Phosphoric acid, bis(1,1-dimethylethyl) ester, potassium salt (1:1)

Endpoint summary

Description of key information

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 423, the test item was administered to two groups of 3 female Wister rats at a single dose level of 2000 mg/kg bw. No mortalities or clinical signs were noted. In conclusion, the LD50 of the test item is determined to be> 2000 mg/kg body weight by oral route in the rat.

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:

from 2012-07-23 to 2012-12-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in compliance with international standard guidelines under GLP conditions. The study report was well documented with all mandatory information included.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: 12 NohSan N° 8147, JMAFF 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

2012-09-07

Test type:

acute toxic class method

Limit test:

no

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
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group (from 159 g to 173 g)
- Fasting period before study: Yes
- Housing: in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK
- Water (e.g. ad libitum): free access to mains drinking
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 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

IN-LIFE DATES: From: 20 September 2012 To: 18 October 2012

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
For the 2000 mg/kg dose level:
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on results of available data

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
+ Observations: The first day: 0.5h, 1h, 2h, 4h and then once daily
+ Weighing: day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Statistics:

No statistics were performed

Preliminary study:

not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No data

Table 1 Individual Bodyweights and Weekly Bodyweight Changes

 

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Female	163	179	187	16	8
	1-1 Female	161	176	193	15	17
	1-2 Female	173	190	205	17	15
	2-0 Female	167	189	220	22	31
	2-1 Female	159	191	202	32	11
	2-2 Female	169	193	216	24	23

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 bodyweight.

Executive summary:

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 423, the test item was administered to two groups of 3 female Wister rats at a single dose level of 2000 mg/kg bw. No mortalities or clinical signs were noted.

In conclusion, the LD50 of the test item is determined to be> 2000 mg/kg body weight by oral route in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Only one study available with a good reliability (K1) performed in 2012 following GLP.

Additional information

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 423, the test item was administered to two groups of 3 female Wister rats at a single dose level of 2000 mg/kg bw. No mortalities or clinical signs were noted. In conclusion, the LD50 of the test item is determined to be> 2000 mg/kg body weight by oral route in the rat.

Justification for selection of acute toxicity – oral endpoint
Only one study available