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Toxicological information

Repeated dose toxicity: oral

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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:
guideline study

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Clariant Genamin OL 100D, CAS 112-90-3, as stated in the EU Risk Assessment Report on Primay Alkyl Amines, 2008

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Analytical verification of doses or concentrations:
yes
Remarks:
according to EU B.7/OECD 407
Duration of treatment / exposure:
28 day, with treatment-free 14 day recovery period
Frequency of treatment:
daily, 7 days per week
Doses / concentrationsopen allclose all
Dose / conc.:
3.25 mg/kg bw/day (nominal)
Dose / conc.:
12.5 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10, with 5 additiona animals per sex in the recovery groups
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Gait abnormalities in high dose (stilted and/or uncoordinated gait)
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean body weight was significantly lower for high dose males and females; mean body weights for mid dose males were significantly lower.
Food efficiency:
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Clinical chemistry changes comprised significantly increased total bilirubin for the high dose group, slightly increased urea nitrogen for mid and high dose females and very slightly increased AST and ALT activity in the liver of high dose males.
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
At the end of 28-day treatment, body weight in males was -5.3% (p > 0.05, ns) at low dose -7.5% (p ≤ 0.05) at mid dose, and -10% (p ≤ 0.05) at high dose compared to the body weight of controls. At the end of recovery, body weight in high dose males remained at the same, significantly lower level (-9.8%, p ≤ 0.05). Body weights in high dose females were -10.4% lower than the control values at the end of treatment and a clear tendency to recover was seen at the end of 4-week recovery (difference was still -5.9%, p > 0.05, ns). Food consumption remained unaffected throughout the study in all dose groups. Hematology findings in high dose groups included significantly increased hematocrit and decreased reticulocyte counts (males only) and slightly increased white blood cell counts with a shift towards increased neutrophils (both genders), all findings were reversible. Clinical chemistry changes comprised significantly increased total bilirubin for the high dose group, slightly increased urea nitrogen for mid and high dose females and very slightly increased AST and ALT activity in the liver of high dose males. Urinalysis remained unaffected in all dose groups. No anatomic pathology correlates (organ weights, macroscopy, microscopy) of toxicological significance were detected.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
3.25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain

Target system / organ toxicity

Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
12.5 mg/kg bw/day (nominal)
System:
nervous system
Organ:
other: motor activity alteratioons
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
The test substance was administered by gavage to CD rats in a 28-day OECD 407 guideline experiment with a 14 day recovery period. Doses were 3.25, 12.5 and 50 mg/kg bw/day. Mean body weight was significantly lower for mid and high dose males and in high dose females. There were no significant clinical effects, clinical chemistry or pathology results associated with treatment. The NOAEL was 3.25 mg/kg bw/d.