Bis(2-hydroxyethyl)ammonium acetate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data are available on DEA acetate. However, a one-generation reproductive toxicity study has been conducted on RA2. This yielded a critical NOAEL of 300 mg/kg bw/day based on an increased number of dead pups and post-implantation losses in females ("possibly test item-related") at 1000 mg/kg bw/day (a paternally, but not maternally, toxic dose).

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Data waiving:

other justification

Justification for data waiving:

other:

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:

subchronic

Species:

rat

Quality of whole database:

Although no relevant data are available on DEA acetate, a good-quality, reliable, GLP-compliant, OECD-guideline one-generation study on RA2 is available (Becker & Ceccatelli, 2007; Becker et al. 2008). Together with exposure-based data waivers, this meets the REACH tonnage-driven data requirements.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

REACH Annex XI states that testing for reproductive toxicity in accordance with Annex VIII may be omitted, based on the exposure scenario(s) developed in the Chemical Safety Report. A low likelihood of human exposure is anticipated, and a log Pow expected to be lower than -1.31 indicated that bioaccumulation is not likely to occur. In addition, no adverse effects were seen on the reproductive organs of the parental animals or on fertility in a reliable oral one-generation reproductive toxicity study on a structurally-related read-across compound, resulting in a fertility NOAEL of 1000 mg/kg bw/day (Becker & Ceccatelli, 2007; Becker et al. 2008). No treatment-related adverse effects on the reproductive organs (including testes, epididymis, seminal vesicles, uterus, ovaries and vagina) was seen in rats administered RA1 at up to 750 mg/kg bw/day (Braun, 2000) or RA2 at up to 1000 mg/kg bw/day (Allard and Becker, 1997) by gavage for 28 days.

Short description of key information:
No data are available on DEA acetate, but a reliable one-generation reproduction toxicity test using read-across substance RA2 was used to address this point. No effects on fertility, or on the reproductive organs, were seen in this study at up to 1000 mg/kg bw/day (considered the fertility NOAEL). In addition, no treatment-related adverse effects on the reproductive organs was seen in rats administered RA1 at up to 750 mg/kg bw/day (Braun, 2000) or RA2 at up to 1000 mg/kg bw/day (Allard and Becker, 1997) by gavage for 28 days.

Justification for selection of Effect on fertility via oral route:
Data waiver based on a GLP, OECD guideline one-generation study (reliability 2) on a related compound, and on the basis of a low likelihood of human exposure

Effects on developmental toxicity

Description of key information

No data are available on DEA acetate, but a one-generation reproduction toxicity test, using read-across substance RA2, was used to address this endpoint.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Data waiving:

other justification

Justification for data waiving:

other:

Abnormalities:

not specified

Developmental effects observed:

not specified

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Species:

rat

Quality of whole database:

Although no relevant data are available on DEA acetate, a good-quality, reliable, GLP-compliant, OECD-guideline one-generation study on RA2 is available (Becker & Ceccatelli, 2007; Becker et al. 2008). Together with exposure-based data waivers, this meets the REACH tonnage-driven data requirements.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

REACH Annex XI states that testing for developmental toxicity in accordance with Annex VIII may be omitted, based on the exposure scenario(s) developed in the Chemical Safety Report. A low likelihood of human exposure is anticipated, and a log Pow expected to be lower than -1.31 indicated that bioaccumulation is not likely to occur. In addition, no teratogenic effects were seen in a reliable oral one-generation reproductive toxicity study on a structurally-related read-across compound at up to 1000 mg/kg bw/day. However, at this top dose, an increased number of dead pups and post-implantation losses ("possibly test item-related") was observed, resulting in a developmental toxicity NOAEL of 300 mg/kg bw/day (Becker & Ceccatelli, 2007; Becker et al. 2008).

Justification for selection of Effect on developmental toxicity: via oral route:
Data waiver based on a GLP, OECD guideline one-generation study (reliability 2) on a related compound, and on the basis of a low likelihood of human exposure

Toxicity to reproduction: other studies

Additional information

No data are available on DEA acetate, but a reliable one-generation reproduction study has been conducted on the structurally-related read-across compound, RA2.

 

Wistar rats (24/sex/dose) were orally given RA2 at up to 1000 mg/kg bw/day. RA2 was administered to males for 70 days before pairing, until the last litter had reached day 4 postpartum. Females were treated for 14 days prior to pairing, then throughout pairing, gestation and lactation.

No effects on fertility or maternal toxicity were seen at any dose. The critical NOAEL was established at 300 mg/kg bw/day, based on reductions in food consumption, body weight gain and liver body weight ratio in paternal males, and increased number of dead pups and post-implantation loss in females ("possibly test item-related") at 1000 mg/kg bw/day. In addition, no teratogenic effects were seen in the offspring (Becker & Ceccatelli, 2007; Becker et al. 2008).

Justification for classification or non-classification

No relevant data are available on DEA acetate, but a one-generation reproductive toxicity study on the structurally-related compound RA2 found increased numbers of dead pups, and possibly treatment-related increases in post implantation loss in females given 1000 mg/kg bw/day, in the absence of maternal toxicity. As such, a critical NOAEL of 300 mg/kg bw/day was reported. No teratogenicity or effects on fertility were observed. As such, there is no evidence to indicate that DEA acetate requires classification, according to Regulation (EC) No. 1272/2008.