P-1057

Endpoint summary

Description of key information

Acute oral toxicity: Key study: Based on read-across approach from analogue substance P0310, the LD50 of the substance P-1057 is calculated to be greater than 2490 mg/kg bw.

Acute dermal toxicity: Key study: Based on read-across approach from analogue substance P0310, the LD50 of the substance P-1057 is calculated to be greater than 2490 mg/kg bw.

Acute inhalation toxicity: Key study: Based on the assumptions for the extrapolation from the acute oral toxicity data, the inhalation 4-h LC50 would be greater than 12.45 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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across from an analogue substance for which a guideline study (Klimish 1) is available.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across approach from experimental data (study according to OECD 423 and GLP) on an analogue substance.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 490 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Based on a read-across from an analogue substance.

Interpretation of results:

other: Not classified based on CLP criteria.

Conclusions:

Based on read-across approach from analogue substance P0310, the LD50 of the substance P-1057 is calculated to be greater than 2490 mg/kg bw.

Executive summary:

Based on experimental results obtained in a study according to OECD 423 on analogue substance P0310 where the LD50 for female rats was determined to be greater than 2000 mg/kg bw, the read-across approach is applied and the LD50 for the substance P-1057 is determined to be greater than 2490 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 490 mg/kg bw

Quality of whole database:

Key study: Read across from a high quality study (Klimish score =1) performed with an analogue substance.

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.

Reason / purpose for cross-reference:

reference to other study

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.

Test type:

other: extrapolation

Key result

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 12.45 mg/L air

Based on:

test mat.

Exp. duration:

4 h

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 read-across approach, it is concluded that the oral LD50 for the substance is greater than 2490 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 greater than 2490 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 2490 mg/kg bw 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 12450 mg/m3 (12.45 mg/l). Therefore, the 4 -h LC50 would be greater than 12.45 mg/l (dust/particles inhalation).

Interpretation of results:

other: Not classified based on CLP criteria.

Conclusions:

Based on the assumptions for the extrapolation from the acute oral toxicity data, the inhalation 4-h LC50 would be greater than 12.45 mg/l.

Executive summary:

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 read-across approach, it is concluded that the oral LD50 for the substance is greater than 2490 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 greater than 2490 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 2490 mg/kg bw 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 12450 mg/m3 (12.45 mg/l). Therefore, the 4 -h LC50 would be greater than 12.45 mg/l (dust/particles inhalation).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

12 450 mg/m³

Quality of whole database:

Key study: Extrapolation from a read across from a high quality study (Klimish score=1) from an analogue substance.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across from an analogue substance for which a guideline study (Klimish 1) is available.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across approach from data on an analogue substance.

Test type:

standard acute method

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 490 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Based on a read-across from an analogue substance.

Interpretation of results:

other: Not classified based on CLP criteria.

Conclusions:

Based on read-across approach from analogue substance P0310, the LD50 of the substance P-1057 is calculated to be greater than 2490 mg/kg bw.

Executive summary:

Based on experimental results obtained in a study according to OECD 402 on analogue substance P0310 where the LD50 for male and female rats was determined to be greater than 2000 mg/kg bw, the read-across approach is applied and the LD50 for the substance P-1057 is determined to be greater than 2490 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 490 mg/kg bw

Quality of whole database:

Key study: Read across from a high quality study (Klimish score =1) performed with an analogue substance.

Additional information

Acute oral toxicity: Key study: Based on experimental results obtained in a study according to OECD 423 on analogue substance P0310 where the LD50 for female rats was determined to be greater than 2000 mg/kg bw, the read-across approach is applied and the LD50 for the substance P-1057 is determined to be greater than 2490 mg/kg bw.

Acute dermal toxicity: Key study: Based on experimental results obtained in a study according to OECD 402 on analogue substance P0310 where the LD50 for male and female rats was determined to be greater than 2000 mg/kg bw, the read-across approach is applied and the LD50 for the substance P-1057 is determined to be greater than 2490 mg/kg bw.

Acute inhalation toxicity: Key study: Based on the assumptions for the extrapolation from the acute oral toxicity data, the inhalation 4-h LC50 would be greater than 12.45 mg/l.

Justification for classification or non-classification

Based on the available information, the substance is not classified for acute toxicity according to CLP criteria.