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Description of key information

Repeated dose toxicity oral: NOAEL (m, f): 20 mg/kg bw/day (OECD 422, GLP)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
20 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Aminoiminomethanesulphinic acid was administered at doses of 4, 20 and 100 mg/kg bw/day in Crj:CD (SD) IGS male and female rats to study repeated dose toxicity and developmental toxicity for parental animals, and reproductive/developmental toxicity in pups due to OECD assessment for existing chemicals in a screening test conducted according to OECD 422 and under GLP conditions. Males were orally administered 14 days before mating, 35 days during and after mating. Females were orally administered during mating period, pregnancy period and until 3 days of lactation. No mortality was observed in animals. Loss of fur was observed in one male and two females at dose of 100 mg/kg. Body weight gain was suppressed after dosing 100 mg/kg in both sexes. In this group, food consumption was also decreased.

Hematological findings of male rats showed a decrease in erythrocyte and hematocrit, an increase in reticulocyte, and a reduction of prothrombin time and APTT.

Myelogram findings of male rats in the 100 mg/kg bw treatment group showed a decrease in nucleated cells, M/E ratio, neutrophil, eosinophil, lymphocyte, basophilic erythroblast, and poly- and orthochrome erythroblast.

Biochemical findings of male rats at doses of more than 20 mg/kg bw/day administered groups showed a decrease in ALP. In the 100 mg/kg bw administered group, albumin, A/G ratio, triglycerides, phospholipids, total bilirubin, BUN, creatinine, inorganic phosphorus and calcium were increased. Glucose, GOT, GPT and potassium were decreased in the 100 mg/kg group bw

An increase in liver and spleen weight was found in males and females of the 100 mg/kg bw group. Organ weight of testis was also increased in this group.

With regard to histopathological findings, hepatocyte hypertrophy of centrilobular, basophilic material in bile duct, vacuolar degeneration of hepatocyte, and hemosiderin deposit of Kupffer cells were observed in males and females of the 100 mg/kg bw group. In kidney, tubular necrosis was observed in only one female of the 100 mg/kg bw group. Basophilic tubule was observed in males and females of the 100 mg/kg bw group. Some of these cases showed also cellular infiltration of lymphocyte and tubule dilatation. Erosion or ulcer of glandular stomach was observed in males and females of the 100 mg/kg bw group. This effect may be related to the irritant properties of the substance. Extramedullary hematopoiesis and hemosiderin deposit of red pulp was observed in both sexes of the 100 mg/kg bw/group. Decreased hematopoiesis of femur bone marrow was observed in males in the 100 mg/kg bw group. Besides, dilatation of seminiferous tubule, degeneration of germ cell, multinucleated giant cell, vacuolization of Sertoli cell, seminiferous tubule atrophy and spermatic granuloma were observed in testis in the 100 mg/kg bw group.

In addition, necrosis of hepatocyte, accumulation of foam cell, mineralization of artery, hemorrhage of lungs and thymus, myocardial degeneration, atrophy of seminiferous tubule, granuloma of spermatic of testis and epididymis were regarded as not relevant toxicological effect but changes caused naturally.

On the basis of the above exposed the NOAEL for the repeated dose toxicity is considered to be 20 mg/kg bw/day for males and females.

In addition aminoiminomethanesulphinic acid was tested in a subacute test according to OECD guideline 407. Groups of 5 male and 5 female Wistar rats each received once per day on 5 days per week during 4 consecutive weeks an oral dose of the test compound per gavage. Doses were 0, 15, 47 and 150 mg/kg body weight per day (OECD SIDS 2002). Changes observed in the high dose group (150 mg/kg bw/day) included reduced body weight gain, reduced food consumption, raised fur, reduction of serum levels of cholesterol, glucose and alkaline phosphatase, elevation of serum levels of bilirubin and inorganic phosphate, reduced weights of the thymus. In the mid dose group only a decrease of serum alkaline phosphatase was found. Histopathological analysis did not reveal unequivocally substance related effects. Since the decreased alkaline phosphatase at the mid dose level was an isolated effect it was concluded that the No-Adverse-Effect-Level was 47 mg aminoiminomethanesulphinic acid per kg body weight in both sexes of rats.

On the basis of the data above exposed aminoiminomethanesulphinic acid (CAS 1758-73-2) meet the criteria for classification STOT RE 2, H373 according to Regulation (EC) No 1272/2008 or Xn, R48/22 according to Directive 67/548/EEC on the basis of the hematological and biochemical changes.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

Test conditions according to GLP and standard method

Justification for classification or non-classification

The available data on the repeated dose toxicity of aminoiminomethanesulphinic acid (CAS 1758-73-2) meet the criteria for classification STOT RE 2, H373 according to Regulation (EC) No 1272/2008 or Xn, R48/22 according to Directive 67/548/EEC.