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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
EC Number:
222-020-0
EC Name:
Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
Cas Number:
3319-31-1
Molecular formula:
C33H54O6
IUPAC Name:
tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot N-80301
- Expiration date of the lot/batch: unknown
- Purity test date: 99%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in airtight opaque containers in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble in corn oil
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: stable

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
No. of animals per sex per dose:
12 Male; 12 Female

Examinations

Parental animals: Observations and examinations:
No effects on appearance, body weight, feed consumption, gross pathology, reporudctive organ weights;
No microscopic effects in the kidneys
Sperm parameters (parental animals):
Number of spermatocytes and spermatids was slightly reduced in 2/12 and 11/12 males of the mid-and high-dose groups, respectively, and moderately decreased in 1 high-dose male.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
No effects on appearance, body weight, feed consumption, gross pathology, reporudctive organ weights;
No microscopic effects in the kidneys
Number of spermatocytes and spermatids was slightly reduced in 2/12 and 11/12 males of the mid-and high-dose groups, respectively, and moderately decreased in 1 high-dose male.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
effects observed, treatment-related
Description (incidence and severity):
Number of spermatocytes and spermatids was slightly reduced in 2/12 and 11/12 males of the mid-and high-dose groups, respectively, and moderately decreased in 1 high-dose male.

Effect levels (P0)

open allclose all
Key result
Dose descriptor:
NOEL
Effect level:
ca. 100 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
clinical signs
Key result
Dose descriptor:
NOAEL
Effect level:
ca. 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
no effects observed

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
ca. 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
100 mg/kg bw/day
Treatment related:
yes

Applicant's summary and conclusion

Conclusions:
NOEL (male) = 100 mg/kg/day; NOEL (female and offspring) = 1000 mg/kg/day;
Triethylhexyl Trimellilate is considered not having reprotoxic effects inn the conditions of a reprotoxic screening test.