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Administrative data

Description of key information

Key study: Acute oral: Experimental results: Similar to OECD guideline 401.

LD50 = 12900 mg/kg bw

Key study: Acute dermal: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

LD50 = 6450 mg/kg bw

Key study: Acute inhalation: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

LC50 = 50 mg/L

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200-300 g
- Fasting period before study: yes, fasted for 24 h
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Doses:
4000, 8000, 10000, 12500, 16000, 20000 and 32000 mg/kg
No. of animals per sex per dose:
Five animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: Two weeks
- Frequency of observations: Animals were observed daily.
- Necropsy of survivors performed: No postmortem, or histopathology examinations were performed in this particular study.
Key result
Dose descriptor:
LD50
Effect level:
12 900 mg/kg bw
Based on:
test mat.
95% CL:
11 500 - 14 400
Dose descriptor:
LD0
Effect level:
10 000 mg/kg bw
Based on:
test mat.
Clinical signs:
Ruffled, unkempt coats were evident at 4000 mg/kg.
Lethargy, unkempt coats and nasal hemorrhage were prevalent in the animals dosed at 8000 mg/kg and 10000 mg/kg.
Staggering gait, impaired locomotion, lethargy and nasal hemorrhage were noted at levels of 12500 mg/kg and above. Comas preceded death in the animals which succumbed.
Equally toxic to male and females.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 was determined to be 12900 mg/kg.
Executive summary:

An acute oral toxicity was performed using albino male and female rats. The oral LD50 was determined to be 12900 mg/kg (95% confidence limits = 11500 -14400 mg/kg).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
12 900 mg/kg bw
Quality of whole database:
Klimisch 2. Non-GLP study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
other: extrapolation from results obtained by the oral route
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
Principles of method if other than guideline:
Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
GLP compliance:
no
Test type:
other: extrapolation
Key result
Dose descriptor:
LC50
Effect level:
50 mg/L air (nominal)

Based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals, an extrapolation based on the acute oral toxicity data is calculated for the inhalation route.

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is 12900 mg/kg bw and the LD0 is 10000 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 100% of an orally administered dose is systemically available. Since no data is available on inhalation absorption, the most precautionary default would be to assume 100% absorption by this route.

Based on this acute oral toxicity data, an oral NOAEL may be identified as 10000 mg/kg bw. This NOAEL can be modified into an inhalation NOAEL using a route-to-route extrapolation based on the assumptions stated above. Taking into account an exposure of 4 hours for the acute inhalation toxicity study, the value of the oral LD50 is divided by the default physiological parameter under the allometric scaling principle which is approximately 0.2 m3/kg bw for rats. This extrapolation leads to a value of 50 mg/l. Therefore, the 4 -h LC50 would be 50 mg/l.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the assumptions for the extrapolation from the acute oral toxicity data, the 4 -h LC50 would be 50 mg/l.
Executive summary:

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is 12900 mg/kg bw and the LD0 is 10000 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 100% of an orally administered dose is systemically available. Since no data is available on inhalation absorption, the most precautionary default would be to assume 100% absorption by this route.

Based on this acute oral toxicity data, an oral NOAEL may be identified as 10000 mg/kg bw. This NOAEL can be modified into an inhalation NOAEL using a route-to-route extrapolation based on the assumptions stated above. Taking into account an exposure of 4 hours for the acute inhalation toxicity study, the value of the oral LD50 is divided by the default physiological parameter under the allometric scaling principle which is approximately 0.2 m3/kg bw for rats. This extrapolation leads to a value of 50 mg/l. Therefore, the 4 -h LC50 would be 50 mg/l.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
50 mg/m³
Quality of whole database:
Klimisch 2. Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
other: extrapolation from results obtained by the oral route
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
Principles of method if other than guideline:
Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
GLP compliance:
no
Test type:
other: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
Key result
Dose descriptor:
LD50
Effect level:
6 450 mg/kg bw

Based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals, an extrapolation based on the acute oral toxicity data is calculated for the dermal route.

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is 12900 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be 6450 mg/kg bw.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the assumptions for the extrapolation from the acute oral toxicity data, the dermal LD50 would be 6450 mg/kg bw.
Executive summary:

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is 12900 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be 6450 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 450 mg/kg bw
Quality of whole database:
Klimisch 2. Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

Additional information

Key study: Acute oral: Experimental results: Similar to OECD guideline 401.

LD50 = 12900 mg/kg bw

Key study: Acute dermal: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

LD50 = 6450 mg/kg bw

Key study: Acute inhalation: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

LC50 = 50 mg/L

Justification for selection of acute toxicity – oral endpoint

Only one study available.

Justification for selection of acute toxicity – inhalation endpoint

Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

Justification for selection of acute toxicity – dermal endpoint

Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

Justification for classification or non-classification

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

LD50 oral > 2000 mg/kg bw

LD50 dermal > 2000 mg/kg bw

LC50 inhalation > 5 mg/L