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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 day (males)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
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'
Justification for type of information:
Peer-reviewed US Government publication
Cross-reference
Reason / purpose for cross-reference:
reference to same study

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

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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
600 mg/kg/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
160 mg/kg/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
43 mg/kg/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
Control 0 mg/kg/day
Basis:
actual ingested
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)

open allclose all
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
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
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'

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.

The similarity in findings with work on primary amines further justifies read-across to these potential metabolites. This is reviewed in the assessment report attached in Section 13.