N-(4-chlorophenyl)-2-[(4-methyl-2-nitrophenyl)azo]-3-oxobutyramide

Short-term toxicity to aquatic invertebrates

Description of key information

EC50> 100 mg/L

Additional information

Read Across Hypothesis

The read across approach covers two Monoazo Yellow Pigments. The pigments encompassed are:

CAS no.	EC no.	Substance Name (C.I. Name)	Substance Name	Substance Role
57206-89-0	260-618-3		N-(4-Chlorophenyl)-2-[(4-methyl-2-nitrophenyl)azo]-3-oxobutyramide	target
6486-23-3	229-355-1	PIGMENT YELLOW 3	2-[(4-chloro-2-nitrophenyl)azo]-N-(2-chlorophenyl)-3-oxobutyramide	source

 

The read across hypothesis is that both substances – based on a very similar chemical structure – have very similar physical-chemical properties, which also govern their toxicokinetic behavior, their toxicity, ecotoxicity and environmental behaviour. These properties

·       very low solubility in water but also in organic solvents

·       non-degradability

lead to inert behaviour and negligible bioavailability for both humans and environmental organisms. This hypothesis is supported by absence of relevant effects in any of the tests for any endpoint (see Data Matrix).

Three dimensional single crystal X-ray analysis (Herbst and Hunger, 2004) showed that the Monoazo Yellow Pigments have a very stable lattice, which is stabilized by intramolecular hydrogen bonds into an almost planar configuration. This, together with relatively high molecular masses suggests low bioavailability. This is supported by the very limited solubility in any kind of media.

Both substances decompose at temperatures below 300 °C. And both are only soluble to a limited extend in water andn-octanol. Water solubility is about 9.3 µg/L (target) and 7.5 μg/L (source). Solubility inn-octanol is low (target: 43.7 mg/L and source 6.0 mg/L). The corresponding n-octanol/water partitioning coefficients were calculated to be 3.67 for the target and 2.9 for the source substance. These values are well below the limit of concern of 4.5 considered to be critical for bioaccumulative properties.

Overall the available toxicological data from the source substance should easily and reliably be used to predict specific endpoints of the target substance.

List of endpoints covered

The read across approach is applied to the following endpoints:

-        Skin irritation

-        Eye irritation

-        Acute toxicity, oral route         

-        Short-term toxicity testing on Daphnia

 

Purities/Impurities

Both substances are synthesized in the same manner by azo coupling in aqueous media. Therefore they share a similar impurity profile. Both substances are of very high purity with > 97%. No noteworthy impurities have been identified. Impurities are most likely derived from the raw materials used.

 

Read Across Justification

The pigments of this approach are structurally similar and contain a substituted phenyl moiety, an azo moiety, and an oxobutyramide moiety. Minor differences are due to the number of Cl- (2 or 1) and methyl-substituents (0 or 1) and its different ring position. Both are solids, which decompose at high temperatures. The solubility of both pigments in water and n-octanol is very limited, < 10 μg/L and < 44 mg/L, respectively, resulting in a low partition coefficient in n-octanol/water (log Pow < 3.7), which is far below the limit of concern considered to be critical for bioaccumulative properties. When suspended in water both pigments yield nearly neutral pH values, which are entirely different from extreme values causing skin or eye corrosive reactions.

Monoazo Yellow Pigments generally show very limited biodegradability, which is assumed to be due to their unavailability for microorganisms. Lacking bioavailability is probably also the reason for the absence of any relevant mammalian toxicity: Both pigments didn’t show relevant toxic effect after single oral exposure up to the limit dose, skin sensitizing effect, or mutagenic properties.

These data indicate that the presence, number, position and identity of substituents do not influence the physico-chemical, ecotoxicological and toxicological behaviour of the pigments in a significant way.

In conclusion, structural similarities with very similar physico-chemical properties, environmental fate, and mammalian toxicity enable the prediction of acute oral toxicity and skin/eye irritation/corrosion of the target substance based on known properties of the source substance. Fulfillment of data requirements by read across from source to target substance is justified.

Data Matrix

Substance Role	Target	Source
Chemical name	N-(4-chlorophenyl)-2-[(4-methyl-2-nitrophenyl)azo]-3-oxobutyramide	PY 3
CAS no	57206-89-0	6486-23-3
Physicochemical Properties
State of the substance at 20° C and 101,3 kPa	Yellow solid	Yellow solid
Melting/freezing point	236 °C; decomp. 253 °C	255 °C; decomp. 256 °C
Relative density	1.4262 g/cm^3at 27°C	1.5640 g/mL at 23 °C
Vapour pressure	<0.001 Pa at 20°C	<0.000001 Pa (EPIWin estimate in agreement with "column 2")
Water solubility	9.3 µg/L at 23°C	7.5 μg/L at 24-25 °C
pH value of an aqueous suspension	6.8	7.5
Partition coefficient n-octanol/water	3.67	2.9
Flammability	No ignition (BZ 1)	non-flammable (BZ 2)
Explosive properties	not explosive	not explosive
Self-ignition temperature	No self-ignition (neat substance), 260 °C (1:1 mixt. with kieselguhr)	no self-ignition (neat substance), 260 °C (1:1 mixt. with kieselguhr)
Oxidizing properties (Ox reduction potential)	not oxidizing (Method A.17)	not oxidising (UN-Test O.1)
Stability in organic solvents and identity of relevant de-gradation products	No data	>72 h in DMSO and in 1,2-propylene glycol
Solubility in org. solvents: octanol solubility	43.7 mg/L at 23°C	5.96 mg/L at 25-26 °C
Mammalian Toxicity
skin irritation	RA: not irritating	not irritating
eye irritation	RA: not irritating	not irritating
Skin sensitisation	not sensitising	not sensitising
In vitrogene mutation study in bacteria	not mutagenic (Prival modif.)	not mutagenic (Prival modif.)
Acute toxicity, oral route	RA: LD50 rat: >2000 mg/kg bw	LD50 rat (f) = 8285 mg/kg bw
Ecotoxicology
Short-term toxicity testing on Daphnia	RA:EC50> 100 mg/L	EC50> 100 mg/L