Reaction mass of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study design according to OECD Guideline 421. Study in Japanese without complete English translation.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene

EC Number:

905-459-9

Molecular formula:

C12H18

IUPAC Name:

Reaction mass of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene

Details on test material:

Lot/batch No.: PAK5633
Purity: 98.3 %

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

males: 50-52 days
females: from 14 days before mating to day 3 of lactation (38 to 54 days according to mating lenght)

terminal kill:
males: days 51-53
females: day 4 of lactation

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 6, 30, 150 or 750 mg/kg bw/day
Basis:

No. of animals per sex per dose:

12 m / 12 f

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: 1 day

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see attached file)
HISTOPATHOLOGY: Yes (see attached file)

Statistics:

Yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

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:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Details on results:

In males, exophthalmos was noted in 2 animals at 750 mg/kg bw. Transiently lowered food consumption was also noted at 750 mg/kg bw. No changes caused by the substance were noted in terms of body weight, necropsy findings, organ weights, or sperm examination. On histopathological examination, vacuolization of lens fibers and hyperplasia of epithelium lentis were noted in 2 and 1 animal, respectively, at 750 mg/kg bw.
In females, mydriasis was noted at 750 mg/kg bw. Transiently lowered body weight were evident at 750 mg/kg bw during the pregnancy period and transiently reduced food consumption was noted before mating. No changes caused by the substance were noted with regard to necropsy, organ weights, or histopathological examination.

The individual results are summarised in the attached file Tables and Figures.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: Limited effects and reversible

2

Dose descriptor:

LOAEL

Effect level:

750 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: exophtalmos in males; mydriasis in females

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

From this study a NOAEL of 150 mg/kg bw for male and female rats was derived.

Executive summary:

In this study performed according to OECD Guideline 421, male and female Crj :CD (SD) rats were dosed orally via gavage with 0, 6, 30, 150 or 750 mg/kg bw over 50-52 days (m) and from 14 days before mating to day 3 of lactation. Terminal kill in males was on days 51-53 and in females on day 4 of lactation.

In males, exophtalmos was noted in 2 animals at 750 mg/kg bw. Transiently lowered food consumption was also noted at 750 mg/kg bw. No changes caused by the substance were noted in terms of body weight, necropsy findings, organ weights, or sperm examination. On histopathological examination, vacuolization of lens fibers and hyperplasia of epithelium lentis were noted in 2 and 1 animal, respectively, at 750 mg/kg bw.

In females, mydriasis was noted at 750 mg/kg bw. Transiently lowered body weight were evident at 750 mg/kg bw during the pregnancy period and transiently reduced food consumption was noted before mating. No changes caused by the substance were noted with regard to necropsy, organ weights, or histopathological examination.

From this study a NOAEL of 150 mg/kg bw for male and female rats was derived.