Esterification products of dihydrofuran-2,5-dione, C16-24 (even numbered) alkenyl with propane-1,2,3-triol and propane-1,2,3-triol oligomers

Endpoint summary

Description of key information

The oral LD50 of the test item in female rats has been determined to be greater than 2500 mg/kg bw. 
The dermal LD50 in rats was determined to be > 2000 mg/kg bw.

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:

31 January 2006 to 21 February 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

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:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 193 to 219g
- Fasting period before study: overnight
- Housing: solid-floor polypropylene cages
- Diet (e.g. ad libitum): BCM IPS rat and mouse diet ad libitum
- Water (e.g. ad libitum): mains drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 31 January 2006 To: 21 February 2006

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The substance did not dissolve in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: available information on toxicity

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 + 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed at 0.5, 1, 2 and 4 hours after dosing and daily thereafter. Animals weighed prior to dosing, seven and fourteen days post dosing.
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% CL not applicable

Mortality:

No premature deaths

Clinical signs:

Signs of systemic toxicity noted during the study were hunched posture and lethargy during the first two days.

Body weight:

No effects on bodyweight were observed.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the reuirements of the OECD Guideline for the Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 17 December 2001) and Method B1 tris Acute Toxicity (Oral) of Commission Directive 2004/73/EC.

Method

A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. The test material was administered orally as a solution in dimethyl sulphoxide. Clinical signs and bodyweight development were monitored during the study. All animals were subject to gross necropsy.

Results

There were no deaths. Signs of toxicity noted during the study were hunched posture and lethargy. All animals were normal two days after dosing. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One study available - Klimisch category 1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One study available - Klimisch category 1

Additional information

Oral

A key study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of OECD TG 423 and EC Method B1 tris. A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bw. This was followed by a further group of three fasted females at the same dose level. The test material was administered orally as a solution in dimethyl sulphoxide. Clinical signs and bodyweight development were monitored during the study. All animals were subject to gross necropsy. There were no deaths. Signs of toxicity noted during the study were hunched posture and lethargy. All animals were normal two days after dosing. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The LD50 in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bw.

Dermal

A key study performed in accordance with OECD Guideline 402, EC Method B3. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. There were no signs of systemic toxicity. Very slight erythema and very slight edema were noted at the test sites of all females one day after dosing. Light brown discoloration of the epidermis was noted at the test sites of males one and two days after dosing.

One female showed body weight loss during the first week with expected gain in body weight during the second week. Two females showed expected gain in body weight during the first week but body weight loss or no gain in body weight during the second week. The remaining animals showed expected gains in body weight over the study period.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose ( LD 50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Inhalation

The substance is a liquid with a vapour pressure of 0.0021 Pa at 25°C and is used primarily as a component of personal hygiene articles. It is expected that inhalation exposure from these uses will be low and that the most likely route of exposure for workers and consumers is the dermal route.

Justification for selection of acute toxicity – oral endpoint
GLP study following OECD guideline, Klimisch category 1

Justification for selection of acute toxicity – dermal endpoint
GLP study following OECD guideline, Klimisch category 1

Justification for classification or non-classification

In an acute oral toxicity study in rats the LD50 was determined to be > 2500 mg/kg bw.

In an acute dermal study in rats the LD50 was determined to be > 2000 mg/kg bw.

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for acute toxicity