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Description of key information

LD50oral (rat; female) > 2000 mg/kg bw/day.

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:
28.06.2017-21.07.2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: V046212201
- Expiration date of the lot/batch: 30 April 2014
- Storage condition of test material: room temperature, in the dark
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approximately 8-12 weeks old)
- Weight at study initiation: 161 to 177 g
- Fasting period before study: overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Individually housed in polypropylene cages containing woodflakes equipped with water bottles. The room(s) in which the animals were kept were documented in the study records. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (2014C Teklad Global Rodent diet; Harlan Laboratories) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility. It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): Fifteen or greater air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Postdose observations were performed at periodic intervals on the day of dosing (0.5, 1, 2, 4 hours) and once daily thereafter. Animals were weighed individually on Day 1 (predose), 7 and 14. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
other: There were no signs of systemic toxicity
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of Reaction Mass of 1-isopropyl-2,2 dimethyltrimethylene diisobutyrate and 3-benzoyloxy-2,2,4-trimethyl pentyl isobutyrate and 2,2,4-trimethylpentane-1,3-diyl dibenzoate in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The objective of this study was to determine the potential toxicity of the test substance, when given by oral gavage at a single dose to rats of a single sex at 2000 mg/kg bw

The test substance was administered by oral gavage to two consecutive 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 14). No mortality occurred. The 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 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, the test substance does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is one good quality guideline compliant acute toxicity study via oral route (OECD 425 - Acute oral toxicity - Up and Down Procedure) conducted for

Reaction Mass of 1-isopropyl-2,2 dimethyltrimethylene diisobutyrate and 3-benzoyloxy-2,2,4-trimethyl pentyl isobutyrate and 2,2,4-trimethylpentane-1,3-diyl dibenzoate

(Sanders, A., 2012). The purpose of the study was to evaluate the potential toxic effect of the test item after single oral administration to rats. A limit dose of 2000 mg/kg body weight was used as starting dose.

In the study three female rats were gavaged with undiluted test substance at a dose level of 2000 mg/kg bw. The post exposure period was 14 days. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy at D14.

No mortalities were observed during the test. No abnormalities were noted at necropsy and there were no signs of systemic toxicity and all animals showed expected gains in bodyweight.

Justification for classification or non-classification

The available data for Reaction Mass of 1-isopropyl-2,2 dimethyltrimethylene diisobutyrate and 3-benzoyloxy-2,2,4-trimethyl pentyl isobutyrate and 2,2,4-trimethylpentane-1,3-diyl dibenzoate

indicate no potential for acute toxicity. Based on the oral LD50 value no classification is warranted for acute toxicity according to CLP Regulation 1272/2008.