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Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated). The study assumed the use of male and female F344 rats . Since no significant treatment related effects were observed, hence the No Observed Adverse Effect Level (NOAEL) for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched is predicted to be 545.0 mg/Kg bw/day.

Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

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
545 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Data is from K2 prediction database

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

Repeated dose toxicity: Oral

Prediction model based estimation and data from read across have been reviewed and summarized to determine the mutagenic nature of

Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated):

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated). The study assumed the use of male and female F344 rats . Since no significant treatment related effects were observed, hence the No Observed Adverse Effect Level (NOAEL) for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched is predicted to be 545.0 mg/Kg bw/day.

Another study was conducted by Tyl et al (Union Carbibe Corporation, 1999) for the target chemcal. Repeated dose oral toxicity study for substance TERGITOL NP-4 (EC name: 4-Nonylphenol, branched, ethoxylated) was conducted using intimed-pregnant CD (Sprague-Dawley) rats. Based on the range finding study dose were selected. Tergitol NP-4 Surfactant was dissolved in corn oil and administered by gavage once daily on gestational days (gd) 6 through 15, to 4 group of 25 sperm-positive at doses of 0,50, 250, or 500 mg/kg/day at a dosing volume of 1.0 ml/kg. The rats were observed for mortality, clincal signs, body weight and feed consumption changes, gross pathology and organ weight changes. One pregnant female rat died at 500 mg/kg/day. Maternal body weights were significantly reduced at all doses and body weight gain were significantly reduced at 250 and 500 mg/kg/day and No effect observed on gestational weight gain, corrected for gravid uterine weight, and gravid uterine weight. Increased absolute and relative liver weight was observed. However, this finding may be due to induction of hepatic metabolizing enzymes and concomitant increase in liver mass and not to toxicity. Maternal treatment-related clinical signs were observed at 250 and 500 mg/kg/day. Maternal feed consumption was significantly reduced at 250 and 500 mg/kg/day and was significantly increased at all doses for gd 18-20. Fetal related observations like increased incidences of fetal skeletal variations, specifically bilateral and unilateral rudimentary ribs on Lumbar I increased at 250 and 500 mgl1<g/day, and normal cartilage, bipartite ossification center in a thoracic centrum apparently increased at 500 mg/kg/day, with no statistically significant difference. The incidence of fetal cleft palate was also observed but was not statistically significantly different among groups. These findings were observed in the absence of any treatment-related effects on pre or postimplantation loss, live litter size, sex ratio (% males), or on fetal body weight per litter. The No Observed Adverse Effect Level (NOAEL) for TERGITOL NP-4 is considered to be 50 mg/kg/day in CD Sprague–Dawley rats.

Repeated dose oral toxicity study was performed (J check, 2017) to determine the toxic nature of 70 -80 % structurraly similar Polyoxyethylene p-nonylphenyl ether (RA CAS no 9016 -45 -9; EC name: Nonylphenol, ethoxylated) by the OECD Guideline 407 (Repeated Dose 28 Day Oral Toxicity in Rodents). Male and femaleCrj:CD (SD)IGS rats.Polyoxyethylene p-nonylphenyl ether was dissolved in water to give a dose range of 0, 20, 200 or 1000 mg/Kg/day. During the dosing and recovery period, no animals died in any group. No abnormalities were noted in clinical signs and general behavior observations. No treatment-related effects were noted in food consumption, body weight, ophthalmology, urinalysis, hematology, blood biochemistry, gross or histopathology and organ weight observed in the 1000 mg/kg/day group. Low food consumption was noted in males in the 200 mg/Kg/day group at week 2 of the dosing period and in females in 1000 mg/Kg/day at week 2 of the recovery period. The prolongation of APTT in males in the 1000 mg/Kg/day group was noted at the end of recovery period.Females in the 20 mg/Kg/day group exhibited low glucose levels at the end of dosing period. High Na was noted in males in the 1000 mg/Kg at the end of recovery period. The effects noted were however not considered to be treatment related. igh protein in females in the 20 mg/Kg/day group was noted at week 4 of dosing period. No abnormalities were noted at week 2 of the recovery period. Males in the 200 mg/kg/day group showed low relative thymic weight at the end of dosing period. High absolute and relative weights of the adrenals and low absolute weight of the spleen and kidneys were noted in the females in the 1000 mg/Kg/day group at the end of recovery period. At the end of dosing and recovery period, red or black focus in the lung, white foci in the liver, cysts in the kidneys and asymmetry in the size of the adrenals was noted. Extramedullary hematopoiesis, hyperplasia in the plasma cells of the submandibular lymph nodes, osseous metaplasia in the lung, foamy cell aggregation in the alveoli of the lungs, focal hemorrhage of the lung, mineralization in the pulmonary artery, microvacuolization in hepatocytes of the periportal liver, mononuclear cell infiltration in the liver, focal necrosis in the liver, mineralization of the renal tubules, eosinophilic bodies in the renal tubules, basophilic changes in the renal tubules, hyaline casts in the dilated tubules of the kidney, mononuclear cell infiltration in the prostrate, mononuclear cell infiltration in the ovary, dilatation in the lumen if the uterus, cysts in the cortex of the adrenal, focal hypertrophy in the cortical cells of the adrenals, ectopic thymus in the thyroid, ultimobranchial bodies in the thyroid, brown pigment and hemorrhage in the periosteum of the femur were noted. However, all these effects observed were judged to be incidental. Thus, the No Observed Adverse Effect Level (NOAEL) for Polyoxyethylene p-nonylphenyl ether is considered to be 1000 mg/Kg/day in male and female Crj:CD (SD)IGS rats.

Meyer et al ( Pharmacology & Toxicology, 1988) reviewed repeated dose toxicity study for the read cross chemical with 50 -60% structurally similarity. As part of the safety evaluation of Polyoxyethylene Alkylphenols a teratology study with nonoxynol-9 (NP-9) (RA CAS no 26027 -38 -3; EC name: 4-Nonylphenol, ethoxylated) administered perorally. Pregnant female rats were given doses of 0, 50, 250 or 500 mg/Kg bw for a period of 6 -15 days and 500 mg/Kg bw for 1 -20 days. The rats were observed for a body weight, food consumption and gross pathology. Rats at 250 mg or 500 mg NP-9/Kg bw/day orally exhibited a statistically significant decrease in weight gain. Sporadic, not dose-related, changes in reproduction parameters were observed in the rats treated orally with NP-9. A slight, but statistically significant, lower average litter size was observed in 250 mg/kg b.wt./day and 500 mg/Kg b.wt/day group and an increase in pre-implantation loss in 250 mg/kg b.wt./day and 500 mg/kg/day groups on days 6-15. A concominant effect in these dams on reproduction, and an increase in the incidence of extra ribs and dilated pelvic cavity in their foetuses was interpreted as a consequence of a toxic effect of high doses of NP-9. The No Observed Adverse Effect Level (NOAEL) for the test compound Nonoxynol 9 is considered to be 50 mg/ Kg bw/day.

Based on the weight of evidence data summarized, Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched is not likely to classify as a toxicant upon repeated application by oral route of administration. Thus, the chemical is not classified as a toxicant as per as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the weight of evidence data summarized, Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (CAS no 127087 -87 -0;

EC name: 4-Nonylphenol, branched, ethoxylated) is not likely to classify as a toxicant upon repeated application by oral route of administration.