Glycine, N-methyl-, N-coco acyl derivs., sodium salts

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive/Developmental Toxicity Screening Test (OECD 421), rat: NOAEL = 1000 mg/kg bw/day

RA from source substance N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3)

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to analogue justification report provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: observed effects were considered secondary effects due to parental toxicity

Remarks on result:

other: Source: EC 701-177-3, vivo science, 2010

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

250 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: reduction of mean relative food consumption and strong increase of mean relative water consumption, reduced mean body weight and body weight gain

Remarks on result:

other: Source: EC 701-177-3, vivo science, 2010

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction

Generation:

F1

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: observed effects are considered to be secondary effects due to parental toxicity

Remarks on result:

other: Source: EC 701-177-3, vivo science, 2010

Reproductive effects observed:

not specified

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 (Klimisch score 1) study from a source substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s) and similar physico-chemical, ecotoxicological and toxicological properties of the source and the target substances. Taken together, the information from this independent source is sufficient for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No. 1907/2006 (REACH). Therefore, the available information is sufficient to fulfil the standard information requirements set out in Annex VIII - IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006 (REACH).

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No data on toxicity to reproduction are available for Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1). Therefore, read across from the analogue substance N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) was applied.

 

Toxicity to reproduction (Reproduction/Developmental Toxicity Screening Test)

N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) was tested for toxicity to reproduction in a Reproduction/Developmental Toxicity Screening Test performed according to OECD TG 421 and in compliance with GLP (vivo Science, 2010). Dose selection was based on the results of a 28-day dose range finding study, performed with 3 animals of each sex per dose which were administered the test material at dose levels of 50, 250 and 1000 mg/kg bw/day via oral gavage. In the main study, groups of 12 Wistar rats of each sex were administered 50, 250 and 1000 mg/kg bw/day of the test material via oral gavage. Male animals were treated with the test material two weeks before mating, throughout the mating period until the study termination. The female animals were administered the test material during 2 weeks before mating, up to 14 days until mating, an average of 21 days of gestation, and a minimum of 4 days of lactation. A concurrent negative control group receiving the vehicle (1% sodium carboxymethyl cellulose + 0,1% Polysorbate 80 (Tween 80), diluted in water) only was included in the study. Examination of the parental animals revealed laboured breathing and vocalisations in animals from all test groups 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. Their 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 inspiration. One rat was euthanised 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. A reduction in the mean relative food consumption and an increase in the mean relative water consumption were 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 groups 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. A statistically highly significant reduction of mean pup body mass and mean litter mass in the high dose group at day four of lactation 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. Thus, a systemic NOAEL for the parental animals of 250 mg/kg bw/day and a NOAEL for reproduction of 1000 mg/kg bw/day was derived in the study.

In summary, a Reproduction/Developmental Toxicity Screening Test with the source substance N-methyl-N-[C18-(unsaturated)alkanoyl]glycine (EC 701-177-3) resulted in a systemic NOAEL for the parental animals of 250 mg/kg bw/day and a NOAEL for reproduction of 1000 mg/kg bw/day. Based on the read-across approach, these NOAELs are concluded also for the target substance Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1).

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 a relevant read-across source substance for toxicity to reproduction do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). Therefore, applying the read-across approach, the target substance Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) is also considered not to meet the criteria for classification for toxicity for reproduction. Data therefore are conclusive but not sufficient for classification.