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Description of key information

The acute median lethal oral dose level of the test article, MonoFA_TETA_PAA_BADGE_BGE_Adduct, was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
The acute median lethal dermal dose of MonoFA_TETA_PAA_BADGE_BGE_Adduct to rats was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
A study on inhalative acute toxicity is not available and was waived due to low vapour pressure indicative of low exposure versus inhalative route.

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 September 2012 to 22 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Fully GLP compliant and in accordance with current test guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HsdHan:WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 11 to 12 weeks
- Weight at study initiation: The weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: From the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing.
- Housing: Housed in groups of up to five during the acclimatisation period in cages that conform to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), the rats were housed in groups of three in similar cages.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): Mains water, ad libitum
- Acclimation period: 28 to 30 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): The animal rooms were designed to permit 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 15 October 2012 To: 01 November 2012
Route of administration:
oral: gavage
Vehicle:
other: PEG 400
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: PEG 400 as this was found to produce a suitable formulation at the highest concentration.
- Lot/batch no. (if required): Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
Doses:
Each rat was dosed twice on Day 1 (with an interval of one hour between administrations) by passing the tip of a catheter along the oesophagus and instilling the test article into the gastric lumen.
No. of animals per sex per dose:
3 animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Clinical signs were recorded immediately after first administration and 15 and 30 minutes after first administration. Clinical signs were then recorded immediately after the second administration, at approximately 15 and 30 minutes after the second, hourly between 1 and 4 hours after the second administration (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.
Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight
Statistics:
Not applicable
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
other: No clinical signs were seen.
Gross pathology:
No abnormalities were noted at necropsy except for red thymus in one animal and gaseous distension of the colon in one other animal.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute median lethal oral dose level of the test article, MonoFA_TETA_PAA_BADGE_BGE_Adduct, was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Executive summary:

This study was conducted to assess the acute toxicity of the test article, MonoFA_TETA_PAA_BADGE_BGE_Adduct following oral administration to rats.

Groups of three female fasted rats were given the test article on Day 1 by oral gavage at a dose level of 2000 mg/kg. The test article was dispersed in PEG 400 at a concentration of 100 mg/mL and administered at a dose volume of 10 mL/kg on two occasions approximately one hour apart. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs were seen.

All rats achieved body weight gains over the study period.

No abnormalities were noted at necropsy except for red thymus in one animal and gaseous distension of the colon in one other animal.

The acute median lethal oral dose level of the test article, MonoFA_TETA_PAA_BADGE_BGE_Adduct, was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 September 2012 to 26 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Fully GLP compliant and in accordance with current test guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: HsdHan:WIST
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 250 to 279 g (males) and 175 to 203 g (females)
- Fasting period before study: Not applicable
- Housing: up to five rats of the same sex were accommodated in cages that conformed to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), each rat was individually housed in a similar cage. After completion of the Day 3 observations animals allocated to the main study were returned to group housing.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): Mains water, ad libitum
- Acclimation period: 7 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): The animal rooms were designed to permit 15 to 20 air changes per hour.
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 01 October 2012 To: 23 October 2012
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsum
- % coverage: 10%
- Type of wrap if used: Dense gauze patch retained by elasticated open-eave adhesive compression bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool
- Time after start of exposure: 24 Hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: Not applicable
Duration of exposure:
15 Days
Doses:
1 Dose
No. of animals per sex per dose:
Five male and five female rats were subjected to single dermal application of the test article at 2000 mg/kg. This group consisted of the two animals used in the preliminary test plus a further four male and four female rats to give the required group size of five males and five females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal signs
Statistics:
Not Applicable
Preliminary study:
A pair of animals (one male and one female) received a single dermal dose of test article at a dose level of 2000 mg/kg.,(no compound related mortality. was observed).
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
other: There were no clinical signs of reaction to treatment.
Gross pathology:
Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site and an isolated incident of pale mucosal surface of the stomach.
Other findings:
Very slight to well-defined erythema was noted in all animals on Day 2. Very slight erythema was noted in two animals up to Day 6 and persisted in one animal until the end of the observation period.
Other adverse dermal reactions noted were brown discolouration of the skin, scabbing and new skin growth.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute median lethal dermal dose of MonoFA_TETA_PAA_BADGE_BGE_Adduct to rats was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Executive summary:

This study was conducted to determine the acute dermal toxicity of the test article, MonoFA_TETA_PAA_BADGE_BGE_Adduct, following a single (24 hour) semi-occluded topical application to the rat.

The test article was applied undiluted to the clipped dorsum of a group of five male and five female rats on Day 1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs of reaction to treatment.

Adverse dermal reactions noted were very slight to well-defined erythema, brown discolouration of the skin, scabbing and new skin growth.

All rats gained weight during the first and second weeks of the study except for one female which showed a slight loss in body weight during the first week.

Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site and an isolated incident of pale mucosal surface of the stomach.

The acute median lethal dermal dose of MonoFA_TETA_PAA_BADGE_BGE_Adduct to rats was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute Oral Toxicity

The acute oral toxicity study on MonoFA_TETA_PAA_BADGE_BGE_Adduct followed oral administration to rats.

No deaths and no clinical signs were seen in this study and all rats achieved body weight gains over the study period.

No abnormalities were noted at necropsy except for red thymus in one animal and gaseous distension of the colon in one other animal.

The acute median lethal oral dose level of the test article, MonoFA_TETA_PAA_BADGE_BGE_Adduct, was found to exceed 2000 mg/kg.

Acute Dermal Toxicity

The acute dermal toxicity study on MonoFA_TETA_PAA_BADGE_BGE_Adduct followed a single (24 hour) semi-occluded topical application to the rat skin.

There were no deaths and no clinical signs of reaction to treatment.

Adverse dermal reactions noted were very slight to well-defined erythema, brown discolouration of the skin, scabbing and new skin growth.

All rats gained weight during the first and second weeks of the study except for one female which showed a slight loss in body weight during the first week.

Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site and an isolated incident of pale mucosal surface of the stomach.

The acute median lethal dermal dose of MonoFA_TETA_PAA_BADGE_BGE_Adduct to rats was found to exceed 2000 mg/kg.

Acute Inhalative Toxicity

Considering the low vapour pressure of the test substance inhalative exposure is unlikely and has not been tested.


Justification for selection of acute toxicity – oral endpoint
Only available study for this endpoint

Justification for selection of acute toxicity – dermal endpoint
Only available study for this endpoint

Justification for classification or non-classification

The test material was considered to have no significant acute toxic risk in respect of its acute oral and dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) respectively CLP (Regulation EC No 1272/2008) or DSD (Directive 67/548/EEC).

Data on acute inhalative toxicity are not available and not required as inhalative exposure is unlikely due to the low vapour pressure of the substance. No effect triggering classification for STOT SE classification according to GHS/CLP were noted in the available studies and hence classification for short term specific target organ toxicity is not required.