Alkanol reaction products with bis(aminoalkyl(C=1~6))carbomonocycle, alkoxy(C=3~8)alkanol(C=2~7) and 2,4-TDI

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 April 2013 --- 13 June 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: 20231250
- Physical state: off-white solid
- Storage conditions: at room temperature, tightly closed in a dry and well-ventilated place

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 204 g (range: 182 g to 222 g)
- Fasting period before study: yes, during the night before treatment
- Housing: the animals were housed by three from the same group in polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 14 May 2013 to 11 June 2013

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Batch N° MKBH4894V

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL
- Justification for choice of vehicle: as unsatisfactory solubility of the test item was obtained in drinking water treated by reverse osmosis, another vehicle was chosen from the following organic solvents (in order of preference): 0.5% methylcellulose aqueous solution and corn oil. A homogenous suspension was obtained in corn oil at the concentration of 200 mg/mL.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw.

DOSAGE PREPARATION (if unusual): the test item was administered as a homogenous suspension in the vehicle. The test item was ground to a fine powder, using a mortar and pestle, and then mixed with the required quantity of vehicle.
Fresh dose formulations were prepared on the day of each administration and kept at room temperature prior to administration.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: since no relevant toxicity data were available for the estimation of a lethal dose-level, the starting dose level was 300 mg/kg bw.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 females per treatment step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment, then on day of treatment (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed in any animals.

Gross pathology:

There were no findings considered to be related to the test item administration.
Dilatation of the uterus with translucent content was seen in one female given the test item at 2000 mg/kg (group 2). This is a common background finding in females rats related to the estrous cycle.
A white mass was found in the mammary gland from one female given the test item at 300 mg/kg. Although this macroscopic finding is unusual at this age, it was considered to be incidental in view of its isolated occurrence and the short duration of the observation period.

Any other information on results incl. tables

 Table 7.2.1/1: Mean body weight and body weight changes (g) in treated animals during the observation period compared to laboratory historical control data

Sex	Female
Group	Laboratory Historical control data	1	2	3
Dose-level (mg/kg)	0	300	2000	2000
Body Weight (g) ± SD
. Day 1	208 (± 11.7)	216 (± 9.8)	207 (± 8.2)	188 (± 10.1)
. Day 8	246 (± 12.7)	251 (± 12.5)	243 (± 16.3)	224 (± 10.7)
. Day 15	266 (± 14.0)	272 (± 12.4)	264 (± 9.6)	245 (± 9.1)
Body weight Change (g)± SD
. Days 1-8	+39 (± 5.1)	+35 (± 3.1)	+36 (± 10.0)	+36 (± 1.2)
. Days 8-15	+20 (± 6.3)	+21 (± 1.0)	+21 (± 6.9)	+21 (± 2.6)
. Days 1-15	+58 (± 5.8)	+56 (± 2.3)	+57 (± 3.5)	+57 (± 2.1)

SD: standard deviations.

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD0 of the test item was equal or higher than 2000 mg/kg bw in rats.

Executive summary:

The substance was tested for acute oral toxicity according to OECD 423 guideline and in compliance with Good Laboratory Practices.

The test item was administered once by gavage to 3 groups of 3 fasted female rats under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil. Since no relevant toxicity data were available for the estimation of a lethal dose-level, the starting dose-level was 300 mg/kg bw for ethical reasons. After the first assay, the next higher dose-level of 2000 mg/kg bw was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other 3 females at 2000 mg/kg bw.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded before treatment then on day 1, 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals. Body weight gain was unaffected by the test item treatment, when compared to laboratory historical control data. The test item administration did not induce any macroscopic findings at necropsy.

The acute oral LD0 of the test item was equal or higher than 2000 mg/kg bw.