Registration Dossier

Administrative data

Description of key information

Key study: Acute oral: Experimental results: Equivalent to OECD 401. GLP study. 
LD50 > 2000 mg/kg bw
Key study: Acute dermal: Experimental results: Equivalent to OECD 402. GLP study.
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Equivalent to OECD 401. GLP study.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: males: 181-197 g; females: 132-142 g
- Fasting period before study: All animals were fasted overnight (18 hours).
- Housing: On arrival, animals were housed in single sex groups of up to 12 to a cage; each cage measured 56 cm x 38 cm x 18 cm. Prior to experimentation the animals were rehoused (as single sex groups of four) in cages with stainless-steel wire-mesh floors and tops; each cage measured 38 cm x 25 cm x 18 cm. At least two days before dosing, the rats were housed in groups of two or three animals of the same sex per cage.
- Diet (e.g. ad libitum): PRD, Labsure Animal Foods, Dorset, ad libitum.
- Water (e.g. ad libitum): Filtered water from the public supply, ad libitum.
- Acclimation period: Two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT)


Route of administration:
other: intraoesophageal intubation using a ballpoint needle fitted to a syringe
Vehicle:
corn oil
Details on oral exposure:
The test material was administered as a 20% m/v suspension in corn oil
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five animals per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs three times a day for the first three days and daily thereafter. The initial (Day 1), Day 7 and Day 14 body weights were recorded.
- Necropsy of survivors performed: necropsy was not performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None of the rats died.
Clinical signs:
There were no clinical signs observed.
Body weight:
All rats had gained weight relative to their day 1 bodyweights by the end of the 14 day observation period.

Table 7.2.1:      Summary of Acute Oral Toxicity

Males

Females

Dose

Mortality

Time of death

Dose

Mortality

Time of death

2000 mg/kg

0/5

--

2000 mg/kg

0/5

--

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the test material in rats administered as a 20% (m/v) suspension in corn oil was greater than 2000 mg/kg.
Executive summary:

Five rats per sex were orally dosed at 2000 mg/kg. Animals were observed for clinical signs three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 7 and Day 14 body weights were recorded. None of the rats died. There were no clinical signs observed. The acute oral LD50 of the test material in rats administered as a 20% (m/v) suspension in corn oil was greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Klimisch 2. Equivalent to OECD 401. GLP study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Equivalent to OECD 402. GLP study.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: males: 204-227 g; females: 145-157 g
- Fasting period before study: All animals were fasted overnight (18 hours).
- Housing: On arrival, animals were housed in single sex groups of up to 12 to a cage; each cage measured 56 cm x 38 cm x 18 cm. Prior to experimentation the animals were rehoused (as single sex groups of four) in cages with stainless-steel wire-mesh floors and tops; each cage measured 38 cm x 25 cm x 18 cm. At least two days before dosing, the rats were housed in groups of two or three animals of the same sex per cage.
- Diet (e.g. ad libitum): PRD, Labsure Animal Foods, Dorset, ad libitum.
- Water (e.g. ad libitum): Filtered water from the public supply, ad libitum.
- Acclimation period: Two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT)
Vehicle:
other: moistened
Details on dermal exposure:
The day before dosing, approximately 60% of the dorsal hair of all animals was closely shorn with fine electric clippers. Before application of the tst material, the skin was visually inspected to ensure that all micro-abrasions of the stratum corneum had healed.

The calculated dose was weighed onto a piece of aluminium foil lined with gauze and applied to the shorn skin. The foil was held in place by a double overwrap of waterproof adhesive tape.

After the 24 h exposure, the tape and foil were removed and the skin washed with warm dilute detergent solution and then dried.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five animals per sex
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for signs of toxicity three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. Initial (Day 1), Day 7 and Day 14 body weights were recorded.
- Necropsy of survivors performed: necropsies were not conducted.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None of the rats died.
Clinical signs:
There were no clinical signs observed.
Body weight:
All rats had gained weight relative to their day 1 bodyweights by the end of the 14 day observation period.

Table 7.2.3:      Summary of Acute Dermal Toxicity

Males

Females

Dose

Mortality

Time of death

Dose

Mortality

Time of death

2000 mg/kg

0/5

--

2000 mg/kg

0/5

--

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute (24 h) percutaneous LD50 of the test powder in rats was greater than 2000 mg/kg.
Executive summary:

Five rats per sex were dermally dosed at 2000 mg/kg. Animals were observed for clinical signs three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 7 and Day 14 body weights were recorded. None of the rats died. There were no clinical signs observed. The acute dermal LD50 of the test material in rats was greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Klimisch 2. Equivalent to OECD 402. GLP study.

Additional information

Key study: Acute oral: Experimental results: Equivalent to OECD 401. GLP study.

LD50 > 2000 mg/kg bw

Key study: Acute dermal: Experimental results: Equivalent to OECD 402. GLP study.

LD50 > 2000 mg/kg bw

Acute inhalation: Data waiving: In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since 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.


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

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since 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.

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

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity.