Registration Dossier

Administrative data

Description of key information

Acute oral toxicity (rat): LD50 > 2000mg/kg body weight. No deaths occured.

Acute dermal toxicity (rat): LD50> 2000mg/kg bodyweight. No deaths occured.

Acute inhalation toxicity: waiver based on PSD.

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:
18/05/1999-04/06/1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Appearance: white powder
Purity: 100%
Batch No. 354009
Expiration date: May 2000



Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: +/- 10 weeks old
- Weight at study initiation: body weight not reported, body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: food was withheld overnight (for a max. of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands.
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C):21°C
- Humidity (%):50%
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light):12hrs light/12hrs dark

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2g in 10ml
- Amount of vehicle (if gavage):10ml/kg bw
- Justification for choice of vehicle: the vehicle was slected based on a pretest performed at NOTOX

DOSAGE PREPARATION (if unusual): the formulations were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustement was made for specific gravity of vehicle.

Doses:
2000mg/kg (10ml/kg)
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. Body weight: day 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality/viability
Statistics:
no statistical analysis was performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occured
Clinical signs:
Lethargy and uncoordinated movements were noted in all animals on day 1 and in addition hunched posture was noted in all females on day 2.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
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 F-2200HM in Wistar rats was established to exceed 2000mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with F-2200HM in the rat (Acute Toxic Class Method).

The study was carried out based on the guideline described in: EC Commission Directive 96/54/EC, Part B.1 tris 'Acute Oral, Acute Toxic Class method' and OECD no. 423, "Acute Oral Toxicity - Acute Toxic Class Method".

F-2200HM was administered by oral gavage to three Wistar rats of each sex at 2000mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

Results:

*No mortality occured.

*Lethargy and uncoordinated movements were noted in all animals on day 1 and in addition hunched posture was noted in all females on day 2.

*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.

Conclusion:

The oral LD50 value of F-2200HM in wistar rats was established to exceed 2000mg/kg bw.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commision Directive 93/21/EEC), F-2200HM does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Key study. Reliable Klimisch 1 guideline study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not 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
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiver based on PSD

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
other: Experimental study conducted on a structural similar substance.
Adequacy of study:
key study
Study period:
01/02/2012-15/02/2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Harlan Laboratories UK Ltd., Oxon, UK
- 5 males and 5 females
- Age at study initiation: 8-12 weeks
- Weight at study initiation: at least 200g
- Fasting period before study:
- Housing:In suspended solid-floor polypropylene cages furnished with woodflakes. 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): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12hours dark/12 hours light
Type of coverage:
semiocclusive
Vehicle:
DMSO
Details on dermal exposure:
TEST SITE
- Area of exposure:back and flanks
- % coverage:10% of the total body surface area, using a graduated syringe.
- Type of wrap if used: surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done):with cotton wool moistened with DMSO
- Time after start of exposure:24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg
- Constant volume or concentration used: yes
-The test material was moistened with the vehicle-DMSO and then was applied evenly on the skin.



Duration of exposure:
24h
Doses:
2000mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, signs of toxicity, irritation
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
95% CL:
>
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
no deaths
Clinical signs:
no signs of systemic toxicity
Body weight:
Animals showed expected gains in bodyweight over the study period except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities
Other findings:
Dermal reactions:
Very slight erythema was noted at the test sites of nine animals. Small superficial scattered scabs and/or hardened light brown coloured scabs were also notated at the test sites of eight animals. Haemorrhage of dermal capillaries and/or glossy skin was noted at the test sites of eight animals. Scab lifting to reveal glossy skin was noted at the test site of one animal. There were no signs of dermal irritation noted at the test site of one male.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000mg/kg bw
Executive summary:

Introduction: The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following: OECD 402, B3 EC, EPA OPPTS 870.1200

Method: A group of ten animals (five males and 5 females) was given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000mg/kg bodyweight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results:

Mortality: there were no deaths

Clinical observations: no signs of systemic toxicity

Dermal irritation: Signs of dermal irritation noted were very slight erythema, haemmorrhage of dermal cappilaries, small superficail scattered scabs, hardened light brown coloured scabs, glossy skin and scab lifting to reveal glossy skin. There were no signs of dermal irritation noted at the test site of one male.

Bodyweight: Animals showed expected gains in bodyweight over the study period, except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.

Necropsy: No abnormalities were noted

Conlusion: The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Key study. Reliable Klimisch 1 guideline study

Additional information

Justification for classification or non-classification

The above results triggered no classification under the EEC criteria for classification and labelling requirements for Dangerous Substances and Preparations (67/548/EEC) and the CLP Regulation (EC No 1272/2008). Therefore, the substance is not classified for acute toxicity.