Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Results 'read across' from study on N,N', N''-nitrilotriethanol, propoxylated, as permitted by Annex XI para 1.5, based on the justification in the report from Paul Illing Consultancy Services Ltd and Marlin Consultancy (Illing and Barratt, 2007, revised 2009). The report identifies that N,N',N''-nitrilotriethanol, propoxylated is the most bioavailable of the NLP polyols linked by an ether group, and that the lack of systemic toxicity seen for it and for both components (propylidyne trimethanol and propane-1,2-diol) of propylidyne trimethanol,, propoxylated can be considered representative of the lack of toxicity of the ether linked NLP polyol. Consult Illing and Barratt (2007 and 2009), for further details.

Toxicity to reproduction of Nitrilotriethanol, propoxylated was investigated in an OECD 421 screening study. Treatment with 2,2',2''-Nitrilotriethanol, propoxylated resulted in increased incidence of salivation at the 1000 mg/kg dose in both genders and possibly transiently in females at 300 mg/kg dose group. Females of the 1000 m/kg dose group showed body weight loss during lactation for which treatment relationship, although unlikely, could not be completely excluded.

The reported NOAEL for male (general toxicity) 1000 mg/kg bw/day

The reported NOAEL for female (general toxicity): 300 mg/kg bw/day

The registrant considers the mild bodyweight loss observed with females at the highest dose group (1000 mg/kg bw/day) as non adverse treatment related effect as it follows a statistically significant increased body weight gain, as compared to control, in the premating phase.

The No Adverse Effect Level (parental toxicity) is therefore concluded to be >=1000 mg/kg bw/day.

There were no detectable effects in offspring. The reported NOAEL (reproduction/development): 1000 mg/kg bw/day.

Toxicity to reproduction of propylidynetrimethaol, ethoxylated was investigated in an OECD 421 screening study.

The NOAEL (no observed adverse effect level) for reproductive performance and fertility is 1000 mg/kg body weight/day for the F0 parental rats. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg body weight/day for the F0 parental animals. The NOAEL for developmental toxicity in the F1 progeny of the test-substance treated groups was found to be 1000 mg/kg body weight/day.

Adequate testing has been undertaken on a sufficient number of the core substances and repeating units. None of the tested core substances and none of the repeating units is classifiable as a reproductive toxin. Hence it would be anticipated that the NLP polyols, as a category, would also not be reproductive toxins. The NLP polyols, nitrilotriethanol, propoxylated andpropylidynetrimethanol, ethoxylatedwere tested to fulfil the requirements of Annex VIII (>10 tonnes/y). The results from these screening reproductive tests confirmed the pre-existing information. The NLP polyols are not reproductive or developmental toxins. Furthermore, a range of studies has been conducted on core substances and repeating units and screening tests have been conducted on most substances in the NLP polyol categories. It is possible to ‘read across’ the results from all of these sources to all substances in these categories. Sufficient data exist to permit robust conclusions that the substances are not reproductive or developmental toxins and that no further testing is required (Illing and Barratt, 2009).

Effects on developmental toxicity

Additional information
A developmental toxicity study was performed with the test substance according to OECD TG 414. Female Wistar rats each were treated daily orally bygavage with 0, 100, 300, and 1000 mg/kg body weight in deminaralized water from day 6 to day 20 p.c. Summarizing and evaluating all data investigated the following no-observed-adverse-effect levels (NOAELs) were determined: for maternal toxicity 1000 mg/kg bw, for developmental toxicity 1000 mg/kg bw.

Justification for classification or non-classification

The findings in the available study do not warrant classification according to the EU criteria.