Benzene, C15-16-alkyl derivs.

Repeated dose toxicity: oral

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

Test material information

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

1

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

2

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.