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EC number: 500-011-5 | CAS number: 9003-80-9
- 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
Acute toxicity via oral route
LD50 >5000 mg/kg/bw in female Wistar rats.
Acute toxicity via dermal route
LD50 >2000 mg/kg bw in male/female Wistar rats.
Acute toxicity via inhalation route
LD50 >5000 mg/m3 bw in male/female Wistar rats.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 12 June 2015 to 12 October 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- yes
- Remarks:
- Deviations from the maximum level of daily mean relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviation.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Deviations:
- yes
- Remarks:
- Deviations from the maximum level of daily mean relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviation.
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- Deviations from the maximum level of daily mean relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviation.
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Species: Rat, Wistar strain Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC)Source: Charles River Deutschland, Sulzfeld, Germany.Number of animals: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.Age and body weight: Young adult animals (approx. 10-11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.Identification: Earmark and tail markHealth inspection: At least prior to dosing. It was ensured that the animals were healthy and without any abnormality that might affect the study integrity.ConditionsEnvironmental controls for the animal room are set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle: the photoperiod is between 07:00 and 19:00 hrs daily. The light/dark cycle may be interrupted for study related activities. Any variations to these conditions will be evaluated and maintained in the raw data.Accommodation: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).Acclimatization period was at least 5 days before start of treatment under laboratory conditions.Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).Water: Free access to tap water.Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.
- Route of administration:
- oral: gavage
- Vehicle:
- propylene glycol
- Details on oral exposure:
- Method: Oral gavage, using plastic feeding tubes. The test item preparations were stirred on a magnetic stirrer during dosing.Fasting: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.Frequency: Single dosage on Day 1.Dose level (volume): 2000 mg/kg (10 mL/kg) body weight.
- Doses:
- Single dose adminstered by oral gavage on day 1
- No. of animals per sex per dose:
- 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals each given 2000 mg/kg (10 mL/kg) body weight.
- Control animals:
- not specified
- Details on study design:
- The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
- Statistics:
- The oral LD50 value of the test substance was ranked within the following ranges: 0-5, 5-50, 50-300 or 300-2000 mg/kg b.w. or as exceeding 2000 mg/kg b.w. The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).The results were evaluated according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (including all amendments) and Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortaility occurs
- Clinical signs:
- Hunched posture and/or uncoordinated movements were noted for all animals on day 1
- Body weight:
- The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
- Gross pathology:
- No abnormalities were found at macroscopic post mortem examination of the animals.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The oral LD50 value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was established to exceed 5000 mg/kg body weight.
- Executive summary:
The aim of the test was to assess the toxicity of the test substance when administered orally in a single dose to female rats. The test was conducted in accordance to:
Organization for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Section 4, Health Effects. No. 423, "Acute Oral Toxicity - Acute Toxic Class Method", 2001.
Commission Regulation (EC) No 440/2008 Part B: Methods for the Determination of Toxicity and other Health Effects; B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method". Official Journal of the European Union No. L142, May 2008, including the most recent amendments.
United States Environmental Protection Agency (EPA). Health Effects Test Guidelines, OPPTS 870.1100, Acute Oral Toxicity. Office of Prevention, Pesticides and Toxic Substances (7101), EPA 712-C-02-190, 2002.
Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
In conclusion the test concluded that the oral LD50 value for Formaldehyde, oligomeric reaction products with acetone and diphenylamine was established to exceed 2000 mg/kg/bw. No mortalities occurred, however, there were clinical signs such as hunched posture, piloerection and/or uncoordinated movements were noted for all animals on Day 1. The body weight gain shown by the animals was considered to be similar to that expected for normal untreated animals of the same age and stain. No abnormalities were found at macroscopic post mortem examination of the animals.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, Formaldehyde, oligomeric reaction products with acetone and diphenylamine does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
Reference
Mortality data
TEST DAY |
1 |
1 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
16 |
HOURS AFTER TREATMENT |
0 |
2 |
4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
FEMALES 2000 MG/KG |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
FEMALES 2000 MG/KG |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Clinical signs
TEST DAY |
Max grade |
1 |
1 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
16 |
HOURS AFTER TREATMENT |
|
0 |
2 |
4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
FEMALES 2000 MG/KG Animal 1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gait / motility. Uncoordinated movements |
(3) |
- |
- |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Skin / fur. Piloerection |
(1) |
- |
1 |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Animal 2 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gait / motility. Uncoordinated movements |
(3) |
- |
- |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Skin / fur. Piloerection |
(1) |
- |
1 |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Animal 3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gait / motility. Uncoordinated movements |
(3) |
- |
- |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Skin / fur. Piloerection |
(1) |
- |
1 |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Animal 4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Posture: Hunched posture |
(1) |
1 |
1 |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Animal 5 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Posture: Hunched posture |
(1) |
1 |
1 |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Animal 6 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Posture: Hunched posture |
(1) |
1 |
1 |
1 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- Sign not observed
Body weight gain
Sex/Dose level |
ANIMAL |
DAY 1 |
DAY 8 |
DAY 15 |
FEMALES 2000 MG/KG |
|
|
|
|
1 |
186 |
206 |
218 |
|
2 |
177 |
191 |
205 |
|
3 |
174 |
204 |
211 |
|
MEAN |
179 |
200 |
211 |
|
ST.DEV. |
6 |
8 |
7 |
|
N |
3 |
3 |
3 |
|
1 |
193 |
212 |
221 |
|
2 |
187 |
209 |
215 |
|
3 |
199 |
216 |
226 |
|
MEAN |
193 |
212 |
221 |
|
ST.DEV. |
6 |
4 |
6 |
|
N |
3 |
3 |
3 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 000 mg/kg bw
- Quality of whole database:
- K1 - GLP accredited laboratory study in accordance with recognised guidelines
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01 August 2016 to 23 August 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- Organisation for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Section 4, Health Effects. No.403, "Acute Inhalation Toxicity", September 2009.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Version / remarks:
- Commission Regulation (EC) No 440/2008 Part B: Methods for the Determination of Toxicity and other Health Effects; B.2. AcuteToxicity (inhalation). Official Journal of the European Communities No. L142, May 2008, including most recent amendments.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1300 (Acute inhalation toxicity)
- Version / remarks:
- EPA Health Effects Test Guidelines OPPTS 870.1300, Acute inhalation Toxicity. EPA 712-C-98-193, August 1998.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Notification No 8147.
- Version / remarks:
- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- traditional method
- Limit test:
- yes
- Specific details on test material used for the study:
- Test item: 206534/B
Identification: Formaldehyde, oligomeric reaction products with acetone and diphenylamine
Appearance: Dark brown flakes
Batch: IC6D11P001
Purity/Composition: 100% Unknown or Variable compositions, Complex reaction products and Biological materials (UVCB)
Test item storage: At room temperature
Stable under storage conditions until: 27 April 2020 (expiry date)
Chemical name (IUPAC), synonym or trade name: Formaldehyde, oligomeric reaction products with acetone and diphenylamine (BXA)
CAS Number: 9003-80-9 - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Species: Rat: Crl:WI(Han) (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nulliparous and nonpregnant) per exposure level. Two exposure levels
Age and body weight: Young adult animals were selected (approximately 10-11 weeks old). Animals used within the study were of approximately the same age and body weight variation did not exceed +/- 20% of the sex mean.
Identification: Individual unique number by tattoo on hind leg.
Health inspection: At least prior to exposure. It was ensured that the animals were healthy and without any abnormality that might affect the study integrity.
Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle.
Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.
Accommodation
Group housing of five animals per sex per cage in labelled Makrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Lignocel S 8-15, JRS -J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cageenrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test item.
Water
Free access to tap water except during exposure to the test item.
Animal husbandry on the day of exposure
The animals were moved to the inhalation area to in order to perform the exposure. During the exposure, there was no access to food and water. After exposure, the animals were returned to their cages which were placed in a fume cupboard for a short time period to allow test item remnants to evaporate. A sheet of filter paper was used to cover the bedding material to prevent suffocation in case of bad health condition and in order to recover and to aid the clinical observations. The sheet was removed and before the end of the exposure day, the surviving animals were returned to the animal room.
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study. - Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Mass median aerodynamic diameter (MMAD):
- >= 3.9 - <= 4.3 µm
- Geometric standard deviation (GSD):
- >= 1.9 - <= 2.1
- Remark on MMAD/GSD:
- The particle size distribution was characterized twice during each exposure period. The samples were drawn (2 L/min) from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters (TE-290-GF. Tisch Environmental, Cleves, Ohio, USA) and a fiber glass back-up filter (SEC-290-F1, Westech, Upper Stondon, Bedfordshire, England). Amounts of test item collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.
- Details on inhalation exposure:
- Exposure Chamber
The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber (volume approximately 150 mL) consisted of three animal sections with eight animal ports each.
Each animal port had its own atmosphere inlet and exhaust outlet. The animals were placed in restraining tubes and connected to the animal ports. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
All components of the exposure chamber in contact with the test material were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained at a slight negative pressure.
Test Atmosphere Generation
The test atmosphere generation was based on the method developed during extensive trial generations.
Administering the test item to a stream of pressurized air using a combination of a brush feeder and micronizing jet mill generated (Bernstein, D.N., Aerosols, pp 721- 723, 1984) generated a dust. The dust was passed through a series of three cyclones, allowing larger particles to settle, and diluted with pressurized air before it entered the exposure chamber. For the exposure at 1 mg/L, the mean total air flow was 23 L/min. and at 5 mg/L the mean total airflow was 20 L/min.
From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.
Test Atmosphere Characterization
Nominal Concentration
The nominal concentration was calculated by dividing the amount of test item used by the volume of pressurized air (average air flow times exposure time) entering the exposure chamber used for exposure of the animals. Due to the small volume of the exposure chamber the equilibrium time was negligible. The volume of air was calculated from the average air flow (measured by means of thermal mass flow meters and was recorded regularly, preferably in 30 minute intervals) and the exposure time.
Actual Concentration
A total of 21 and 28 representative samples were taken for determination of the actual concentrations during exposure at 5 and 1 mg/L, respectively. Samples were drawn from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. Samples were drawn through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of the test item in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands). Subsequently the timeweighted mean concentrations with the standard deviations were calculated. - Analytical verification of test atmosphere concentrations:
- no
- Duration of exposure:
- 4 h
- Concentrations:
- The study was performed following a stepwise exposure scenario. Target concentrations were based on the cut off concentration values specified in the UN and EC classification guidelines for dusts and mists (0.05, 0.5, 1 or 5 mg/L.).
- No. of animals per sex per dose:
- Toxicity data of the test item indicated that severe effects may be expected at the highest target concentration as indicated above. Therefore, as a first step the study was initiated with the exposure of five animals of each sex to 1 mg/L for 4 hours. Based on the results, five animals of each sex were exposed to 5 mg/L
- Control animals:
- no
- Details on study design:
- Stability Monitoring
It was considered that the opacity of the test atmosphere could not be reliably monitored by means of an aerosol monitoring system. An indication of the stability of the test atmosphere was obtained from the concentration measurements, which were equally distributed over time.
Temperature and Relative Humidity
The temperature and relative humidity were measured with a humidity and temperature indicator (E+E Elektronik, Engerwitzdorf, Austria) and were recorded after the animals were placed in the experimental set-up and at 30 minute intervals after initiation of the exposure.
The probe was inserted in a tube mounted in one of the free animal ports of the middle section of the exposure chamber.
The temperature of the atmosphere during the exposures were between 21.1 and 22.8°C and relative humidity was between 16 and 39%. These conditions were considered appropriate for this relatively short 4 hours exposure duration.
Treatment
Prior to each exposure, both eyes of each rat were instilled with Opthosan (AST Farma BV, Oudewater, The Netherlands) to protect the eyes against potential irritation by the test item.
Prior to exposure the animals were restrained in polycarbonate restraining tubes; these tubes were connected to the exposure chamber. Sixteen or eighteen minutes after the last animal was placed the generation of the test atmosphere was started. The exposure time was 4 hours.
Observations
Mortality/Viability: Twice daily.
Clinical signs: During exposure
Three times during exposure for mortality, behavioural signs of distress and effects on respiration.
Clinical signs: After exposure
On Day 1, one and three hours after exposure and once daily thereafter until Day 15. The clinical signs were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Body weights: Days 1 (pre-administration), 2, 4, 8 and 15.
Necropsy: All animals were sacrificed at the end of the observation period by an intraperitoneal injection with Euthasol® (AST Farma BV, Oudewater, The Netherlands). All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded. Particular attention was given to any changes in the respiratory tract. - Statistics:
- No statistical analysis was performed.
- Preliminary study:
- For the 1 mg/L exposure group, the time-weighted mean actual concentration was 1.1 ± 0.03 mg/L.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5 mg/L air (nominal)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- No mortality occurred.
- Clinical signs:
- other: At 1 mg/L, quick breathing was seen during exposure. After exposure, one male showed hunched posture on Day 1. Brown staining by test item remnants of the skin and fur was seen between Days 1 and 6. At 5 mg/L, quick breathing was seen during exposure. Aft
- Body weight:
- Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study and were therefore considered not indicative of toxicity.
- Gross pathology:
- Macroscopic post mortem examination revealed several purple foci on the left side of the thymus of one female exposed to 1 mg/L. Macroscopic examination of the other animals did not reveal further abnormalities.
- Other findings:
- Concentration
For the 1 mg/L exposure group, the time-weighted mean actual concentration was 1.1 ± 0.03 mg/L. The nominal concentration (amount of test item used divided by the volume of pressurized air used) was 9.7 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 11%.
The concentration was measured at time points (n=28) that were equally distributed over the exposure period, the results of which demonstrated that it was difficult to maintain the test item stable. The generation was interrupted on two occasions in order to make adjustments to the system. To compensate for these interruptions, the generation time was elongated by 9 minutes in order to achieve an actual exposure time of 240 minutes. By calculating the time weighted mean concentration, the effect of the interruptions and variations were taken into account. Overall, it was considered that the generation represented the intended exposure to the 1 mg/L target concentration for 4 hours.
For the 5 mg/L exposure group, the time-weighted mean actual concentration was 5.3 ± 0.4 mg/L. The nominal concentration was 64.1 mg/L and the generation efficiency was 8%.
The concentration was measured at time points (n=21) that were equally distributed over the exposure period, the results of which showed that it was difficult to maintain a stable concentration. The generation was interrupted twice and the set-up was changed within the first 50 minutes after start. The generation time was elongated with 12 minutes in order to achieve an actual exposure time of 240 minutes. By calculating the time weighted mean concentration, the effect of the interruptions and variations were taken into account. Overall, it was considered that the generation represented the intended exposure to the 5 mg/L target concentration for 4 hours.
Particle Size
The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice during the exposure period. At 1 mg/L, the MMAD was 3.9 μm (gsd 1.9) and 4.0 μm (gsd 2.1). At 5 mg/L, the MMAD was 4.0 μm (gsd 2.1) and 4.3 μm (gsd 2.0). - Interpretation of results:
- GHS criteria not met
- Conclusions:
- Based on the results, the inhalatory LC50, 4h value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was considered to exceed 5 mg/L.
- Executive summary:
Assessment of acute inhalation toxicity with Formaldehyde, oligomeric reaction products with acetone and diphenylamine in the rat (nose-only)
The study was carried out based on the guidelines described in:
OECD Guidelines, Section 4, Health Effects. No.403, "Acute Inhalation Toxicity", Sep 2009.
Commission Regulation (EC) No 440/2008, B.2. Acute Toxicity (inhalation), L142, May 2008.
EPA OPPTS 870.1300, Acute inhalation Toxicity. EPA 712-C-98-193, August 1998.
JMAFF Guidelines (2000), including the most recent revisions.
Formaldehyde, oligomeric reaction products with acetone and diphenylamine was administered as a dust by nose-only inhalation for 4 hours to two groups of five male and five female Wistar rats. Mortality and clinical signs were observed daily during the observation period and body weights were determined on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (Day 15).
For the 1 mg/L exposure group, the time-weighted mean actual concentration was 1.1 ± 0.03 mg/L. The nominal concentration (amount of test item used divided by the volume of pressurized air used) was 9.7 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 11%. The concentration was measured at time points (n=28) that were equally distributed over the exposure period, the results of which demonstrated that it was difficult to maintain the test item stable. Overall, it was considered that the generation represented the intended exposure to the 1 mg/L target concentration for 4 hours.
For the 5 mg/L exposure group, the time-weighted mean actual concentration was 5.3 ± 0.4 mg/L. The nominal concentration was 64.1 mg/L and the generation efficiency was 8%. The concentration was measured at time points (n=21) that were equally distributed over the exposure period, the results of which showed that it was difficult to maintain a stable concentration. Overall, it was considered that the generation represented the intended exposure to the 5 mg/L target concentration for 4 hours.
The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice during the exposure period. At 1 mg/L, the MMAD was 3.9 μm (gsd 1.9) and 4.0 μm (gsd 2.1). At 5 mg/L, the MMAD was 4.0 μm (gsd 2.1) and 4.3 μm (gsd 2.0).
No mortality occurred.
At 1 mg/L, quick breathing was seen during exposure. After exposure, one male showed hunched posture on Day 1. Brown staining by test item remnants of the skin and fur was seen between Days 1 and 6.
At 5 mg/L, quick breathing was seen during exposure. After exposure, no systemic clinical signs were seen. Brown and green staining by test item remnants of the skin and fur was seen between Days 1 and 4.
Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study and were therefore considered not indicative of toxicity.
Macroscopic post mortem examination revealed several purple foci on the left side of the thymus of one female exposed to 1 mg/L. Macroscopic examination of the other animals did not reveal further abnormalities.
The generation of high dust concentrations is technically challenging. In this study, the concentration varied considerably during the first 2 hours. Over the total 4 hour exposure period, the time weighted mean concentration exceeded 5 mg/L. Considering the absence of mortality and severe signs, no significant mortality would be expected after exposure to 5 mg/L with less variation.
Based on the results, the inhalatory LC50, 4h value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was considered to exceed 5 mg/L.
Based on this study, Formaldehyde, oligomeric reaction products with acetone and diphenylamine does not have to be classified and has no obligatory labelling requirement for acute inhalation toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments.
Reference
Gravimetric Concentration of Test Item
1 mg/L exposure group
Start of generation of test atmosphere: 09:55
End of generation of test atmosphere: 14:04
Time (hh:mm) |
Action |
Sample volume (L) |
Mass sampled (mg) |
Concentration (mg/L) |
% of total exposure time |
Weight concentration (mg/L) |
9:55 9:59 10:03 10:10 10:18 10:24 10:31 10:48 11:02 11:08 11:14 11:20 11:32 11:51 12:09 12:24 12:31 12:37 12:43 12:49 12:54 13:00 13:03 13:10 13:11 13:17 13:23 13:28 13:34 13:38 13:40 13:42 13:59 14:04 |
Start of generation Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Stop generation Start of generation Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Stop generation Start of generation Start of sampling Start of sampling End of generation |
n.a. 5 5 5 5 6 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 n.a. n.a. 5 5 5 5 5 n.a. n.a. 5 5 n.a. |
n.a. 3.90 4.62 4.02 4.84 6.34 5.40 6.07 7.45 8.60 8.08 5.91 5.02 5.97 6.71 6.98 7.53 7.62 4.45 3.52 1.91 0.83 n.a. n.a. 8.34 8.80 4.34 4.85 4.09 n.a. n.a. 5.55 4.48 n.a. |
n.a. 0.780 0.924 0.804 0.968 1.057 1.080 1.214 1.490 1.720 1.616 1.182 1.004 1.194 1.342 1.396 1.506 1.524 0.890 0.704 0.382 0.166 0.166 1) n.a. 1.668 1.760 0.868 0.970 0.818 0.818 1) n.a. 1.110 0.896 0.896 1) |
0.0 1.7 1.7 2.9 3.3 2.5 2.9 7.1 5.8 2.5 2.5 2.5 5.0 7.9 7.5 6.3 2.9 2.5 2.5 2.5 2.1 2.5 1.3 n.a. 0.4 2.5 2.5 2.1 2.5 1.7 n.a. 0.8 7.1 2.1 |
n.a. 0.013 0.015 0.023 0.032 0.026 0.032 0.086 0.087 0.043 0.040 0.030 0.050 0.095 0.101 0.087 0.044 0.038 0.022 0.018 0.008 0.004 0.002 n.a. 0.007 0.044 0.022 0.020 0.020 0.014 n.a. 0.009 0.063 0.019 |
Time-weighted mean concentration Standard deviation Number of samples |
1.115 0.028 28 |
1) Assumed concentration, based on the last sample
2) n.a. = not applicable
Gravimetrical Concentration of Test Item
5 mg/L exposure group
Start of generation of test atmosphere: 09:14
End of generation of test atmosphere: 13:26
Time (hh:mm) |
Action |
Sample volume (L) |
Mass sampled (mg) |
Concentration (mg/L) |
% of total exposure time |
Weight concentration (mg/L) |
9:14 9:17 9:22 9:28 9:31 9:34 9:35 9:42 9:48 9:58 10:07 10:08 10:11 10:19 10:21 10:29 10:35 10:41 10:46 10:54 11:16 11:20 11:37 11:59 12:21 13:20 13:26 |
Start of generation Start of sampling Start of sampling Start of sampling Stop generation Start of generation Start of sampling Start of sampling Start of sampling Stop generation Start of generation Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling Start of sampling End of generation |
n.a. 5 5 5 n.a. n.a. 5 5 6 n.a. n.a. 5 5 5 5 5 5 5 5 5 5 5 5 5 5 8 n.a. |
n.a. 12.74 8.56 3.98 n.a. n.a. 14.91 1.00 0.49 n.a. n.a. 41.86 5.51 79.38 40.47 8.27 33.03 39.39 9.42 38.13 10.64 36.97 32.38 39.08 37.05 49.66 n.a. |
n.a. 2.548 1.712 0.796 0.796 1) n.a. 2.982 0.200 0.082 0.082 1) n.a. 8.372 1.102 15.876 8.094 1.654 6.606 7.878 1.884 7.626 2.1228 7.394 6.476 7.816 7.410 6.208 6.208 1) |
0.0 1.3 2.1 2.5 1.3 n.a. 0.4 2.9 2.5 4.2 n.a. 0.4 1.2 3.3 0.8 3.3 2.5 2.5 2.1 3.3 9.2 1.7 7.1 9.2 9.2 24.6 2.5 |
n.a. 0.032 0.036 0.020 0.010 n.a. 0.012 0.006 0.002 0.003 n.a. 0.035 0.014 0.529 0.067 0.055 0.165 0.197 0.039 0.254 0.195 0.123 0.459 0.716 0.679 1.526 0.155 |
Time-weighted mean concentration Standard deviation Number of samples |
5.331 0.351 21 |
1) Assumed concentration, based on the last sample
2) n.a. = not applicable
Aerodynamic Particle Size Distribution in the Test Atmosphere
1 mg/L exposure group
Start of generation of test atmosphere: 09:55
End of generation of test atmosphere: 14:04
Sampling speed (L/min): 2
Measurement 1:
Sampling time: 10:56
Sample volume (L): 8
Stage |
Cut point (μm) |
Mass sampled (mg) |
Relative mass (%) |
Cumulative mass (% of total sampled) |
1 2 3 4 5 6 7 8 Back up |
21.0 15.0 10.0 6.0 3.5 2.0 0.9 0.5 0.25 |
0.01 0.07 1.00 1.89 3.25 1.32 0.48 0.15 0.14 |
0.12 0.84 12.03 22.74 39.11 15.88 5.78 1.81 1.68 |
99.88 99.04 87.00 64.26 25.15 9.27 3.49 1.68 0.00 |
MMAD1 (μm): gsd2: |
|
3.9 1.9 |
|
1Mass Median Aerodynamic Diameter
2Geometric standard deviation
Measurement 2:
Sampling time: 13:47
Sample volume (L): 9
Stage |
Cut point (μm) |
Mass sampled (mg) |
Relative mass (%) |
Cumulative mass (% of total sampled) |
1 2 3 4 5 6 7 8 Back up |
21.0 15.0 10.0 6.0 3.5 2.0 0.9 0.5 0.25 |
0.00 0.07 1.23 1.66 2.34 1.17 0.38 0.09 0.26 |
0.00 0.97 17.08 23.06 32.50 16.25 5.28 1.25 3.61 |
100.00 99.03 81.94 58.89 26.39 10.14 4.86 3.61 0.00 |
MMAD1 (μm): gsd2: |
|
4.0 2.1 |
|
1Mass Median Aerodynamic Diameter
2Geometric standard deviation
Aerodynamic Particle Size Distribution in the Test Atmosphere
5 mg/L exposure group
Start of generation of test atmosphere: 09:14
End of generation of test atmosphere: 13:26
Sampling speed (L/min): 2
Measurement 1:
Sampling time: 11:54
Sample volume (L): 2
Stage |
Cut point (μm) |
Mass sampled (mg) |
Relative mass (%) |
Cumulative mass (% of total sampled) |
1 2 3 4 5 6 7 8 Back up |
21.0 15.0 10.0 6.0 3.5 2.0 0.9 0.5 0.25 |
0.00 0.00 0.24 0.48 0.47 0.66 0.26 0.06 0.00 |
0.00 0.00 11.06 22.12 21.66 30.41 11.98 2.76 0.00 |
100.00 100.00 88.94 66.82 45.16 14.75 2.76 0.00 0.00 |
MMAD1 (μm): gsd2: |
|
4.0 2.1 |
|
1Mass Median Aerodynamic Diameter
2Geometric standard deviation
Measurement 2:
Sampling time: 13:24
Sample volume (L): 2
Stage |
Cut point (μm) |
Mass sampled (mg) |
Relative mass (%) |
Cumulative mass (% of total sampled) |
1 2 3 4 5 6 7 8 Back up |
21.0 15.0 10.0 6.0 3.5 2.0 0.9 0.5 0.25 |
0.00 0.00 0.84 0.95 1.76 0.79 0.72 0.14 0.01 |
0.00 0.00 16.12 18.23 33.78 15.16 13.82 2.69 0.19 |
100.00 100.00 83.88 65.64 31.86 16.70 2.88 0.19 0.00 |
MMAD1 (μm): gsd2: |
|
4.3 2.0 |
|
1Mass Median Aerodynamic Diameter
2Geometric standard deviation
Mortality
TEST DAY HOURS AFTER TREATMENT |
1 1 |
1 3 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
MALES 1 MG/LITER FEMALES 1 MG/LITER MALES 5 MG/LITER FEMALES 5 MG/LITER |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
- - - - |
Clinical Signs
TEST DAY HOURS AFTER TREATMENT |
MAX GRADE |
1 1 |
1 3 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
MALES 1 MG/LITER |
|||||||||||||||||
ANIMAL 1 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 2 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 3 Posture Hunched posture Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1)
(1) (1) (1) |
-
- - 1 |
1
- - 1 |
-
1 1 - |
-
1 1 - |
-
1 1 - |
-
1 1 - |
-
- - - |
-
- - - |
-
- - - |
-
- - - |
-
- - - |
-
- - - |
-
- - - |
-
- - - |
-
- - - |
-
- - - |
ANIMAL 4 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 5 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
FEMALES 1 MG/LITER |
|||||||||||||||||
ANIMAL 6 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 7 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
- 1 - |
- 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 8 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 9 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 10 Skin / fur Brown staining (Ear left) Brown staining (Ear right) Brown staining (General) |
(1) (1) (1) |
- - 1 |
- - 1 |
1 1 - |
1 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
MALES 5 MG/LITER |
|||||||||||||||||
ANIMAL 11 Skin / fur Green staining (General) Brown staining (Ears) |
(1) (1) |
1 - |
1 - |
- 1 |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
ANIMAL 12 Skin / fur Green staining (General) Brown staining (Ears) |
(1) (1) |
1 - |
1 - |
- 1 |
- 1 |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
ANIMAL 13 Skin / fur Green staining (General) Brown staining (Ear right) Brown staining (Ears) |
(1) (1) (1) |
1 - - |
1 - - |
- - 1 |
- 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 14 Skin / fur Green staining (General) Brown staining (Ear right) Brown staining (Ears) |
(1) (1) (1) |
1 - - |
1 - - |
- - 1 |
- 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 15 Skin / fur Green staining (General) Brown staining (Ears) |
(1) (1) |
1 - |
1 - |
- 1 |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
FEMALES 5 MG/LITER |
|||||||||||||||||
ANIMAL 16 Skin / fur Green staining (General) Brown staining (Ears) |
(1) (1) |
1 - |
1 - |
- 1 |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
ANIMAL 17 Skin / fur Green staining (General) Brown staining (Ears) |
(1) (1) |
1 - |
1 - |
- 1 |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
ANIMAL 18 Skin / fur Green staining (General) Brown staining (Ear right) Brown staining (Ears) |
(1) (1) (1) |
1 - - |
1 - - |
- - 1 |
- 1 - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
- - - |
ANIMAL 19 Skin / fur Green staining (General) Brown staining (Ears) |
(1) (1) |
1 - |
1 - |
- 1 |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
ANIMAL 20 Skin / fur Green staining (General) Brown staining (Ears) |
(1) (1) |
1 - |
1 - |
- 1 |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
- - |
Body Weights (Gram)
SEX/DOSE LEVEL |
ANIMAL |
DAY 1 |
DAY 2 |
DAY 4 |
DAY 8 |
DAY 15 |
MALES 1 MG/LITER |
1 2 3 4 5
MEAN ST.DEV. N |
299 334 318 313 326
318 13 5 |
294 328 316 307 320
313 13 5 |
300 336 321 314 325
319 13 5 |
312 350 332 320 335
330 15 5 |
331 376 356 340 360
353 18 5 |
FEMALES 1 MG/LITER |
6 7 8 9 10
MEAN ST.DEV. N |
195 198 196 200 214
201 8 5 |
194 200 201 209 211
203 7 5 |
191 198 208 211 213
204 9 5 |
194 202 207 209 215
205 8 5 |
216 219 221 220 224
220 3 5 |
MALES 5 MG/LITER |
11 12 13 14 15
MEAN ST.DEV. N |
279 285 276 290 264
279 10 5 |
266 264 263 276 252
264 9 5 |
277 276 273 289 259
275 11 5 |
291 297 292 308 273
292 13 5 |
315 319 313 335 290
314 16 5 |
FEMALES 5 MG/LITER |
16 17 18 19 20
MEAN ST.DEV. N |
184 206 187 181 194
190 10 5 |
178 195 184 180 186
185 7 5 |
182 195 188 179 196
188 8 5 |
193 204 199 185 209
198 9 5 |
198 207 212 202 215
207 7 5 |
Macroscopic Findings
ANIMAL |
ORGAN |
FINDING |
DAY OF DEATH |
MALES 1 MG/LITER 1
2
3
4
5 |
|
No findings noted
No findings noted
No findings noted
No findings noted
No findings noted |
Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment |
FEMALES 1 MG/LITER 6
7
8
9
10 |
Thymus |
No findings noted
No findings noted
Left side: focus/foci, several, purple
No findings noted
No findings noted |
Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment |
MALES 5 MG/LITER 11
12
13
14
15 |
|
No findings noted
No findings noted
No findings noted
No findings noted
No findings noted |
Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment |
FEMALES 5 MG/LITER 16
17
18
19
20 |
|
No findings noted
No findings noted
No findings noted
No findings noted
No findings noted |
Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment Scheduled necropsy Day 15 after treatment |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 5 000 mg/m³
- Quality of whole database:
- Klimisch 1 study
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25 July 2016 to 09 August 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- Organization for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Section 4, Health Effects, No. 402, "Acute Dermal Toxicity", Paris, 1987.
- Deviations:
- yes
- Remarks:
- See "Any other information"
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Version / remarks:
- Commission Regulation (EC) No 440/2008 Part B: Methods for the Determination of Toxicity and other Health Effects; B.3: "Acute Toxicity (Dermal)". Official Journal of the European Union No. L142, May 2008, including most recent amendments.
- Deviations:
- yes
- Remarks:
- see "Any other information"
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1200 (Acute Dermal Toxicity)
- Version / remarks:
- United States Environmental Protection Agency (EPA). Health Effects Test Guidelines, OPPTS 870.1200, Acute Dermal Toxicity. Office of Prevention, Pesticides and Toxic Items (7101), EPA 712-C-98-192, August 1998.
- Deviations:
- yes
- Remarks:
- see "Any other information"
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- Test substance: 206534/AIdentification: Formaldehyde, oligomeric reaction products with acetone and diphenylamineAppearance: Dark brown flakesBatch: IC5B04P006Purity/Composition: 100% Unknown or Viable compositions, Complex reaction products and Biological materials (UVCB)Test substance storage: At room temperatureStable under storage conditions until: 26 February 2019 (expiry date)Chemical name (IUPAC), synonym or trade name: Formaldehyde, oligomeric reaction products with acetone and diphenylamine (BXA)CAS Number: 9003-80-9pH (1% in water, indicative range): 7.76 – 7.37 (determined by Charles River Den Bosch)
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Species: Rat, Wistar strain, Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany. Number of animals: 5 males and 5 females (females were nulliparous and non-pregnant). Age and body weight: Young adult animals (approx. 10 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean. Identification: Tail mark with indelible ink. Health inspection: At least prior to dosing. It was ensured that the animals were healthy and that the skin to be treated was intact and free from any abnormality.Conditions: Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle: the photoperiod was between 07:00 and 19:00 hrs daily. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study. Accommodation: Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom). Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm). Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany). Water: Free access to tap water. Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.
- Type of coverage:
- occlusive
- Vehicle:
- propylene glycol
- Details on dermal exposure:
- Test Item Preparation Vehicle: Propylene glycol (Merck, Darmstadt, Germany) (specific gravity 1.036) Rationale: The vehicle was selected based on trial preparation performed at Charles River Den Bosch and on test item data supplied by the Sponsor. There was no information available regarding the solubility or stability in vehicle. Preparation: The preparation (w/w) was kept at room temperature and dosed within 4 hours after adding the vehicle to the test item. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test item.Treatment Method: Dermal application. The test item (preparation) was stirred on a magnetic stirrer during application. Clipping One day before exposure (Day -1) an area of approximately 5x7 cm on the back of each animal was clipped. Application: The test item preparation was applied on an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test item preparation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.Application: period 24 hours, after which dressings were removed and the skin cleaned of residual test item using tap water. The skin was dried by gentle padding using a tissue.
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg (10 mL/kg) body weight.
- No. of animals per sex per dose:
- 10 animals (5 male/5 female)
- Control animals:
- not required
- Details on study design:
- Mortality/Viability: Twice daily. Body weights: Days 1 (pre-administration), 8 and 15. Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1). Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Statistics:
- Not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality occurred.
- Clinical signs:
- Flat posture, ptosis and/or chromodacryorrhoea (snout) were noted for all animals on Day 1.Black discoloration was seen in the treated skin-area of all animals on Days 2 and/or 3. This was considered due to the colour of the formulation. Scales and/or scabs were noted for animals no. 3, 4, 5 and 9 between Days 5 and 15. These local effects were considered not to have affected the conclusion of the study.
- Body weight:
- The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
- Gross pathology:
- No abnormalities were found at macroscopic post mortem examination of the animals.
- Other findings:
- No further findings specified in the study report
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The dermal LD50 value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was established to exceed 2000 mg/kg body weight.
- Executive summary:
Assessment of acute dermal toxicity with Formaldehyde, oligomeric reaction products with acetone and diphenylamine in the rat.
The study was carried out based on the guidelines described in:
OECD No.402 (1987) "Acute Dermal Toxicity"
Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)"
EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity"
JMAFF Guidelines (2000), including the most recent revisions.
Formaldehyde, oligomeric reaction products with acetone and diphenylamine was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).
No mortality occurred.
Flat posture, ptosis and/or chromodacryorrhoea (snout) were noted for all animals on Day 1.
Black discoloration was seen in the treated skin-area of all animals on Days 2 and/or 3. This was considered due to the colour of the formulation. Scales and/or scabs were noted for animals no. 3, 4, 5 and 9 between Days 5 and 15. These local effects were considered not to have affected the conclusion of the study.
The mean body weight gain during the observation period was within the range expected for rats used in this type of study.
No abnormalities were found at macroscopic post mortem examination of the animals.
The dermal LD50 value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results, Formaldehyde, oligomeric reaction products with acetone and diphenylamine does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Reference
MORTALITY DATA
TEST DAY |
1 |
1 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
HOURS AFTER TREATMENT |
0 |
2 |
4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
MALES 2000 MG/KG |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
FEMALES 2000 MG/KG |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
CLINICAL SIGNS
TEST DAY |
|
1 |
1 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
HOURS AFTER TREATMENT |
MAX GRADE |
0 |
2 |
4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
MALES 2000 MG/KG |
||||||||||||||||||
ANIMAL 1 Posture Flat posture Various Ptosis Black (Treated skin) |
(1)
(3) (1) |
-
- - |
-
- - |
1
3 - |
-
- 1 |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
ANIMAL 2 Posture Flat posture Various Ptosis Black (Treated skin) |
(1)
(3) (1) |
-
- - |
-
- - |
1
2 - |
-
- 1 |
-
- 1 |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
ANIMAL 3 Posture Flat posture Skin / fur Scales (Treated skin) Various Ptosis Black (Treated skin) |
(1)
(3)
(3) (1) |
-
-
- - |
-
-
- - |
1
-
2 - |
-
-
- 1 |
-
-
- - |
-
-
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
ANIMAL 4 Posture Flat posture Skin / fur Scales (Treated skin) Scabs Secretion / excretion Chromodacryorrhoea (Snout) Various Ptosis Black (Treated skin) |
(1)
(3) (3)
(3)
(3) (1) |
-
- -
1
- - |
-
- -
1
- - |
1
- -
1
3 - |
-
- -
-
- 1 |
-
- -
-
- 1 |
-
- -
-
- - |
-
1 -
-
- - |
-
1 -
-
- - |
-
1 -
-
- - |
-
1 -
-
- - |
-
1 1
-
- - |
-
1 1
-
- - |
-
1 1
-
- - |
-
- 1
-
- - |
-
- 1
-
- - |
-
- 1
-
- - |
-
- 1
-
- - |
ANIMAL 5 Posture Flat posture Skin / Fur Scales (Treated skin) Various Ptosis Black (Treated skin) |
(1)
(3)
(3) (1) |
-
-
- - |
-
-
- - |
1
-
3 - |
-
-
- 1 |
-
-
- 1 |
-
-
- - |
-
-
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
1
- - |
-
-
- - |
-
-
- - |
-
-
- - |
FEMALES 2000 MG/KG |
||||||||||||||||||
ANIMAL 6 Posture Flat posture Secretion / excretion Chromodacryorrhoea (Snout) Various Ptosis Black (Treated skin) |
(1)
(3)
(3) (1) |
-
-
- - |
-
1
- - |
1
1
3 - |
-
-
- 1 |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
-
-
- - |
ANIMAL 7 Posture Flat posture Various Ptosis Black (Treated skin) |
(1)
(3) (1) |
-
- - |
-
- - |
1
3 - |
-
- 1 |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
ANIMAL 8 Posture Flat posture Various Ptosis Black (Treated skin) |
(1)
(3) (1) |
-
- - |
-
- - |
1
2 - |
-
- 1 |
-
- 1 |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
ANIMAL 9 Posture Flat posture Skin / fur Scales (Treated skin) Scabs Various Ptosis Black (Treated skin) |
(1)
(3) (3)
(3) (1) |
-
- -
- - |
-
- -
- - |
1
- -
2 - |
-
- -
- 1 |
-
- -
- 1 |
-
- -
- - |
-
1 -
- - |
-
1 -
- - |
-
1 -
- - |
-
1 -
- - |
-
1 1
- - |
-
1 1
- - |
-
1 1
- - |
-
1 1
- - |
-
1 1
- - |
-
1 1
- - |
-
1 1
- - |
ANIMAL 10 Posture Flat posture Various Ptosis Black (Treated skin) |
(1)
(3) (1) |
-
- - |
-
- - |
1
3 - |
-
- 1 |
-
- 1 |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
-
- - |
- = sign not observed
BODY WEIGHTS (GRAM)
SEX/DOSE LEVEL |
ANIMAL |
DAY 1 |
DAY 8 |
DAY 15 |
MALES 2000 MG/KG |
||||
|
1 2 3 4 5 |
276 286 276 277 284 |
286 291 287 278 300 |
303 314 306 291 327 |
MEAN ST. DEV. N |
280 5 5 |
288 8 5 |
308 13 5 |
|
FEMALES 2000 MG/KG |
||||
|
6 7 8 9 10 |
182 182 189 189 186 |
181 198 186 194 188 |
195 206 192 210 191 |
MEAN ST. DEV. N |
186 4 5 |
189 7 5 |
199 9 5 |
MACROSCOPIC FINDINGS
ANIMAL |
ORGAN |
FINDING |
DAY OF DEATH |
MALES 2000 MG/KG |
|||
1 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
2 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
3 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
4 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
5 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
FEMALES 2000 MG/KG |
|||
6 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
7 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
8 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
9 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
10 |
|
No findings noted |
Scheduled necropsy Day 15 after treatment |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- K1 - GLP accredited laboratory study in accordance with recognised guidelines
Additional information
Acute toxicity via oral route
The aim of the test was to assess the toxicity of the test substance when administered orally in a single dose to female rats. The test was conducted in accordance with OECD Guideline 423. The oral LD50 value for Formaldehyde, oligomeric reaction products with acetone and diphenylamine was established to exceed 5000 mg/kg/bw. No mortalities occurred, however, there were clinical signs such as hunched posture, piloerection and/or uncoordinated movements were noted for all animals on Day 1. The body weight gain shown by the animals was considered to be similar to that expected for normal untreated animals of the same age and stain. No abnormalities were found at macroscopic post mortem examination of the animals.
Acute toxicity via dermal route
The aim of the test was to assess the toxicity of the test substance when administered by the dermal route to rats. The test was conducted in accordance with OECD Guideline 402. Formaldehyde, oligomeric reaction products with acetone and diphenylamine was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Flat posture, ptosis and/or chromodacryorrhoea (snout) were noted for all animals on Day 1. Black discoloration was seen in the treated skin-area of all animals on Days 2 and/or 3. This was considered due to the colour of the formulation. Scales and/or scabs were noted for animals no. 3, 4, 5 and 9 between Days 5 and 15. These local effects were considered not to have affected the conclusion of the study. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was established to exceed 2000 mg/kg body weight.
Acute toxicity via inhalation route
The aim of the test was to assess the toxicity of the test substance when administered by the inhalation route (nose-only) to rats. The test was conducted in accordance with OECD Guideline 403. Formaldehyde, oligomeric reaction products with acetone and diphenylamine was administered as a dust by nose-only inhalation for 4 hours to two groups of five male and five female Wistar rats. Mortality and clinical signs were observed daily during the observation period and body weights were determined on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (Day 15).
For the 1 mg/L exposure group, the time-weighted mean actual concentration was 1.1 ± 0.03 mg/L. The nominal concentration (amount of test item used divided by the volume of pressurized air used) was 9.7 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 11%. The concentration was measured at time points (n=28) that were equally distributed over the exposure period, the results of which demonstrated that it was difficult to maintain the test item stable. Overall, it was considered that the generation represented the intended exposure to the 1 mg/L target concentration for 4 hours.
For the 5 mg/L exposure group, the time-weighted mean actual concentration was 5.3 ± 0.4 mg/L. The nominal concentration was 64.1 mg/L and the generation efficiency was 8%. The concentration was measured at time points (n=21) that were equally distributed over the exposure period, the results of which showed that it was difficult to maintain a stable concentration. Overall, it was considered that the generation represented the intended exposure to the 5 mg/L target concentration for 4 hours.
The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice during the exposure period. At 1 mg/L, the MMAD was 3.9 μm (gsd 1.9) and 4.0 μm (gsd 2.1). At 5 mg/L, the MMAD was 4.0 μm (gsd 2.1) and 4.3 μm (gsd 2.0).
No mortality occurred. At 1 mg/L, quick breathing was seen during exposure. After exposure, one male showed hunched posture on Day 1. Brown staining by test item remnants of the skin and fur was seen between Days 1 and 6. At 5 mg/L, quick breathing was seen during exposure. After exposure, no systemic clinical signs were seen. Brown and green staining by test item remnants of the skin and fur was seen between Days 1 and 4. Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study and were therefore considered not indicative of toxicity. Macroscopic post mortem examination revealed several purple foci on the left side of the thymus of one female exposed to 1 mg/L. Macroscopic examination of the other animals did not reveal further abnormalities.
The generation of high dust concentrations is technically challenging. In this study, the concentration varied considerably during the first 2 hours. Over the total 4 hour exposure period, the time weighted mean concentration exceeded 5 mg/L. Considering the absence of mortality and severe signs, no significant mortality would be expected after exposure to 5 mg/L with less variation. Based on these results, the inhalatory LC50, 4h value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was considered to exceed 5 mg/L.
Justification for classification or non-classification
Acute toxicity via oral route
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, formaldehyde, oligomeric reaction products with acetone and diphenylamine does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
Acute toxicity via dermal route
The dermal LD50 value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results, Formaldehyde, oligomeric reaction products with acetone and diphenylamine does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Acute toxicity via inhalation route
Based on the results, the inhalatory LC50, 4h value of Formaldehyde, oligomeric reaction products with acetone and diphenylamine in Wistar rats was considered to exceed 5 mg/L. Based on the results of this study, formaldehyde, oligomeric reaction products with acetone and diphenylamine does not have to be classified and has no obligatory labelling requirement for acute inhalation toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments.
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