Docosyltrimethylammonium methyl sulphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Sufficient.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a weight-of-evidence approach, the following data was considered.

The OECD TG 421 study of the the closely related substance C20-22-alkyltrimethylammonium chloride is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item to rats. The test item was administered in Milli-Q-Water as vehicle at dosages of 10, 30, and 75 mg/kg body weight/day, and controls received the vehicle only. The test item was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum.

Based on the decreased food consumption and lower body weights in males and females and gains in females at 75 mg/kg/day and the lower food consumption in males at 30 mg/kg/day which did not affect body weight, the parental NOAEL (No Observed Adverse Effect Level) was established at 30 mg/kg/day. The NOAEL (No Observed Adverse Effect Level) for reproduction (fertility) was considered to be 75 mg/kg/day. The NOAEL for developmental toxicity was considered to be 30 mg/kg/day based on the lower pup weight gain at 75 mg/kg/day, which was probably secondary to lower food consumption of the dams.

In a published 2-generation reproductive toxicity study in rats which received 0, 300, 750 or 1500 ppm of the related substance didecyldimethyl ammonium chloride in the diet (corresponding to 0, 20, 50, or 103 mg/kg/day for males and 0, 24, 61, or 122 mg/kg/day for females) effects in offspring (decreased pup body weight and body weight gain) occurred at the same dose level of 1500 ppm as parental effects (decreased body weight, body weight gain and food consumption). The NOAEL for parental toxicity was 750 ppm (56 mg/kg/day) and the NOAEL for reproductive toxicity was 750 ppm (56 mg/kg/day).

The purpose of the supporting dose-range-finder study for the OECD TG 421 study of the the similar supporting substance C20-22-alkyltrimethylammonium chloride was

to select suitable dosages and appropriate administration method of the test item to be used in the subsequent reproduction/developmental toxicity screening test in the Han Wistar rat. The test item was therefore administered by gavage and by feeding. Additional biological assays and clinical pathology were also performed in order to evaluate further findings from previous studies. The test item was administered orally by gavage once daily at dose levels of 50 and 150 mg/kg body weight/day and by feeding at dose levels of 600, 1800 and 6000 ppm. Severe adverse effects occurred at dietary levels of 1800 and 6000 ppm and at the gavage dose level of 150 mg/kg/day. Consequently, these groups were terminated due to humane reasons. At the dietary level of 600 ppm and the gavage dose level of 50 mg/kg/day, similar findings were noted. There were no striking differences in findings when the test item was administered in the diet or by gavage. Based on these results dose levels of 10, 30 and 75 mg/kg bw/day were considered apriopriate for the subsequent Reproduction/Developmental Toxicity Screening Test in the Han Wistar Rat.

Short description of key information:
The closely related substance C20-22-alkyltrimethylammonium chloride was tested in a reproductive toxicity screening study. No relevant effects on fertility/reproduction or development were observed. The parental NOAEL was 30 mg/kg/day (based on reduced body weight), the NOAEL for reproduction/fertility was 75 mg/kg/day and the NOAEL for developmental toxicity was 30 mg/kg/day (based on lower pup weight, secondary to reduced maternal food consumption).
In a published 2-generation reproductive toxicity study in rats which received the related substance didecyldimethyl ammonium chloride in the diet, the NOAEL for parental toxicity was 750 ppm (56 mg/kg/day) and the NOAEL for reproductive toxicity was 750 ppm (56 mg/kg/day).
The substance is considered not to exert any reproductive toxic effects (fertility).

Justification for selection of Effect on fertility via oral route:
Weight-of-evidence; several studies.

Effects on developmental toxicity

Description of key information

In accordance with Section 1.2 of REACH Annex XI, there is sufficient weight of evidence from several independent sources of information leading to the conclusion that the submission substance does not cause developmental toxicity and thus does not have to be classified, because 
- it is considered to have a very limited systemic bioavailability via the dermal route due to its low water solubility and ionic nature; this conclusion is  supported by experimental data for the closely related analogue substance C20-22-alkyltrimethylammonium chloride, which show a very low dermal absorption (<0.5%)
- the analogue substance C20-22-alkyltrimethylammonium chloride did not cause any developmental/teratogenic effects or fertility/reproductive effects in a reproductive toxicity screening study in rats,
- this conclusion is also supported by read-across data for a chemically similar substance that did not cause any fertility/reproductive effects in a 2-generation reproductive toxicity feeding study.
It can therefore be concluded that the submission substance will not cause developmental toxicity and that testing is not scientifically necessary.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

The closely related substance C20-22-alkyltrimethylammonium chloride does not cause toxicity to reproduction and thus does not have to be classified according to the criteria laid down in the EU Dangerous Substances Directive (67/548/) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC), because it did not cause any developmental/teratogenic effects or fertility/reproductive effects in a reproductive toxicity screening study in rats. This conclusion is also supported by read-across data for a chemically similar substance that did not cause any fertility/reproductive effects in a 2-generation reproductive toxicity study with oral administration.

It can therefore be concluded that the submission substance will also not cause toxicity to reproduction and that testing is not scientifically necessary.