Bis(2-ethylhexyl) 2-(4-hydroxy-3,5-dimethoxybenzylidene)malonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-02-21 to 2003-06-23

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)

Version / remarks:

adopted 17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 September 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Test system
Species: Rat, Wistar HsdCpb: WU, males (m) and females (f)
Age: approx. 6 to 8 weeks
Mean initial body weight at the start of the study: 177 g (range from 156 to 196 g).

- Identification and adaptation
Healthy young animals were allocated to the study group at least 7 days before dosing to allow for acclimatization.
The rats were identified by an ear tattoo.

- Housing and diet
The rats were housed in an air-conditioned room of about 25 m^2 in the institute. Lighting was controlled by a timer to provide a 12 hour light - 12 hour dark regime.

The rats were kept separately in type III Makrolon cages with a shelter, placed on mobile racks. Conventional softwood granulate was used
as the bedding. One day before treatment, and up to 24 hours after dosing, metal grids were placed above the softwood granulate.
The cages and the metal grids had been machine-cleaned before the start of the experimental part. The bedding was changed two times per
week.

Temperature and humidity were measured using a thermohygrograph. The room temperature during the experimental period was 22 °C
and the relative atmospheric humidity 44 to 68 %.

Diet was withheld from 17 hours before until up to 4 hours after treatment. At all other times food and tap water from Makrolon drinking
bottles were available to the rats ad libitum.

According to the specifications given by the manufacturer, the diet, Provimi Kliba 3433.0, had been checked by independent laboratories.
Analysis included qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.
The drinking water was periodically analyzed according to the German regulations for human drinking water.

The softwood granulate was analytically checked by independent laboratories.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Methocel K4M premium (hydroxypropyl methylcellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: standard vehicle for this type of studies

Doses:

2000 mg/kg bw (limit test)

No. of animals per sex per dose:

3 males / 3 females

Control animals:

no

Details on study design:

Observation for clinical symptoms
The behavior and general condition of all rats were monitored for at least 6 hours after administration and then checked daily.

Body weight
All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.

Pathology
All rats were sacrificed at the end of the experimental part by C02-asphyxia and subjected to a gross pathological investigation.

Statistics and evaluation
The body weight data recording and statistical evaluations were performed using a PC-program. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed. All rats survived the observation period.

Clinical signs:

No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg of test material.

Body weight:

Body weight development of the treated rats was inconspicuous.

Gross pathology:

At necropsy no organ alterations were seen.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to the results of this study in rats the test material is not toxic/harmful after acute oral administration i.e. the LD50 value (rat, oral) exceeds the limit dose of 2000 mg/kg body weight.

Executive summary:

Purpose

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute oral toxicity of the test item in man.

Study design

This study was performed according to the OECD TG 423 ,,Acute toxic class method" (ATC).

Results

No signs of toxicity were detected in 3 male and 3 female rats after treatment and no rat died.

The gross pathological examination revealed no organ alterations.

Conclusions

According to the results of this study the test material can be allocated to ATC class 0 i.e. the LD50 value exceeds the limit dose of 2000 mg/kg body weight.