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Substance Flow Analysis of 4-nitrotoluene
5 Environmental and health hazards of 4-nitrotoluene
5.1 Toxicity and ecotoxicity of 4-nitrotoluene
5.1.1 Classification and labelling
5.1.2 Human toxicity
5.1.3 Animal toxicity
5.1.4 Carcinogenicity
5.1.5 Endocrine disruption
5.1.6 Environmental fate and exposure
5.1.7 Ecotoxicity
5.1 Toxicity and ecotoxicity of 4-nitrotoluene
5.1.1 Classification and labelling
4-nitrotoluene shall in Denmark and the EU be classified as Toxic (T) and dangerous to the environment (N) and shall be labelled as such with the following risk and safety phrases
- R23/24/25 (Toxic by inhalation, in contact with skin and if swallowed)
- R33 (Danger of cumulative effects)
- R51/53 (Toxic to aquatic organisms, may cause long-term adverse effect in the aquatic environment).
- S(1/2) Keep locked up and out of the reach of children
- S28 After contact with skin, wash immediately with plenty of water
- S37 (Wear suitable gloves)
- S45 (In case of accident or if you feel unwell seek medical advice immediately)
- S61 (Avoid release to the environment. Refer to special instructions/safety data sheets)
The following details provide some of the background data for the classification of the compound.
5.1.2 Human toxicity
4-nitrotoluene is classified as toxic to humans by all routes (i.e. inhalation, ingestion and dermal absorption). Effects from exposure may include contact burns to the skin and eyes, headache, weakness,
dizziness, nausea, shortness of breath, tachycardia and methaemoglobinemia. The onset of symptoms may be delayed by up to 4 hours following exposure (HSDB, 2003).
The classification as toxic is not in accordance with the LD50-values reported in animal tests. An explanation for the classification can be the effects observed in human poisoning (Larsen, 2000).
5.1.3 Animal toxicity
4-nitrotoluene is toxic by ingestion and inhalation in animal tests. NTP (2003) reports the following values in animal tests:
LD50 (oral, rat): 1960 mg/kg
LD50 (oral, mouse): 1231 mg/kg
LD50 (ip, rat): 940 mg/kg
LD50 (skin, rat): 16000 mg/kg
RTECS (2003) reports some additional data:
LD50 (inh, rat): 975 mg/m³
LD50 (inh, mouse): 419 mg/m³
LD50 (oral, rabbit): 150 mg/kg
5.1.4 Carcinogenicity
IARC (1996) has made the following evaluation of 4-nitrotoluene: There is inadequate evidence in humans for the carcinogenicity of nitrotoluenes. There is inadequate evidence in experimental animals for the
carcinogenicity of 4-nitrotoluene. The overall evaluation of IARC is that nitrotoluenes are not classifiable as to the carcinogenicity to humans (Group 3).
5.1.5 Endocrine disruption
4-Nitrotoluene has been assessed at an expert panel meeting as a step in the procedure towards the establishment of a priority list of substances for further evaluation of their role in endocrine disruption
(BKH, 2000).
The expert panel concluded that human health relevant endocrine disruption data were of category 1, i.e. that at least one study providing evidence on endocrine disruption in an intact organism was
identified. Wildlife endocrine disruption data were evaluated as category 3, i.e. there was no scientific basis for inclusion in the list or no data.
Due to the use pattern of 4-nitrotoluene (in closed systems as an intermediate in the varnish industry, pharmaceuticals and fragrances) and because it does not bioaccumulate, 4-nitrotoluene was prioritised as
low concern and is not expected to present a risk to vulnerable groups or create high risk situations.
5.1.6 Environmental fate and exposure
If released to water, 4-nitrotoluene would be susceptible to photolysis, volitilization (estimated half-time in water 1 m deep flowing 1 m/sec is 25 hours), and possibly aerobic degradation provided suitable
acclimatization has take place.
If released to soil, 4-nitrotoluene should be resistant to oxidation and chemical hydrolysis. The compound is reported to degrade under anaerobic conditions to form toluidine, but insufficient data are
available to indicate the significance of anaerobic degradation as a possible removal mechanism. One study under aerobic conditions resulted in persistence > 64 days. It is expected to be moderately to
highly mobile in soil and volatilize slowly from dry soil surfaces.
If released to the atmosphere, 4-nitrotoluene is expected to exist almost entirely in the vapour phase. The dominant removal mechanism would be reaction with photochemically generated hydroxyl radicals
(estimated half-life 19.9 days) and direct photolysis.
The bioconcentration factor (BCF) for 4-nitrotoluene has been measured to be less than 100 in carp. BCF values of 37 and 20 have been calculated based on a log octanol/water coefficient of 2.37 and a
measured water solubility of 442 mg/l at 30°C. These values suggest that 4-nitrotoluene will not bioaccumulate significantly in aquatic organisms.
5.1.7 Ecotoxicity
4-nitrotoluene is toxic to aquatic organisms. The following excerpt from the data in the AQUIRE database demonstrate this (AQUIRE, 2003):
EC50 (daphnia): 9 mg/l
LC50 (daphnia): 6.6-7.5 mg/l
LOEC (algae): 3.3 mg/l
LC50 (fish): 19-50 mg/l
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