Methoxyammonium chloride

Endpoint summary

Description of key information

No reliable data are available for the test substance. The toxicological assessment is based on read-across to CAS 10039-54-0.

NOAEL = 0.9 mg/kg bw/d; 90 d, rat, oral (similar to OECD 408, GLP, reliability 2) 

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

0.9 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The quality of the whole database is high.

System:

haematopoietic

Organ:

blood

spleen

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

In a subchronic oral toxicity study similar to OECD TG 408 (but without recovery period) and in compliance with GLP, the test material was administered to 60 Wistar rats (30 males and 30 females ) via the drinking water (in Milli-Q extra pure water) for 90 consecutive days. For comparison, one group of untreated animals (10 males and 10 females) was used as control.
The doses in the drinking water were 10 ppm (test group 1), 50 ppm (test group 2) and 250 ppm (test group 3). The doses administered corresponded to a mean daily test substance intake of approx. 0.9, 4 and 21 mg/kg bw/day. The average daily food intake in mg/kg bw was calculated for each animal at the time intervals when the water consumption was determined.

Regarding mortality, general appearance and behaviour of the animals there was no difference between treated and untreated animals. No toxicologically relevant differences in mean feed consumption per animal/d or per kg bw/d as well as body weight and body weight development were detected in male and female rats. The following findings were obtained and assessed as substance-induced.

At 250 ppm, rats of both sexes showed dark coloration of the urine. This is considered to be due to the substance-related effects on the blood. The hematological examination revealed indications of an increased destruction of red blood cells. At 250 ppm in both sexes and at 50 ppm in females there was a reduction of the erythrocytes and haemoglobin values. In addition there were an increase of the MCH values in both sexes at 250 ppm and in females at 50 ppm, furthermore reduced values of hematocrit in females and of the MCHC in males at 250 ppm. In males receiving 50 ppm, decreased counts of red blood cells and decreased values of haemoglobin were also apparent during the treatment period, although these did not attain statistical significance. These findings are considered to be related also to an increased decay of erythrocytes. The increase of the MCV, and reticulocyte counts at 250 ppm in males and females were assessed as sign of compensate increased erythropoiesis. As a consequence of an increased leaving of juvenile erythrocytes out of the bone marrow a reinforced polychromasia was seen dose-dependent at 250 and 50 ppm in both sexes. At 50 ppm, a slight increase of reticulocytes in male and female rats was noted, and moreover in females a marginal increase of the MCV values. Furthermore, an increase of bilirubin concentration in both sexes at 250 ppm was observed. In males and females receiving 50 ppm, increased values of bilirubin were also apparent during the treatment period, although these did not attain statistical significance. This finding appears to be due to the increased decay of erythrocytes. The elevated methaemoglobin concentration and the reinforced evidence of Heinz bodies in both sexes at 250 ppm are indicative for methaemoglobinemia. Increased absolute and relative spleen weights were seen at 250 ppm in male and female rats. Increase of relative liver weights were noted only in males. In males and females receiving 50 ppm, increased absolute and relative adrenal weights were noted.
Histopathological findings representing secondary effects to the anemia included increased hemosiderin deposits in the spleen and liver of both males and females given 250 ppm. At 50 ppm, moderate increased hemosiderin deposits in the spleen were revealed in both sexes. In addition, sinus dilatation together with congestion of the spleen were observed dosedependent in both sexes at 50 and 250 ppm. 10 ppm did not alter the blood parameters in rats of both sexes.

Based on the results of this study, 50 ppm (equivalent to about 4 mg/kg bw/d) can considered to be the LOAEL for systemic effects in male and female rats. No local toxic effects were seen in male and female rats treated with the highest tested dose level of 250 ppm, equivalent to about 21 mg/kg bw/day.

The Technical Committee on Classification and Labelling (TC C&L) and the Specialised Experts group considered the effects at 50 ppm not to be serious to an extent that would warrant a classification. Thus, according to this expert judgment, the results of this study also do not warrant a classification as STOT RE 1.

 

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. There were significant hematotoxic effects at doses of 0.9 mg/kg bw/day upon subchronic oral exposure in rats. Based on expert group judgement the substance is considered to be classified for repeated dose toxicity in Category 2 under Regulation (EC) No. 1272/2008, as amended for the seventeenth time in Regulation (EC) No. 2021/849.