5,5'-diisopropyl-2,2'-dimethylbiphenyl-4,4'-diyl dihypoiodite

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 March 2018 to 27 March 2018

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147

Version / remarks:

Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000, including the most recent revisions.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5,5'-diisopropyl-2,2'-dimethylbiphenyl-4,4'-diyl dihypoiodite

EC Number:

209-007-5

EC Name:

5,5'-diisopropyl-2,2'-dimethylbiphenyl-4,4'-diyl dihypoiodite

Cas Number:

552-22-7

Molecular formula:

C20H24I2O2

IUPAC Name:

4-[4-(iodooxy)-2-methyl-5-(propan-2-yl)phenyl]-5-methyl-2-(propan-2-yl)phenyl hypoiodite

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: yellowish powder
- Storage conditions of test material: at room temperature

Test animals

Species:

rat

Strain:

other: Wistar Han

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ca 8 - 9 weeks old
- Weight at study initiation: 142 - 172 g
- Fasting period before study: yes, animals were fasted overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test material
- Housing: animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilised sawdust as bedding material
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21 °C
- Humidity (%): 28 - 51 %
- Air changes: 10 or more air changes per hour
- Photoperiod: 12 hour light/12 hour dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

DOSE SOLUTIONS
Test material dosing formulations (w/w) were homogenised to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing.
Adjustment was made for specific gravity of the vehicle. No correction was made for the purity/composition of the test material.
The dosing formulations were stirred continuously during dose administration.

DOSE VOLUME
The dose volume for each animal was based on the body weight measurement prior to dosing. A dose volume of 10 mL/kg body weight was used for each dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

The first group of three female rats was treated at a dose level of 2000 mg/kg. Based on the results, one additional group of three female rats was dosed at 2000 mg/kg.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes. All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

Hunched posture, uncoordinated movements and/or piloerection were noted for the animals on Days 1 and/or 2.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of the study the acute oral LD50, to female Wistar Han rats, was determined to be in excess of 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and Japanese (JMAFF) No. 12 -Nousan-8147, under GLP conditions, following the Acute Toxic Class Method.

During the study, the toxicity of the test material 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, one additional group was dosed at 2000 mg/kg.

Under the conditions of the study none of the animals died. Hunched posture, uncoordinated movements and/or piloerection were noted for the animals on Days 1 and/or 2. The body weight gain shown by the animals 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 acute oral LD50, to female Wistar Han rats, was therefore determined to be in excess of 2000 mg/kg bw, the highest dose level tested.