Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
The 90-day oral rat and oral mouse studies and the 2-year chronic dermal rat and mouse studies conducted on sodium xylene sulfonate included examination of sex organs of both sexes. No treatment related effects on reproductive organs were reported.
Effect on fertility: via oral route
Endpoint conclusion:
no study available (further information necessary)
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information
Short description of key information:
No fertility studies are available for the hydrotrope category substances. Three 90-day oral studies on rat and mouse (according to / similar to OECD 408) and two 2-year chronic dermal studies on rat and mouse (OECD 453) were performed using sodium xylenesulphonate and gave no adverse results or hints for any reproductive or developmental toxicity. Against the background of the available data and due to animal welfare reasons (Article 25 of the REACH regulation), a two generation reproductive toxicity study is scientifically unjustified and will most probably not contribute to the overall risk assessment.

Nevertheless, a 2-generation reproductive toxicity study is proposed to address the strict data requirement. The registrant proposes to perform the OECD 416, oral route using rats, in a tiered approach (assess if 2nd generation part in OECD 416 is needed). This test will be started after the final decision is taken pursuant to Article 51 of the REACH regulation.

Effects on developmental toxicity

Description of key information
A single developmental toxicity study is available for the hydrotrope category substances, which was conducted on calcium xylene sulphonate. The 1994 developmental study did not follow a specific guideline but was fully documented and conducted in accordance with GLP requirements.  No adverse effects were reported.  The NOAEL for both maternal and foetal toxicity was the highest dose tested - 3000 mg/kg bw /day which is equivalent to 936 mg active ingredient per kilogram body weight per day.  The conclusion of the study was no indications of developmental toxicity including teratogenesis.  
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
936 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The available developmental study was full documented and conducted in accordance with GLP. A study in a second species is scientifically unjustified based on adequate data and in terms of animal welfare, noting testing on vertebrate animals for the purposes of Article 25 of the REACH regulation shall be undertaken only as a last resort. This finding is consistent with moves to reduce, refine or replace the use of vertebrates in toxicity tests on ethical grounds, and would avoid testing on more than 500 rabbits including offspring (Oberg M, 2010).
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In the developmental toxicity study on calcium xylene sulphonate, thirty (30) female rats received 0, 150, 1500 or 3000 mg test substance per kilogram body weight by oral gavage on days 6 to 15 of gestation. Clinical symptoms were noted daily through day 20. Body weight and food consumption were recorded every three days through day 20. All females were macroscopically examined on day 20. The uteri were removed, weighed and examined for number of corpora lutea, implant sites, and number and location of fetuses and resorptions. Fetuses were inspected on total number, sex, weight and external, visceral (one-half) and skeletal (one-half) defects. One death occurred at the 1500 mg/kg/day dose but it was considered a gavage injury. There were no abnormal clinical observations or necropsy findings. There were no effects on body weight or body weight gain. There was a significant increase in food consumption for the 3000 mg/kg/day dose during gestation interval (day) 12-16 but this was considered normal biological variation and not a direct effect of the test substance. All indices were comparable to the corresponding controls. The NOAEL based on active ingredient of the test substance is 936 mg/kg bw/day.

Justification for classification or non-classification

On the basis of the available data there is no justification to classify for reproductive toxicity.

Additional information