bis(2-ethylhexyl) (4-hydroxy-3,5-dimethoxybenzyl)malonate

Endpoint summary

Description of key information

The acute toxicity of the test item was investigated in rats after oral and dermal administration. In both studies no mortality or any other adverse effect was observed in rats treated orally or dermally with the limit dose. The studies are performed according to international accepted Guidelines (OECD, EU) and under GLP regulation and, thus, of very high quality.

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

Study period:

2006-02-27 to 2006-05-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 September 1996

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species: Rat, Wistar HsdCpb: WU
- Source: F. Winkelmann, Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation:
males: 177 g (mean)
females: 166 g (mean)
- Fasting period before study: 17 hours
- Housing: type III Makrolon cages
- Diet: ad libitum, Provimi Kliba 3433.0
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23°C
- Humidity (%): 45 - 58%
- Air changes (per hr):
- Photoperiod: 12 hrs light - 12 hrs dark

IN-LIFE DATES: From: 2006-03-07 To: 2006-04-04

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg bw (limit test)

No. of animals per sex per dose:

3 (m) / 3 (f)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
- Clinical signs: at least 6 hours after administration and then daily
- Body weight: On days 2, 4, 6, 8, 11, 13, and 15 of the experimental part
- Other examinations performed: no

Statistics:

The body weight data were analysed 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 spread sheets.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality observed. All rats survived the observation period.

Clinical signs:

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

Gross pathology:

At necropsy no organ alterations were seen.

Other findings:

None

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

All rats survived the observation period. Body weight development of the treated rats was inconspicuous. At necropsy no organ alterations were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, it is concluded, that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw following oral treatment in rats.

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

The test material was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. The substance was administered unchanged, i.e. without a vehicle.

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

Results

No signs of toxicity were detected in the 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 is expected to exceed 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

very high quality

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-05-02 - 2007-11-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

29 December 1992

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Species: Rat, Wistar HsdCpb: WU
Breeder: F. Winkelmann, 33178 Borchen
Age: approx. 9 to 11 weeks

- 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 punching and additionally with an ear tattoo.

- Housing and diet
The rats were housed in an air-conditioned room of about 25 m^2. 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 21 to 23 °C
and the relative atmospheric humidity 46 to 71 %.

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.

The diet, Provimi Kliba 3433.0, had been checked, according to the specifications of the manufacturer 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.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 6 cm
- Type of wrap used: gauze patch, kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Removal procedure: the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied (weight with unit): 2000 mg/kg
- Concentration (if solution): undiluted

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 (m) / 5 (f)

Control animals:

no

Details on study design:

-- Observation for clinical symptoms
On the day of treatment the general condition and motility of the rats were slightly affected by the tape. It was difficult to distinguish between slight clinical findings and reactions due to fixation by the tape. 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. They were subjected to a gross pathological investigation.

Statistics:

The body weight data were processed 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.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

All rats survived the observation period. The lethal dose was regarded to be > 2000 mg/kg.

Clinical signs:

other: No signs of toxicity were detected in the 5 male and 5 female rats after dermal treatment with 2000 mg/kg of the test item.

Gross pathology:

At necropsy, no organ alterations were seen.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, the test substance can be considered to have no acute toxic potential and the expected LD50 value is higher than 2000 mg/kg after dermal administration to rats.

Executive summary:

Purpose

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

Study design

The test material was tested for acute toxicity in rats after dermal administration of 2000 mg/kg body weight.

The study reported here was performed according to the OECD Guideline for Testing of Chemicals, No. 402 and according to Commission Directive 92/69/EEC.

Results

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. There were no deaths during the course of the study. The body weight development was inconspicuous The gross pathological examination revealed no organ alterations.

Conclusions

Based on the result of this study, the test item can be considered to have no acute toxic potential and the expected LD50 value is higher than 2000 mg/kg after dermal administration to rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

very high quality

Additional information

Oral route of administration

The test substance was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. This study was performed according to the ,,Acute toxic class method" (ATC). No signs of toxicity were detected in the 3 male and 3 female rats after treatment and no rat died. The gross pathological examination revealed no organ alterations.

Dermal route of administration

The test substance was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight.

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. There were no deaths during the course of the study. The body weight development was inconspicuous.The gross pathological examination revealed no organ alterations. Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not require classification for acute toxicity via the oral route according to Regulation (EC) No 1272/2008 (CLP).