Sodium sulphamidate

Endpoint summary

Description of key information

The oral administration of Sodium sulphamate to rats by gavage, at dose levels of 100, 300 and 1000 mg/kg bw/day, did not result in any toxicologically significant effects.  The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was therefore considered to be 1000 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

The study was designed to investigate the systemic toxicity and potential adverse effects of the test item on reproduction (including offspring development) and was designed to be compatible with the requirements of the OECD Guidelines for Testing of Chemicals No. 422 “Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test” (adopted 22 March 1996).

The oral administration of Sodium sulphamate to rats for a period of up to eight weeks (including two weeks pre-mating, gestation and early lactation period for females) at dose levels of up to 1000 mg/kg bw/day resulted in treatment related effects detected in animals of either sex treated with 1000 mg/kg bw/day.

No clinical signs of toxicity were detected in treated animals however the physical condition of males treated with 1000 mg/kg bw/day was affected slightly with reductions in body weight development during the first and last weeks of treatment. Subsequently a slight reduction in overall body weight gain, a slight reduction in overall food consumption and a slight reduction in food efficiency was evident in these males.

Haematological investigations revealed increases in haemoglobin, haematocrit and clotting time in females treated with 1000 mg/kg bw/day. This together with the slight decline in male health was probably associated with the bone marrow and spleen changes seen microscopically. Changes were identified as increased hematopoiesis in the spleen and an increased incidence and mean severity of erythroid hyperplasia in the bone marrow in animals of either sex treated with 1000 mg/kg bw/day. The findings detected in the spleen and bone marrow are considered to be related to treatment however are considered not to be an adverse effect of treatment. Therefore the slight decline in health detected in males and the changes detected in the haematological parameters measured are considered not to be of toxicological significance.

Absolute and relative kidney weights were elevated in females treated with 1000 mg/kg bw/day and microscopic examination of kidney sections revealed focal and multifocal occurring basophilic tubules in females treated with 1000 mg/kg bw/day. The majority of individual organ weight values were within the normal range for rats of the strain and age used. The basophilic tubules detected in female kidneys did not reveal a true dose-relationship and they were also present in a few control animals. The kidney changes were also only minimally increased in incidence therefore, this finding was considered to be still within the biological range known for rats of this age and strain used and as such was considered not to be of toxicological importance.

There were no toxicologically significant effects observed during the weekly open field arena observations, in the blood chemical parameters measured or at necropsy.

There were no treatment-related effects detected in the reproductive parameters observed.

Justification for classification or non-classification

The oral administration of Sodium sulphamate to rats by gavage, at dose levels of 100, 300 and 1000 mg/kg bw/day, did not result in any toxicologically significant effects (see discussion for details on effects observed). The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was therefore considered to be 1000 mg/kg bw/day.

Based on the determined NOAEL of 1000 mg/kg bw/day and assessment of effects seen in the study, it is considered that the test substance does not meet the criteria for classification for repeat dose toxicity.