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Description of key information

Oral: LD50 = 681 mg/kg bw (similar to OECD 401, BASF, 1985)
Dermal: No data available for test substance.
LD50 = 765 mg/kg bw (read across from CAS 95-74-9, Bayer, 1972)
Inhalative: No data available for test substance.
LC0 > 1.76 µg/L/4 hr (read across from CAS 95-74-9, Bayer, 1972)
Oral and dermal application of 3-chloro-p-toluidine (CAS 95-74-9) leads to an increase of methaemglobin (Bayer, 3538, 1972).

Key value for chemical safety assessment

Additional information

Oral:

In an acute oral toxicity study (OECD 401, BASF, 85/48, 1985), groups of fasted 6 -8 week old rats (5/sex) were given a single oral dose of the test substance in 0.5% aqueous carboxymethyl cellulose at 1000, 681, 464, and 316 mg/kg bw and observed for 14 days. Mortality occurred in the two highest dose groups. Normal body weight gain was found in this study. Dyspnea, apathy, abnormal position, staggering and a general poor state were seen in this study. The animals recovered within 1 day. At autopsy, no abnormalities were observed.

Oral LD50Males = 754 mg/kg bw, Females = 681 mg/kg bw, Combined = 681 mg/kg bw

The test substance is classified as being of moderate toxicity (Category 4).

Furthermore, methaemglobin studies with the structurally similar 3 -chloro-p-toluidine showed an increase of methaemglobin after oral application (Bayer, 3538, 1972). In this study two male cats which were treated with 10 mg/kg bw 3 -chloro-p-toluidine (CAS 95 -74 -9) showed marked increased levels of methaemglobin 3 hours after application (at maximum: 38% and 54%). Application of 2.5 mg/kg bw leads to an increase of 9% and 14% 3 hours after application. Those increases reversed after 48 hours. 1 mg/kg bw did not increase methaemglobin. A further study with rats with 5 -chloro-o-toluidine (also a structurally similar substance) did not show a marked increase (2%) of haemglobin after 1.5 hours after oral application of 85 mg/kg bw test item (Bierner, 1988).

Dermal:

The test substance was only tested for acute dermal toxicity in a study with cats (Lehmann, 1933). One female cat was treated dermally with 2.1 or 2.5 g/kg bw, respectively. The treatment duration was not given. The cat treated with the lower dose died after 5 days and that treated with the higher dose died one day after application.

A further study done with the structural similar substance 3-chloro-p-toluidine (CAS 95 -74 -9) can be used to support the above results. In this acute dermal toxicity study (Bayer, 3538, 1972), to groups of male rats the test substance diluted in polyethylene glycol was applied to the shaved abdomen once for four hours in different doses. The animals died within one to two days. Cyanosis, labour respiration and sedation were seen 6 hours after application. Animals which did not die recovered within 4 to 7 days. The highest dose tested without lethal effects was 118 mg/kg bw and the highest dose without symptoms was 59 mg/kg bw.

 

Dermal LD50Males = 765 mg/kg bw

The test substance is classified as being of pronounced toxicity (Category 3).

Dermal application of the structurally similar 3 -chloro-p-toluidine lead to an increase of methaemglobin (Bayer, 3538, 1972). In this study cats were treated dermally for four hours with 10, 25, 100, 250, 1000 and 2000 mg/kg bw. Four hours after application the cats showed MetHb levels of 59.6% at 100 mg/kg bw, 64.3% at 250 mg/kg bw, 56.0% at 1000 mg/kg bw and 67.1% at 2000 mg/kg bw.

Inhalation:

No study is available for 3-chloro-o-toluidin. 3-chloro-p-toluidin is a substance with a similar structure and can be used as read across substance. In an acute inhalation toxicity study (Bayer, 3538, 1972), groups of male rats (5/dose) were exposed by inhalation route to 3-chlor-p-toluidin (as vapor) in air for 4 hours to whole body at concentrations of 1.3, 1.4, and 1.76 mg/m³ air. Animals then were observed for 7 days. No mortality occurred and at no time point of exposure the rats showed intoxication symptoms. The same results were found when the animals were exposed for 7 hours or for 4 hours on 5 consecutive days.

LC0> 1.76 µg/L/4 hours 

Since the concentrations tested are far below the concentrations needed for classification a reliable statement cannot be given.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is considered to be classified for acute oral and dermal toxicity as harmful if swallowed (R21/22) under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC. The classifcation for acute dermal toxicity is based on the result of the read across substance with CAS 95 -74 -9. For acute inhalatory toxicity no reliable data is available.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for acute oral as harmul if swallowed (Acute Toxicity 4), for acute dermal toxicity as toxic in contact with skin (Acute Toxicity 3) under Regulation (EC) No. 1272/2008. The classification for acute dermal toxicity is based on the result of the read across substance with CAS 95 -74 -9.

For inhalatory toxicity no reliable data is available.