Reaction mass of Ammonium dihydrogenorthophosphate and diammonium hydrogenorthophosphate.

Endpoint summary

Description of key information

No study with ammonium dihydrogenorthophoshate is present. Based on a reliable oral OECD 422 study with diammonium hydrogenorthophoshate 
in rats, local effects were observed in the stomach at the lowest dose tested (250 mg/kg bw/day). However, the systemic NOAEL is determined to be 
250 mg/kg bw/day based on horizontal banding of dental surface at mid dose (LOAEL), with effects on haematological and clinical chemistry 
parameters at highest dose level (1500 mg/Kg bw/day).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

No reliable study is present for ammonium dihydrogenorthophosphate.

In a reliable oral OECD 422 study, rats (5/sex/dose) were dosed 250, 750 and 1500 mg/kg bw/day diammonium hydrogenorthophoshate. Males and females were treated until termination during week 6 of treatment. The body weight gain of males at 1500 mg/kg/day appeared to be suppressed between Weeks 0 -5. There was a reduction in activated partial thromboplastin time for males at 750 and 1500 mg/kg/day, although this was not dosage related. No treatment related changes in these parameters were observed for females. Reviewer considers this not toxicologically relevant at 750 mg/kg bw, due to no dose response, high standard deviation, no effects in the liver, control value very high (historical control data Charles River, hematology parameters for the Crl:CDBR Rat, 1993). Males showed a non dosage-dependant elevation of alkaline phosphatase levels at 750 and 1500 mg/kg/day, reduced glucose and phosphorous levels at 1500 mg/kg/day, a small but dosage-dependant reduction in total protein at 750 and

1500 mg/kg/day with a slightly elevated albumin/globulin ratio at the top dosage. Changes in females were limited to a decrease in phosphorous levels at 1500 mg/kg/day although a non-significant increase in alkaline phosphatase levels at 1500 mg/kg/day in particular suggested a similar change to that recorded in males. Reviewer: Effect on total protein (at 750 mg/kg bw) although dose related was marginal (<10% compared to control), no change in albumin or A/G ratio and within the historical range of control data (Clinical Laboratory Parameters for Crl:CD(SD) rats, 2006, Charles River Laboratories). Therefore not considered adverse.

Bodyweight relative kidney and liver weights for toxicity subgroup females at 1500 mg/kg/day were increased, but in the absence of a histological correlate for these findings, this was of uncertain toxicological significance. A number of males and females at 750 and 1500 mg/kg/day had thickened stomachs and associated findings, and exhibited horizontal bands on the incisors. Stomachs of animals showed minimal or slight submucosal inflammation at all doses (0/5, 3/5, 4/5 and 2/5 males and 0/5, 2/5, 4/5 and 4/5 females at 0, 250, 750 and 1500 mg/kg bw respectively). It is thought that these findings may have been associated with an irritant effect of the test formulations rather than systemic toxicity. Reviewer considers this a comon local effect which is reversible.

Histological processing of the teeth that showed horizontal banding failed to detect any involvement of areas examined suggesting that the banding was probably restricted to the enamel of the teeth. This directs to an effect on the mineralisation process of tooth and bones. Reviewer: The roots of the teeth were not examined, so whether the cells that produce emaille are affected remains unknown.Based on this a systemic NOAEL of 250 mg/kg bw/day is derived.

No dermal or inhalation toxicity studies are present. Although dermal exposure is likely, dermal absorption is considered to be very low and thus a dermal exposure study would be of limited value. In addition, the vapour pressure of the liquid reaction is assumed to be low, indicating that only very limited inhalation exposure is possible. Moreover, since the aerodynamicaerodynamic diameter of the solid form of the reaction mass is high (D50 =3.25 mm) it is not expected that this substance will reach the nasopharyncheal region or subsequently the tracheobronchial or pulmonary region.

Justification for classification or non-classification

Based on the available data, the reaction mass of ammonium dihydrogenorthophosphate and diammonium hydrogenorthophosphate does not have to be classified according to Directive 67/548/EC and the CLP Regulation for general toxicity.