Phosphoric acid, mono- and di-isotridecyl esters, potassium salts

Endpoint summary

Description of key information

Based on the results of the read across studies, a NOAEL of 1000 mg/kg bw/day from the longer duration combined repeated dose and reproductive and development toxicity study (OECD 422) conducted with mono- and di- C12 PSE, Na+ has been considered further for hazard assessment. This is further supported by a similar NOAEL observed in a longer duration (90-day) repeated dose study available with mono- and di- C12 PSE, K+ in rats.

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

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Guideline compliant read across study

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

Study 1:A dose range finding study was conducted to determine the oral repeated dose toxicity of the read across substance, mono- and di- C12 PSE, K+, according to OECD Guideline 407 and EU Method B.7, in compliance with GLP. In this study, 3 male and female Wistar rats each received by gavage 10 mL/kg bw test substance at concentrations of 0 (water), 60, 600 and 1000 mg/kg bw, 7 days per week for a period of 14 days. During the treatment period, the animals were observed precisely each day for signs of toxicity. Body weight and food consumption were measured once weekly. At the conclusion of the treatment period, hematological and clinical biochemistry parameters were analyzed and all animals were sacrificed and subjected to necropsy. The wet weight of a subset of tissues was taken and a set of organs/tissues was preserved. The test substance formulations (test substance suspended in aqua ad injectionem) were prepared freshly on each day of administration. Dose volumes were adjusted individually based on weekly body weight measurement. No mortality occurred in the control or any of the dose groups during the treatment period of this study. Slight to moderate clinical signs (pilo erection and salivation) were observed during the first treatment week in 1/3 female animals of the high dose (HD) group. Besides, there were no considerable test substance-related clinical signs in this study. In 1/3 male animals of the HD group, body weight and food consumption decreased in the first treatment week. As the animal recovered in the second treatment week, it is not considered to be a sign of systemic toxicity but rather a local reaction. Besides, treatment with the test substance did not influence food consumption and body weight gain of male and female animals of this study. Test substance administration had a slight effect on haematological parameters analyzed at the end of the treatment period. In the HD group and in female animals of the mid dose (MD) group, a slight to moderate increase in neutrophils with a concurrent slight decrease in lymphocytes was observed in the differential blood cell count at the end of the treatment period. These findings in the differential white blood cell count were assumed to be related to a piece of gavaging cannula that had been swallowed and had subsequently affected food consumption and body weight development. At the end of the treatment period, a slightly and dose dependent elevated serum level of alkaline phosphatase was found in male and female animals of the MD and HD group when compared to the control group. This was not associated with considerable differences in other serum markers for hepatotoxicity (ALT, ASAT, Chol). No specific test substance-related gross pathological changes were recorded for the male and female animals of this study. In male animals of the HD group prostate gland was slightly reduced and epididymis weight was slightly increased in weight, compared to controls. Based on the results of the read across study, the 14 d NOAEL of the test substance was determined to be 600 mg/kg bw/day (Allingham, 2012).

Study 2:A study was conducted to determine the toxicity to reproduction of the read across substance, mono- C12 PSE, Na+, according to OECD Guideline 422, in compliance with GLP. The test substance was administered at 0 (control group), 250, 500 or 1000 mg/kg bw to male Sprague-Dawley SPF rats for 14 days before mating, through the mating period, and up to 1 day before necropsy (42 days in total) and to female Sprague-Dawley SPF rats for 14 days before mating, through the mating period and the gestation period, up to day 4 of lactation (42 to 45 days in total) to investigate the repeated-dose, reproductive and developmental toxicities. In the 0 and 1000 mg/kg bw groups, a 14-day recovery period was allowed after the 42-day administration period to investigate the reversibility of the toxic changes. Administration of the test substance had no effect on any of the following: general condition, findings on detailed observation of the general condition, results of function tests, grip strength, spontaneous motor activity, body weight, food consumption, results of urinalysis (including water intake), or in the results of hematological or blood chemistry tests. Administration of the test substance had no effect on any of the following: general condition, findings on detailed observation of the general condition, results of function tests, grip strength, spontaneous motor activity, body weight, food consumption, results of urinalysis (including water intake), or in the results of hematological or blood chemistry tests. Changes in the forestomach may be considered to be adverse; however, they are also considered to be a result of local irritation of the (irritant) test item (which is brought directly in contact to the mucosa in a massive amount by gavage application) than a true effect of systemic toxicity. Furthermore, in the light of the absence of a forestomach in humans, observed effects on this tissue are of questionable relevance with reference to the extrapolation of the toxic properties of a test substance in humans. Therefore, based on the results of the read across study, the NOAEL for systemic effects is considered to be 1000 mg/kg bw/day(METI, 2005).

Justification for classification or non-classification

Based on the results of the read across studies, the test substance does not meet the criteria for classification for this endpoint according to CLP (Regulation 1272/2008/EC) criteria.​​