Ephedrine hydrochloride

Endpoint summary

Description of key information

Oral: The acute oral LD50 was calculated to be 710 mg/kg bw in rats. 
Inhalation: The LC50 was determined to be > 5.2 mg/L in rats.
Dermal: The acute dermal LD50 was determined to > 2000 mg/kg bw in rats. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

710 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 200 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Oral:

In an acute oral toxicity study single doses of 215, 316, 464, 681 or 1000 mg/kg bw of the test item (-)-Ephedrine-Hydrochloride (preparation in 0.5 % aquaeous CMC solution) were administered to groups of 5 fasted Wistar rats per sex and dose by gavage. The following test substance-related clinical observations were recorded in all dose groups: Dyspnoe, apathy, excitation, abnormal position, atonia, no pain reflex, no corneal reflex, exophthalmus, salivation, blood in the saliva, exsiccosis, clonic conculsions, piloerection. The acute oral LD50 was calculated to be 710 mg/kg bw.

Three further acute oral toxicity studies with the read-across substances DL-Ephedrin-HCl (CAS 134-71-4), (-)-Ephedrine-Sulfate (CAS 134-72-5) and (+)-Ephedrin-HCl (CAS 24221-86-1) in rats are in line with this result, with LD50 values 527 , 368 and 1290 mg/kg bw for males and females, respectively.

Furthermore, two acute oral toxicity studies in rodents with the read-across substance (-)-Ephedrine-Sulfate (CAS 134-72-5) are available (NIH, 1986). These studies underlines in principle the given LD50 data for evaluation of the acute toxicity of the test item.

Inhalation:

The acute inhalation toxicity of (-)-Ephedrine-Hydrochloride was investigated at a single concentration of 5.2 mg/L in a group of 10 male and 10 female Sprague-Dawley rats following head-nose exposure for 4 hours of an aerosol mixture with a mass median aerodynamic diameter (MMAD) of 2.8 µm. The respirable fraction was 84 %. The observation period was 14 days. No animal died and all gained body weight. The LC50 was determined to be > 5.2 mg/L after 4 hours.

In a supporting study with the read-across substances DL-Ephedrin-HCl (CAS 134-71-4), a LC50 values of > 2.2 mg/L was determined.

Dermal:

In an acute dermal toxicity study (BASF AG, 11A0597/891149, 1989), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of (-)-Ephedrin-Hydrochloride (as suspension in water) on the clipped epidermis (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity were seen. Only slight erythemas were noted on day 1 after exposure, but fully disappeared until day 7. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted.

Accordingly, the LD 50 was determined to be > 2000 mg/kg bw.

Other route:

One acute toxicity study (Fairchild et al., 1967) with mice revealed a LD50 value ca. 200 mg/kg bw when given intraperitoneally.

Justification for selection of acute toxicity – oral endpoint
The key study was selceted.

Justification for selection of acute toxicity – inhalation endpoint
The key study was selected

Justification for selection of acute toxicity – dermal endpoint
The key study was selected.

Justification for classification or non-classification

Based on the results of the acute toxicity studies, the test item has to be classified Acute Tox. Cat. 4 according to Regulation EC No 1272/2008 and Xn, R22 according EU Directive 67/548/EEC.