10/07/2008

Toxicity and Safety -Toxicity in Animals - LD 50 and acute toxicity in mice

• LD50 in Mice - Oral Administration

 

Oral doses up to 30 g/kg of P-MAPA in 0.9% saline solution were administrated, using the gavage method in a dose/volume of 20 mL/kg in a group of 10 Albine Swiss mice (female and male, 30 ± 5 g).

 

None of the animals died during the 14 days observation period after P-MAPA administration.

 

• LD50 in Mice -Subcutaneous Administration

 

Subcutaneous doses up to 30 g/kg of P-MAPA in a 0.9% saline solution were administrated, in a dose/volume ratio of 10 ml/kg, in a group of 10 Albine Swiss mice (female and male, 30 ± 5 g).

 

None of the animals died after P-MAPA administration during 14 days.

 

• LD50 in Mice - Intraperitoneal Administration

 

A LD50 of 2.71 ± 1.55 g/kg of body weight was obtained by P-MAPA intraperitoneally administered (0.9% saline solution), in a dose/volume ratio of 10 mL/kg to a group of 10 Albine Swiss mice (female and male, 30 ± 5 g). All the deaths occurred after 48 h of P-M.A.P.A.. administration by respiratory collapse. The microscopic examination revealed a large blood vessels congestion in the peritoneal cavity.

 

• Oral Acute Toxicity in Mice (single dose)

 

Doses of 500, 1000 and 2000 mg/kg of P-MAPA in 0.9% saline solutions were orally administered to a group of 10 Albine Swiss mice (female and male, 30 ± 5 g) , using the gavage method in a dose/volume ratio of 10 and 20 ml/kg.

 

Results

 

None of animals died during this experiments during 14 days of observation.

 

Animals receiving the largest P-MAPA dose had lower weight gain than the untreated mice (38.3 ± 3.9 and 48.1 ± 3.7 ) for the males and (31.4 ± 3.3 and 39.8 ± 4.1 ) for the female, respectively).

 

The weight loss compared to the control group occurred with treated animals with a low and medium doses in the males, but not in the females.

 

Male cases did not exhibit any dose-effect relationship, neither any statistic significance for the differences observed.

 

Therefore, the weight loss of the treated animals should not be attributed only to the toxic effect of P-MAPA.