Safety evaluation of certain food additives - ipcs inchem

ETHYL LAUROYL ARGINATE 53
stomach lining, resulting in migration of white blood cells into the tissues (Brown,
2008).
2.2.3 Long-term studies of toxicity
In a 52-week study conducted to GLP and in accordance with OECD
guidelines, three groups of 20 male and 20 female Crl:CD(SD)IGS BR rats were
given diets containing ethyl lauroyl arginate (purity, 88.2% ethyl-N -lauroyl-Larginate
HCl) at concentrations of 0, 2000, 6000 or 18 000 mg/kg diet (equal to 0,
106, 307 and 907 mg/kg bw per day for males; and 0, 131, 393 and 1128 mg/kg bw
per day for females) continuously. During the study, animals were inspected for
clinical condition, and body weight and food consumption were recorded. Prior to
commencement and during each week of treatment, the animals were assessed for
physical condition and behaviour; during week 49 of treatment, sensory reactivity,
grip strength and motor activity assessments were performed on 10 males and
10 females from each group. Ophthalmic examinations of all animals in the control
and top-dose groups were carried out before treatment and during week 51. During
weeks 14, 26 and 52, blood samples were taken from the retro-orbital sinus of
10 males and 10 females from each group for analysis of an extensive range of
haematological and blood chemistry parameters. Additional blood samples were
also withdrawn from 18 males and 18 females in each treatment group for
toxicokinetic and bioanalytical investigations. During weeks 12, 25 and 51, urine
samples were collected from all animals for urinalysis. At the end of the treatment
period, all animals were subjected to a detailed necropsy. Bone marrow samples
were taken from the tibia during necropsy and smears prepared for a full myelogram.
A full macroscopic examination was performed, and weights of adrenals, brain,
kidneys, liver, ovaries and testes were recorded. An extensive range of tissue
samples were collected for microscopic examination.
There were six unscheduled deaths during the study, considered by the
authors not to be attributable to treatment: one control male, two males and one
female in the 2000 mg/kg diet dose group, and one male and one female in the
18 000 mg/kg diet dose group. Females in the 18 000 mg/kg diet dose group and,
to a lesser extent, in the 6000 mg/kg diet dose group showed higher weekly
incidences of brown fur staining and ungroomed coats, compared with the controls,
during the period from week 1 to week 13. By week 14, no clear difference between
groups was observed. At 6000 and 18 000 mg/kg diet, both males and females
showed low body weight gain compared with controls throughout the treatment
period, but particularly so during the first 3 weeks (in week 1, animals treated with
18 000 mg/kg diet showed gains that were less than 50% of the control values).
Food consumption was reduced in both males and females at 18 000 mg/kg diet
throughout the treatment period (particularly in week 1, when consumption was 69%
and 76%, respectively, of that of controls); and in males at 6000 mg/kg diet
throughout the treatment period. Reduced food conversion efficiency was observed
in both males and females at 6000 and 18 000 mg/kg diet, during the 1st week of
treatment only. The authors attributed the lower weight gains to a lower food intake.
The only effect noted in the neurobehavioural screening was higher total high- and
low-beam motor activity scores for males receiving 18 000 mg/kg diet, compared