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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 July 2011 - 02 March 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was conducted in accordance with International guidelines and in accordance with GLP. All guideline validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Commission Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, Test Data for Registration of Agriculture Chemicals, Acute Oral Toxicity (2-1-1), 12 Nousan No. 8147, Agriculture Protection Bureau
Version / remarks:
24 November 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid
EC Number:
813-120-0
Cas Number:
1262967-45-2
Molecular formula:
C21H36O8 C26H46O8 C31H56O8 C36H66O8 C41H76O8
IUPAC Name:
Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid
Test material form:
liquid
Specific details on test material used for the study:
RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark and under nitrogen.
- Stability under test conditions: Asumed stable.
- Solubility and stability of the test substance in the solvent/vehicle: The test substance was formulated at a concentration of 200 mg/mL in corn oil. Assumed stable.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: N/A.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: N/A
- Preliminary purification step (if any): N/A
- Final dilution of a dissolved solid, stock liquid or gel: N/A
- Final preparation of a solid: N/A

FORM AS APPLIED IN THE TEST (if different from that of starting material): Applied as liquid formulant.

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable): N/A

OTHER SPECIFICS: No

Test animals

Species:
rat
Strain:
other: Crl:CD'SD'
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 217-240 g
- Fasting period before study: Yes, overnight and 4 hours prior to dosing
- Housing: Animals were housed inside a barriered rodent facility. The facility was designed and operated to minimise the entry of external biological and chemical agents and to minimise the transference of such agents between rooms. During the acclimatisation period, each cage of animals was provided with a soft white untreated chew block and plastic shelter for environmental enrichment.
- Diet (e.g. ad libitum): Ad libitum, excpet during fasting.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: ≥5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 ºC
- Humidity (%): 40-70 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12:12 light:dark

IN-LIFE DATES: From: 09 August 2011 To: 25 August 2011

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: Test item not soluble in water. Corn oil is an accepted alternative vehicle.
- Lot/batch no. (if required): Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION (if unusual): Formulation was stirred prior to and continuously throughout the dosing process.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000 mg/kg is the class method starting point.
Doses:
2000 mg/kg bw (limit test)
No. of animals per sex per dose:
Females: 2 groups of three rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, macroscopic pathology
Statistics:
Not required (no effect)

Results and discussion

Preliminary study:
N/A
Effect levels
Key result
Sex:
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:
There were no deaths during the study.
Clinical signs:
There were no clinical signs of reaction to treatment throughout the study.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study, the bodyweight gains were lower during the second week.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
Other findings:
N/A

Any other information on results incl. tables

Table 2      Number of animals dead (and with evident toxicity)

 

Dose

(mg/kg bw)

Mortality

(# dead / total)

Time range of deaths

(hours)

Number with evident toxicity

(# / total)

Male

Female

Combined

Male

Female

Combined

2000

-

0 / 6

0 / 6

n/a

-

0 / 6

0 / 6

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the test article, Tetraesters of pentaerythritol with 2- methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid, was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification under Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures.
Executive summary:

OECD 423 (2012) - In an acute oral toxicity study, a group of fasted, 8-12 week old female, nulliparous Crl:CD’SD’ rats were given a single oral dose of Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid at a single dose rate of 2000 mg/kg bw (limit test) and observed for 14 days.

 

In the absence of mortality during the observation period, the oral LD50 was estimated to be greater than 2000 mg/kg bw.

 

In addition, there were no treatment related clinical signs, necropsy findings or changes in body weight observed in any of the individuals.

 

Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixture.