3-bis(diisopropylamino)phosphanyloxypropanenitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 26 April 2019 to 11 July 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-({bis[bis(propan-2-yl)amino]phosphanyl}oxy)propanenitrile

EC Number:

600-337-9

Cas Number:

102691-36-1

Molecular formula:

C15H32N3OP

IUPAC Name:

3-({bis[bis(propan-2-yl)amino]phosphanyl}oxy)propanenitrile

Test material form:

liquid

Details on test material:

clear, colourless liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Young adult animals (approximately 11-12 weeks old) were selected.
Weight at the Initiation of Dosing: 180 to 204 g.

On arrival and following assignment to the study, animals were group housed (up to 3
animals of the same dosing group together) in polycarbonate cages (Makrolon MIV type;
height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS -
J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
The room in which the animals were kept was documented in the study records.
Animals were separated during designated procedures/activities. Each cage was clearly
labeled.
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were
maintained. The actual daily mean temperature during the study period was 21°C with an
actual daily mean relative humidity of 40 to 57%. A 12-hour light/12-hour dark cycle was
maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation)
were maintained in the animal rooms.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose of test item was administered to the appropriate animals by oral gavage on
Day 1, using a syringe with a plastic gavage cannula attached.
The dose volume for each animal was based on the body weight measurement prior to dosing.
Dose volume (mL/kg body weight) was calculated as follows:
Dose level (g/kg) / spec.gravity or density (g/mL).
The dosing formulations were stirred continuously during dose administration.
Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and
until 3-4 hours after administration of the test item. Water was available.

Doses:

The first group was treated at a dose level of 2000 mg/kg.
Based on the results, two additional groups were dosed at 300 mg/kg.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based
on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose
groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, two additional groups were dosed at 300 mg/kg.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, two animals were found dead and one animal was killed in extremis on Day 1.

Clinical signs:

other: At 2000 mg/kg, prior to death, no clinical signs were recorded. At 300 mg/kg, clonic spasms, tremor, hunched posture, uncoordinated movements, piloerection, hypersensitivity to touch and/or ptosis were noted between Days 1 and 5.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of the substance in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.

Executive summary:

The objective of this study was to assess the toxicity of the test item when administered in a single dose to female rats at one or more defined dosages. Furthermore, the results of the study allowed the test item to be ranked according to most classification systems, currently in use. This study should provide a rational basis for risk assessment in man.

Initially, the substance was administered by oral gavage to three female Wistar Han rats at 2000 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed at 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

At 2000 mg/kg, two animals were found dead and one animal was killed in extremis on Day 1. At 300 mg/kg, no mortality occurred. At 2000 mg/kg, prior to death, no clinical signs were recorded. At 300 mg/kg, clonic spasms, tremor, hunched posture, uncoordinated movements, piloerection, hypersensitivity to touch and/or ptosis were noted between Days 1 and 5.

The mean body weight gain shown by the surviving animals (300 mg/kg) over the study period was considered to be similar to that expected for normal untreated animals of the same

age and strain.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of the substance in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.