Benzenamine, N-phenyl-, styrenated

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

review article or handbook

Title:

SCREENING-LEVEL HAZARD CHARACTERIZATION, Substituted Diphenylamines Category

Author:

U.S. Environmental Protection Agency

Year:

2009

Bibliographic source:

U.S. Environmental Protection Agency, Hazard Characterization Document, September, 2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD guideline

Principles of method if other than guideline:

To evaluate the toxicity of Benzenamine, N-phenyl-, styrenated in Sprague-Dawley rats by combined repeate dose/reproductive/developmental toxicity screening test.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzenamine, N-phenyl-, styrenated

EC Number:

270-485-3

EC Name:

Benzenamine, N-phenyl-, styrenated

Cas Number:

68442-68-2

Molecular formula:

not applicable (UVCB substance)

IUPAC Name:

4-(1-phenylethyl)-N-[4-(1-phenylethyl)phenyl]aniline

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report): Benzenamine, N-phenyl-, styrenated- Molecular formula (if other than submission substance): No data available- Molecular weight (if other than submission substance): 320g/mol- Substance type: Organic- Physical state: Liquid- Impurities (identity and concentrations): No data available

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

No data available.

Administration / exposure

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Benzenamine, N-phenyl-, styrenated suspension in corn oil at 0, 50, 250 and 600 mg/kg-bw/day were prepared. DIET PREPARATION- Rate of preparation of diet (frequency): No data available - Mixing appropriate amounts with (Type of food): No data available- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): Corn oil - Concentration in vehicle: 0, 50, 250 and 600 mg/kg-bw/day - Amount of vehicle (if gavage): No data available- Lot/batch no. (if required): No data available- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data available

Details on mating procedure:

- Impregnation procedure: [artificial insemination / purchased timed pregnant / cohoused]: No data available.- If cohoused: No data available.- M/F ratio per cage: 1: 1 ratio - Length of cohabitation: 15 days - After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: No data available.- Further matings after two unsuccessful attempts: [no / yes (explain)]: No data available.- Verification of same strain and source of both sexes: [yes / no (explain)]: No data available.- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: No data available.- Any other deviations from standard protocol: No data available.

Frequency of treatment:

Daily

Duration of test:

43 days for male 53 days for female(14 days –Pre-mating, 14 days mating period,21 days of Gestation,4 days of Lactation)

No. of animals per sex per dose:

Total no. of animals 800 mg/kg-bw/day – 10 male and 10 female50 mg/kg-bw/day- 10 male and 10 female250 mg/kg-bw/day -10 male and 10 female600 mg/kg-bw/day -10 male and 10 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data available.

Examinations

Maternal examinations:

Survival, clinical sign, body weight, food consumption, water consumption, clinical chemistry, Organ weight, gross pathology and gross pathology were observed.

Ovaries and uterine content:

Pre-implantation losses was observed.

Fetal examinations:

Clinical sign, body weight and surface righting and macroscopic abnormality were observed.

Statistics:

No data available.

Indices:

Fertility and gestation were observed

Historical control data:

No data available

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yesDetails on maternal toxic effects:Mortality : No mortality were observed in treated group.Clinical signs : No treatment-related changes in behavioral were observed in treatment groups.Body weight:No effect was observed on body weight of treated rats. Food consumption:No effect was observed on food consumption of treated rats.Water consumption:No effect was observed on water consumption of treated rats.Clinical chemistry:Decreased cholesterol levels was observed in male rats at 250 and 600 mg/kg bw/day and increased activity for alkaline phosphatase was observed in male rats at 600 mg/kg-bw/day. Both the observed effects are indicative of liver toxicity Reproductive performance:Inceased in pre-implantation losses were observed in 600 mg/kg-bw/day reated female rats as compared to control.Organ weights:Absolute and relative liver and adrenal weights were increased in male and female rats at 600 mg/kg-bw/day.Histopathology:Centrilobular hepatocyte enlargement of liver at 250 and 600 mg/kg-bw/day.Follicular cell hypertrophy of thyroid glands were observed in male rats at 600 mg/kg-bw/day.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yesDetails on embryotoxic / teratogenic effects:Mortality : Less offspring/litter were observed in 600 mg/kg bw/day treated group.Clinical signs : No treatment-related clinical signs of toxicity were observed in treatment groups.Body weight:No effect was observed on body weight of offsprings of treated female rats as compared to control.Gross pathology:No gross pathological abnormalities were observed in offsprings of treated female rats as compared to control.Nurobehaveral effect:Decreased completion of surface righting were observed in offsprings of 600 mg/kg bw/day treated female rats as compared to control.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: No effect on offsprings survival, clincal sign, body weigth, nurobehaveral effect and gross pathology was observed on F1 male/female test animal.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 250 mg /kg /day for F0 and F1 generation when Sprague-Dawley male and female rats were exposed to Benzenamine, N-phenyl-, styrenated.

Executive summary:

In a combined repeate dose/reproductive/developmental toxicity screening test, Sprague-Dawleymale and female rats were exposed toBenzenamine, N-phenyl-, styrenated in the concentrations of 0, 50, 250 and 600 mg/kg bw/day orally by gavage.  No effect were observed on survival, clinical sign, body weight, food consumption and water consumption of F0 treated rats as compared to control. However, changes were observed as decreased cholesterol levels in F0 male rats at 250 and 600 mg/kg bw/day and increased activity for alkaline phosphatase was observed in male rats at 600 mg/kg-bw/day. Similarly, less offspring/litter and higher percentage of pre-implantation losses were observed in 600 mg/kg bw/day treated group. No effect was observed on clinical sign and body weight of F1 offsprings. In addition, increased absolute and relative liver and adrenal weights were observed in F0 male and female rats at 600 mg/kg-bw/day. Centrilobular hepatocyte enlargement of liver at 250 and 600 mg/kg-bw/day and follicular cell hypertrophy of thyroid glands were observed in F0 male rats at600mg/kg-bw/day. Decreased completions of surface righting were observed in F1 offsprings of 600 mg/kg bw/day. Therefore, NOAEL was considered to be 250 mg /kg /day for F0 and F1 generation when Sprague-Dawley male and female rats were exposed to Benzenamine, N-phenyl-, styrenated orally by gavage for 53 days.