Reaction products of alkenyl dihydrofuran-2,5-dione and polyisoalkenyl dihydro-2,5-furandione with alkylene glycol

Endpoint summary

Description of key information

The acute, oral toxicity of the test material was assessed in accordance with OECD Guideline 401.  The acute oral median lethal dose (LD5O) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.  As such, the test material does not meet the criteria for classification. 
The acute, dermal toxicity of the test material was assessed in accordance with OECD Guideline 402.  The acute dermal median lethal dose (LDSo) of the test material in the Sprague- Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.  As such, the test material does not meet the criteria for classification.

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:

12 November 2013 to 05 December 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: US Environmental Protection Agency (EPA) Toxic Substances Control Act (TSCA)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Australian Guideline

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River (UK) Ltd., Margate, Kent, UK.
- Weight: Start of the main study the males weighed 158 to 188g, and the females 139 to 175g
- Age at study initiation: 5 to 8 weeks
- Weight at study initiation: 193.4 to 213.7g
- Fasting period before study: Overnight
- Housing: groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK)” was allowed throughout the study
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-24 °C
- Humidity (%): 48-66%
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 females+ 5 males

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No statistical analysis was performed.

Preliminary study:

A preliminary study was performed in a single animal at 2000 mg/kg body weight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occured during the course of the study.

Clinical signs:

No signs of systemic toxicity were noted during the study.

Body weight:

All animals showed expected bodyweight gain during the study.

Gross pathology:

No abnormalities were recorded at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute, oral toxicity of the test material was assessed in accordance with OCED Guideline 401. The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. As such, the test material does not meet the GHS criteria for classification.

Executive summary:

Guideline

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The method also complies with the requirements of US Environmental Protection Agency (EPA) Toxic Substances Control Act (TSCA) and Australian Toxicology Guidelines.

Method

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material as a solution in arachis oil B.P. at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

Results

There were no deaths. No signs of systemic toxicity were noted during the study.

All animals showed expected bodyweight gain during the study.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD5O) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

20 July and 3 August 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Environmental Protection Agency (EPA) Toxic Substances Control Act (TSCA

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Australian Guidelines

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent
- Age at study initiation: approximatively 12 Weeks
- Weight at study initiation: Males 233 to 257 g, Females 205 to 227 g
- After a minimum acclimatisation period of five days the animals were selected at random and given a number unique within the study by
indelible ink-marking on the tail and a number written on a cage card.
- Housing: in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Teklad Rat-Mouse Rodent Diet. ad libitum
- Water (e.g. ad libitum):ad libitum
- Environement: animal room was maintained at a temperature of 19 to 25 C and relative humidity of 50 to 60%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3 °C
- Humidity (%): >30 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light/dark cycle


IN-LIFE DATES: 12 November 2013 to 03 December 2013

Type of coverage:

semiocclusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: ca. 10%
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage
(HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil B.P. to remove any residual test material
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

Single dose level of 2000 mg/kg bodywight

No. of animals per sex per dose:

5m, 5f, dosed at 2000 mg/kg bw

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: gross pathological examination, behaviour or clinical signs, body weight, dermal reaction

Statistics:

No statistical analysis was performed.

Preliminary study:

not applicable.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occured during the course of the study.

Clinical signs:

No signs of systemic toxicity were noted during the study.

Body weight:

All animals showed expected bodyweight gain during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Very slight or well-defined erythema was noted at the treatment sites of the female animals on removal of the patches and persisted for 3 or 4 days after treatment. Crust formation was evident at one treatment site 3 and 4 days after treatment. All treatment sites appeared normal 5 days after treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute, dermal toxicity of the test material was assessed in accordance with OECD Guideline 402. The median lethal dose of the test material after single dermal application to rats of both sexes, is greater than 2000 mg/kg body weight. As such, the test material does not meet the GHS criteria for classification.

Executive summary:

Guideline

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method 83 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The method also complies with the requirement of US Environmental Protection Agency (EPA) Toxic Substances Control Act (TSCA) and Australian Toxicology Guidelines.

Method

A group of ten animals (five males and five females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then

killed for gross pathological examination.

Results

There were no deaths. No signs of systemic toxicity were noted during the study. Signs of irritation noted in the female animals were very slight to well-defined erythema with crust formation evident at one treatment site.

All animals showed expected bodyweight gain during the study.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague- Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

The key acute toxicity studies were performed on the read-across substance Ethylene glycol, reaction products with polyisobutenyl succinic anhydride and hexadecenyl succinic anhydride, salts with dimethylethanolamine. The justification for read-across is attached in Section 13 of the IUCLID.

Oral

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The method also complies with the requirements of US Environmental Protection Agency (EPA) Toxic Substances Control Act (TSCA) and Australian Toxicology Guidelines.

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material as a solution in arachis oil B.P. at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study.

All animals showed expected bodyweight gain during the study.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD5O) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Dermal

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24

February 1987) and Method 83 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The method also complies with the requirement of US Environmental Protection Agency (EPA) Toxic Substances Control Act (TSCA) and Australian Toxicology Guidelines.

A group of ten animals (five males and five females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then

killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study. Signs of irritation noted in the female animals were very slight to well-defined erythema with crust formation evident at one treatment site.

All animals showed expected bodyweight gain during the study.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LDSo) of the test material in the Sprague- Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Justification for classification or non-classification

In accordance with the CLP Regulation, No 1272/2008, classification is required for acute oral toxicity and acute dermal toxicity if the LD50 values are less than or equal to 2000 mg/kg bw. The acute, oral LD50 value was determined to be >2000 mg/kg and the median lethal dose, LDSo, for acute, dermal toxicity was determined to be >2000 mg/kg. Therefore, as the data of the surrogate substance showed no evidence of acute toxicity by either the oral or dermal route, the reference substance does not meet the criteria for classification.