Safety evaluation of certain food additives - ipcs inchem

50 ETHYL LAUROYL ARGINATE
50 000 mg/kg diet (equal to 0, 384, 1143 and 3714 mg/kg bw per day for males; and
0, 445, 1286 and 3915 mg/kg bw per day for females) continuously. The study was
conducted in accordance with GLP and OECD guidelines. Animals were inspected
at least twice daily throughout the study. Body weights were recorded on the day
that treatment commenced and then weekly throughout the remainder of the
treatment period. Mean weekly food consumption for each animal was calculated,
as well as mean food conversion efficiencies for each treatment group. A number
of functional observations were performed at various times throughout the study.
Just prior to necropsy, blood samples were taken from the retro-orbital sinus, and
an extensive range of haematological and blood chemistry tests were performed.
During the final week of treatment, urine was collected for urinalysis and
microscopy; and the eyes of 10 males and 10 females from each group were
examined. A wide range of organs and tissues were collected for weight
measurement and histopathology at necropsy.
There were no deaths. There was evidence of mild toxicity during the in-life
assessments of animals receiving 15 000 and 50 000 mg/kg diet, observed as
effects on appearance (ungroomed coat and brown staining on the muzzle),
reduced body weight gains and reduced food consumption and food conversion
efficiencies. During the 1st week of treatment, animals receiving 50 000 mg/kg diet
had a marked loss of body weight (–16% and –13% for males and females,
respectively). Body weight gain was also significantly lower in animals receiving
15 000 mg/kg diet and males receiving 5000 mg/kg diet. Overall, the body weights
of animals receiving 50 000 mg/kg diet and of males receiving 15 000 mg/kg diet
did not fully recover by the end of the treatment period. During week 1, food
consumption was markedly lower for animals receiving 50 000 mg/kg diet (33% and
39% of that of the controls for males and females, respectively). Food consumption
for animals receiving 15 000 mg/kg diet and males receiving 5000 mg/kg diet was
also slightly lower than that of the controls. Food consumption remained low during
the remainder of the study in animals receiving 50 000 mg/kg diet (overall, 79% and
78% of control values for males and females, respectively). Food conversion
efficiencies were incalculable during the 1st week of treatment for animals receiving
50 000 mg/kg diet because of the body weight losses; thereafter, food conversion
efficiency was slightly higher than or similar to that of the controls. The battery of
functional observations revealed no evidence of neurotoxicity. There were no
treatment-related ophthalmological findings. Minor changes were observed in
haematological parameters of males receiving 50 000 mg/kg diet (slightly higher
mean cell haemoglobin, mean cell haemoglobin concentration and mean cell
volume, and slightly lower total white blood cell and lymphocyte counts compared
with controls). These changes were not evident in females. Blood chemistry
investigations revealed lower total protein and albumin concentrations,
predominantly for animals receiving 50 000 mg/kg diet. Slightly lower cholesterol
concentrations were also apparent for females receiving 50 000 mg/kg diet. Such
findings are indicative of an effect on the liver. However, in the absence of any effect
on liver weight or findings at macroscopic examination, these changes were
considered by the authors to be of doubtful toxicological significance. Urinalysis
revealed a low pH in males receiving 15 000 and 50 000 mg/kg diet. Macroscopic
examination did not reveal any treatment-related findings, nor were there any organ