Registration Dossier

Administrative data

Description of key information

- Acute toxicity: 
-oral: LD50 >5000 mg/kg bw (limit test, Guidelines for Toxicity Studies of Drugs (Japan) , GLP conditions, fixed dose procedure);
-inhalation: waiver;
-dermal: waiver.

Key value for chemical safety assessment

Additional information

Only 1 acute toxicity (oral) test is available on beta-alanine. The single oral dose toxicity test of beta-alanine was conducted according to the Guidelines for Toxicity Studies of Drugs (Japan) under GLP conditions (fixed dose procedure). 6 Sprague-Dawley rats were dosed by gavage to 0 and 5000 mg/kg bw beta-alanine dissolved in water. The animals were subsequently observed for a period of 14-day. In the preliminary test, no mortality occurred at 5000 mg/kg, which is the maximum dose level that could be administered. Therefore, 5000 mg/kg was determined as the dosage level. No male or female rats in any groups died throughout the observation period. No male or female rats with abnormal findings were observed in the control group throughout the observation period.
In the 5000 mg/kg group, decrease in voluntary movement was observed in 4 male and 6 female rats for the first 0 to 30 minutes after dosing, and the incidences of the finding in male and female rats of the 5000 mg/kg group were significantly higher than those in the control group. In the 5000 mg/kg group, diarrhoea was observed in male rat for the first 0 to 30 minutes after dosing, 2 male rats at 3 hours and 3 male and 3 female rats at 6 hours after dosing. It is concluded that LD50of beta-alanine in both male and female rats by a single oral administration is higher then 5000 mg/kg.

No acute toxicity test conducted via inhalation or dermal route is available. However acute toxicity tests via inhalation and dermal route do not need to be conducted. In fact, according to Regulation No 1907/2006 (REACH) Annex VIII, Section 8.5.2, Column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. Beta-alanine vapour pressure is very low (0.00000674 Pa at 25 °C). Exposure to vapour can thus be precluded. Moreover, as the beta-alanine Mean Mass Areodynamic Diameter (MMAD) is > 100 µm, an inhalative exposure will be only likely, if beta-alanine would be used in a spray application. As a spray use of beta-alanine was excluded by the dossier submitter, exposure by inhalation can be precluded. Furthermore, the results of acute oral toxicity conducted with the substance showed no acute systemic toxicity after oral administration (LD50> 5000 mg/kg bw). Therefore, based on the low vapour pressure, exposure considerations, and on the available data on the toxicity of the substance additional testing on the acute inhalation toxicity is not considered necessary, will not be proposed and should be avoided in terms of animal welfare. Furthermore, according to Regulation No 1907/2006 (REACH) Annex VIII, Section 8.5, Column 2, information about at least one further route shall be provided. If there is only one route of exposure, information needs to be provided only for that route. Danish (Q)SAR Database predicts a low dermal absorption (0.001 mg/cm²/event) for beta-alanine. DERMWIN Skin Permeability Model predicts a very low dermal absorption for beta-alanine (0.00029 mg/cm²/h). Moreover, the results of acute oral toxicity as well as skin and eye irritation studies conducted with the substance showed no acute systemic toxicity after oral administration (LD50> 5000 mg/kg bw) and no skin and/or eye irritation potential. Therefore, based on the available data on the toxicological properties of the substance, systemic toxic effects after acute dermal exposure are unlikely to occur. Testing on the acute dermal toxicity of the substance is not considered necessary and should be avoided in terms of animal welfare.

Justification for classification or non-classification

Overall, beta-alanine is not to be classified according to DSD or CLP classification criteria.