10-methoxy-6-methylergoline-8β-methanol

Endpoint summary

Description of key information

Oral:

The oral LD50 value of test item in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

One in vivo study is available. According to the OECD 423 test guideline, initially, the test substacne was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure three additional groups of three females were dosed at 300 mg/kg body weight.

At 2000 mg/kg, all animals were found dead on Day 1 or 2. At 300 mg/kg, one out of nine animals was found dead on Day 1. No further mortality occurred.

At 2000 mg/kg, lethargy, lateral recumbency, flat posture, hunched posture, uncoordinated movements, shallow respiration, slow breathing, piloerection, pale appearance and/or ptosis were noted for all animals on Day 1. At 300 mg/kg, lethargy, lateral recumbency, tremor, hunched posture, uncoordinated movements, shallow respiration, quick breathing, piloerection, salivation, ptosis and/or hypothermia were noted for all animals on Day 1. Additionally piloerection was noted for two animals on Day 2.

At 2000 mg/kg, distention of the stomach with gas was found in the animal which was found dead on Day 2. At 300 mg/kg, watery-clear fluid in the stomach was found in the animal which was found dead on Day 1. Macroscopic post mortem examination of the other animals that died during the study and of the surviving animals at termination did not reveal any abnormalities.

The oral LD50 value of test substance in Wistar rats was established to be within the range of 300-2000 mg/kg body weight, the LD50 cut-off value was considered the LD50 cut-off value was considered to be 500 mg/kg body weight.

Justification for classification or non-classification

Oral LD50: 300-2000 mg/kg body weight

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1 , this substance should be classified as Category 4.

 

Specific target organ toxicity-single exposure:

Death: At 2000 mg/kg, all animals were found dead on Day 1 or 2. At 300 mg/kg, one out of nine animals was found dead on Day 1. No further mortality occurred.

Clinical observations: At 2000 mg/kg, lethargy, lateral recumbency, flat posture, hunched posture, uncoordinated movements, shallow respiration, slow breathing, piloerection, pale appearance and/or ptosis were noted for all animals on Day 1. At 300 mg/kg, lethargy, lateral recumbency, tremor, hunched posture, uncoordinated movements, shallow respiration, quick breathing, piloerection, salivation, ptosis and/or hypothermia were noted for all animals on Day 1. Additionally piloerection was noted for two animals on Day 2.

Macroscopic Findings: At 2000 mg/kg, distention of the stomach with gas was found in the animal which was found dead on Day 2. At 300 mg/kg, watery-clear fluid in the stomach was found in the animal which was found dead on Day 1.

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1 and 3.8.2, this substance should be classified as Category 2.