Formaldehyde, oligomeric reaction products with aniline

Ecotoxicological Summary

Hazard for aquatic organisms

Freshwater

Hazard assessment conclusion:

PNEC aqua (freshwater)

PNEC value:

0 mg/L

Assessment factor:

50

Extrapolation method:

assessment factor

PNEC freshwater (intermittent releases):

0.001 mg/L

Marine water

Hazard assessment conclusion:

PNEC aqua (marine water)

PNEC value:

0 mg/L

Assessment factor:

500

Extrapolation method:

assessment factor

STP

Hazard assessment conclusion:

PNEC STP

PNEC value:

10 mg/L

Assessment factor:

10

Extrapolation method:

assessment factor

Sediment (freshwater)

Hazard assessment conclusion:

PNEC sediment (freshwater)

PNEC value:

0.074 mg/kg sediment dw

Extrapolation method:

equilibrium partitioning method

Sediment (marine water)

Hazard assessment conclusion:

PNEC sediment (marine water)

PNEC value:

0.007 mg/kg sediment dw

Extrapolation method:

equilibrium partitioning method

Hazard for air

Air

Hazard assessment conclusion:

no hazard identified

Hazard for terrestrial organisms

Soil

Hazard assessment conclusion:

PNEC soil

PNEC value:

0.128 mg/kg soil dw

Assessment factor:

1 000

Extrapolation method:

assessment factor

Hazard for predators

Secondary poisoning

Hazard assessment conclusion:

PNEC oral

PNEC value:

0.3 mg/kg food

Assessment factor:

270

Additional information

Justification on read-across of data for the 4,4´-isomer of MDA for oligomeric MDA in the scope of REACH.

Oligomeric MDA (oMDA) is produced by a condensation reaction between aniline and formaldehyde. The main component of the crude product is 4,4’-MDA, which makes up 46 to 65%. Further, the crude product contains minor amounts of methylene-2,4’-dianiline and traces of methylene-2,2’-dianiline. The other main component is a mixture of higher oligomers.

The general molecular formula is:

 H₂N-C₆H₄-[H₂N-C₆H₄]_m-C₆H₄-NH₂

The higher oligomers include mainly 3-ring (m=1; product of 3 aniline + 2 formaldehyde) together with other higher number ring types (m=4-7; 4 to 7 aniline with 3-6 formaldehyde) as shown in the table below.

 Following nomenclature for the isoformes are defined:

1) CAS name: Benzenamine, 4,4'-methylenebis- (mono constituent substance), CAS number: 101-77-9. EC name: 4,4'-methylenedianiline, EC number:202-974-4

2) CAS name: Formaldehyde, polymer with benzenamine (UVCB), CAS number 25214-70-4. EC name: Formaldehyde, oligomeric reaction products with aniline, EC number: 500-036-1.

Concentration ranges of MDA-isoforms [%]:

CONTENT	4,4’-MDA	Oligomeric MDA
4,4’-MDA	75-100	46-65
2,4’-MDA	0-20	0.8-1.4
2,2’-MDA	0-5	<0.1
Formaldehyde, oligomeric reaction products with aniline	0-15	3- to 7-ring isomers concentrations shown below
3-ring isomers	No data	22-28
4-ring isomers	No data	12-14
5-ring isomers	No data	6-8
6-ring isomers	No data	3-5
7-ring isomers	No data	1-3

2,4'-methylenedianiline: CAS number 1208-52-2, EC number 214-900-8

2,2'-methylenedianiline: CAS number 6582-52-1, EC number 229-512-4

 

Comparison of physico-chemical properties of MDA-isoforms:

Property	4,4’-MDA	oligomeric MDA
Melting range	83 - 92°C	30 - 70°C
MW [g/mol]	198.26	233 (average)
water solubility [g/l]	1.01 (at 25°C)	0.36-1.22 (at 20°C)
logPow(at 25°C)	1.55	1.3 - 2.5
Vapor pressure [hPa]	0.00025 Pa at 25°C	<0.000001hPa at 20°C

The higher oligomers are substantially less soluble than the diamine (4,4’-MDA: 1.25 g/l; 3-core-MDA: 42.5 mg/l) (EU RAR, 2001) and are emitted into the environment in much lower amounts than the diamines. If waste water is monitored, only the 4,4’-MDA is detected. It is unlikely the higher ring oligomers will significantly raise the total emissions and are therefore of less importance in any exposure assessment. Therefore as 4,4’-MDA is the main constituent of both isoforms, ecotoxicological properties of the incompletely tested oMDA can be extrapolated from this isomer in the absence of further data on oligomeric MDA.

Effects on Aquatic Organisms

Micro-organisms

An inhibition of respiration using activated sludge study was performed (Caspers et al) where a 3 hour EC₅₀value of >100 mg/l and an NOEC = 100 mg/l was calculated. These values may be used to determine aPNEC_wwtpvalue of 10 mg/l, using an assessment factor of 10 for 4,4'-MDA according to table R.10 -6 of the Guidance document.

Method	Results	Reference
activated sludge OECD Guideline 209 (Activated Sludge, Respiration Inhibition Test)	EC50(3 h): > 100 mg/L	Caspers N, Hamburger B, Kanne R & Klebert W (1986b)

Water compartment

The current strategy for deriving a protective PNEC_water, outlined in the REACH Guidance R10, indicates that the appropriate assessment factor should be applied to the lowest acute L(E)C₅₀value obtained from toxicity testing in fish, aquatic invertebrate and algal species. In the event that chronic toxicity data are available from three separate trophic levels, the lowest NOEC value is used with an assessment factor of 10 applied for fresh water and 100 applied for marine water.

Detailed below is an assessment of the available ecotoxicological data together with recommendations for the endpoints which should be used to determine the Predicted No Effect Concentration for oligomeric MDA in the fresh water environment (PNEC_{fresh water}) and marine environment (PNEC_{marine water}):-

Fish

A study was conducted exposingOryzias latipes(Mitsubishi (2002a)) to4,4'-MDAover 96 h. ALC₅₀(96 h) of 20.6 mg/l was determined.

There were no long-term fish studies.

Method	Results	Comment	Reference
Oryzias latipes freshwater semi-static OECD Guideline 203 (Fish, Acute Toxicity Test)	LC50(96 h): 20.6 mg/L test mat. (nominal)	4,4'-MDA	Mitsubishi (2002a)

Invertebrates

Method	Results	Comment	Reference
Daphnia magna freshwater static Screening test	EC50(48 h): > 0.1 — < 1 mg/L test mat. (nominal) based on: mobility	oligomericMDA	BASF SE (2010b)
Daphnia magna freshwater semi-static OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)	EC50(48 h): 2.47 mg/L test mat. (nominal) based on: mobility EC50(24 h): 8.08 mg/L test mat. (nominal) based on: mobility	4,4'-MDA	Mitsubishi (2002b)
Daphnia magna freshwater semi-static OECD Guideline 211 (Daphnia magna Reproduction Test)	NOEC (21 d): 0.00525 mg/L test mat. (meas. (TWA)) based on: reproduction LOEC (21 d): 0.0182 mg/L test mat. (meas. (TWA)) based on: reproduction	4,4'-MDA	Mitsubishi (2002c)

Two studies were conducted usingDaphnia Magna; one study tested the active ingredient 4,4’-MDA and one screening study investigated oligomeric MDA.

The EC₅₀(48 h) was found to be 2.47 mg/l (Mitsubishi (2002b))indicating that MDA is toxic to invertebrates. A screening study performed using oligomeric MDA produced an EC₅₀(48 h) of >0.1 - <1 mg/L(BASF SE (2010b)). The result from this study indicates that oligomeric MDA may be more toxic than 4,4’-MDA. Further work is proposed to investigate this effect.

A long-term test was also conducted onDaphnia magnawith 4,4’-MDA which resulted in a NOEC of 0.00525 mg/L.

Aquatic Plants

Method	Results	Comment	Reference
Scenedesmus subspicatus (new name: Desmodesmus subspicatus)(algae) freshwater static National industrial standard test guideline DIN 38 412 part 9	EC50(72 h): 11 mg/L test mat. (nominal) based on: growth rate EC50(72 h): 9.8 mg/L test mat. (nominal) based on: biomass EC10(72 h): 0.3 mg/L test mat. (nominal) based on: growth rate EC10(72 h): 2.4 mg/L test mat. (nominal) based on: biomass	Phenylbase MDA	Bayer AG (1992)

One study was conducted to investigate toxicity to aquatic plants. In this study, usingDesmodesmus subspicatusand a phenylbase MDA (Bayer AG (1992)), an EC₅₀of 11 mg/L was determined.

There were no long-term aquatic plant studies.

Summary Water Compartment

The most sensitive species of the three trophic levels of the base-set (fish, daphnia and algae) was determined to be invertebrates. Oligomeric MDA, based on the results from a screening study, appears to be more toxic than 4,4’-MDA. In order to produce a PNEC_aquaticthat is protective to the aquatic environment the result of 0.1 mg/L will be used for the invertebrate acute toxicity test. The invertebrate long-term study provides the most sensitive endpoint overall and will be used for the PNEC_aquaticderivation.

As there are results from 3 short-term tests (fish, invertebrates and algae) and 2 long-term tests (invertebrates and algae) an assessment factor of 50 will be used to calculate the PNEC_freshwater. Accordingly thePNEC_freshwateris 1.05E-04 mg/L.

The proposedPNEC_{marine water}1.05E-05 mg a.i./Lis based on the application of an additional assessment factor of 10 to the assessment factor of 50 applied to the EC₅₀value obtained in the invertebrate toxicity study.

Sediment

A PNEC_{sediment,freshwater}has been determined using the equilibrium partitioning method based on the PNEC_freshwaterderived above, in accordance with the TGD (equation 70).

Where:-

RHO_susp= 1150 kg/m³

PNEC_freshwater= 1.05E-04 mg/l

K_susp-water= 177 m³/m³(calculated using TGD equation 24)

PNEC_{sediment,freshwater}= 0.0162 mg/kgwwt(0.0743 mg/kg dwt)

A PNEC_{sediment,marine}has been determined using the equilibrium partitioning method based on the PNEC_marinewaterderived above, in accordance with the TGD (equation 70).

Where:-

RHO_susp= 1150 kg/m³

PNEC_marinewater=1.05E-05mg/l

K_susp-water= 177 m³/m³(calculated using TGD equation 24)

PNEC_{sediment,marine}= 1.62E-03 mg/kgwwt(7.43E-03 mg/kg dwt)

Terrestrial Compartment

A study was conducted to assess the effect on earthworms from 4,4’-MDA. The LC₅₀value was determined to be 444 mg/kg dwt.

Method	Results	Remarks	Reference
Eisenia fetida(annelids) short-term toxicity (laboratory study) Substrate: artificial soil OECD Guideline 207 (Earthworm, Acute Toxicity Tests)	NOEC (14 d): 180 mg/kg soil dw based on: mortality NOEC (14 d): 32 mg/kg soil dw based on: weight LC50 (14 d): 444 mg/kg soil dw based on: mortality	4,4'-MDA	van der Hoeven N, Roza P & Henzen L (1992a)

Two studies were conducted to assess the effects on plants. The lowest EC₅₀was determined to be 128 mg/kg dwt.

Method	Results	Remarks	Reference
Lactuca sativa(Dicotyledonae (dicots)) short-term toxicity (laboratory study) 1. seedling emergence toxicity test 2. early seedling growth toxicity test 3. survival Substrate: artificial soil OECD Guideline 208 (Terrestrial Plants Test: Seedling Emergence and Seedling Growth Test)	Lactuca sativa: NOEC (17 d): 100 mg/kg soil dw based on: seedling emergence Lactuca sativa: EC50 (14 d): 128 mg/kg soil dw based on: growth Lactuca sativa: NOEC (14 d): 10 mg/kg soil dw based on: growth Lactuca sativa: NOEC (14 d): >= 1000 mg/kg soil dw based on: survival	4,4'-MDA	van der Hoeven N, Roza P & Henzen L (1992b)
Avena sativa(Monocotyledonae (monocots)) short-term toxicity (laboratory study) 1. seedling emergence toxicity test 2. survival Substrate: artificial soil OECD Guideline 208 (Terrestrial Plants Test: Seedling Emergence and Seedling Growth Test)	Avena sativa: NOEC (17 d): 320 mg/kg soil dw based on: seedling emergence Avena sativa: EC50 (14 d): 353 mg/kg soil dw based on: growth Avena sativa: NOEC (14 d): 100 mg/kg soil dw based on: growth Avena sativa: NOEC (14 d): >= 1000 mg/kg soil dw based on: survival	4,4'-MDA	van der Hoeven N, Roza P & Henzen L (1992b)

Summary Terrestrial Compartment

Based upon the results of the 3 terrestrial studies, the lowest result was found to be the EC₅₀from the plant study (128 mg/kg dwt). Applying an assessment factor of 1000 to the EC₅₀value, the PNEC_soilcan be determined to be 0.128 mg/kg dwt (0.113 mg/kg wwt).

PNEC_oral

The PNEC_oral(0.30 mg/kg food) was based on the LOAEL of 80 ppm from the subchronic drinking water study with rats (Ciba Geigy 1982). A factor of 3 was used to derive a NOAEL, and a factor of 90 to extrapolate from the subchronic study (Guidance chapter R.10.8).

It is not expected that MDA will enter the foodchain therefore the dervivation of the PNEC oral was a theoretical exercise.

Conclusion on classification

According to regulation 1272/208/EC, oligomeric MDA is classified as:

H410: very toxic to aquatic life with long lasting effects.

According to 67/548/EC, oligomeric MDA is classified as:

R50/53: very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.