D-Glucitol, propoxylated

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

Result 'read across' from study on 2,2’,2’’- Ntrilotriethanol, 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 2,2’,2’’-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 the components (glucitol and propane-1,2-diol) of glucitol, propoxylated can be considered representative of the lack of toxicity of the ether-linked NLP polyol. Consult Illing and Barratt (2009 and 2009) attached in Section 13 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 mg/kg dose group showed body weight loss during lactation for which a treatment relationship, although unlikely, could not be completely excluded.

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 NOAEL (reproduction/developmental toxicity) is >1000 mg/kg bw/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. Three of the NLP polyols, nitrilotriethanol, propoxylated, diaminotoluene, propoxylated and ethylenediamine, ethoxylated and propoxylated, were 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.

Short description of key information:
NOAEL (reproduction/developmental toxicity, oral gavage OECD 421) >= 1000 mg/kg bw/day.

Effects on developmental toxicity

Additional information

Adequate testing has been undertaken on 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. There is

sufficient information from a qualitative and quantitative understanding of the toxicological properties of the core substance (glucitol is listed on Annex IV of the REACH Regulation) and the repeating unit, propane-1,2-diol. D-glucitol enters endogenous carbohydrate metabolism and is converted metabolically to fructose (Illing and Barratt, 2009 and 2009; see Section 13).  Propane-1,2 -diol resulted in no developmental toxicity in rats, mice, rabbits or hamsters (NOAELs range from 1.2 -1.6 g/kg bw/d) (Illing and Barratt, 2009 and 2009; see Section 13).

In a developmental toxicity study with mice (Bushy Run Research Center, 1993), monopropylene glycol (propane-1,2 -diol) was

administered to pregnant mice at dose levels of 0, 0.5, 5.0 and 10.0 ml/kg bw/day (0, 52, 520 and 10400 mg/kg

bw/day) on gestation days 6 through 15. Mice were sacrificed on gestation day 18 and evaluation of fetuses, uterine

weight, number of corpora lutea and implantation sites was performed. Increased water consumption was observed

in the 10.0 ml/kg bw/day group and, although not statistically significant, in the middle dose group. No further

treatment-related clinical signs, effects on maternal body weights and body weight gains, food consumption were

observed at any dose level and no treatment-related necropsy findings of the dams at the scheduled sacrifice on

gestation day 18 were found. Therefore, the increase in water consumption is likely to be a normal physiological

reaction to the administration of a high quantity of substance by gavage, which may cause a surge in the osmolarity

of body fluids. Consequently, this effect is not considered to be of toxicological significance.

There were no effects of treatment on gravid uterine weight, the number of ovarian corpora lutea, the number of

total, viable or nonviable implantations/litter or on sex ratio. Also no effects on fetal body weights/litter were

observed which were attributed to treatment. There were no treatment related increases in the incidences of

individual fetal external or visceral variations. Based on the results of the study, the NOAEL for developmental

toxicity was established to correspond to 10400 mg/kg bw/day.

Three of the NLP polyols, nitrilotriethanol, propoxylated, diaminotoluene, propoxylated and ethylenediamine, ethoxylated and propoxylated, were tested to fulfil the requirements of Annex VIII (>10 tonnes/y).In addition, ethylenediamine, ethoxylated and propoxylated,was tested in a developmental toxicity study (OECD 414).

The results from these screening reproductive tests and the developmental toxicity test confirmed the pre-existing information. Sufficient data exist to permit robust conclusions that the substances are not reproductive or developmental toxins and that no further testing is required.

Justification for classification or non-classification

On the basis of read across it is anticipated that the substance does not meet criteria for classification.