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EC number: 232-650-8 | CAS number: 9002-07-7
Trypsin was tested in Sprague-Dawley rats for 4 weeks.
It was concluded that the twice-daily oral administration of SP387/TL-1 to Sprague-Dawley rats for 4 weeks at a range of enzyme activities up to a total daily dose of 6841 KMTU/kg bwt/day was generally well-tolerated, though at the highest dose level there were stomach erosions that were considered responses to an irritant test material and these findings were considered adverse. In view of the presence of these erosions in the high dose animals, the no-observed-adverse-effect level (NOAEL) was considered to be 3420 KMTU/kg bwt/day (1.96 g TOS/kg bw).
The objective of this study was to assess and compare the systemic toxic potential of a range of percentage enzyme activities of SP387/TL-1 (an enzyme used in the food industry), after twice-daily oral (gavage) administration to Sprague-Dawley rats for 4 weeks. The control group received the vehicle (reverse osmosis water) at a total volume-dose of 20 mL/kg body weight (bwt). The test concentrations were 67, 217, 435, 870, 3420, and 6841 KMTU/kg bw/day.
During the study, clinical condition, detailed physical examination and arena observations, sensory reactivity observations, grip strength, motor activity, body weight, food and water consumption, hematology (peripheral blood), blood chemistry, urinalysis, organ weight, macropathology and histopathology investigations were undertaken.
There were no deaths associated with SP387/TL-1. The general appearance and behavior of the animals and sensory activity, grip strength and motor activity were unaffected by treatment. There was no effect of treatment upon body weight and on food and water consumption. Females receiving 6841 KMTU/kg bwt/day showed an approximately 29% higher weight gain, than the controls but this was due to their higher food intake, compared to controls, which was a trend that was present before treatment commenced. There were no treatment-related haematology or blood chemistry findings. Urine analysis revealed slightly low pH at all doses and in both sexes but there was no dose-response and the findings were considered to be incidental and of no toxicological importance.
The statistical analysis of organ weights indicated high liver weights in males and females which received 6841 KMTU/kg bwt/day and in females which received 67 or 870 KMTU/kg bwt/day. In addition, there was a small increase of spleen weights in males which received 67 or 6841 KMTU/kg bwt/day and of heart weights in females at 6841 KMTU/kg bwt/day. There were no associated histopathological findings, the values were within concurrent or historical control ranges and these organ weight variations were considered to be due to normal biological variation not related to treatment.
The macroscopic examination revealed the presence of depressions in the glandular mucosa of the stomach of two males and four females given 6841 KMTU/kg bwt/day, with two of these females also having thickening of the non-glandular mucosa. This correlated with epithelial hyperplasia and erosion of the non-glandular region of the stomach and these findings were considered related to treatment and adverse.
In the liver there was a minor but treatment-related histopathology finding to just above background levels, in the form of periportal vacuolation in males given 67, 870 or 6841 KMTU/kg bwt/day and at all doses in females; in females the extent of this finding was greatest at 67, 870 and 6841 KMTU/kg bwt/day. As these groups received the highest dose in terms of g TOS, they represented expected (and reversible) findings in response to the administration of high doses of protein and, as such, were considered toxicologically insignificant and non-adverse.
It was concluded that the twice-daily oral administration of SP387/TL-1 to Sprague-Dawley rats for 4 weeks at a range of enzyme activities up to a total daily dose of 6841 KMTU/kg bwt/day was generally well-tolerated, though at the highest dose level there were stomach erosions that were considered responses to an irritant test material and these findings were considered adverse. In view of the presence of erosions in the high dose animals the no-observed-adverse-effect level (NOAEL) was considered to be 3420 KMTU/kg bwt/day (corresponding to 1.96 g TOS/kg bw/day).
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