N,N-diethylaniline

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary literature

Data source

Reference

Reference Type:

secondary source

Title:

Repeated dose oral toxicity study of the test chemical

Author:

USEPA

Year:

2018

Bibliographic source:

HPVIS

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Subacute repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-diethylaniline

EC Number:

202-088-8

EC Name:

N,N-diethylaniline

Cas Number:

91-66-7

Molecular formula:

C10H15N

IUPAC Name:

N,N-diethylaniline

Details on test material:

- Name of test material: N,N-Diethylaniline
- Molecular formula: C10H15N
- Molecular weight: 149.236 g/mol
- Substance type: organic
- Physical state: solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10, 50 or 250 mg/kg-bw/day
Basis:
no data

No. of animals per sex per dose:

unspecified

Control animals:

yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Clinical signs of toxicity consisted of increased frequency of respiratory sounds in males at 50 mg/kg-bw/day, and increased frequency of respiratory sounds and salivation in females at 250 mg/kg-bw/day.

Mortality:

mortality observed, treatment-related

Description (incidence):

No mortalities observed.

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Hematological effects (decreased red cell counts, decreased hemoglobin concentrations, decreased packed cell volume (PCV) in both sexes and increased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in females) were reported at all dose

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Histological effects were reported for the liver and spleen.

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

Details on results:

HISTOPATHOLOGY:
Histological effects were reported for the liver and spleen. In the liver, hemosiderosis of the Kupffer cells at 10 mg/kg-bw/day and extra medullary hematopoeisis at 50 and 250 mg/kg-bw/day were observed. In the spleen, hemosiderosis, extramedullary hematopoiesis and splenic hyperemia were reported at 10 mg/kg-bw/day. Swollen spleens were observed at 50 and 250 mg/kg-bw/day. Increased absolute and relative weights and black pigmentation of the spleen were also reported at 10mg/kg-bw/day. At 50 and 250 mg/kg-bw/day, hyperbilirubinemia, polychromasia were reported, and at 250 mg/kg-bw/day, decreased potassium levels, histopathological findings in the kidneys of both sexes, black pigmentation in the kidneys of females, and increased albumin levels in males were reported.

Effect levels

Dose descriptor:

LOAEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on hematological and histopathological changes in the spleen and liver consistent with hemolytic anemia

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The Low observed adverse effect level (LOAEL) for the test chemical using Wistar rats was considered to be 10 mg/kg-bw/day

Executive summary:

In a subacute repeated-dose toxicity study, Wistar rats (male and female; number unspecified) were administered the test chemical via gavage at 0, 10, 50 or 250 mg/kg-bw/day, 7 days/week for 28 days. No mortalities were observed. No changes in body weight, food, and water consumption were reported. Clinical signs of toxicity consisted of increased frequency of respiratory sounds in males at 50 mg/kg-bw/day, and increased frequency of respiratory sounds and salivation in females at 250 mg/kg-bw/day. Hematological effects (decreased red cell counts, decreased hemoglobin concentrations, decreased packed cell volume (PCV) in both sexes and increased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in females) were reported at all doses (dose-response not specified). Histological effects were reported for the liver and spleen. In the liver, hemosiderosis of the Kupffer cells at 10 mg/kg-bw/day and extra medullary hematopoeisis at 50 and 250 mg/kg-bw/day were observed. In the spleen, hemosiderosis, extramedullary hematopoiesis and splenic hyperemia were reported at 10 mg/kg-bw/day. Swollen spleens were observed at 50 and 250 mg/kg-bw/day. Increased absolute and relative weights and black pigmentation of the spleen were also reported at 10mg/kg-bw/day. At 50 and 250 mg/kg-bw/day, hyperbilirubinemia, polychromasia were reported, and at 250 mg/kg-bw/day, decreased potassium levels, histopathological findings in the kidneys of both sexes, black pigmentation in the kidneys of females, and increased albumin levels in males were reported. Dose-response and statistical significance were not indicated for any of these observed effects. Based on hematological and histopathological changes in the spleen and liver consistent with hemolytic anemia observed the Low observed adverse effect level (LOAEL) for the test chemical using Wistar rats was considered to be 10 mg/kg-bw/day.