N-lauroylsarcosine

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

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2, due to read across) from a reference substance with similar structure and intrinsic properties. The available information comprises an adequate and reliable study (Klimisch score 2, due to read across) from a reference substance with similar structure and intrinsic properties. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There is no data available on the toxicity to reproduction of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.7.1 and IX, 8.7.3 in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from structurally related substances is done.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5., of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances listed below are selected as basis for hazard assessment.

Discussion

No studies are available investigating the toxicity to reproduction of N-lauroylsarcosine (CAS 97-78-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.7.1 and IX, 8.7.3 and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from the structurally related category members (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) and Sodium N-lauroylsarcosinate (CAS 137-16-6) was conducted.

(Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) was tested for toxicity to reproduction in a 28-day screening study according to OECD guideline 421 under GLP conditions (Stein, 2010). The doses were based on the results of a 28-day dose range finding study, with 3 animals per dose and sex orally exposed to 50, 250 and 1000 mg/kg bw/day. In the main study, groups of 12 Wistar rats (m, f) were given 50, 250 and 1000 mg/kg bw/day of the test material by gavage. Male animals were treated with the test material two weeks before mating, throughout the mating period and until the study was terminated. The female animals were exposed for 2 weeks before mating, up to 14 days until mating, for an average of 21 days of gestation, and a minimum of 4 days of lactation. A concurrent negative control group receiving the vehicle only (1% sodium carboxymethyl cellulose + 0.1% Polysorbate 80 (Tween 80), diluted in water) was included in the testing as well.

Examination of the parental animals revealed laboured breathing and vocalisations in animals from all groups treated with test item, probably due to the high surface activity of the test item. Small amounts of test item solution reached the respiratory tract, some leading to fatalities by acute exogenous lipid pneumonia. Eight animals died spontaneously or were killed during the course of the study. The premature death of most of these animals is considered to be most likely due to an inadvertent deposition of a small amount of the test item at the laryngeal orifice that was inhaled during respiration. One rat was euthanized due to an application error. In high dose males, body weight and relative body weight gain were prominently reduced throughout the study with a net mean body mass loss in the first two weeks of application. In females of the high dose group, a significantly lowered relative body weight gain during gestation and lactation was observed. However, the decreased body weights are considered to be a secondary effect due to the reduction in the mean relative food consumption and an increase in the mean relative water consumption observed in all animals from the high dose groups during the first two weeks of application. No effects on the organ mass of the sexual organs and no histomorphological effects on the genital system were observed. In addition, no test item related abnormalities were found during gross necropsy.

Regarding the reproductive performance, animals of the high dose groups showed a slightly but statistically significantly reduced mean number per dam of corpora lutea. Furthermore, in the medium and high dose group a weak evidence for a delayed conception was apparent. In the high dose group significantly reduced mean numbers of live pups at Day 4 were observed. However, the numbers of abnormal pups born and the pre-implantation and pre-natal loss were normal for rats of this strain and age, indicating that the post-natal loss was significantly raised in the high dose group. A statistically highly significant reduction of mean pup body mass and mean litter mass in the high dose group at day four was apparent. A mild and statistically significant reduced mean pup body mass (males) was found at day of birth in the high dose group when compared to the vehicle control as well. Considering the fact that no abnormalities were found by a gross necropsy and in the following histopathological examination of the reproductive organs of the parental animals, the authors concluded that the negative effects of the high dose of the test item on reproduction were not caused by its toxic properties on those organs directly, but rather on other secondary local or systemic factors affecting parental animal health, for example reduced food intake during pregnancy. Thus, a systemic NOAEL for the parental animals (m, f) of 250 mg/kg bw/day and a NOAEL (m, f) for reproduction of 1000 mg/kg bw/day was evaluated in the study.

In addition, data is available from a 2-year study with 200 rats treated with Sodium N-lauroylsarcosinate (CAS 137-16-6), that included a fertility assessment (CIR, 2001; Technology Science Group Inc., 1994). Groups of 25 Wistar rats per sex and dose were given 0.05, 0.2 and 1% of the test material in the diet, 7 days/week for 24 months. The concentration of the test material in the low dose group was increased to 2% (equiv. to 1000 mg/kg bw/day) after 6 months. A concurrent negative control group receiving the plain diet was included. At one, three and six months no significant differences were observed in mortality, body weight gain and haematology. At the end of the study period, the only consistent difference observed in gross pathology was minor hyperplasia of the stratified squamous epithelium with excess keratin formation of the cardiac mucosa of the stomach in rats receiving the highest dose of the test article (group 1: 2%; group 3: 1% in the diet). No details of the fertility assessment were given; however the authors reported that the test material did not show any significant effects on reproductive function of the parental animals.

In summary, both studies with the category members (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) and Sodium N-lauroylsarcosinate (CAS 137-16-6) showed no effects on reproductive performance, and a NOAEL for reproductive toxicity of 1000 mg/kg bw/day was defined.

Conclusion for toxicity to reproduction

In summary, both studies for the category members with the longest and the shortest carbon chain length, one of them representing the acid form, the other one representing the sodium salts, (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) and Sodium N-lauroylsarcosinate (CAS 137-16-6), respectively, showed no effects on reproductive performance, and a NOAEL for reproductive toxicity of 1000 mg/kg bw/day was adopted for the Sarcosine category.

Short description of key information:
NOAEL (OECD 421), rat, systemic and reproductive toxicity = 1000 mg/kg bw/day, based on read-across

Justification for selection of Effect on fertility via oral route:
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties among the category members and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Effects on developmental toxicity

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 available data on toxicity to reproduction of substances structurally related to N-lauroylsarcosine (CAS 97-78-9) do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.