Phenol, sulfonated

Endpoint summary

Description of key information

NOAEL (male): 100 mg/kg bw/d
NOAEL (female): 300 mg/kg bw/d

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subchronic

Species:

rat

System:

other: Not specified

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

The substance DHDPSwas tested according the OECD 408. The following test substance-related, relevant findings were noted:

Soft and discolored (light brown) feces were observed in all animals of mid and high dose groups starting on different days. These findings were assessed as being treatment-related.

Salivation after treatment was observed in most mid and high dose animals as well as in 6 of 10 male and 4 of 10 female animals of the low dose. From the temporary, short appearance immediately after dosing (or shortly before) it was concluded that salivation was induced by a bad taste of the test substance or local affection of the upper digestive tract. The effect was assessed to be non-adverse.

Cecum dilation was macroscopically identified in all high dose males. Histopathological cecum effects were noted in all male and female animals of the high dose group and in one mid dose female animal. Cecum dilation may have had a significant contribution to the decreased bw observed in the high dose males. Though the human relevance of these observations is questionable due to significant anatomical and functional differences of the cecum to rodents in which this structure is large and has a significant function in the digestion.

Regenerative anemia was identified in high dose animals (male and female) characterized by increased extramedullary hematopoiesis in the spleen correlated by findings in clinical pathology (decreased red blood cell counts and hemoglobin values, in females decreased hematocrit values, higher relative reticulocyte counts at least in males, low total bilirubin levels in males).

A weight increase of the adrenal glands of high dose male animals, which correlated with hypertrophy/hyperplasia in the cortex was regarded as adverse and treatment related.  

In absence of degenerative findings, multifocal mineralization of kidney tubules noted in males of all treatment groups was regarded as nonadverse.

In the mammary gland of male animals of the mid and high dose animals, a change from the physiological lobulo - alveolar morphology to a tubulo-alveolar appearance with smaller more basophilic epithelial lining cells (atrophy) was seen. In the literature (Rudmann et al., 2012; see also OECD, Series on Testing and Assessment, No. 106, 2009, Part4: Mammary gland [http://www.oecd.org/chemicalsafety/testing/43754898.pdf])), the occurrence of atrophy has been correlated to altered hormone levels (increased prolactin or decreased androgen) or with emaciation in male animals. This finding was regarded as adverse.

 

Increased liver weights in females of the mid and high dose was correlated with a dose-dependent centrilobular hypertrophy was seen in 2/10, 5/10, and 10/10 animals in low, mid and high dose group, respectively. Gradings were minimal in low to moderate in high dose animals correlating with the macroscopic finding “enlarged” in the high dose. In the livers of the high dose females, there was also an increased incidence of mainly eosinophilic foci of hepatocellular alteration, which were confirmed by GSTP immunohistochemistry, and considered to be adverse. Only the hypertrophy in the liver in combination with the increased liver weight of high dose females was assessed as adverse due to the presence of these foci. The hypertrophy alone in low and mid dose groups was assessed as non-adverse as no concurrent findings in clinical pathology were noted.

The increased relative liver weight in high dose males was assessed as adverse together with clinical pathology findings (lower cholesterol and higher triglyceride levels).

In the uterus, focal squamous cell metaplasia of glandular epithelium was observed in 2 females of low and mid dose group and in 5 of 10 females of the high dose group. In the high dose group this finding was assessed as possibly treatment-related and adverse due to the higher incidence. For low and mid dose group animals the finding was assessed as non-adverse as it can occur in single animals in control groups.

The increased weights of the ovaries of test group 3 females were assessed as treatment related although there were no correlating histopathological findings.

 

Justification for classification or non-classification

Based on the information available for repeated dose toxicity and according to the CLP Regulation n.1272/2008, table 3.9.1 , the substance is not classified for specific target organ toxicity-repeated exposure.