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Description of key information

Acute oral (OECDTG423): LD50 >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:
11 November 2019 - 03 December 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
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 Guidelines (2000), including the most recent revisions
Version / remarks:
2000
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approximately 10-11 weeks old)
- Weight at study initiation: 182 to 207 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: Animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilized sawdust as bedding material.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to municipal tap-water
- Acclimation period: At least 5 days
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to the study at the discretion of the coordinating biotechnician, with all animals within ± 20% of the sex mean body weights.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50 to 53
- Air changes (per hr): ten or greater
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 November 2019 To: 03 December 2019
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / specific gravity or density (g/mL) * purity correction factor.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. 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 for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Moribundity Checks:
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.
Clinical Observations:
Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate).
Body Weights:
Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing. Terminal body weights were collected from animals found dead or euthanized moribund after Day 1.
- Necropsy of survivors performed: All animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
Not performed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was found dead on Day 9. No further mortality occurred.
Clinical signs:
other: Hunched posture was noted for all animals between Days 1 and 11 and piloerection was noted for all animals between Days 1 and 10. Salivation was noted for three out of six animals on Day 1.
Gross pathology:
Abnormalities of the thymus (reduced in size) and the forestomach (irregular surface) were found in the animal that died during the study, at macroscopic post mortem examination. Macroscopic examination of the surviving animals at termination did not reveal any abnormalities.
Interpretation of results:
other: Not classified.
Remarks:
According to Regulation (EC) No. 1272/2008.
Conclusions:
In an acute oral toxicity study with female rats, performed according to OECD 423 test guideline and GLP principles, a LD50 >2000 mg/kg bw was determined.
Executive summary:

The substance was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight, performed according to OECD 423 test guideline and GLP principles.

One female was found dead on Day 9. No further mortality occurred. Hunched posture was noted for all animals between Days 1 and 11 and piloerection was noted for all animals between Days 1 and 10. Salivation was noted for three out of six animals on Day 1. In the animal that died during the study, body weight loss was seen. Body weight loss was noted in one surviving animal and reduced body weight gain was noted for the majority of surviving animals. Abnormalities of the thymus (reduced in size) and the forestomach (irregular surface) were found in the animal that died during the study, at macroscopic post mortem examination. Macroscopic examination of the surviving animals at termination did not reveal any abnormalities.

Based on the results, a LD50 >2000 mg/kg bw was determined and the substance does not have to be classified for acute oral toxicity according to Regulation (EC) No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has klimisch code 1.

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

Acute oral:

The substance was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight, performed according to OECD 423 test guideline and GLP principles.

One female was found dead on Day 9. No further mortality occurred. Hunched posture was noted for all animals between Days 1 and 11 and piloerection was noted for all animals between Days 1 and 10. Salivation was noted for three out of six animals on Day 1. In the animal that died during the study, body weight loss was seen. Body weight loss was noted in one surviving animal and reduced body weight gain was noted for the majority of surviving animals. Abnormalities of the thymus (reduced in size) and the forestomach (irregular surface) were found in the animal that died during the study, at macroscopic post mortem examination. Macroscopic examination of the surviving animals at termination did not reveal any abnormalities.

Acute inhalation:

According to conditions described in Column 2 of Section 8.5.2 of Annex VIII testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

As the substance has a low vapor pressure (6.1 x 10-7 Pa at 25°C), therfore exposure by inhalation of vapor is unlikely to occur. Furthermore the substance is only used as a liquid substance (as such or in a formulation (of lubricant additives, lubricants and greases)). Based on its use the possibility of exposure of workers to aerosols, particles or droplets of an inhalable size can be excluded. Since the criteria in Column 2 of Section 8.5.2 are not fulfilled testing by the inhalation route for the substance is considered not appropriate and thus testing is waived.

Acute dermal:

According to conditions described in Column 2 of Section 8.5.3 of Annex VIII testing by the dermal route does not need to be conducted if: (1) the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and (2) no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation). Since the substance does not meet the criteria for classification as acute toxicity by the oral rout (LD50 > 2000 mg/kg bw). No signs of systemic toxicity were observed in an in vivo study with dermal exposure (guinea pig maximisation test), it is therefore unlikely that the acute dermal toxicity will exceed the oral toxicity.

Since this substance does not meet the criteria for classification as acute toxicity by the oral route and no systemic effects have been observed in an in vivo study with dermal exposure, testing by the dermal route for the substance is considered scientifically not justified.

Justification for classification or non-classification

Based on the available information, the substance does not have to be classified and has no obligatory labelling requirement for acute oral, acute inhalation and acute dermal toxicity according to Regulation (EC) No 1272/2008 and its amendments.