2-Butenedioic acid (Z)-, ester with 1,2-propanediol, compd. with 2-(dibutylamino)ethanol

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS: CRL:(WI) rats
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 188 – 207 g
- Fasting period before study: overnight prior administration
- Housing: 3 animals/cage (Type II polypropylene/polycarbonate)
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg b.w.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As the chemical type of test material tested in the present study was not expected to cause any mortality, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 and 300 mg/kg b.w.

No. of animals per sex per dose:

3 female rats/2000 mg/kg b.w. and 2 x 3 female rats/300mg/kg b.w. (incl. the confirmatory group)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
Frequency of observations (clinical signs, see below): at 15 and/or 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
Frequency of weighing: on the day before treatment (Day -1), on the day of treatment (Day 0, prior to dosing) and weekly thereafter.
- Necropsy of survivors performed: yes

Clinical signs observed: skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/3 animals died at 2000 mg/kg. 0/6 animals died at 300 mg/kg.

Mortality:

WS400402 caused mortality at a single dose of 2000 mg/kg bw in two of three animals (2/3), but did not cause mortality at the dose of 300 mg/kg bw (0/6).

Clinical signs:

other: Treatment with WS400402 at the dose of 2000 mg/kg bw caused decreased activity (3/3), hunched back (3/3), incoordination (3/3), continuous tremors (3/3), tonic convulsion (1/3) and death (2/3). Treatment with 300 mg/kg bw did not cause any clinical signs

Gross pathology:

Found dead animals:
Dark/red discoloration/focus of the non-collapsed lungs was found at necropsy.
Terminal animals:
There were no macroscopic findings noted in the surviving animals

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test material WS400402 was found to be between 300 and 2000 mg/kg bw in female CRL:(WI) rats.
According to Regulation (EC) No 1272/2008 WS400402 should be classified as "harmful" and “Category 4” for acute oral exposure, respectively.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of acute toxicity – oral endpoint

LD50: between 300 and 2000 mg/kg body weight

Justification for classification or non-classification

In the acute oral toxicity study, the LD50 after a single dose of WS400402 was determined to range between 300 mg/kg (0/6 animals died) and 2000 mg/kg body weight (2/3 animals died). Therefore, WS400402 has to be classified for acute oral toxicity as acute tox 4 according to REGULATION (EC) 1272/2008.

 

Non-classification of WS400402 by the dermal route was reasonable, because it is not to be expected that systemic availability of WS400402 would be higher by the dermal than by the oral route.

 

Non-classification of WS400402 by the inhalation route was justified, because the substance has a very low vapour pressure making the inhalation exposure of humans unlikely.