COAGULANT 122 (SOLID)

Endpoint summary

Description of key information

No toxicokinetic data (animal or human studies) are available on Coag 122 (solid).  The data present in this dossier are based on physico-chemical parameters and will allow a qualitative assessment of the toxicokinetic behaviour of this substance.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Additional information

Coagulant 122 (solid), N,N-bis(2-hydroxypropyl)-hydroxylamine (HPHA) is typically 88% pure and contains the

major impurities 1-(N-(2-hydroxypropoxy-2-methyl-ethyl)-hydroxylamino)propane-2-ol and 2-(N-2-hydroxypropyl-hydroxylamino)propane-1-ol.

It is a stabiliser used as an oxygen scavenger in boiler feed water and as a polymerisation inhibitor in the petrochemical and refining industries. It is an off white waxy solid, with a melting point of 13 - 38 °C and a molecular weight of 149.21 Coagulant 122 (solid) has a vapour pressure of 0.0135 Pa, a partition coeficient (log Pow) of -0.53 and is miscible with water (>92.6% w/w at 20°C).

Toxicity

Acute oral toxicity. At a limit dose of 2500 mg/kg, there were no mortalities. All animals of both sexes appeared normal through out the 14 day observation period.

Acute dermal toxicity. At a limit dose of 2000 mg/kg there were no mortalities, systemic reactions or local reactions to treatment. There were slightly low body weight gains in three male and three female animals on Day 8, with a similar trend noted for three males and one female on Day 15. All other rats achieved a satisfactory body weight gain throughout the study.

Skin írritation. A single semi-occlusive application of Coagulant 122 (solid) produced no irritation. There were no signs of toxicity or ill health in any rabbit.

Eye initaion. A single instillation of Coagulant 122 (solid) elicited very slight transient conjunctival irritation. All reactions were resolved one or two days after instillation.

28 day sub-acute toxicity study. Groups of five male and five female rats received 15 or 150 or 1000 mg/kg/day via oral gavage. No animals died during the study and there were no clinical signs of toxicological importance. Body weight and food consumption were not affected. There were no changes in macro- or microscopic pathology, haematology, biochemistry or urinalysis, that were considered to be treatment related or of toxicological importance.

1000 mg/kg/day was considered to represent a no-observed-effect level for Coagulant 122 (solid) in rats.

Mutagenicity : Metabolism.

No toxicity or mutagenic activity were seen in the Ames test either in the absence or presence of S-9 mix. In the in vitro cytogenetics assay Coagulant 122 (solid) was clastogenic in the absence of S-9 mix but not in its presence. In addition, Coagulant 122 (solid) was slightly less toxic in the presence of S-9 mix. These findings might indicate Cytochrome P450 detoxification, but might also be a consequence of the reduced exposure time in the presence of S-9 mix due to its inherent toxicity.

Assessment

Coagulant 122 (solid) is miscible with water and has a low molecular weight indicating that the chemical has potential for bioavailability although the low partition coefficient indicates that it is unlikely to accumulate.

The solid is waxy and thus it is unlikely to be an inhalation hazard in terms of dust but the vapour pressure does suggest that exposure to vapour is a possibility, especially on heating. The results of the acute oral toxicity study indicate that the substance was systemically nontoxic, in the repeat dose study there was no evidence of toxict or accumulation. The results of the acute dermal toxicity test indicate that when applied dermally, Coagulant 122 (solid) is neither systemically nor topically toxic. In the in vitro cytogenetics assay the fact that the test substance was clastogenic without S-9 mix but not with S-9 mix may indicate that Coagulant 122 (solid) is metabolised by Cytochrome P450, but alternatively might also be a reflection of the longer exposure time used in the absence of S-9 mix.

Based on molecular weight and log P between -1 and 4, the dermal absorption factor might therefore be set to 100% ( ECHA guidance on IR&CSA, R.7c).

Based on high water solubility and high hydrophilicity of the substance, the oral absorption factor might therefore be set to 100% ( ECHA guidance on IR&CSA, R.7c).

Conclusion

The results of the toxicity studies conducted on Coagulant 122 (solid) show no evidence of systemic toxict. Consequently, little can be inferred about the systemic absorbtion of the material, other than to speculate, on the basis of the complete lack of toxicologically significant effects in any of the pararmeters investigated in the 28 day study, that the material is indeed poorly absorbed.

The in vitro cytogenetics study provides circumstantial, but not conclusive evidence of metabolism and due to the lack of clinical, biochemical or pathological findings (in turn quite possibly due to lack of absortition) no comment can be made about distribution or excretion.