Reaction mass of (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl palmitate and (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl stearate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

445-990-9

EC Name:

-

Cas Number:

376588-17-9

Molecular formula:

C38 H71 N O6

Test animals

Species:

rat

Strain:

other: HanBrI: Wist (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 12-13 weeks
- Weight at study initiation: 170 - 195 g
- Fasting period before study: 17 hours
- Housing: Groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland)
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 84/02 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum.
- Water: Community tap water from Fiillinsdorf ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 ml/kg body weight
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. : 442989/154502013

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight

DOSAGE PREPARATION: The test item was weighed Into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Doses:

2000 mg/kg

No. of animals per sex per dose:

2 x 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. During days 2-15 twice daily for viability and once daily for clinical signs.
- Frequency of weighing: On test days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, viability

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived until the end of the study period.

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Any other information on results incl. tables

Body weights (g)

Dose (mg/kg)	Animal No.	Sex	Day 1(treatment)	Day 8	Day 15
2000	1	F	185.0	193.3	197.4
	2	F	170.6	185.4	193.0
	3	F	178.4	189.0	200.4
2000	4	F	181.1	188.3	187.4
	5	F	177.6	191.4	196.6
	6	F	194.7	200.5	205.6

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

The acute oral LD50 of the test substance in female rats is greater than 2000 mg/kg body weight.

Executive summary:

Six female HanBrI: WIST (SPF) rats were treated with the test substance by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a volume dosage of 10mL/kg. All animals survived until the end of the study period. No clinical signs were observed during the course of the study. One female showed a loss of body weight (0.5 %) between test day 8 and the end of the observation period. The body weight of the other animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

 

In conclusion, the median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days is greater than 2000 mg/kg body weight.