Aniline

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

2004

Reference 2

Reference Type:

publication

Title:

The No-effect dose of aniline in human subjects and a comparison of aniline toxicity in man and the rat

Author:

Jenkins FP, Robinson JA, Gellatly JB, Salmond GW.

Year:

1972

Bibliographic source:

Food Cosmet Toxicol. 10, 671-679

Materials and methods

Study type:

other: oral exposure study with volunteers

Endpoint addressed:

acute toxicity: oral

Principles of method if other than guideline:

The effects of oral administration of aniline have been investigated in human volunteers.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Aniline

EC Number:

200-539-3

EC Name:

Aniline

Cas Number:

62-53-3

Molecular formula:

C6H7N

IUPAC Name:

aniline

Details on test material:

- Name of test material (as cited in study report): aniline,
- Supplier: Hopkin and Williams Ltd. Chadwell Heath, Essex
- Analytical purity: no data; redistilled

Method

Type of population:

other: 20 healthy volunteers, age 22 - 45 yr

Ethical approval:

not specified

Details on study design:

The volunteers consisted of 17 males and 3 females ranging in age from 22 to 45 yr. A health.check prior to the investigation included tne examination of urine and blood samples. Urine samples were examined for glucose and protein. Blood samples were examined for evidence of a deficiency of erythrocyte glucose-6-phosphate dehydrogenase by means of the in vito test of BeutIer et al (1955). Erythrocyte sedimentation rate, packed cell volume, percentage of reticulocytes and the differential white cell count were also examined.

Oral doses of 5, 15 and 25 mg aniline, respectively, were administered at 10 a.m. on three successive days to each of 20 volunteers. Higher doses of
aniline (35, 45, 55, and 65 mg ) were then administered to some of these volunteers

METHOD OF DATA COLLECTION
Blood was taken 1, 2,3, 4 and 24 hours after application in order to analyse methaemoglobin levels according to the method of Fleisch (1959) as well as Heinz bodies, packed cell volume, percentage reticulocytes, total serum proteins, serum albumin, globulin, glutamic-oxalacetic and glutamic-pyruvic transaminases and alkaline phosphatase, total serum bilirubin, direct-reading bilirubin and blood urea. Urine was sampled and tested for urobilinogen, glucose and protein; thymol turbidity test.
In order to investigate the mechanism of methaemoglobin formation, blood samples were obtained from six male and six female human volunteers and the effects of phenylhydroxylamine (a metabolite of aniline) and glucose were measured in vitro.

Exposure assessment:

not specified

Details on exposure:

TYPE OF EXPOSURE: oral, bolus dose


EXPOSURE LEVELS: Doses of 5, 15 and 25 mg aniline were administered on three successive days to each of 20 volunteers.

Results and discussion

Results:

Screening tests before administration of aniline revealed no evidence of deficiency of red cell glucose-6-phosphate dehydrogenase in aiiy of the volunteers and no other abnormalities were detected in their blood and urine samples. Blood samples taken 24 hr after each dose of aniline revealed no adverse effect upon packed cell volume, reticulocyte count, bilirubin or urobilinogen, except for a slight increase of serum bilirubin in two males following the administration of high doses of aniline, namely 45 and 65 mg.
Aniline had no adverse effect on serum proteins, serum enzymes, blood urea or the thymol turbidity test. No Heinz bodies were detected and the examination of blood films and buffy coat preparations revealed no abnormal features.

The mean maximum increase in percentage of methaemoglobin (MetHB) was obtained in less than 4 hours after intake. Doses of 5 and 15 mg aniline produced no significant increase of methaemoglobin but the dose of 25 mg raised the level to 2.5% versus 1.2/1.8% in the lower doses. 35 mg/person led to a maximal increase of MetHb of 3.7%.
The dose of 45 mg raised the level to 7% (5 volunteers) and one volunteer who received a dose of 65 mg had a level of 16% Met-Hb two hours after administration but one hour later the level was within normal limits. The blood samples taken 24 hours after each dose revealed no adverse effects upon packed cell volume, reticulocyte count, bilirubin or urobilinogen, except for a slight increase of serum bilirubin in two male volunteers following the administration of 45 and 65 mg (0.6 and 0.9 mg/kg bw, respectively). Aniline had no adverse effects on serum proteins, serum enzymes, blood urea and thymo turbidity test. No Heinz bodies were detected. The authors conclude that this investigation supports the view that the production of methaemoglobin is due to a metabolite of aniline, namely phenylhydroxylamine (measured in the blood in vitro), and that the catalytic effect of phenylhydroxylamine is promoted by glucose.
The no-effect dose of aniline in adult man is in the region of 15 mg/man (about 0.21 mg/kg body weight). Based on a MetHb increase of 3.7%, which is considered as uncritical for humans, the NOAEL of the study was 35 mg/man.

Any other information on results incl. tables

Table 1. Maximum increase in methemoglobin following oral administration of aniline to men

Dose (mg)	No. of volunteers tested	Mean maximum increase of MetHB in %
5	20	1.16
15	20	1.81
25	20	2.46
35	5	3.68
45	5	7.08
55	2	5.17
65	1	16.11