal observations were mucoid or soft feces and/or brown material around the anogenital area at approximately 4 hours following dose administration in all animals. One animal in the highest dose group showed brown material around the anogenital area on study days 1 and 2. There were no remarkable body weight changes noted during the study and there were no macroscopic findings at necropsy. Based on the results of this study, the estimated LD50 of BTPP:BPA salt was > 2000 mg/kg body weight and therefore BTPP:BPA salt does not have to be classified according to GHS criteria.