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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 (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

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 1) from a source substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus 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.
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 the target substance Potassium (Z)-N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 76622-74-7). Therefore, read across from the source substance (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8) was applied.

 

(Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8) was tested for toxicity to reproduction in a subacute 28-day 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 62.5, 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. 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 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 significant 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 subacute 28-day Reproduction/Developmental Toxicity Screening Test with the source substance (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8) 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 analogue approach, these NOAELs are concluded also for the target substance Potassium (Z)-N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 76622-74-7).

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. Therefore, applying the RA-A approach, the target substance Potassium (Z)-N-methyl-N-(1-oxo-9-octadecenyl)aminoacetate (CAS 76622-74-7) is also considered not to meet the criteria for classification for toxicity for reproduction according to Regulation (EC) No 1272/2008. Data therefore are conclusive but not sufficient for classification.

Additional information

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