trisodium ({3-[(carboxylatomethyl)amino]propyl}{3-[(carboxylatomethyl)(C16-18, C18 unsat alkyl)amino]propyl}amino)acetate

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 Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1)in rats, the NOAEL of 1000 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 69 days, i.e. during 20 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 37-38 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):           100       mg/kg body weight/day

Medium Dose (MD):    300      mg/kg body weight/day

High Dose (HD):          1000    mg/kg body weight/day

 

The dose levels referred to active ingredient Sodium oleylamphopolycarboxyglycinate(1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1). In order to correct for the purity of 40.5 % of active ingredient, the test material was weighed under consideration of a correction factor of 2.469. 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 withSodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1)in male and female Wistar rats with dose levels of 100, 300 and 1000 mg/kg body weight/day the following conclusions can be made:

 

No adverse effects of test item were found on male and female clinical observations, functional observations, body weight development, food consumption, estrous cyclicity, litter data, litter weight data,precoital interval and duration of gestation, pre and post-natal data, reproductive indices, pup survival data, anogenital distance and nipple retention, pup thyroid weight and thyroid hormone analysis in parental males and pups sacrificed on PND 13, pup external findings, haematology and coagulation, clinical biochemistry, urinalysis, gross macroscopic findings at necropsy, organ weights and histopathology in all treatment groups.

 

The NOAEL of Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1) in this study for general toxicity and reproductive toxicity screening is considered to be 1000 mg/kg bw/day.

 

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 and are based on the highest dose tested. For Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1 the NOAEL is 675.50 mg a.i./kg bw/day and for Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1) the NOAEL is 1000 mg a.i./kg bw/day.

 

Based on structural similarity, the NOAEL of Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1), which is based on a short chain (mainly C12-18) diamine substance, is used for read across to the Sodium cocoamphopolycarboxyglycinate, which is a triamine based substance with the same short alkyl chain (mainly C12-C18). The same approach is used for the NOAEL of Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1), which is a tetramine with predominantly longer (C18:1) alkyl chains. Read across is applied to the other tetramine based substance Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopropyl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9), which has slightly shorter alkyl chains (C16-18, C18:1). These NOAEL values have been used for the derivation of the relevant DNEL values used in each of the risk assessment for the different amphoteric, glycinate substances.

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 repeated dose data on this endpoint is consistent within the group. The 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 parental effects were seen in any of the doses tested.

The NOAEL values from these two studies are comparable and are based on the highest dose tested. For Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1 the NOAEL is 675.50 mg a.i./kg bw/day and for Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1) the NOAEL is 1000 mg a.i./kg bw/day.

Based on structural similarity, the NOAEL of Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1), which is based on a short chain (mainly C12-18) diamine substance, is used for read across to the Sodium cocoamphopolycarboxyglycinate, which is a triamine based substance with the same short alkyl chain (mainly C12-C18). The same approach is used for the NOAEL of Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1), which is a tetramine with predominantly longer (C18:1) alkyl chains. Read across is applied to the other tetramine based substance Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopropyl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9), which has slightly shorter alkyl chains (C16-18, C18:1). These NOAEL values have been used for the derivation of the relevant DNEL values used in each of the risk assessment for the different amphoteric, glycinate substances.

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

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:

1 000 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:

The available in vivo repeated dose data on this endpoint is consistent within the group. The 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 parental effects were seen in any of the doses tested.

The NOAEL values from these two studies are comparable and are based on the highest dose tested. For Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1 the NOAEL is 675.50 mg a.i./kg bw/day and for Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1) the NOAEL is 1000 mg a.i./kg bw/day.

Based on structural similarity, the NOAEL of Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1), which is based on a short chain (mainly C12-18) diamine substance, is used for read across to the Sodium cocoamphopolycarboxyglycinate, which is a triamine based substance with the same short alkyl chain (mainly C12-C18). The same approach is used for the NOAEL of Sodium oleylamphopolycarboxyglycinate, (1,3 -Propanediamine, N1 -(3 -aminopropyl)-N3 -[3 -[(9Z)-9 -octadecen-1 -ylamino]propyl]-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541 -49 -1), which is a tetramine with predominantly longer (C18:1) alkyl chains. Read across is applied to the other tetramine based substance Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopropyl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9), which has slightly shorter alkyl chains (C16-18, C18:1). These NOAEL values have been used for the derivation of the relevant DNEL values used in each of the risk assessment for the different amphoteric, glycinate substances.

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:

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 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), or in the other available study on Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1). 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.