1,3-bis(trimethylsilyl)urea

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 Jul - 20 Aug 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 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted in 2001

Deviations:

yes

Remarks:

On 3 days the temperature was approx. 20 - 27 °C instead of 19 - 25 °C; the age of the animals was 7 - 12 weeks instead of 8 - 12 weeks

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

adopted in 2008

GLP compliance:

yes (incl. QA statement)

Remarks:

Hessisches Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3-bis(trimethylsilyl)urea

EC Number:

242-177-9

EC Name:

1,3-bis(trimethylsilyl)urea

Cas Number:

18297-63-7

Molecular formula:

C7H20N2OSi2

IUPAC Name:

1,3-bis(trimethylsilyl)urea

Specific details on test material used for the study:

Dose calculation was adjusted to purity with a correction factor of 1.03.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Han TM

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS B.V., Inc, AD Horst, The Netherlands
- Females nulliparous and non-pregnant: yes
- Age at beginning of treatment: 7 - 12 weeks
- Weight at beginning of treatment: 159.7 - 197.9 g
- Fasting period before study: The animals were fasted over night before treatment, with constant ad libitum access to drinking water.
- Housing: In groups of 5 in Makrolon Type IV cages with wire mesh top and granulated soft wood bedding.
- Diet: certified 2018C Teklad Global 18% protein rodent diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 45 - 65
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: The test item was not stable in water due to hydrolysis.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

Pilot study: 300 and 2000 mg/kg bw
Main study: 300 mg/kg bw

No. of animals per sex per dose:

Pilot study: 1 female per dose
Main study: 4 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations and inspections for morbidity / mortality were performed at least 3 times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing), thereafter at least once daily for 14 days. All surviving animals were observed for 14 days after dosing.
- Frequency of weighing: Body weights were recorded on Day 0 (prior to dosing), Day 7 and 14.
- Necropsy of survivors performed: Yes, gross necropsy was performed on all animals that died or were humanely killed during the study and at the end of the in-life part. Any macroscopic abnormalities were recorded.

Statistics:

No statistical analysis was performed.

Results and discussion

Preliminary study:

In the sighting study, two single females each were dosed at 300 and 2000 mg/kg bw/day. The animal dosed at 2000 mg/kg bw/day had to be humanely sacrificed 4 h after application due to moribund condition and unconsciousness. The animals showed clinical signs of toxicity starting 30 minutes after dosing, including decreased activity, ataxia, decreased respiration rate, sunken flanks, piloerection, lethargy, and laboured respiration. At macroscopical examination, a full urinary bladder was observed. Based on these findings, the main study was conducted at 300 mg/kg bw.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Pilot study:
300 mg/kg bw: 0/1 females died
2000 mg/kg bw: 1/1 females was sacrificed for humane reasons 4 hours post-dosing.
Main study: No mortality occured during the study period.

Clinical signs:

other: Pilot study: 300 mg/kg bw: 1/1 females showed piloerection, hunched posture, decreased activity and a decreased respiration rate within 4 hours post-administration. The effects were fully reversible by study Day 1. 2000 mg/kg bw: 1/1 females showed decr

Gross pathology:

Pilot study:
300 mg/kg bw: There were no abnormal findings at gross necropsy.
2000 mg/kg bw: The animal sacrificed for humane reasons was found to have a full urinary bladder.

Main study: 3 - 4 red nodules above the thymus were noted in 1/4 females, being indicative of enlarged lymph nodes. The effect was not attributed to treatment. There were no findings in the remaining animals.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

In this acute oral toxicity study in rats a LD50 value between 300 - 2000 mg/kg bw was determined.