Esterification product of castor oil and tetrahydromethyl-1,3-isobenzofuranedione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - June 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Esterification product of castor oil and tetrahydromethyl-1,3-isobenzofuranedione

EC Number:

700-064-6

Cas Number:

2105830-60-0

Molecular formula:

Not applicable as this is a UVCB substance

IUPAC Name:

Esterification product of castor oil and tetrahydromethyl-1,3-isobenzofuranedione

Test material form:

liquid

Details on test material:

- Molecular weight: 2800-3000
- CAS Name: Castor oil, polymer with tetrahydromethyl-1,3-isobenzofurandione
- Description: Very viscous amber liquid
- Test substance storage: At room temperature in the dark under nitrogen
- Stebility under storage conditions: Stable
- Expiry date: 01 January 2009

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Husbandry
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +/- 3.0°C (actual range: 19.3 - 21.3°C), a relative humidity of 30-70% (actual range: 31 - 80%) and 12 hours artificial ftuorescent light and 12 hours darkness per day.
Cleaning procedures in the room might have caused the temporary ftuctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these
fluctuations were considered not to have affected the study integrity.
- Accommodation
Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm,) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and
paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham MiIIltd), Surrey, United Kingdom).
Acclimatization peried was at least 5 days belere start 01 treatment under laboratory conditions.
- Diet
Free access to pelleted rodent diet (SM R/M-Z lrom SSNIFF® Spezialdiaten GmbH, Soest, Germany).
- Water
Free access to tap water.

Results of analysis for each batch of diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificales and results of analysis are retained in the NOTOX archives.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

The formulations were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle and the density of the test substance. The test substance could technically not be dosed undiluted as delivered by the sponsor. In order to obtain homogeneity, the test substance formulations were heated in a water bath with a maximum temperature of 65 °C for a maximum of 25 minutes.

- Method: Oral gavage, using plastie feeding tubes
- Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Frequency: Single dosage, on Day 1
- Dose level (volume): 2000 mg/kg (10 mL/kg) body weight

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 per step

Control animals:

no

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females.
The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account lor determination of the time interval between the dose groups.

Statistics:

No statistical analysis was performed. The method used is not intended to allow the calculation of a precise LD50 value.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality occurred.

Clinical signs:

No clinical signs were observed in the first group of three females. The second group showed hunched posture on Days 1 and 2 and uncoordinated movements on Day 1. There is no indication in the raw data that could explain the difference in clinical signs observed between both groups.

Body weight:

The mean body weight gain shown by the animals over the study period was considered to be normal.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of the substance in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results the substance does not have to be classified and has no obligatory labeling requirement for oral toxicity according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007) and EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

Executive summary:

The study was carried out based on the guidelines described in: OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method" EC, Council Directive 67/548/EEC, Annex V, B.1 tris (2004) "Acute Toxic Class Method" EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity" JMAFF guidelines (2000) including the most recent partial revisions.

The substance was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. No clinical signs were observed in the first group of three females. The second group showed hunched posture on Days 1 and 2 and uncoordinated movements on Day 1. There is no indication in the raw data that could explain the difference in clinical signs observed between both groups. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of the Substance in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results the substance does not have to be classified and has no obligatory labeling requirement for oral toxicity according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007) and EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).