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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 268-776-5 | CAS number: 68140-14-7
- 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
This endpoint is addressed based on read across to repeated dose oral toxicity data for the major components (AAI_DETA and Rosin) of the submission substance DTO_DETA.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- It is considered appropriate to address the data requirements for DTO_DETA by read-across to the available studies on the main components of DTO_DETA: AAI_DETA and Rosin.
DTO_DETA contains comparatively lower levels of imidazolines and higher levels of resin acids than AAI_DETA and therefore consideration of data for resin acids is also considered necessary. The main resin acid in DTO_DETA is abietic acid, but abietic acid derivatives and other acids, such as pimaric acid, are also found in notable quantities, and the resin acids collectively are known as ‘rosin’. DTO_DETA contains up to 25% unreacted rosin, and taking into account the compositional information available for the rosin in DTO_DETA and Rosin (CAS# 8050-09-07, EC# 232-475-7), the latter was considered appropriate for read-across to DTO_DETA.
A recent guideline (OECD 408) 90-day rat study has been conducted with the read across (source) substance AAI_DETA (WIL Research, 2014). In addition, a combined repeated dose oral toxicity study with reproduction/developmental toxicity (OECD 422) conducted with AAI_DETA is available (NOTOX, 2010). Read across to these studies is considered appropriate since AAI_DETA is the main component in the target substance, DTO_DETA. The lowest NOAEL is 10 mg/kg bw/d (90-day) and this value will be used for DNEL derivation. A number of studies conducted with Rosins are available as supporting information; the studies are generally older and predate current guidelines however when taken as a weight of evidence approach they indicate low toxicity following repeated exposure in rats and dogs. The 90-day NOAEL for systemic toxicity following exposure to rosin and its derivatives was found to be 400-500 mg/kg bw/d. Based on these results, the Rosin content is not considered to affect the hazard profile of DTO_DETA following sub-chronic exposure, and therefore read across to AAI_DETA is both justified and conservative. - Reason / purpose for cross-reference:
- read-across source
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Males at 30 and 100 mg/kg showed a lower mean body weight and body weight gain from Week 5 of the treatment period onwards, being statistically significant at 100 mg/kg. The lower mean body weight at 100 mg/kg was considered to be primarily due to a lower weight gain of two males. Mean body weight and body weight gain of females at 100 mg/kg also appeared slightly lower than controls during the last weeks of treatment.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Males at 30 and 100 mg/kg showed a slightly lower food intake during the larger part of the treatment period. After correction for body weight, food consumption of these males was similar to control levels. Food consumption before or after correction for body weight for females remained similar to control means over the study period.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- Based on subjective appraisal.
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The following (statistically significant) changes in clinical biochemistry parameters distinguished treated animals from control animals:
- Higher alanine aminotransferase activity (ALAT) in males and females (most notably for one female) at 100 mg/kg,
- Higher aspartate aminotransferase activity (ASAT) in males (most notably for one male) and females at 100 mg/kg,
- Lower total protein levels in males (most notably for one male) and females at 100 mg/kg,
- Lower albumin levels in males (most notably for one male) and females at 100 mg/kg,
- Higher glucose levels in males at 100 mg/kg (upon excluding one male),
- Lower urea levels in males at 100 mg/kg (a trend towards an increase was also apparent among female dose groups),
- Higher bile acid levels in females at 100 mg/kg,
- Lower calcium levels in females at 100 mg/kg.
One male at 100 mg/kg also showed a lower glucose value and a higher total bilirubin, bile acid and inorganic phosphate level. - Urinalysis findings:
- not specified
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- Males at 100 mg/kg showed a statistically significantly lower motor activity (based on counts for total movements). Females also showed a trend towards lower motor activity at 30 and 100 mg/kg, but means did not achieve a level of statistical significance.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- The following (statistically significant) changes in absolute organ weights and relative organ weights (organ to body weight ratio) were considered to be related to treatment:
- Lower liver weights in males at 100 mg/kg (with a decreasing trend for absolute liver weights across other male groups),
- Lower thymus weights in males at 100 mg/kg (with a decreasing trend for absolute thymus weights across other male groups),
- Lower spleen weights in males at 100 mg/kg (with a decreasing trend for absolute spleen weights across other male groups).
- Lower prostate weights at 100 mg/kg. - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The following microscopic findings were considered to be related to treatment:
- Lung (alveolar (mainly foamy) macrophage aggregations):
At 100 mg/kg: increased incidence and severity in females (6/10 females, 4 minimal, 2 slight).
- Small intestines (foamy macrophages in the lamina propria):
At 10 mg/kg: in jejunum in 1/10 males and 3/10 females and in ileum in 3/10 males and 3/9 females (all minimal).
At 30 mg/kg: in duodenum in 1/10 males (slight), in jejunum in 1/10 males (minimal) and 4/10 females (minimal) and in ileum in 8/10 males (6: minimal, 2: slight) and females 10/10 females (5: minimal, 5: slight).
At 100 mg/kg: in duodenum in 8/10 males (7: minimal, 1:slight) and in 5/10 females (4: minimal, 1: slight), in jejunum in 10/10 males (2: minimal, 8: slight) and 8/10 females (6: minimal, 2: slight) and in ileum in 10/10 males (1: minimal, 7: slight, 2: moderate) and in 10/10 females (8: slight, 2: moderate).
- Kidneys (foamy macrophages in the glomeruli):
At 100 mg/kg: in 7/10 males (6: minimal, 1: slight) and in 9/10 females (minimal).
- Mesenteric lymph node (foamy macrophages):
At 10 mg/kg: in 1/10 female (slight),
At 30 mg/kg: in 2/10 males (minimal) and in 3/10 females (minimal)
At 100 mg/kg: in 10/10 males (7: slight, 2: moderate, 1: marked) and in 8/10 females (1: slight, 7: moderate).
- Mesenteric lymph node (pigmented macrophage foci):
At 30 mg/kg: slightly increased incidence and/or severity in 9/10 males (4: minimal, 5: slight) and in 9/10 females (7: minimal, 2: slight).
At 100 mg/kg: slightly increased incidence and/or severity in 10/10 males (5: minimal, 5: slight) and in 7/10 females (3: minimal, 4 slight). - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- ESTROUS CYCLE DETERMINATION
No treatment related changes in estrous cycle length were noted across the dose groups during the period in which estrous cycle length was determined (Day 72 up to and including Day 92). One control female, and three females at 30 mg/kg showed an irregular estrous cycle length. All other females showed a normal (regular) estrous cycle of 4 days. The incidence of irregular estrous cycle length showed no relationship to the dose, and was therefore considered unrelated to treatment.
SPERM ANALYSIS
The spermatogenic staging profiles were normal for all males of the control group and the 100 mg/kg group, except for one male at 100 mg/kg (all stages missing). The macroscopic and microscopic findings recorded for this male at 100 mg/kg included effects in the reproductive organs (flaccid and reduced size of testes, microscopic correlate: undeveloped testes; reduced size of epididymides, microscopic correlate: reduced sperm; reduced size of prostate gland, microscopic correlate: immature) and liver (reduced size, no microscopic correlate and accentuated lobular pattern, microscopic correlate: difference in cell size periportal-centrilobular). These findings for this single male at 100 mg/kg were considered to be incidental findings and unrelated to treatment. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 30 mg/kg bw/day (nominal)
- System:
- gastrointestinal tract
- Organ:
- intestine
- mesenteric lymph node
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
- Conclusions:
- The 90-day NOAEL is considered to be 10 mg/kg bw/d. At higher dose levels an increase of the presence of foamy macrophages in the lamina propria of the small intestines and mesenteric lymph nodes is observed, as well as lower mean body weight and body weight gain, especially in the males, with lower food intake, essentially during the second half of the treatment period.
- Executive summary:
A guideline (OECD 408) 90-day rat study has been conducted with the read across (source) substance AAI_DETA (WIL Research, 2014). AAI_DETA was administered to rats by daily gavage at dose levels of 0, 10, 30 and 100 mg/kg bw/d for 90 days. The NOAEL was determined to be 10 mg/kg bw/d based on the presence of foamy macrophages in the lamina propria of the small intestines and mesenteric lymph nodes, as well as lower mean body weights and body weight gain with lower food intake at 30 mg/kg bw/d and above. AAI_DETA is a major component of DTO_DETA therefore read across is considered justified. A number of other repeated dose toxicity studies are available for AAI_DETA and Rosins, and are provided as supporting information; the NOAEL obtained in the 90-day rat study with AAI_DETA (WIL Research, 2014) is the lowest available NOAEL and is therefore used for DNEL derivation.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 10 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Read across to OECD guideline and GLP-compliant study
- System:
- gastrointestinal tract
- Organ:
- intestine
- mesenteric lymph node
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose oral toxicity
No repeated dose oral toxicity data are available for DTO_DETA; this endpoint is addressed based on read across to studies conducted on the main components of DTO_DETA: AAI_DETA and Rosin. Studies available in the rat and dog with Gum Rosin indicate low toxicity with minor effects linked to poor palatability; these studies demonstrate that the rosin component will not significantly impact on the overall toxicity profile of DTO_DETA. A guideline (OECD 408) 90-day rat study is available with AAI_DETA (WIL Research, 2014). The NOAEL was determined to be 10 mg/kg bw/d based on the presence of foamy macrophages in the lamina propria of the small intestines and mesenteric lymph nodes, as well as lower mean body weights and body weight gain with lower food intake at 30 mg/kg bw/d and above. A number of other repeated dose toxicity studies are available for AAI_DETA and are provided as supporting information; the NOAEL obtained in the 90-day rat study with AAI_DETA is the lowest available and is therefore used for DNEL derivation.
Justification for classification or non-classification
Based on the results of the available studies, DTO_DETA does not require classification for repeated exposure (STOT-RE) according to Regulation (EC) No. 1272/2008.
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.