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Description of key information

Acute toxicity: oral: LD50 (combined, rat) > 5000 mg/kg bw (OECD 401, GLP, K, rel.2)

Acute toxicity: dermal: LD50 (combined, rat) > 2000 mg/kg bw (OECD 402, GLP, K, rel.1)

Acute toxicity: inhalation: waiving

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A.smith, Warlingham, Surrey
- Housing: in single sex groups of five in grid bottomed polypropylene cages
- Diet (e.g. ad libitum): commercial available pelleted rodent diet (modified 41B supplied by Pilsbury's Ltd of Birmingham), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 54-64
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: 0.25% aqueous solution of gum tragacanth
Details on oral exposure:
The material was suspended in a 0.25% aqueous solution of gum tragacanth to give a dose volume of 10mL/kg at a dose level of 5.0g/kg. The material was dosed by peroral onjection using a rubber cathether attached to a syringe of suitable capacity. After dosing animals were returned to their cages and permitted access to food and water.
Doses:
5.0 g / kg bw
No. of animals per sex per dose:
five male and five female
Control animals:
no
Details on study design:
All animals were examined frequently after dosing and then daily for fourteen consecutive days. Any signs of toxicity or other effects were noted along with the time of onset and duration. Animals were weighed at weekly intervals.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Clinical signs:
No effects of treatment were observed throught the duration of the study and no abnormalities were detected at necropsy
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the substance is not classified according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated oral LD50 is higher than 5000 mg/kg bw.
Executive summary:

In an acute oral toxicity study performed according the OECD Guideline 401, following overnight fasting a group of five male and five female rats were administered the test material, by peroral injection, at a dose level of 5.0g/kg bodyweight in a dose volume of 10mL/kg. All animals were observed for fourteen day period for any signs of toxicity or other effects of treatment. No effects of treatment were observed throughout the duration of the study and no abnormalities were detected at necropsy.

The results of this study indicate that the test material has no toxic effect when administrated as a single oral dose to the rat at a level of 5.0g/kg bodyweight.

Oral LD 50 Combined > 5000 mg / kg bw

Under the test conditions, test material is not classified according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the oral LD50 is higher than 5000 mg/kg bw.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The key study is GLP compliant and of high quality (Klimisch score = 2)

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:
4/6/2008-14/08/2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
According to the OECD Guideline and in compliance with GLP
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:
Wistar
Remarks:
HanRcc:WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd
- Age at study initiation: male: 9 weeks; female: 11 weeks
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, ad libitum
- Water (e.g. ad libitum): Community tap water, ad libitum
- Housing: groups of five per sex in Makrolon type-4 cages with standard sotwood bedding during acclimatisation ; then individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation period.
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
purified water
Details on dermal exposure:
TEST SITE
- % coverage: 10

TEST MATERIAL
- Concentration (if solution): 0.5g /mL
- Volume dosage: 4 mL / kg bw
Duration of exposure:
The application period was 24 hours.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males
5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1, and twice daily during days 2-15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, local signs, body weight, macroscopic examinations at necropsy.
Statistics:
No statistical analysis was used.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths ocurred during the study
Clinical signs:
No clinical signs were during the course of the study.
A moderate erythema was noted in all animals on test day 2 and persisted as slight up to test days 9 or 10. Slight to moderate scaling was observed in all animals from test days 3 or 6 to up to test days 10 or 15. Slight crusts were noted in two males on test days 6 to 10. slight oedema was noted in all females on test days 3 to 5.
Body weight:
One female lost weight during the first week after treatment (body weight loss 2.7%) but it recovered until the end of the study. Otherwise, the body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic finding were observed at necropsy
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the dermal LD50 for the registered substance is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute dermal toxicity study (limit test) performed according to the OECD test guideline No. 402 and in compliance with GLP, five male and five female rats were treated with the substance at 2000 mg/kg by dermal application. The test item was diluted in vehicle (purified water) at a concentration of 0.5g/mL and administered at a volume dosage of 4mL/kg. The test site was covered with a semi-occlusive dressing for 24 hours. Animals were observed for mortality, clinical signs, local signs and body weights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No clinical signs were observed throught the duration of the study. A moderate erythema was noted in all animals on test day 2 and persisted as slight up to test days 9 or 10. Slight to moderate scaling was observed in all animals from test days 3 or 6 to up to test days 10 or 15. Slight crusts were noted in two males on test days 6 to 10. Slight oedema was noted in all females on test days 3 to 5. No abnormalities were detected at necropsy.

Bodyweights were within the range commonly recorded for this strain and age. No abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg / kg bw

Under the test conditions, the dermal LD50 for the registered substance is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study is GLP compliant and of high quality (Klimisch score = 1)

Additional information

Acute toxicity: oral:

A key study was identified (Toxicol lab. 1986). In this limit acute oral toxicity study performed according to the OECD test guideline No. 401 and in compliance with GLP, fasted rats (5 males and 5 females) were treated with the test material at a dose level of 5000 mg/kg bw. The animals were observed for any signs of toxicity or other effects for 14 days. No effects of treatment were observed throught the duration of the study and no abnormalities were detected at necropsy.

Oral LD50 (combined rats) > 5000 mg/kg bw.

Acute toxicity: dermal:

A key study was identified (RCC, 2008). In this limit acute dermal toxicity study performed according to the OECD test guideline No. 402 and in compliance with GLP, HanRcc:WIST (SPF) rats (5 males and 5 females) were treated with the test material at a dose level of 2000 mg/kg bw. The animals were observed for mortality, clinical signs, irritation and body weight for 15days. No clinical signs were observed throught the duration of the study. A moderate erythema was noted in all animals on test day 2 and persisted as slight up to test days 9 or 10. Slight to moderate scaling was observed in all animals from test days 3 or 6 to up to test days 10 or 15. Slight crusts were noted in two males on test days 6 to 10. Slight oedema was noted in all females on test days 3 to 5. No abnormalities were detected at necropsy.

Dermal LD50 (combined rats) > 2000 mg/kg bw.

However, according to ECHA R7a guidance (2016), further study need not to be conducted because the substance does not meet the criteria for classification for acute toxicity or STOT-SE by the oral route and no systemic toxicity was observed in the existing acute dermal toxicity study up to 2000 mg/kg bw, nor in the GPMT study. Thus, the dermal LD50 is expected to be higher than 5000 mg/kg bw.

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Under the test conditions, the substance is not classified according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated oral LD50 is higher than 5000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the substance is not classified according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated oral LD50 is expected to be higher than 5000 mg/kg bw.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex I of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex I of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

Based on available data via both the oral and dermal route, the classification criteria according to the Annex I of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single dermal exposure Category 1 or 2 are not considered to be met. No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex I of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.

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