Manganese Violet

Endpoint summary

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:

other: 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

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)

Clinical signs:

other:

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 air

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