N-(2-carboxyethyl)-N-octyl-β-alanine

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Work performed to OECD guidelines in 2009 and approved by the US Environmental Protection Agency Statement in report claiming the data covers range of alklyimines; specifically, "sodium and potassium salts of N-alkyl (C8-C18)-beta-iminodipropionic acid where the C8-C18 is linear and may be saturated and/or unsaturated, (CAS Reg. Nos. 110676-19-2, 3655-00-3, 61791-56-8, 14960-06-6, 26256-79-1, 90170-43-7, 91696-17-2, and 97862-48-1) [Ref 40 CFR Part 180, Federal Register Volume 76, number 24, 4 February 2011'

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

not specified

Remarks:

Claimed GLP but no detail

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium N-(2-carboxyethyl)-N-dodecyl-β-alaninate

EC Number:

222-899-0

EC Name:

Disodium N-(2-carboxyethyl)-N-dodecyl-β-alaninate

Cas Number:

3655-00-3

IUPAC Name:

disodium N-(2-carboxyethyl)-N-dodecyl-beta-alaninate

Constituent 2

Reference substance name:

sodium and potassium salts of N-alkyl (C8-C18)-beta-iminodipropionic acid

IUPAC Name:

sodium and potassium salts of N-alkyl (C8-C18)-beta-iminodipropionic acid

Test material form:

semi-solid (amorphous): gel

Remarks:

migrated information: paste

Details on test material:

Batch number 184, state 87% purity
Dose levels were corrected for purity (ie reported figures are for nominal 100% purity)

Test animals

Species:

rat

Strain:

other: HanRcc:WIST (SPF)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Details on mating procedure:

Cohabitation

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Dosing began 14 days before mating and continued for 28 days for males and for day four of lactation for females

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

600 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

160 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

43 mg/kg bw/day (actual dose received)

Doses / concentrations 4

Dose / conc.:

0 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

10 males and 10 females per group

Control animals:

yes, concurrent no treatment

Positive control:

None

Examinations

Parental animals: Observations and examinations:

Clinical signs daily (including maternal behaviour)
Functional observation battery (FOB)
Food consumption
Body weights
Blood sampling
Body temperature (during FOB)

Litter observations:

Litter size and viabilty

Postmortem examinations (parental animals):

Yes

Postmortem examinations (offspring):

Yes, macroscopic examinations for malformation

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Taste aversion behaviour

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Yes, intermediate and high dose

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Yes, intermediate and high dose

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Liver and kidney

Other effects:

effects observed, treatment-related

Description (incidence and severity):

Test substance intake: Decrease in top groups pre-mating

Reproductive function / performance (P0)

Reproductive performance:

no effects observed

Details on results (P0)

Diffuse hypertrophy of the liver in males and females
Tubular degeneration/regeneration and hyaline droplets/granulation of the kidneys in males
Follicular hypertrophy of the thyroid in males and females
Acanthosis of the non-glandular stomach in males and females
Inflammation of the non-glandular stomach in males; and congestion, thrombosis and inflammation of the glandular stomach in females

Effect levels (P0)

1

Dose descriptor:

NOEL

Effect level:

> 43 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Reduced weight gain, adaptive changes to liver and kidneys

2

Dose descriptor:

NOAEL

Effect level:

ca. 160 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Reduced weight gain, adaptive changes to liver and kidneys

3

Dose descriptor:

LOAEL

Effect level:

ca. 600 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Details on results (F1)

No adverse effects on litter size or viability
No abnormalities reported

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

> 600 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: No adverse effects on litter size or viability No malformations reported

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

No treatment-related effects on litter size or survival were observed. No treatment-related effects on body weight were observed in offspring. Body weight gain was slightly decreased in males and females at 160 and 600 mg/kg/day, but there was no dose response.

No findings were observed on macroscopic examination of the offspring. The reproductive/developmental LOAEL for Sodium coco β-iminodipropionate in rats is not established.

The reproductive/developmental NOAEL is 600 mg/kg bw/day, the highest dose tested, in males and females.

Applicant's summary and conclusion

Conclusions:

No treatment-related effects on litter size or survival were observed. No treatment-related effects on body weight were observed in offspring. Body weight gain was slightly decreased in males and females at 160 and 600 mg/kg/day, but there was no dose response.

No findings were observed on macroscopic examination of the offspring. The reproductive/developmental LOAEL for Sodium coco β-iminodipropionate in rats is not established.

The reproductive/developmental NOAEL is 600 mg/kg bw/day, the highest dose tested, in males and females.

Executive summary:

This EPA study is considered valid in terms of grouping of substances. Examination of data on various primary alkylamines show little difference in repeat toxicity effects, including reproduction, suggesting that there is minimal difference in terms of systemic toxicity between the different alklyamines, including branched and linear.

The comparison of sub-acute toxicity between the tested substance and the result of this EPA study are consistent and read-across is considered valid; the EPA study shows slightly more adverse effects than the Key Study (on the registered substance) over 28 days and is therefore considered a suitable surrogate for the reporting of reproductive effects.