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

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

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

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

Positive control:

No

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

Sperm parameters (parental animals):

Yes

Litter observations:

Yes

Postmortem examinations (parental animals):

Yes

Postmortem examinations (offspring):

Yes

Statistics:

Yes

Reproductive indices:

Yes

Offspring viability indices:

Yes

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Details on results (P0)

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.

No changes caused by the substance were noted in terms of the copulation index, gestation length, delivery conditions, nursing conditions, fertility index, number of corpora lutea, implantation rate, or gestation index.
The NOELs for reproductive performance are considered to be 750 mg/kg/day for both sexes. Regarding the pups, no changes caused by the substance were noted in the number of pups, number of stillbirths, number of live pups born, sex ratio, delivery index, birth index, live birth index, viability index or body weight. The NOEL for pup development is considered to be 750 mg/kg/day.

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

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

750 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive performance

2

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

gross pathology

histopathology: non-neoplastic

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Gross pathological findings:

no effects observed

Details on results (F1)

Regarding reproductive/developmental toxicity, no changes caused by the substance were noted in terms of the copulation index, gestation length, delivery conditions, nursing conditions, fertility index, number of corpora lutea, implantation rate, or gestation index.
Regarding the pups, no changes caused by the substance were noted in the number of pups, number of stillbirths, number of live pups born, sex ratio, delivery index, birth index, live birth index, viability index, or body weight.

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

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

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

Sex:

male/female

Basis for effect level:

other: Pup development

Overall reproductive toxicity

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

From this study a NOAEL of 750 mg/kg bw for reproductive performance and pup development 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.

Regarding reproductive/developmental toxicity, no changes caused by the substance were noted in terms of the copulation index, gestation length, delivery conditions, nursing conditions, fertility index, number of corpora lutea, implantation rate, or gestation index.

Regarding the pups, no changes caused by the substance were noted in the number of pups, number of stillbirths, number of live pups born, sex ratio, delivery index, birth index, live birth index, viability index, or body weight.

From this study a NOAEL of 750 mg/kg bw for reproductive performance and pup development was derived.