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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD 416 2-generation reproductive study
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
Benzene, C10-16-alkyl derivs.
EC Number:
272-008-4
EC Name:
Benzene, C10-16-alkyl derivs.
Cas Number:
68648-87-3
IUPAC Name:
tridecylbenzene
Details on test material:
- Composition of test material, percentage of components: <1% C9, 16% C10, 43% C11, 40% C12, 1% C13, <1% C14; avg C11.26
- Analytical purity: 98.5

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Housing: wire mesh cages
- Diet: Ralson Purina commercial laboratory feed, ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65 - 79
- Humidity (%): 17 - 76
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Daily
Frequency of treatment:
F0: Treatment was started 10 weeks before mating.
For males, dosing continued for 2 weeks after mating (total of 105 days). For females, dosing continued through lactation for a total of 127 treatment days.
Doses / concentrationsopen allclose all
Dose / conc.:
5 mg/kg bw/day (actual dose received)
Dose / conc.:
50 mg/kg bw/day (actual dose received)
Dose / conc.:
500 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
30
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: males - weekly, females - weekly before mating, days 0, 7, 14, and 20 of gestation, and days 0, 4, 14, and 21 of lactation

FOOD CONSUMPTION: weekly
Sacrifice and pathology:
SACRIFICE
- Male animals: All surviving animals 2 weeks after mating.
- Maternal animals: All surviving animals at weaning.

GROSS NECROPSY
- Gross necropsy consisted of examination for gross lesions.

HISTOPATHOLOGY / ORGAN WEIGHTS
pituitary glands, testes and epididymides, prostate and seminal vesicles, vagina, uterus, ovaries, and gross lesions.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Description (incidence):
No mortality attributed to treatment was observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean body weights of high-dose-group (500 mg/kg bw/d) males were significantly and consistently reduced (12 = 0.01) in the F0 (since premating week); mean body weights of high-dose females were significantly decreased in the F0 generation since the 9th week of premating until the first week of lactation (p = 0.05); body weight reduction was significant on day 20 of gestation in both generations (p = 0.01)
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Description (incidence and severity):
No gross postmortem findings.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No histopathological findings.
Histopathological findings: neoplastic:
no effects observed

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw (total dose)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Dose descriptor:
LOAEL
Effect level:
500 mg/kg bw (total dose)
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:
not specified

Applicant's summary and conclusion

Conclusions:
Under the conditions in this study the NOAEL was 50 mg/kg bw/day in both male and female rats.
Executive summary:

In this study in accordance with OECD TG 416 and in compliance with GLP the effects of repeated exposure to the test substance was examined. Groups of 30 female and 30 male rats were exposed to concentrations of 0, 5, 50 and 500 mg/kg day of test substance by oral gavage beginning ten weeks before mating. Animals were then mated. The resulting generation was also exposed to the test substance and mated. Exposure continued through the mating period, and in females through the gestation and lactational periods. Males were exposed for a total of 105 days, and females 127 days. All animals were sacrificed and necropsied after exposure. During the study, animals were observed for clinical signs, mortality, and body weight. The NOAEL was 50 mg/kg/day and the LOAEL was 500 mg/kg/day based on reduced weight gain in the high dose group.

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