Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: - | CAS number: -
The concentrations analysed in the formulations of Group 2 (95mg/kg), Group 3 (298mg/kg) and Group 4 (893mg/kg) were in agreement with target concentrations (i.e. mean accuracies between 85% and 115%).
No test substance was detected in the Group 1 (control) formulation.
The formulations of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation≤ 10%).
Formulations at the entire range were stable when stored at room temperature under normal laboratory light conditions for at least 6 hours.
A Combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test ofdi C8-C10, branched, C9 rich, alkylnaphthalene sulphonic acid (DNNSA) was conducted in rats by oral gavage (OECD 422).
Based on the results of a 10-day dose range finding study, the dose levels for this combined 28-day oral gavage study with reproduction/developmental toxicity screening test were selected to be 95, 298 and 893 mg/kg.
After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test substance at 0, 95, 298, and 893 mg/kg/day. Males were exposed for 31 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 41-52 days, i.e. during 2 weeks prior to mating, during mating, duringpost-coitum, and during at least 4 days of lactation.
The following observations and examinations were evaluated: mortality / viability, clinical signs (daily), functional observations and locomotor activity (Week 4 (males); end of lactation (females)), body weight and food consumption (at least at weekly intervals), clinical pathology (Week 4 (males); end of lactation (females)), macroscopy at termination, organ weights and histopathology on a selection of tissues, and reproduction/developmental parameters, consisting of mating, fertility and conception indices, precoital time, number of corpora lutea and implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs, body weights and macroscopy).Formulations were analyzed once during the study to assess accuracy, homogeneity and stability.
Accuracy, homogeneity and stability of formulations were demonstrated by analyses.
At 893 mg/kg, four males were sacrificed in extremis during the first week of treatment, and one female was sacrificed in extremis on Day 23 of the post-coitum phase. At 298 mg/kg, one female was sacrificed in extremis on Day 27 of the post-coitum phase. This single death at 298 mg/kg was considered to be related to treatment considering the mortality incidence at 893 mg/kg.
Animals sacrificed in extremis showed clinical signs including lethargy, hunched posture, piloerection, diarrhoea and/or a lean appearance. All these animals showed weight loss, and food intake was reduced among these sacrificed animals. Food intake of surviving animals was similar to control levels. Some of these clinical signs noted for sacrificed animals were also noted among surviving animals at 298 and 893 mg/kg, albeit at much lower incidence.
At 893 mg/kg, surviving males showed a lower mean body weight (gain) throughout the mating period, with occasional weight loss among two surviving animals towards the end of their scheduled treatment period. Changes in clinical biochemistry parameters consisted of higher alanine aminotransferase activity in males and females, higher aspartate aminotransferase activity in males, higher alkaline phosphataseactivity in males and females at 893 mg/kg, higher albumin and total bilirubin level in females, higher urea level in males, lower cholesterol level in males and females, and higher calcium level in females.
At 298 mg/kg, changes in clinical biochemistry were confined to a higher alkaline phosphatase activity in females, and lower cholesterol level in males.
Treatment-related microscopic findings in surviving animals at 893 mg/kg (correlating to necropsy findings) were noted in the gastro-intestinal tract, and included hyperkeratosis of the forestomach epithelium, mucosal hyperplasia and increased severity of lymphogranulocytic inflammation in the caecum and increased amounts of mucus in the large intestines. Other microscopic findings at this dose included lymphoid atrophy of the thymus, decreased severity of hemopoietic foci in the spleen, increased severity of alveolar foamy macrophages in the lungs and scattered hepatocellular vacuolation in the liver. Reduced contents in the prostate gland, seminal vesicles and preputial gland among some males at 893 mg/kg were considered to have occurred secondary to lower body weights. Microscopic findings observed in early sacrifices were generally similar in nature and severity as those recorded for surviving animals. The female at 893 mg/kg additionally showed mucosal hyperplasia of the small intestines, reduced red pulpa of the spleen and cortical necrosis in the adrenals.
The increased severity of myeloid hyperplasia with increased granulopoiesis in the sternal bone marrow at 893 mg/kg (all sacrificed males and one surviving male) was in line with the higher neutrophil count (and resulting higher white blood cell count) for males at this dose level.
At 95 mg/kg, no toxicologically relevant effects were noted in any of the parameters examined.
In conclusion, treatment with di C8-C10, branched, C9 rich, alkylnaphthalene sulphonic acid (DNNSA) by oral gavage in male and female Wistar Han rats at dose levels of 95, 298, and 893 mg/kg body weight/day revealed parental toxicity at 298 and 893 mg/kg body weight/day. Based on these results, the No Observed Adverse Effect Levels (NOAEL) for repeat dose exposure to adult parental animals was 95 mg/kg/day.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again