Registration Dossier

Administrative data

Description of key information

No adverse effects were observed in acute toxicity studies

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:
13 January 1998 to 29 January 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU & OECD test guidance in compliance with GLP.
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
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 and environmental conditions:
TEST ANIMALS
- Source: HARLAN WINKELMANN
- Age at study initiation: 6-10 weeks
- Weight at study initiation: Mean weight - Males; 188g (183-193g), Females; 167g (151-179g)
- Fasting period before study: from about 16 hours before
- Housing: in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): ssniff® R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (± 3°C)
- Humidity (%): 50 (± 20 %)
- Photoperiod (hrs dark / hrs light): 12 hours daily

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Deionised
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 80%
- Justification for choice of vehicle: No data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight

Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the whole study.
Clinical signs:
No symptoms were observed after administration of 2000 mg/kg body weight.
Body weight:
Development of body weight was not impaired.
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes.
Other findings:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 2000 mg/kg body weight.
Executive summary:

Study conducted to EU test guidance 92/69/EEC part B1 and to OECD guideline 401 in compliance with GLP.

Based on the results of the study the LD50 > 2000 mg/kg body weight. The substance is not classified as harmful by acute oral exposure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

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:
20 January to 03 February 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU & OECD test guidance in compliance with GLP.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal 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 and environmental conditions:
TEST ANIMALS
- Source: HARLAN WINKELMANN
- Age at study initiation: 6-10 weeks
- Weight at study initiation: Mean - Males; 245g (237-261g), Females; 195g (183-216g)
- Fasting period before study: No
- Housing: in fully air-conditioned rooms in macrolon cages (type 3) on soft wood granulate, one animal per cage
- Diet (e.g. ad libitum): ssniff® R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (± 3°C)
- Humidity (%): 50 (± 20 %)
- Photoperiod (hrs dark / hrs light): 12 hours daily

Type of coverage:
occlusive
Vehicle:
water
Remarks:
deionised
Details on dermal exposure:
TEST SITE
- Area of exposure: 30cm3
- % coverage:
- Type of wrap if used: foil with elastic plaster bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.4ml deionised water
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Males 5
Females 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
None reported
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the whole study.
Clinical signs:
No symptoms were observed after administration of 2000 mg/kg body weight.
Body weight:
Development of body weight was not impaired.
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes
Other findings:
The treated skin areas of the animals were sporadically discolored orange up to the end of the study (day 15).
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 2000 mg/kg body weight.
Executive summary:

Study conducted to EU test guidance 92/69/EEC part B3 and OECD test guideline 402 in compliance with GLP.

Based on the results of the study the LD50 > 2000 mg/kg body weight. The substance is not classified as harmful by acute dermal exposure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

A study was conducted according to EU test guidance 92/69/EEC part B1 and to OECD guideline 401 in compliance with GLP.

Based on the results of the study the LD50 > 2000 mg/kg body weight. The substance is not classified as harmful by acute oral exposure.

A study was conducted according to EU test guidance 92/69/EEC part B3 and OECD test guideline 402 in compliance with GLP.

Based on the results of the study the LD50 > 2000 mg/kg body weight. The substance is not classified as harmful by acute dermal exposure.

Acute toxicity via inhalation route was not tested as the test substance has very low vapour pressure and is a granular product or well de-dusted powder, hence the potential for the generation of inhalable forms is low. In addition, production and use is done in a closed process without isolation of reaction products. The isolated product are dust free granules or well de-dusted powder (non-dusty solid) and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Dermal exposure is considered to be the appropriate route of exposure and has been assessed accordingly. No acute inhalation test was performed.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.