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EC number: 206-735-5 | CAS number: 371-40-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Read-across approach to structural analogue substances were used.
Skin irritation: In the skin irritation test the test substance 3,5-Difluoroaniline (CAS 372-39-4) was determined to be corrosive to the skin of rabbit.
Eye irritation: In the eye irritation test the test substance 3-Chloro-4-fluoroaniline (CAS 367-21-5) was determined to cause severe non reversible damage to the eye of rabbit.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1994-03-14 to 1994-03-27
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- Adopted: 12 May 1981
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation: 10--1 weeks
- Weight at study initiation: 2.3- 2.6 kg
- Housing: Individually in metal cages with perforated floors
- Diet: SDS Stanrab (P) Rabbit Diet, ad libitum
- Water: Drinking water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature: 19°C
- Humidity: 30-70 %
- Air changes: 19 air changes per hour
- Photoperiod: 12 hours light in each 24 hours period - Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- water
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.5 g - Duration of treatment / exposure:
- 4 hours
- Observation period:
- 14 days
- Number of animals:
- 3
- Details on study design:
- TEST SITE
- Area of exposure: Dorso-lumbar region
-Coverage area: 25 mm x 25 mm
- Type of wrap if used: Gauze pad, each treatment site was covered with "Elastoplast" elastic adhesive dressing
REMOVAL OF TEST SUBSTANCE
- Washing: Yes, warm water (30°C-40°C)
- Time after start of exposure: At the end of the exposure period.
SCORING SYSTEM:
Erythema and eschar formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth)preventing erythema reading: 4
Oedema formation:
No oedema: 0
Very slighr oedema (barely perceptible): 1
Slight oedema (edges of area weII-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4 - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 3.33
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: Necrosis
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Remarks on result:
- other: Brown hardening of the skin
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1.67
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Remarks on result:
- other: Necrosis
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Remarks on result:
- other: Brown hardening of the skin
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Remarks on result:
- other: Desquamation of the stratum corneum
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2.33
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Irritant / corrosive response data:
- Clinical signs:
There were no signs of toxicity or ill health in any rabbit during the observation period.
Dermal responses
Moderate to severe erythema with slight to moderate oedema was seen following removal of the dressings. On day 3 severe erythema with necrosis was seen. Necrotic reactions, brown hardening of the skin and desquamation of the stratum corneum was seen between day 6 and 14. - Interpretation of results:
- Category 1C (corrosive)
- Remarks:
- Migrated information
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (corrosive)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1979-01-22
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: Federal Register 38, No. 187, Para. 1500.42, P.27029 from 27.09.1973
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- Vienna White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: M: 3220 g F: 2950 g
- Diet: SSNIFF der Firma Intermast - Controls:
- not specified
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied: 81 mg - Observation period (in vivo):
- 8 days
- Number of animals or in vitro replicates:
- 3 (2 male, 1 female)
- Irritation parameter:
- cornea opacity score
- Remarks:
- opacity
- Basis:
- animal #1
- Remarks:
- male
- Time point:
- other: 24, 72 hours
- Score:
- 1.5
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: no information on 48h available
- Irritation parameter:
- cornea opacity score
- Remarks:
- opacity
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- cornea opacity score
- Remarks:
- opacity
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Remarks:
- male
- Time point:
- other: 24, 72 hours
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: no information on 48h available
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 2
- Reversibility:
- fully reversible within: 8 days
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- conjunctivae score
- Remarks:
- redness
- Basis:
- animal #1
- Remarks:
- male
- Time point:
- other: 24, 72 hours
- Score:
- 2
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: no information on 48h available
- Irritation parameter:
- conjunctivae score
- Remarks:
- redness
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- conjunctivae score
- Remarks:
- redness
- Basis:
- animal #3
- Time point:
- other: 24,48, 72 hours
- Score:
- 2
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Remarks:
- male
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Irritant / corrosive response data:
- For animal no. 1 the scores at 48 hours could not be evaluated.
The mean cornea score opacity was >= 1 at all animals.
The mean iris score was 1 at 2 animals.
The mean conjunctivae score redness was 2 at all animals.
The mean chemosis score was 2 at 2 animals.
Following symptoms after 8 days were observed:
Animal no.1: Norrowed pupil, intergrown vessels, scar
Animal no.2: Scar
Animal no.3: Scar - Interpretation of results:
- Category 1 (irreversible effects on the eye)
- Remarks:
- Migrated information
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation
No data for this endpoint with the test substance is available. Thus, data from the similar substance 3,5-difluoroaniline (CAS 372-39-4) and3-Chloro-4-fluoroaniline (CAS 367-21-5) was summarised to cover these endpoints. For further justification see IUCLID section 13.
Key study
Sandoz Crop Protection Ltd., study no.: 180/940203/SE, 1994
Read-across approach to structural analogue substance 3,5-difluoroaniline (CAS 372-39-4) was used.
A study was performed to assess the skin irritation potential of the test substance to the rabbit. The method followed was that described in OECD Guideline for Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion”. Adopted: 12 May 1981.
Three rabbits were each administered a single dermal dose of 0.5 g of the test substance and observed for 14 days.
A single semi-occlusive application of the test substance to intact rabbit skin for four hours elicited severe dermal reactions with necrosis.
The mean erythema and edema scores at the time point of 24, 48 and 72 hours were as following for the three animals:
Erythema score: 3.33, 3, 1.67
Edema score: 2, 2, 2.33
All reactions persisted at day 14. Based on these results the test substance is determined to be corrosive to the skin of rabbits
Supporting study
BASF SE, study no. 78/176, 1980 (a)
Read-across approach to structural analogue substance 3-Chloro-4-fluoroaniline (CAS 367-21-5) was used.
In the neither guideline nor GLP compliant skin irritation study, an 80 % aqueous test solution was applied to the rabbit to the intact and scarified skin.The rabbits were observed over a period time of 8 days. Observations of erythema and edema scores were recorded after 24 and 72 hours.
The mean erythema and edema scores at the time point of 24 and 72 hours were as following for the three animals:
Erythema score: 4, 4, 2
Edema score: 2, 2, 1.5
The effects were not reversible after 8 days. Leather like necrosis was observed at two animals.
The results revealed that the test substance is corrosive to the skin.
Supporting study
BASF SE, study no. 78/176, 1980 (b)
Read-across approach to structural analogue substance 3-Chloro-4-fluoroaniline (CAS 367-21-5) was used.
In the neither guideline nor GLP compliant skin irritation study, an 80 % aqueous test solution was applied to the rabbit. The rabbits were observed over a period time of 8 days. Observations of erythema and edema scores were recorded after 24 and 48 hours. At the exposure time of 1 hour 4 animals were used.
At the exposure time of 4 hours only 2 animals were used.
The mean erythema score at 24 and 48 hours was for animal no. 1 and 2 as following: 3 and 2.
The mean edema score at 24 and 48 hours was for animal no.1 and 2 as following: 2.5 and 2.
At the end of the observation period of 8 days the erythema was fully reversible but necrosis was still observed, the edema was not reversible within 8 days.
Based on these results the test substance is determined to be corrosive to the skin of rabbits
Eye irritation test
Key study
BASF SE, substance no.78/176, 1980
Read-across approach to structural analogue substance 3-Chloro-4-fluoroaniline (CAS 367-21-5) was used.
In the neither guideline nor GLP compliant eye irritation study 82 mg of the test substance was applied to the eye of three rabbits. Effects like cornea opacity, iris, conjunctivae redness and chemosis were reported at 24, 48 and 72 hours. The mean cornea score opacity was >= 1 at all animals.
The mean iris score was 1 at 2 animals. The mean conjunctivae score redness was 2 at all animals. The mean chemosis score was 2 at 2 animals.
Based on these results it can be stated that the test substance causes severe non reversible damage to the eye.
Literature data with the test substance
In Gilleron et a. (1997) a Hen’s Egg Test-Chorioallantoic Membrane Test Substance Applicator (HET-CAM TSA) with the test substance was reported.
Based in the overall irritation score of 15.49, the test substance was determined to be an irritant.
In a EpiOcular-EIT PM test cited in Kaluzhny et al. (2011), the mean tissue viability was determined to be 6.28.
Based on this result the test substance was determined to be irritating.
In the ECETOC technical report no. 48 (2), (1998), an in vivo test with 6 rabbits was conducted similar to OECD 405.
The mean scores of 6 animals at the time point of 24, 48 and 72 hours were as following:
Cornea score (opacity): 1.6
Iris score: 0.6
Conjunctivae score (redness): 2.7
Chemosis score: 2.2
As the animals were observed only 3 days and no information about reversibility is given it cannot be clearly defined if the test item is irritating or corrosive.
In Verstraelen et al. (2013) in a Bovine Corneal Opacity and Permeability (BCOP) in vitro test, the test item was classified as category 1 irritating based on laser light-based opacitometer (LLBO) measurements.
Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant study. The test substance was a structural analogue substance, please refer to IUCLID section 13 for read across justification.
Justification for selection of eye irritation endpoint:
Neither guideline nor GLP compliant study but nevertheless well documented and scientifically acceptable. The test substance was a structural analogue substance.
Effects on skin irritation/corrosion: corrosive
Effects on eye irritation: corrosive
Justification for classification or non-classification
Skin irritation
Dangerous Substance Directive
(67/548/EEC)
The available study is considered reliable and suitable for
classification purposes under Directive 67/548/EEC. As a result
the substance is considered to be classified for skin corrosive C; R34:
Causes burns under Directive 67/548/EEC, as amended for the 31st time in
Directive 2009/2/EG.
Classification, Labelling, and Packaging
Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. As a result
the substance is considered to be classified for skin corr. 1C, H314:
Causes severe skin burns and eye damage under Regulation (EC) No
1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014.
Eye irritation
Dangerous Substance Directive
(67/548/EEC)
The available study is considered reliable and suitable for
classification purposes under Directive 67/548/EEC. As a result
the substance is considered to be classified for eye damage Xi; R41:
Risk of serious damage to eyes under Directive 67/548/EEC, as amended
for the 31st time in Directive 2009/2/EG.
Classification, Labelling, and Packaging
Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. As a result
the substance is considered to be classified for eye damage cat. 1,
H318: Causes serious eye damage under Regulation (EC) No 1272/2008, as
amended for the sixth time in Regulation (EC) No 605/2014.
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