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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study published in peer-reviewed journal.

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

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 (e.g. ad libitum): Ralson Purina commercial laboratory feed, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum


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

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 / concentrations
Remarks:
Doses / Concentrations:
0, 5, 50 and 500 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
30 animals of each sex per dose
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
Body weight and weight changes:
effects observed, treatment-related
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
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
No mortality attributed to treatment was observed.


BODY WEIGHT AND FOOD CONSUMPTION
Mean body weights of high-dose-group (500 mg/kg bw/d) males were significantly and consistently reduced {12 = 0.01) in the FO (since premating week); mean body weights of high-dose females were significantly decreased in the FO 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


GROSS PATHOLOGY (PARENTAL ANIMALS)
No gross postmortem findings.

HISTOPATHOLOGY (PARENTAL ANIMALS)
No histopathological findings.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw (total dose)
Sex:
male/female
Basis for effect level:
other: reduced weight gain in the high dose group
Dose descriptor:
LOAEL
Effect level:
500 mg/kg bw (total dose)
Sex:
male/female
Basis for effect level:
other: reduced weight gain

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEL was 50 mg/kg bw/day in both male and female rats.
Executive summary:

In cases where no data were available on the target substance, Benzene, C15 -16 -alkyl derivs., data were read across from a structurally related material (the test substance).

This study examined the effects of repeated exposure to the test substance. 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.