Safety evaluation of certain food additives - ipcs inchem

CALCIUM LIGNOSULFONATE (40–65) 25
body weight gain of the dose groups were similar to those of the control groups. At
scheduled necropsy, no test item–related findings were noted. The relevant
reproduction data (number of implantation sites, post-implantation loss, number of
live fetuses and number of embryo or fetal resorptions) from dose groups were
similar to those of the control.
The mean fetal weights were not considered to be influenced by treatment
with the test item, as observed changes were minimal and within the historical
control database. The sex ratio was comparable with that of controls. External
examination at caesarean section did not reveal any test item–related findings.
Visceral examination of bones and cartilage also revealed no test item–related
findings. Local thinning of the diaphragm was found in one fetus (one litter), three
fetuses (three litters), six fetuses (five litters) and seven fetuses (six litters) in the
control, low-dose, mid-dose and high-dose groups, respectively. In the additional
control and additional high-dose group, the incidences were three fetuses (three
litters) and six fetuses (four litters), respectively. The historical reference data for
this finding show an incidence of 0–8 occurrences. Thus, the finding of local thinning
of the diaphragm was considered to be within known background and not of
biological and toxicological relevance.
Under the conditions of this study, the oral treatment with the test item was
well tolerated in all dose groups. Mean food consumption and body weight
development of dams were similar in all groups. The relevant reproduction data, sex
ratios of fetuses and fetal weights were similar in all groups. There were no abnormal
embryo or fetal findings that were considered to be related to test item treatment.
The NOEL was at the high dose of 1000 mg/kg bw per day.
2.2.4 Special study on immune responses
After oral exposure of rats via the diet for 13 weeks (for study details, see
section 2.2.1), examination of total and differential white blood cell count as well as
determination of T-cell type distribution did not show any indication of different
distribution in comparison with control. Further, the primary immune response to
sheep red blood cells was comparable with control levels (Thiel et al., 2007).
2.2.5 Special study on skin sensitization
The potential of calcium lignosulfonate (40–65) to induce contact
hypersensitivity was investigated in mice using the local lymph node assay (van
Huygevoort, 2004). Groups of five animals each were epidermally exposed to 0,
2.5, 10 and 25% solutions of the test substance in propylene glycol on 3 consecutive
days. Three days after the last exposure, animals received injections with [ 3 H]methyl
thymidine; 5 h later, they were sacrificed, lymph nodes were excised and
incorporated radioactivity in precipitated deoxyribonucleic acid (DNA) was
determined. No skin irritation during induction was observed, and excised nodes
were normal. The stimulation index (SI) values for the substance at concentrations
of 2.5, 10 and 25% were 0.8, 0.5 and 0.9, respectively. There was no indication that
the compound could elicit SI values higher than 3, and it was concluded that the
compound should not be regarded as a skin sensitizer.