Bis(O,O-diisopropyl dithiophosphate)bis(cyclohexylamine) zinc

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 - 28 Apr 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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:

08 Feb 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom, UK

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

O,O-bis(propan-2-yl) [({[bis(propan-2-yloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}bis(cyclohexylazaniumyl)zinciodiuide)sulfanyl]phosphonothioate

EC Number:

809-986-4

Cas Number:

52585-16-7

Molecular formula:

C24H54N2O4P2S4Zn

IUPAC Name:

O,O-bis(propan-2-yl) [({[bis(propan-2-yloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}bis(cyclohexylazaniumyl)zinciodiuide)sulfanyl]phosphonothioate

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 162 - 211 g
- Fasting period before study: animals were fasted overnight before dosing
- Housing: in groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 33.3 and 221.8 mL/kg bw
- Justification for choice of vehicle: DMSO was used because the test item did not dissolve/suspend in distilled water or arachis oil BP

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: The recommended starting dose of 300 mg/kg bw according to the current OECD TG was used

Doses:

300 and 2000 mg/kg bw (Due to the purity of the test material, the animals were dosed with 333 and 2218 mg/kg bw of the test material, respectively.)

No. of animals per sex per dose:

3 (2000 mg/kg bw/day) and 6 (300 mg/kg bw/day)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 30 min, 1, 2 and 4 h after dosing and subsequently once daily for up to 14 days. Body weights were determined prior to dosing and on Day 7 and 14 after treatment or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg bw: 0/6 animals died
2000 mg/kg bw: 1/3 animals killed for humane reasons on Day 1, 2/3 animals died on Day 1

Clinical signs:

other: 300 mg/kg bw: no clinical signs of toxicity were observed up to the end of the 14-day observation period in 6/6 animals 2000 mg/kg bw: hunched posture in 3/3 animals, piloerection, lethargy, diarrhea, hypothermia, tonic convulsions, chromodacryorrhea and

Gross pathology:

300 mg/kg bw: necropsy revealed no substance-related findings in 6/6 animals
2000 mg/kg bw: dark kidneys, gaseous stomach, pale brown colored liquid present in the stomach, hemorrhage and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach in 3/3 animals. Dark liver in 2/3 animals and patchy pallor of the liver in 1/3 animals

Any other information on results incl. tables

Table 1: Acute oral toxicity

Dose	Mortality	Clinical signs
[mg/kg bw]
	N*	N*
Females
300	0/3	0/3
300	0/3	0/3
2000	3/3	3/3

*N = Number of animal / number of animals used

Applicant's summary and conclusion

Interpretation of results:

other: Cat. 4, H302 according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Acute Oral 4, H302