Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
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'
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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
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

Observations and examinations performed and frequency:
Clinical signs daily (including maternal behaviour)
Functional observation battery (FOB)
Food consumption
Body weights
Blood sampling
Body temperature (during FOB)
Sacrifice and pathology:
Full pathological examination as described in guidelines

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Reduced food intake in highest dose
Mortality:
mortality observed, treatment-related
Description (incidence):
Reduced food intake in highest dose
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Reduced weight gain in top and intermediate group
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
reduced top group
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Increased liver weights in top group
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Mainly liver and kidney
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
43 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
160 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Based on decreased body weight gain in males and females during the pre-mating period, and an increased incidence of microscopic lesions in the kidneys of males and acanthosis of the glandular and non-glandular stomach of females.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

[Extracted from test report]

Clinical signs:

Mild signs of local irritation / taste in top group. Food consumption during the pre-mating period was decreased in males and females (19% and 16% below control value, respectively) at 600 mg/kg/day. No other treatment-related effects on food consumption, body weight or body weight gain were observed during the post-mating, gestation and lactation periods. Locomotor activity was not affected by treatment. The reproduction parameters were unaffected by treatment.

Body-weight

Body weight gain was decreased at 160 and 600 mg/kg/day in males (23% and 51% below control value, respectively) and in females (37% and 56% below control value, respectively).

Haemotology

No treatment-related hematology parameters were observed.

Clinical chemistry

In males at 600 mg/kg/day, urea and potassium concentrations were statistically significantly increased (24% and 15% above control value, respectively). The changes correlated with the histopathological findings in the kidney. No treatment-related effects on clinical chemistry parameters were observed in females.

Organ weights

Mean absolute liver weight was slightly increased (12% above control value) and mean relative liver and kidney weights were statistically significantly increased in males at 600 mg/kg/day (18% and 11% above control value, respectively). Mean absolute and relative liver weights were significantly increased in females at 600 mg/kg/day (19% and 24% above control value, respectively).

Histology

No treatment-related macroscopic findings in treated males were observed, except possibly enlarged liver in one male at 600 mg/kg/day. At 600 mg/kg/day, dark red foci in the stomach of a female were observed. Since changes in the stomach were noted on histopathological examination, this finding could be treatment-related. On microscopic examination, the incidence of the following findings was increased in the high-dose group: 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. The severity of hyaline droplets/granulation in males and thyroid follicular cell hypertrophy in males and females was also increased. The increased thyroid follicular cell hypertrophy may have been secondary to the enhanced liver cell metabolism. The incidence of splenic congestion was increased in males at 600 mg/kg/day. In females, hematopoiesis was reported in all animals, including the control; the severity was slightly increased in females at 600 mg/kg/day. In females, the incidence of thymus atrophy was slightly increased (3/5 vs. 2/5 in control group), but there was no effect in severity. At 160 mg/kg/day, the incidence of the following was increased: hypertrophy in the liver in males, tubular degeneration/ regeneration and hyaline droplets/granulation of the kidneys in males, and congestion and inflammation of the glandular plus non-glandular stomachs in females.

The changes in the liver of males and females at the mid and high doses are considered adaptive in nature and not toxicologically significant.

Applicant's summary and conclusion

Conclusions:
NOAEL concludes to be 43 mg/kg/day for purposes of US EPA reporting.
The figure of 160 mg/kg/day is used to estimate the DNEL on the basis that the effects are likely to be adaptive and reversible.
Executive summary:

The test report concludes :

The parental systemic LOAEL for Sodium coco β-iminodipropionate in rats is 160 mg/kg bw/day, based on decreased body weight gain in males and females during the pre-mating period, and an increased incidence of microscopic lesions in the kidneys of males and glandular and acanthosis of the non-glandular stomach of females. The parental systemic NOAEL is 43 mg/kg bw/day.