3,5-xylidine

Endpoint summary

Description of key information

OECD 407, GLP, rats,: NOEL 10 mg/kg/day for males and females.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Qualifier:

according to guideline

Guideline:

other: Guideline for 28-day repeated dose toxicity testing of chemicals (Japan)Japanese

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

1 per day

Dose / conc.:

10 mg/kg bw/day (nominal)

Remarks:

Basis:
no data

Dose / conc.:

60 mg/kg bw/day (nominal)

Remarks:

Basis:
no data

Dose / conc.:

360 mg/kg bw/day (nominal)

Remarks:

Basis:
no data

No. of animals per sex per dose:

6 and 12 (0 and 360 mg/kg)

Control animals:

yes, concurrent vehicle

Dose descriptor:

NOEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Critical effects observed:

not specified

Abstract from original report from JECDB-Database 2012:

 

3,5-Dimethylaniline was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 10, 60 and 360 mg/kg.

Cyanosis, blanching, salivation, exophthalmos and staggering gait were observed in males and/or females of the 360 mg/kg group, along with decreased body weight gain and food consumption. Urinalysis showed increase in urine volume, increases in sodium, potassium and chloride excretion, and decreases in osmotic pressure and specific gravity in males and females of the 360 mg/kg group. Hematological examination showed increases in methemoglobin and reticulocytes, and decreases in erythrocytes, hemoglobin and hematocrit in males and females of the 60 mg/kg and 360 mg/kg groups. Further, increase in leukocytes in males and females of the 360 mg/kg group, increase in segmented neutrophils in males of the 360 mg/kg group, and shortening of activated partial thromboplastin time in females of the 360 mg/kg group were detected. Blood chemical examination showed increases in total bilirubin, GOT, GPT, phospholipids and inorganic phosphorus in males and females of the 360 mg/kg group. Further, decreases in potassium and chloride in males of the 360 mg/kg group, and increases in total cholesterol and calcium in females of the 360 mg/kg group were detected. Spleen weights were increased in males and females of the 60 mg/kg and 360 mg/kg groups, and the thyroid, liver and kidney weights in both sexes of the 360 mg/kg group. In addition, the testis weights were increased in the 360 mg/kg group. Histopathologically, hemosiderin deposits in the liver and spleen, and extramedullary hematopoiesis of the spleen were apparent in males and females of the 60 mg/kg and 360 mg/kg groups. Hemosiderin deposits in the kidney and extramedullary hematopoiesis in the liver were also observed in males and females of the 360 mg/kg group. Hypertrophy of hepatocytes and follicular cells in the thyroid was noted in males of the 60 mg/kg group and males and females of the 360 mg/kg group. In the kidney, papillary necrosis was observed in males and females of the 360 mg/kg group, and hyaline droplets in the tubular epithelium in males of the 360 mg/kg group. In the recovery test, papillary necrosis in the kidney, and hemosiderin deposit in the liver, spleen and kidney persisted in males and females of the 360mg/kg group. However, the other changes observed during the administration period demonstrated recovery. The NOEL is considered to be 10 mg/kg/day for males and females.

Conclusions:

The NOEL is considered to be 10 mg/kg/day for males and females.

Executive summary:

3,5-Dimethylaniline was studied for oral toxicity in rats in a GLP 28-day repeated dose toxicity test according to OECD Guideline 407 at doses of 0, 10, 60 and 360 mg/kg. The NOEL is considered to be 10 mg/kg/day for males and females.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

Study duration:

subacute

Species:

rat

Quality of whole database:

Guideline study

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No classification is warranted according to Regulation (EC) No 1272/2008 based on the findings of an OECD 407 guideline study.