Propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (1:1), (2R)-

Endpoint summary

Description of key information

Oral, LD50, rat [(R)-2-(4-hydroxyphenoxy)-propanoic acid] > 2000 mg/kg bw (Lheritier 1988) 
Inhalation, 4 hours, LC50 [(R)-2-(4-hydroxyphenoxy)-propanoic acid] > 1.84 mg/L  (Young 1996)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity of potassium (R)-2-(4-hydroxyphenoxy)propionate, (CAS 1184648-08-5) was determined by read-across from acute toxicity studies conducted with the free acid, namely (R)-2-(4-hydroxyphenoxy)propanoic acid (CAS 94050-90 -5).

Oral:

Only a single oral toxicity study conducted according to guideline OECD 401 and under GLP is available for the source substance, (R)-2-(4-hydroxyphenoxy)-propanoic acid (CAS 94050-90-5). The study is considered to be relevant, reliable (Klimisch 1) and adequate for the purposes of risk assessment, classification and labelling. The LD50 in male and female rats was determined to be >2000 mg/kg bw, since no mortality, clinical signs, or macropathological findings were observed in the limit test with the source substance, the free acid (R)-2-(4-hydroxyphenoxy)-propanoic acid.

The acute oral toxicity of the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) (CAS 1184648-08-5) is determined by read-across from the limit test with the free acid. The analogue approach is based on the facts that source and target contain the identical molecular structure and the same functional groups (except the K+ counterion), form a pH-dependent equilibrium, and the salt is rapidly converted to the free acid under the acidic conditions in the stomach. Upon neutralization in the duodenum (with a large excess of sodium ions), source and target become fully indistinguishable in their bioavailability and metabolic fate.

The only difference, the presence of equimolar quantities of potassium ions in the target substance, is expected to have no toxicological consequences, since the quantity of K+ administered with a limit test dose (2000 mg/kg bw) of the target substance amounts to only 26% of a conservative estimate for the oral LD50 of potassium ions, derived from KCl data.

As a conclusion, the acute oral toxicity of propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) is estimated to be >= 2000 mg/kg bw.

Inhalation:

Only a single inhalation toxicity study conducted according to guideline OECD 403 and under GLP is available for the source substance, (R)-2-(4-hydroxyphenoxy)-propanoic acid (CAS 94050-90-5). The study is considered to be relevant, reliable (Klimisch 1) and adequate for the purposes of risk assessment, classification and labelling. The LC50 in male and female rats upon 4-hour nose-only exposure to the test substance dust was determined to be > 1.84 +/- 0.31 mg/L air (analytical, highest achievable concentration), since no mortality and no clinical symptoms were observed with the source substance, the free acid (R)-2-(4-hydroxyphenoxy)-propanoic acid.

The acute inhalation toxicity of the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) (CAS 1184648-08-5) is determined by read-across from the limit inhalation test with the free acid. The analogue approach is based on the facts that source and target contain the identical molecular structure and the same functional groups (except the K+ counterion), form a pH-dependent equilibrium, and both are rapidly converted to the sodium salt in plasma (due to the large excess of sodium ions) after uptake via the lungs, which makes both substances indistinguishable in their bioavailability and metabolic fate.

The only difference, the presence of equimolar quantities of potassium ions in the target substance, is expected to have limited toxicological consequences, since the quantity of K+ administered per hour during inhalation of a limit concentration (5000 mg/m3 of the target substance) amounts to approx. 99% of a non-lethal intravenous and ca. 58% of a lethal intravenous K+ infusion rate determined for KCl.

As a conclusion, the acute inhalation LC50 of propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) is estimated to be > 1840 mg/m3.

For Classification purposes it should also be considered that there is no sign of any clinical effect at the highest technically achievable concentration in the respective test so that it is highly likely that the real LC50 level is even higher than the limit concentration for classification purposes. This is supported by another LC50 measurement reported in UBE Industries Ltd., Tokyo, Japan (2002): Safety Data Sheet of R-HPPA (CAS 94050-90-5), Version 1, 2002/07/15 with LC50 > 5.2 mg/L (inh. rat). Based on these findings the substance is not classified due to acute inhalation toxicity.

Justification for classification or non-classification

Acute Oral Toxicity

The key value selected for the acute oral toxicity, LD50>2000mg/kg bw does not lead to classification, according to the criteria in Directive 2001/59/EC, Annex VI, 3.2.3.

The key value selected for the acute oral toxicity, LD50>2000mg/kg bw does not lead to classification, according to the criteria in Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2.

Acute Inhalation Toxicity

The key value selected for the acute oral toxicity, LD50 >1.84 mg/L bw together with other information provided as part of a weight of evidence does not lead to classification, according to the criteria in Directive 2001/59/EC, Annex VI, 3.2.3.

The key value selected for the acute oral toxicity, LD50 >1.84 mg/L bw together with other information provided as part of a weight of evedince does not lead to classification, according to the criteria in Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2.

Acute Dermal Toxicity

No experimental data are available which are suitable for the purposes of classification and labelling.