pentasodium 3,7,11-tris(carboxylatomethyl)-15-(C12-18)-alkyl-3,7,11,15-tetraazaheptadecane-1,17-dioate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Based on the generated data from the available OECD 422 study on Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) in rats, the NOAEL of 675.50 mg a.i./kg bw/day was identified for the reproduction/developmental toxicity. The study is performed according to OECD 422 guideline and under GLP and has reliability rating 1.

 

The test item was administered daily in graduated doses to 3 groups of test animals, one dose level per group for a treatment period of a maximum of 63 days, i.e. during 14 days of pre-mating and maximum 14 days of mating in both males and females, during the gestation period and up to post-natal day 12 in females. Males were dosed after the mating period until the minimum total dosing period of 28 days was completed. Animals of an additional control group were handled identically as the dose groups but received sterile water, the vehicle used in this study. The 4 groups comprised 10 male and 10 female Wistar rats.

 

The following doses were evaluated:

Control (C):                 0           mg/kg body weight/day

Low Dose (LD):          67.55    mg/kg body weight/day

Medium Dose (MD):   202.65  mg/kg body weight/day

High Dose (HD):         675.50  mg/kg body weight/day

 

The dose levels referred to active ingredient Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1). In order to correct for the purity of 40.8 % of active ingredient, the test material was weighed under consideration of a correction factor of 2.451. Dose volumes were adjusted individually based on the body weight most recently measured. The administration volume was 5 mL/kg body weight.

 

On the basis of this combined repeated dose oral toxicity and reproduction/ developmental toxicity screening test with Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) in male and female Wistar rats with dose levels of 67.55, 202.65 and 675.50 mg/kg body weight/day the following conclusions can be made:

 

The percentage of pre- and post- implantation losses were higher in HD group (10.20 % and 24.36, respectively) compared to corresponding control (3.77 % and 19.33, respectively). This is based on an incidental finding, single female no. 79 whose number of implantation sites was lower and who did not litter. In absence of associated findings is assumed to be without relation to the test item.

 

The delivery index was lower in HD group i.e., 83 % compared to 100 % of control. The lower delivery index in HD group is based on single female no. 79 who did not litter. In absence of associated findings is assumed to be without relation to the test item. Based on the generated data the high dose (HD) level 675.50 mg/kg body weight/day is considered to be the NOAEL for the systemic toxicity for male and female rats. The high dose (HD) level 675.50 mg/ kg body weight/day is considered to be the NOAEL for the reproduction/ developmental toxicity.

 

Available endpoint data within the substance group covers the smallest (shortest alky, lowest number amine and carboxymethylated groups, CAS no 2098351-38-1) as well as the biggest structure (longest alkyl-unsaturated, highest number amine and carboxymethylated groups, CAS no 2060541-49-1) within the amphoteric, glycinate group. The NOAEL values from these two studies are comparable, but thestudy on Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) is identified to have the lowest NOAEL value.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Read-across (Category)

The available in vivo reproduction toxicity data on this endpoint is consistent within the group. Available endpoint data covers the smallest (shortest alky chain, lowest number of amine and carboxymethylated groups, CAS no 2098351-38-1) as well as the biggest structure (longest alkyl-unsaturated chain, highest number of amine and carboxymethylated groups, CAS no 2060541-49-1) within the amphoteric, glycinate group. Both the substances have been recently tested according to the OECD 422 Guidance document under GLP. In the two studies no adverse effects were seen on reproduction or developmental endpoints in any of the doses tested. The NOAEL values from these two studies are comparable, but the study on Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) is identified to have the lowest NOAEL value. Therefore, the NOAEL for the reproduction/ developmental toxicity from the available OECD 422 study in rats is determined to be 675.50 mg a.i./kg bw/day.

Dose descriptor:

NOAEL

Effect level:

675.5 mg/kg bw/day

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: No clinical substance related effects seen in any of the dose groups

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

675.5 mg/kg bw/day

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: No clinical substance related effects seen in any of the dose groups

Reproductive effects observed:

no

Conclusions:

On the basis of this combined repeated dose oral toxicity and reproduction/ developmental toxicity screening test with Coco iminodiglycinate (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) in male and female Wistar rats with dose levels of 67.55, 202.65 and 675.50 mg/kg body weight/day the following conclusions can be made: Based on the generated data the high dose (HD) level 675.50 mg/kg body weight/day is considered to be the NOAEL for the systemic toxicity for male and female rats. The high dose (HD) level 675.50 mg/kg body weight/day is considered to be the NOAEL for the reproduction/ developmental toxicity.

Available endpoint data within the substance group covers the smallest (shortest alky, lowest number amine and carboxymethylated groups, CAS no2098351-38-1) as well as the biggest structure (longest alkyl-unsaturated, highest number amine and carboxymethylated groups, CAS no 2060541-49-1) within the amphoteric, glycinate group. The NOAEL values from these two studies are comparable, but thestudy on Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) is identified to have the lowest NOAEL value.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

675.5 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Good. The study is performed according to OECD 422 guideline and under GLP and has reliability rating 1. It is sufficient to cover the information requirement for this tonnage band.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

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

There were no indications of any substance related toxicity to reproduction in any of the dose groups of Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1), or in the other available study on Sodium oleylamphopolycarboxyglycinate (1,3-Propanediamine, N1-(3-aminopropyl)-N3-[3-[(9Z)-9-octadecen-1-ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts, CAS no 2060541-49-1). Based on the read across within the substance group, none of the substances have to be classified and has no obligatory labelling requirement according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), nor the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.