Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 212-661-4 | CAS number: 840-65-3
- 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 - Oral: NDC has an LD50 >5,000 mg/kg b.w .
Acute toxicity - Inhalation: The 4-hour acute inhalation median lethal concentration (LC50) of NDC in rats in a nose-only exposure is > 2.15 mg/L air.
Acute toxicity - Dermal: The acute dermal median lethal dose (LD50) of NDC is > 2,000 mg/kg b.w..
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:
- supporting study
- Study period:
- November to December 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study run to a reliable method and to GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- Principles of method if other than guideline:
- The study was performed to evaluate the acute oral toxicity of NDC was prepared as a 50% (w/v) suspension in corn oil and administered by oral gavage to a group of five male and five female Sprague-Dawley rats. The animals were administered 5 g of test article per kg of body weight, at a dosing volume of 10 ml/kg. Mortality, clinical observations, body weights and gross pathology were examined in the test.
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: approximately 6 weeks of age
- Weight at study initiation: 116-147 g
- Fasting period before study: 18 hours
- Housing: Housed individually in stainless steel wire cages (24.0 x 17.8 x 17.6 cm) suspended over deotized animal cage boards.
- Diet (e.g. ad libitum): Purina Rodent Chow 5001 (Ralston Purina Co., St. Louis, MO) was provided ad libitum.
- Water (e.g. ad libitum): Reverse-osmosis purified water was supplied ad libitum by means of an automatic watering system.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): 20 %
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
IN-LIFE DATES: From 19 November 1990 To: 3 December 1990
No additional information. - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 50% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg of body weight
- Justification for choice of vehicle:
- Lot/batch no. (if required): 127F-0373
DOSAGE PREPARATION (if unusual): DM-2,6-NDC was mixed thoroughly with corn oil and homogenized using a Polytron. The suspension was stirred continuously while being administered at a dosing volume of 10 mL/kg of body weight.
No additional information. - Doses:
- 5 g/kg bw
- No. of animals per sex per dose:
- A group of five male and five female
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The study animals were observed at approximately 3/4, 1-1/4, 2, 2-1/2, 4-1/4 and 6 hours after dosing and at least once per day for the balance of the 14-day observation period. All study animals were weighed prior to fasting and immediately prior to dosing. All surviving rats were also weighed on days 8 and 14 of the study.
- Necropsy of survivors performed: yes
No additional information - Statistics:
- None stated.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No deaths occurred during the study.
- Clinical signs:
- other: All of the rats appeared normal immediately following NDC administration and remained so for the duration of the study. One male rat developed sores on its forepaws and a female rat exhibited alopecia on its forepaws; these observations were not considere
- Gross pathology:
- Gross necropsy findings were within normal limits in all rats.
- Other findings:
- No information provided.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Based on the results of this study, the median acute lethal oral dose (LD50) of NDC was estimated to be greater than 5 g/kg of body weight in male and female rats.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 000 mg/kg bw
- Quality of whole database:
- 1
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:
- October 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Limited study summary, no guideline and no GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Deviations:
- no
- Principles of method if other than guideline:
- The test was made to determine the acute inhalation toxicity of Dimethyl-2,6-Naphthalene Dicarboxylate when administered to rats by a single nose-only exposure. A single group of five male and five female rats were exposed to respirable concentration of 2.15 mg/L for 4 hours. Clinical signs observed, body weights and necropsy findings were made during the test.
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Portage, MI
- Weight at study initiation: 125-150 g
- Housing: The rats were housed individually in suspended stainless steel cages measuring 15.8 x 15.5 x 17.0 cm.
- Diet (e.g. ad libitum): Purina Rodent Chow 5001 was available ad libitum
- Water (e.g. ad libitum): Water supplied from a reverse-osmosis purifier by an automatic watering system was available ad libitum
-Acclimation period: Approximately four weeks.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): 40%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
IN-LIFE DATES: From 2 October 1987 To: 16 October 1987
No additional information - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The chamber was made of glass and stainless steel.
- Exposure chamber volume: 0.5 m3
- Source and rate of air: 37 L/min.
- System of generating particulates/aerosols: The generator was a dry materials feeder (Model 310, AccuRate, Whitewater, WI) which contained a reservoir into which the ground Dimethyl-2,6-Naphthalene Dicarboxylate was placed.
- Method of particle size determination: The particle size of the aerosol was determined twice during the exposure using an Andersen cascade impactor (Andersen Samplers, Atlanta, GA).
- Treatment of exhaust air: The chamber air was exhausted into a waste collecting drum before being discharged to the outside environment.
- Temperature, humidity, pressure in air chamber: 21°C, relative humidity of 33%.
TEST ATMOSPHERE
- Brief description of analytical method used: The aerosol concentration was determined gravimetrically by drawing a known volume of the test atmosphere across an open-face filter and dividing the weight of Dimethyl-2,6-Naphthalene Dicarboxylate collected by the sample volume.
- Samples taken from breathing zone: yes
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The average particle size was 10.74 microns with a geometric standard deviation of 2.20.
No additional information. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- Nominal concentrations: 273 mg/L
Test concentration: 2.15 mg/L - No. of animals per sex per dose:
- A single group of five male and five female
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The test rats were observed approximately 1/2 and 3 hours after the exposure, and at least once per day for the balance of the 14-day observation period. All test rats were weighed prior to the exposure, weekly thereafter, and immediately prior to necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: Chamber concentration and chamber condition monitoring. - Statistics:
- None stated.
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 2.15 mg/L air
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- No rats died during the study.
- Clinical signs:
- other: Salivation, redness around the nose and eyes, and discolored facial fur were observed immediately following exposure. The inguinal fur of all rats was also soiled due to confinement in the nose-only exposure tubes. A single incident of discolored paws, ab
- Body weight:
- The mean initial body weights of the male and female rats were 353 g and 242 g, respectively. Mean body weights increased during the study, although several rats lost weight during the first week following exposure.
- Gross pathology:
- Necropsy findings consisted of grey lungs in nine rats and distended large intestines in one rat. One rat had no gross lesions.
- Other findings:
- Chamber concentration:The Dimethyl-2,6-Naphthalene Dicarboxylate was generated as a particulate aerosol The nominal concentration based on the total amount of Dimethyl-2,6-Naphthalene Dicarboxylate consumed was 273 mg/L. The gravimetric time weighted average (TWA) concentration was calculated to be 4.03 mg/L with 53.3% of the particles measuring less than 10 microns, thus resulting in an actual respirable concentration of 2.15 mg/L The average particle size was 10.74 microns with a geometric standard deviation of 2.20.
Chamber Conditions: The average chamber temperature was 21°C with a relative humidity of 33%. Temperature and relative humidity could not be monitored during the entire exposure, due to the heavy dust concentration. - Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The 4-hour acute inhalation median lethal concentration (LC50) of NDC in rats in a nose-only exposure ≥2.15 mg/L.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 2.15 mg/m³ air
- Quality of whole database:
- 1
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:
- November to December 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study run to a reliable method and to GLP
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Principles of method if other than guideline:
- NDC was applied at a dose of 2 g/kg of body weight to the shaved backs of five male and five female rabbits. The test article was left in contact with the skin for 24 hours and then removed. The rabbits were observed during this time and for 14 days thereafter.
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Johnson Rabbit Ranch
- Age at study initiation: 3-4 months of age
- Weight at study initiation: 2.33-3.00 kg
- Housing: Housed individually in stainless steel cages measuring 61.0 x 45.5 x 41.0 cm.
- Diet (e.g. ad libitum): Provided with approximately 150 g of Purina Lab Rabbit Chow HF #5326 daily.
- Water (e.g. ad libitum): Reverse osmosis-purified water was supplied ad libitum by means of an automatic watering system.
-Acclimation period: Approximately three weeks.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 20%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
IN-LIFE DATES: From:29 November 1990 To 14 December 14 1990
No additional information - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: 240 cm2
- Type of wrap if used: Covered with12.8 x 11.5 cm surgical dressing. The dressing was then covered by plastic film and secured by lint-free cloth and an elastic adhesive bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was wiped gently with gauze and 0.9% saline to remove residual Dimethyl-2,6-Naphthalene Dicarboxylate.
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg body weight
No additional information. - Duration of exposure:
- 24 hours
- Doses:
- 2 g/kg of body weigh
- No. of animals per sex per dose:
- five male and five female
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All test rabbits were observed approximately 3/4, 2, 3, 4-1/4 and 5 hours after dosing and at least once per day for 14 days after removal of the wrappings. All test animals were weighed immediately prior to dosing and the weights used for dosage calculations. The rabbits were also weighed seven days following Dimethyl-2,6-
Naphthalene Dicarboxylate application and at study termination.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
No additional information. - Statistics:
- None stated
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- >= 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No deaths occurred during the study.
- Gross pathology:
- Gross necropsy findings was within normal limits in all study rabbits.
- Other findings:
- No information provided
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The median acute lethal dermal dose (LD50) for NDC is greater than 2 g/kg of body weight.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- 1
Additional information
- naphthalene-2,6-dicarboxylic acid (CAS number 1141-38-4).
- Acute oral toxicity (supporting study); and
- Acute dernal toxicity (supporting study).
This registration contains a combined approach for addressing the required endpoints. The required endpoints are addressed using, when available, data on the substance to be registered, dimethyl naphthalene-2,6-dicarboxylate (CAS Number 840-65-3) (NDC). When these data are not available, data from the following close structural analogs is used to address the required endpoints.
Naphthalene-2,6-dicarboxylic acid is structurally similar to NDC, the registered substance, with a smiles code of c12c(cc(C(O)=O)cc2)ccc(c1)C(O)=O compared to that of c12c(cc(C(OC)=O)cc2)ccc(c1)C(OC)=O of NDC. The additional two methyl groups present in NDC are not expected to cause any significant differences in the toxicological effects of the registered substance nor it's degradation products.
Naphthalene-2,6-dicarboxylic acid data are used to address the following endpoints:
Oral route
Key study:
Following test conditions similar to OECD Guideline 401, conducted according to GLP, using male and female Sprague-Dawley rats,
the median acute oral LD50 of NDC is >5 g/kg b.w. (IIT Research, 1991).
Supporting studies:
In an OECD Guideline 401 study, conducted according to GLP, using male and female Crj: CD(SD) rats
the oral LD50 of NDC is >2,000 mg/kg b.w. (Ministry of Health and Welfare (MHW), 1997).
Following test conditions similar to OECD 401 (not conducted to GLP), using male and female Charles River rats,
the oral LD50 of NDC is >15,380 mg/kg (Industrial BIO-TEST Laboratories, Inc., 1974).
In a read-across study, following test conditions similar to OECD 401 (not conducted to GLP), using male and female Charles River rats, the oral LD50 of 2,6-Dimethylnaphthalene (CAS 581-42-0 and EC 209-464-0) is ≥ 13,430 mg/kg (Industrial BIO-TEST Laboratories, Inc., 1974).
Inhalation route
Following test conditions similar to OECD Guideline 403 (not conducted to GLP), using male and female Sprague-Dawley rats,
the 4 hour inhalation median LC50 of NDC to is >2.15 mg/L air (IIT Research Institute, 1987).
Dermal route
Key study:
Following test conditions similar to OECD Guideline 402, conducted according to GLP, using male and female New Zealand White rabbits, the dermal LD50 of NDC is >2 g/kg b.w. (IIT Research Institute, 1991).
Supporting studies:
Following test conditions similar to OECD 402 (not conducted to GLP), using male and female New Zealand White rabbits, the dermal LD50 of NDC is >3,000 mg/kg b.w. (Industrial BIO-TEST Laboratories, Inc., 1974).
In a read-across study, following test conditions similar to OECD 402 (not conducted to GLP), using male and female New Zealand White rabbits, the dermal LD50 of 2,6-Dimethylnaphthalene (CAS 581-42-0 and EC 209-464-0) is > 3,000 mg/kg (Industrial BIO-TEST Laboratories, Inc., 1974).
Justification for selection of acute toxicity – oral endpoint
Well conducted study in accordance with OECD Guideline 401 and GLP.
Justification for selection of acute toxicity – inhalation endpoint
Well conducted study, test conditions similar to OECD 402 (no GLP). Only one inhalation route study available.
Justification for selection of acute toxicity – dermal endpoint
Well conducted study , test conditions similar to OECD Guideline 403, conducted according to GLP.
Justification for classification or non-classification
Oral route:
The oral LD50 of NDC is >5,000 mg/kg b.w., therefore, according to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, Table 3.1.1, NDC is not classified for Acute Oral Toxicity.
Inhalation route
The 4 hour inhalation median LC50 of NDC is >2.15 mg/L air, therefore, according to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, Table 3.1.1, NDC is not classified for Acute Inhalation Toxicity.
Dermal route
The dermal LD50 of NDC is estimated to be >2 g/kg b.w., therefore, according to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, Table 3.1.1, NDC is not classified for Acute Dermal Toxicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.